Evidence for Carcinogenicity:
Classification of carcinogenicity: 1) evidence in humans: sufficient; 2)
evidence in animals: sufficient; Overall summary evaluation of carcinogenic risk
to humans is group 1: The chemical is carcinogenic to humans. /From table/
A2. A1= Confirmed Human Carcinogen (2000)
WEIGHT-OF-EVIDENCE CHARACTERIZATION: Benzene
is classified as a "known" human carcinogen (Category A) under the
Risk Assessment Guidelines of 1986. Under the proposed revised Carcinogen Risk
Asessment Guidelines (USEPA, 1996), benzene
is characterized as a known human carcinogen for all routes of exposure based
upon convincing human evidence as well as supporting evidence from animal
studies. Epidemiologic studies and case studies provide clear evidence of a
causal association between exposure to benzene
and acute nonlymphocytic leukemia and also suggest evidence for chronic
nonlymphocytic leukemia and chronic lymphocytic leukemia. Other neoplastic
conditions that are associated with an increased risk in humans are hematologic
neoplasms, blood disorders such as preleukemia and aplastic anemia, Hodgkin's
lymphoma, and myelodysplastic syndrome. These human data are supported by animal
studies. The experimental animal data add to the argument that exposure to benzene
increases the risk of cancer in multiple species at multiple organ sites (hematopoietic,
oral and nasal, liver, forestomach, preputial gland, lung, ovary, and mammary
gland). It is likely that these responses are due to interactions of the
metabolites of benzene with DNA ...
Recent evidence supports the viewpoint that there are likely multiple
mechanistic pathways leading ... to leukemogenesis from exposure to benzene.
HUMAN CARCINOGENICITY DATA: Benzene is
a known human carcinogen based upon evidence presented in numerous occupational
epidemiological studies. Significantly increased risks of leukemia, chiefly
acute myelogenous leukemia, have been reported in benzene-exposed
workers in the chemical industry, shoemaking and oil refineries. ANIMAL
CARCINOGENICITY DATA:... many experimental animal studies, both inhalation and
oral, also support the evidence that exposure to benzene
increases the risk of cancer in multiple organ systems, including the
hematopoietic system, oral and nasal cavities, liver, forestomach, preputial
gland, lung, ovary, and mammary gland ....
Human Toxicity Excerpts:
Benzene is irritant to skin, &
by defatting the keratin layer may cause erythema, vesiculation, & dry &
scaly dermatitis.
AFTER A SHORT EXPOSURE TO A LARGE AMT OF BENZENE,
BY INGESTION OR BY BREATHING CONCENTRATED VAPORS, THE MAJOR TOXIC EFFECT IS ON
THE CNS. SYMPTOMS FROM MILD EXPOSURE INCL DIZZINESS, WEAKNESS, EUPHORIA,
HEADACHE, NAUSEA, VOMITING, TIGHTNESS IN CHEST, & STAGGERING. IF EXPOSURE IS
MORE SEVERE, SYMPTOMS PROGRESS TO BLURRED VISION, TREMORS, SHALLOW & RAPID
RESP, VENTRICULAR IRREGULARITIES, PARALYSIS, & UNCONSCIOUSNESS.
Long-term exposure to benzene
usually is due to the inhalation of vapor or to contact with the skin. Signs and
symptoms of long-term exposure to benzene
incl effects on the CNS & the GI tract (headache, loss of appetite,
drowsiness, nervousness, & pallor), but the major manifestation of toxicity
is aplastic anemia. Bone marrow cells in early stages of development are most
the sensitive ... & arrest of maturation leads to gradual depletion of
circulating cells.
BENZENE (BENZOL)
... HAS SPECIFIC TOXIC EFFECT ON BLOOD FORMATION, CAUSING APLASTIC ANEMIA &
TENDENCY TO HEMORRHAGE. OCCASIONALLY HEMORRHAGES IN RETINA & IN CONJUNCTIVA
ARE FOUND IN SYSTEMIC POISONING BY BENZENE.
IN RARE INSTANCES NEURORETINAL EDEMA & PAPILLEDEMA HAVE BEEN DESCRIBED
ACCOMPANYING RETINAL HEMORRHAGES. IT HAS NOT BEEN ESTABLISHED THAT BENZENE
CAN INDUCE RETROBULBAR NEURITIS OR OPTIC NEURITIS ...
PATHOLOGICAL FINDINGS FROM ... INHALATION INCL ACUTE GRANULAR TRACHEITIS,
LARYNGITIS & BRONCHITIS, MASSIVE HEMORRHAGE OF LUNG, CONGESTIVE GASTRITIS,
INFARCT OF SPLEEN, ACUTE CONGESTION OF KIDNEYS, & MARKED CEREBRAL EDEMA.
Many acute deaths /from benzene
exposure at high concn have been/ ... due to ventricular fibrillation ...
/caused by exertion/ & release of epinephrine. This was probably the
mechanism involved in the death of workers in tank cars which had contained benzene.
Frequently, the man who went into the tank car to carry out an unconscious
worker died during the effort of lifting the unconscious man up the ladder.
... A large number of workers exposed to but not seriously intoxicated by benzene
/were studied & results showed/ that serum complement levels, IgG, & IgA,
were depressed but that IgM levels did not drop & were in fact slightly
higher (Lange et al 1973; Smolik et al 1973). ... These /& other/
observations, taken together with well-known ability of benzene
to depress leukocytes ... may explain why benzene-intoxicated
individuals readily succumb to infection & why terminal event in severe ...
toxicity is often an acute, overwhelming infection.
IN EXPT IN VITRO, BENZENE DID NOT
CHANGE THE NUMBER OF SISTER-CHROMATID EXCHANGES OR THE NUMBER OF CHROMOSOMAL
ABERRATIONS IN HUMAN LYMPHOCYTES.
THE MUTAGENIC ACTIVITY UPON HUMAN LYMPHOCYTES WAS STUDIED AFTER ITS ADDN TO
CULTURE ON THE 28TH HR OF CULTIVATION (G1-S PERIODS). CONCN OF 1, 10, 25, 50,
100, & 250 UG/ML WERE STUDIED. BENZENE
IS A WEAK MUTAGEN. IT CAUSED ELONGATION OF CENTROMERE PORTIONS OF CHROMOSOMES
& CHROMOSOMAL ABERRATIONS WERE MAINLY OF SINGLE & PAIRED FRAGMENT TYPE.
MUTAGENIC ACTIVITY WAS ABOUT THE SAME IN THE G0 & G1-S PERIODS.
A major concern is the relationship between long-term exposure to benzene
& leukemia. Epidemiological studies have been conducted on workers in the
tire industry & in shoe factories, where benzene
was used extensively. Among workers who died from exposure to benzene,
death was caused by either leukemia or aplastic anemia, in approx equal
proportions.
CHRONIC BENZENE TOXICITY IS
EXPRESSED AS BONE MARROW DEPRESSION RESULTING IN LEUCOPENIA, ANEMIA, OR
THROMBOCYTOPENIA (LEUKEMOGENIC ACTION). WITH CONTINUED EXPOSURE THE DISEASE
PROGRESSES TO PANCYTOPENIA RESULTING FROM BONE MARROW APLASIA. EVIDENCE HAS
ACCUM IMPLICATING BENZENE IN THE
ETIOLOGY OF LEUKEMIAS IN WORKERS IN INDUSTRIES WHERE BENZENE
WAS HEAVILY USED. IT HAS BEEN SUGGESTED THAT LEUKEMIA IS AS FREQUENT A CAUSE OF
DEATH FROM CHRONIC BENZENE EXPOSURE AS
IS APLASTIC ANEMIA.
MANY CASES OF ACUTE LEUKEMIA DEVELOPING AS TERMINAL STAGE OF APLASTIC ANEMIA
RESULTING FROM EXPOSURE TO BENZENE MAY
HAVE BEEN MISSED BECAUSE BONE MARROW PUNCTURE WAS NOT PERFORMED. BENZENE
LEUKEMIA IS ACUTE STEM CELL OR MYELOBLASTIC LEUKEMIA, SOMETIMES ALEUKEMIA. THERE
MAY BE A LATENT PERIOD EXTENDING OVER SEVERAL YEARS BETWEEN CESSATION OF
EXPOSURE WITH MORE OR LESS PRONOUNCED ANEMIA, & THE ONSET OF LEUKEMIA.
A dose-related increase in the number of cells with chromosomal aberrations
occurred in human lymphocyte cultures treated with 4X10-5 M and 3.0X10-3 M benzene
for 53 hr prior to metaphase analysis. Cells in late G2 stage were the most
susceptible to the effect of benzene.
Epidemiological studies (exposure to high concn is associated with
hematotoxicity and acute myelocytic leukemia in humans ...)
Italian shoemakers exposed to 200-500 ppm benzene
in inks and glues showed an incidence of leukemia of 1 per 1,000.
Follow up study at Massachusetts rubber coating plants of 38 workers exposed
over 1-24 yr at 5-50 ppm (140 ppm peak) showed no evidence of blood dyscrasias
or leukemia.
A significantly incr frequency of chromatid and isochromatid breaks in the
cultured lymphocytes of workers in chemical laboratories and in the printing
industry has been reported.
A significant incr of peripheral blood lymphocyte chromosomal aberrations in
workers exposed to benzene was
reported, but not in those exposed to toluene and xylene.
A report on 52 workers exposed to benzene
found chromosomal aberrations (chromosome breaks, dicentric chromosomes,
translocations, and exchange figures) in peripheral lymphocytes at 2-3 times the
rates found in controls. The 8 hr TWA exposure was 2-3 ppm, the average concn
determined by 15 min sampling was 25 ppm, and the peak concn was 50 ppm.
An epidemiological study implicating benzene
as a leukemogen (acute myelocytic leukemia) followed 748 white males exposed to benzene
in the manufacture of a rubber product from 1940-1949. A statistically
significant (p < or = 0.002) excess of leukemia was found when compared
against two control populations. There was a 5 fold excessive risk of all
leukemias and a 10 fold excessive risk of myelocytic and monocytic leukemias
combined.
A hematological investigation was carried out on 147 workers (employed for
+10 years) exposed to high benzene
levels (320-470 ppm). Abnormalities were noted in at least one parameter in 73%,
the most common one being thrombocytopenia, which occurred in 62% followed by
anemia (35%) and leucopenia (32%). Pancytopenia occurred in 21% of the workers.
During the 3 months following removal from exposure, hematological parameters
returned to normal in 120 workers, and one subject died. After one year, 20 of
the remaining workers had only minor abnormalities, six were still off work, and
one was still hospitalized.
A retrospective mortality study of a cohort of 594 men exposed to benzene
at levels ranging between 2 and 25 ppm (TWA) was carried out at the Dow Chemical
Co between 1940-1973. No incr in total mortality was noted with 102 observed/128
expected (Standard Mortality Ratio (SMR) 80). A slight increase was noted in
total deaths due to malignancies (30 observed/22.8 expected, SMR 132) and
suicide (5 observed/3.2 expected, SMR 147) as well as deaths from leukemia (3
observed/0.8 expected) and cancers of the digestive organs and peritoneum (9
observed/6.9 expected, SMR 125). If 53 workers exposed to other chemicals are
excluded from malignancies, the results would then be 24 observed/20.3 expected,
SMR 108.
/A subset of 292 men of the 594 in the benzene
exposure of Dow cohort who were still employed in 1967/ had an examination of
the health status /evaluation/ carried out between 1967-1974 and compared to a
control population selected from employees not exposed to benzene,
using a matched pair design (matched for age, cigarette smoking habits and
length of employment). No clinically significant differences were reported
although slight decr in total bilirubin levels and red blood cell counts were
noted.
Thirty two patients who had recovered from a blood disease (bone marrow
impairment) caused by benzene
poisoning had significantly increased rates of "unstable" and
"stable" chromosomes. Aberrations of chromosomes were present for
several years after cessation of the exposure and after recovery from poisoning.
Persistence of an increase of the "stable" changes was particularly
remarkable.
NUMEROUS STUDIES HAVE BEEN CARRIED OUT ON THE CHROMOSOMES OF BONE-MARROW
CELLS & PERIPHERAL LYMPHOCYTES FROM PEOPLE KNOWN TO HAVE BEEN EXPOSED TO BENZENE.
... IN MANY OF THESE STUDIES, SIGNIFICANT INCR IN CHROMOSOMAL ABERRATIONS HAVE
BEEN SEEN, WHICH IN SOME CASES HAVE PERSISTED FOR YEARS AFTER CESSATION OF
EXPOSURE. ... BONE-MARROW CELLS & PERIPHERAL LYMPHOCYTES /HAVE BEEN EXAM/
FROM WORKERS WITH CURRENT SEVERE BLOOD DYSCRASIAS, & ... /FOLLOW-UP STUDIES
HAVE BEEN DONE ON/ SEVERAL WORKERS BY REPEATED CYTOGENETIC STUDIES UP TO 12 YR
AFTER RECOVERY FROM BENZENE-INDUCED
PANCYTOPENIA. GROSS CHROMOSOMAL ABNORMALITIES WERE CHARACTERISTIC OF THESE
CELLS; 70% OF THE BONE-MARROW CELLS & LYMPHOCYTES IN PT WITH ACUTE POISONING
SHOWED KARYOTYPIC ABNORMALITIES. THE AUTHORS COULD NOT RELATE THE FREQUENCY OR
TYPE OF CHROMOSOMAL ALTERATIONS TO THE SEVERITY OF BLOOD DYSCRASIA. FIVE YR
AFTER POISONING, ALL ... 5 PATIENTS STUDIED STILL SHOWED STABLE (Cs) &
UNSTABLE (Cu) CHROMOSOMAL ABERRATIONS IN ... LYMPHOCYTES, ALTHOUGH ONLY 40% OF
CELLS WERE NOW ABNORMAL. BY 12 YR ... NO CYTOGENETIC ABNORMALITIES REMAINED IN
THE 4 PATIENTS STUDIED.
METABOLIC ACTIVATION OF BENZENE BY
RAT LIVER MICROSOMES & A REDUCED NADP-GENERATING SYSTEM (S-9 MIX) INDUCED
SISTER CHROMATID EXCHANGES (SCE) & CELL DIVISION DELAYS IN CULTURED HUMAN
LYMPHOCYTES. THERE WERE OPTIMAL CONCN OF S-9 MIX FOR THE CONVERSION OF BENZENE
INTO THE ACTIVE METABOLITES THAT EXERTED THESE CYTOTOXIC EFFECTS.
... INCIDENCE OF ACUTE LEUKEMIA OR 'PRELEUKEMIA' AMONG 28,500 SHOE-WORKERS IN
TURKEY /WAS ESTIMATED/ ON BASIS OF CASE ASCERTAINMENT BY CONTACT WITH MEDICAL
CARE. THIRTY FOUR CASES WERE IDENTIFIED. ... INCIDENCE OF ACUTE LEUKEMIA WAS
SIGNIFICANTLY GREATER AMONG WORKERS CHRONICALLY EXPOSED TO BENZENE,
WHICH WAS USED AS A SOLVENT BY THESE WORKERS, THAN IN THE GENERAL POPULATION.
OCCUPATIONAL EXPOSURES WERE DETERMINED BY WORK HISTORIES & BY ENVIRONMENTAL
MEASUREMENTS. THERE WAS SAID TO BE EXPOSURE ONLY TO BENZENE
IN SMALL, POORLY VENTILATED WORK AREAS; PEAK EXPOSURES ... WERE REPORTED TO BE
210-650 PPM (670-2075 MG/CU M). DURATION ... WAS EST TO HAVE BEEN 1 TO 15 YR
(MEAN 9.7 YR). ANNUAL INCIDENCE WAS EST TO BE 13/100000, GIVING APPROX RELATIVE
RISK OF 2 WHEN COMPARED WITH ANNUAL EST FOR GENERAL POPULATION, 6/100000. (THESE
EST ARE LIMITED BY STUDY DESIGN CHARACTERISTICS & BY UNCERTAINTY ABOUT THE
WAY IN WHICH CASES WERE ASCERTAINED, & HOW MANY OF THE STUDY POPULATION WERE
EXPOSED & HOW MANY UNEXPOSED).
OCCUPATIONAL EXPOSURES WERE IDENTIFIED IN ROTOGRAVURE PLANTS & SHOE
FACTORIES. BENZENE CONCN NEAR
ROTOGRAVURE MACHINES WERE 200-400 PPM (640-1280 MG/CU M), WITH PEAKS UP TO 1500
PPM (4800 MG/CU M); BENZENE CONCN IN
AIR NEAR WORKERS HANDLING GLUE IN SHOE FACTORIES WERE 25-600 PPM (80-1920 MG/CU
M), BUT WERE MOSTLY AROUND 200-500 PPM (640-1600 MG/CU M). EST LATENCY (YEARS
FROM START OF EXPOSURE TO CLINICAL DIAGNOSIS OF LEUKEMIA) RANGED FROM 3-24 YR
(MEDIAN, 9 YR). ... THE RELATIVE RISK OF ACUTE LEUKEMIA WAS /EST TO BE/ AT LEAST
20:1 FOR WORKERS HEAVILY EXPOSED TO BENZENE
IN ROTOGRAVURE & SHOE INDUSTRIES IN THE PROVINCES STUDIED, WHEN COMPARED
WITH GENERAL POPULATION. (THE RELATIVE RISK IS BASED ON A NON-VALIDATED
ESTIMATE).
A HISTORICAL COHORT MORTALITY STUDY WAS CONDUCTED OF 259 MALE EMPLOYEES OF A
CHEM PLANT WHERE BENZENE HAS BEEN USED
IN LARGE QUANTITIES. THE STUDY GROUP INCL ALL PERSONS WHO WERE EMPLOYED BY THE
COMPANY ANY TIME BETWEEN JAN 1, 1947 & DEC 31, 1960. THE COHORT WAS FOLLOWED
THROUGH DEC 31, 1977 AT WHICH TIME 58 KNOWN DEATHS WERE IDENTIFIED. THE ONLY
UNUSUAL FINDING WAS FOUR DEATHS FROM LYMPHORETICULAR CANCERS WHEN 1.1 WOULD HAVE
BEEN EXPECTED ON THE BASIS OF NATIONAL MORTALITY RATES. THREE OF THE DEATHS WERE
DUE TO LEUKEMIA & 1 WAS CAUSED BY MULTIPLE MYELOMA. IN ADDN, 1 OF THE
LEUKEMIA DEATHS HAD MULTIPLE MYELOMA LISTED ON THE DEATH CERTIFICATE. THE
FINDINGS ARE CONSISTENT WITH PREVIOUS REPORTS OF LEUKEMIA FOLLOWING OCCUPATIONAL
EXPOSURE TO BENZENE & RAISE THE
POSSIBILITY THAT MULTIPLE MYELOMA COULD BE LINKED TO BENZENE,
ALSO.
HEMATOLOGIC & IMMUNOCHEMICAL INVESTIGATIONS CARRIED OUT IN 270 WORKERS
WITH CHRONIC EXPOSURE TO BENZENE
DEMONSTRATED CHANGES OF THE NUCLEOLOGRAM & OF THE AREA OF LYMPHOCYTE
NUCLEOLI & DISORDERS OF THE HUMORAL IMMUNE RESPONSE REVEALED BY RADIAL
IMMUNODIFFUSION. THE NUMERICAL RISE OF BI- & POLYNUCLEOLATED CELLS, OF CELLS
WITH IRREGULAR MACRONUCLEOLI & AN ENLARGEMENT OF THE NUCLEOLAR AREA
REFLECTED INCR ENDOLYMPHOCYTIC AMT OF RNA. AN INCR CAPACITY OF IG FORMATION,
PARTICULARLY OF IGM, WAS ALSO OBSERVED.
SOME ASPECTS OF QUANTITATIVE CANCER RISK ESTIMATION: ... RISK IS GREATEST
AMONG THOSE WITH LONGEST EXPOSURE, RELATIVE RISKS OF APPROX 2, 14 & 32 BEING
OBSERVED FOR EXPOSURES OF LESS THAN 5 YR (2 CASES), 5-9 YR (2 CASES) & 10+
YR (3 CASES), RESPECTIVELY. THE RELATIVE RISK ASSOC WITH AT LEAST 5 YR OF
EXPOSURE IS THUS LIKELY TO BE LOWER BOUND FOR RISK ASSOC WITH LIFETIME EXPOSURE
AT SIMILAR LEVELS. FOR THOSE WITH AT LEAST 5 YR EXPOSURE, 5 CASES WERE OBSERVED
COMPARED WITH AN EXPECTED NUMBER OF 0.237, GIVING A RELATIVE RISK OF 21.1. SINCE
THE EXPECTED CUMULATIVE MALE ADULT LIFETIME (FROM 20 YR TO END OF LIFE, TAKEN AS
AGE 75) PROBABILITY OF DYING FROM LEUKEMIA IS APPROX 7 PER 1000 IN THE GENERAL
POPULATION OF THE USA, AN EXPECTED RELATIVE RISK OF 21.1 WOULD GIVE AN EXTRA
(21.1-1.0)X7= 141 CASES OF LEUKEMIA PER 1000 EXPOSED POPULATION.
The hematotoxicity of benzene is
expressed primarily as a bone marrow effect leading eventually to complete
destruction of myeloid and erythroid marrow components. This is manifested as a
marked decrease in circulating formed elements, ie red blood cells, and
platelets. The resultant aplastic anemia is a potentially fatal disorder which
in its severe form has better than a fifty percent mortality rate. In both man
and laboratory animals the extent of bone marrow damage appears proportional to
the dose of benzene. Lesser degrees of
bone marrow toxicity than aplastic anemia are more common in occupational
exposure situations. Classically, the discovery of one individual with
significant bone marrow toxicity has led to evaluation of the exposed work force
and the finding of a wide variation in the extent of hematotoxicity. This has
ranged from clinically significant pancytopenia, in which are decreases in white
blood cells (leukopenia), red blood cells (anemia), and platelets (thrombocytopenia)
to a situation in which only one of these is slightly below normal range. In the
latter case it is of course difficult to distinguish a benzene
effect from that due to the extremes of normal variation or to mild intercurrent
disease.
The type of leukemia most commonly associated with benzene
is acute myelogenous leukemia and its variants, including erythroleukemia and
acute myelomonocytic leukemia. Acute myelogenous leukemia is the adult form of
acute leukemia and, until recent advances in chemotherapy, it was a rapidly
fatal disease. The other major acute form of leukemia, acute lymphocytic
leukemia, has been reported to be associated with benzene
exposure but evidence of a causal association is weak. There is a somewhat
stronger, although still inconclusive, association in the literature between benzene
exposure and the two common forms of chronic leukemia: chronic myelogenous
leukemia and chronic lymphocytic leukemia. Other hematological disorders
possibly associated with benzene
exposure include Hodgkin's disease, lymphocytic lymphoma, myelofibrosis and
myeloid metaplasia, paroxysmal nocturnal hemoglobinuria, and multiple myeloma.
An acute hemorrhagic pneumonitis is highly likely if ... aspirated into lung.
Three cases of chronic leukemia were presented which had a history of chronic
benzene exposure. These three patients
were part of a larger group of 58 leukemia patients with benzene
exposure histories. Case 1 presented at age 43 due to cardiac complaints. The
patient owned a printing shop at which he mixed pigmented dyes with solutions of
toluene or methyl alcohol ketone. The individual had a practice of sniffing the
solutions as control measure. The toluene solution on analysis was shown to
contain 2.8% benzene 95.3% toluene.
Blood and bone marrow examination revealed chronic lymphatic leukemia. Case 2
was a 51 year old man with pain in the right quadrant. This individual had owned
a small plastics facility between 1955 and 1965 where he was intermittently
exposed to thinners containing 27.3% benzene.
Subsequent exposure included cleaning solutions without benzene.
He was also diagnosed with chronic lymphatic leukemia. The third case was a 50
year old manager of a plastic facility who was diabetic for 15 years and was
hospitalized due to recurrent gluteal and inguinal furunculosis during the last
3 years. He had been heavily exposed to benzene
between 1957 and 1965. He admitted having removed the dirt from his hands using
thinners containing benzene. Hairy
cell leukemia was diagnosed. The data suggests that differences in distribution
of acute or chronic leukemias in chronic benzene
exposure may be related to exposure levels, mode of exposure, or exposure to benzene
homologs or other chemicals.
A study conducted to measure the concentration of benzene
in the air and solvents at 40 small and large workplaces in Turkey where workers
had contracted leukemia and lymphoma. In addition, hematological examinations
were performed on the 231 workers employed at the facilities. The facilities
manufactured and repaired shoes, tires, leather works, automobiles, and farm
equipment. The age of the workers ranged from 14 to 57 years and the mean
duration of exposure was 8.8 years (range 1 month to 40 years). Case reports
were presented for five workers with 2 to 15 years of exposure who had developed
acute myeloblastic leukemia, acute lymphoblastic leukemia, acute myelomonocytic
leukemia, Hodgkin's disease and poorly differentiated lymphoma. Benzene
concentrations in the solutions and thinners used ranged from 3 to 7.5%. The
concn of benzene in air samples from
the plants ranged from 0 to 110 ppm while 76.4% of solvents contained more than
1% of benzene. Hematological
examinations of the workers showed that 32% of them had abnormal values. There
has been a decline in the use of benzene
in Turkey since an earlier study in 1972, but that the percentages of benzene
in most of the materials are still above permissible limits.
Benzene is widely recognized as a
leukemogen, and the Occupational Safety and Health Administration is currently
attempting to limit exposure to it more strictly. The proposed new regulation is
a limit of an eight hr time-weighted average of 1 ppm in place of the current
limit of 10 ppm. The fundamental rationale for the change is a perception that
the current standard is associated with an inordinate excess of leukemia. The
epidemiologic literature on benzene
and leukemia supports the inference that benzene
causes acute myelocytic leukemia. However, the available data are too sparse, or
/have/ other limitations, to substantiate the idea that this causal association
applies at low levels (ie, 1-10 ppm) of benzene.
Nonetheless, under the assumption that causation does apply at such low levels,
a number of researchers have performed risk assessments using similar data but
different methodologies. The assessments that is considered acceptable suggest
that, among 1,000 men exposed to benzene
at 10 ppm for a working lifetime of 30 years, there would occur about 50 excess
deaths due to leukemia in addition to the baseline expectation of seven deaths.
However, this estimate is speculative and whether or not enough confidence can
be placed in it to justify a lower occupational benzene
standard remain a decision for policy makers.
Results of epidemiologic studies indicating an association between solvent
exposure and the development of malignancies affecting hematopoietic and
lymphatic tissues are reviewed. Clinical and cytogenetic data supporting this
association are discussed. A variety of malignant disorders have been associated
with solvent exposure, ie acute leukemia, Hodgkin's disease (odds ratio
2.8-6.6), non-Hodgkin's lymphoma (odds ratio 3.3) and myeloma, and there are
some indications that solvent exposure may be a risk factor for myelofibrosis.
The carcinogenic effect of benzene is
epidemiologically and experimentally well documented and there are some
indications that other solvents may also be hazardous. Possible mechanisms
bringing about malignant transformation are discussed. The need for further
epidemiologic, cytogenetic and clinical studies on the association between
solvent exposure and malignant diseases is emphasized.
Currently the most applied technique for monitoring biological effects of
exposure to genotoxic chemicals in industrial workers is the measurement of
chromosome aberrations in peripheral blood lymphocytes. In the Shell
petrochemical complex in the Netherlands cytogenetic monitoring studies have
been carried out from 1976 till 1981 inclusive, in workers potentially exposed
to a variety of genotoxic chemicals, ie vinyl chloride, ethylene oxide, benzene,
epichlorohydrin, epoxy resins. Average exposure levels to these chemicals were
well below the occupational exposure limits. Results of thesse studies indicate
that no biologically significant increase in the frequencies of chromosome
aberrations in the exposed populations occurred compared with control
populations. ... Experience with this methodology has shown that the results of
chromosome analyses are difficult to interpret, due to the variable and high
background levels of chromosome aberrations in control populations and in
individuals. It is concluded that the method is not sufficiently sensitive for
routine monitoring of cytogenetic effect in workers exposed to the low levels of
genotoxic compounds.
The possibility of there being a link between the apparent predominance of
men with specific on the job exposures to toxic materials among patients with
hairy cell leukemia was explored. Of a total of 105 hairy cell leukemia
patients, eight were in the medical profession (two X-ray technicians, one
radiologist, two pneumologists, two orthopedists, and one internist), 21 were
garage mechanics or divers of trucks or other heavy vehicles, eight worked in
construction as painters, decorators or masons, three were in the printing
industry as photogravure and equipment maintenance workers, ten were farmers,
six were engineers and 49 held various technical or office positions. Interviews
were conducted with 69 of the patients. All those in medicine had used
radioscopy for periods exceeding 10 years. Exposure to petroleum derived
substances was high not only among the garage mechanics and drivers, but among
those 49 individuals whose occupations did not have particular exposure, but
whose hobbies and paraprofessional activities involved use of benzene
or other solvents. Of the 69 interviewed, 52 were able to document exposure to benzene
or other solvents.
The case of a 55 year old male with hairy cell leukemia associated with
chronic exposure to benzene in an
occupational setting was described. The subject had been employed as a coach
paint sprayer for over 25 years at the time of diagnosis. When that patient was
questioned, it was admitted that at the job site he did not usually take the
normal protective measures to prevent exposure to the chemicals in the paints.
The /investigators noted/ that spray painting is the one of the occupations
which can involve exposure to benzene,
due to the use of benzene containing
solvents. The /researchers/ concluded that since three other cases of chronic
leukemia have been previously associated with exposure to benzene,
more retrospective demographic studies which take occupational exposures into
account confirm the possible link between chronic benzene
toxicity and leukemia, particularly the very rare hairy cell leukemia.
The mutual metabolic suppression between benzene
and toluene was studied. The subjects, 190 male Chinese workers employed in shoe
manufacturing, printing, audio equipment manufacture, and automobile industries,
were divided into four groups based on occupational exposure: 65 were exposed to
benzene, 35 to toluene, 55 to both
compounds, and 35 served as comparisons. The arithmetic mean exposure level of benzene
was 31.9 and of toluene 44.7 ppm. The mixture contained benzene
at 17.9 + - 29.3 and toluene at 20.5 + - 25.8 ppm. The exposure levels were
measured using individual diffusive samplers. The geometric mean levels of the
metabolites, phenol, catechol, hydroquinone, hippuric acid, and o-cresol, in
unexposed workers were 6.9, 9.4, 4.8, 72.5, and 0.066 mg/l, respectively. Values
corrected for creatinine and specific gravity were different from the values
cited above. Multiple correlation coefficients for benzene
exposure versus its three metabolites were for phenol, 0.740; for catechol,
0.629; and for hydroquinone, 0.762. Multiple correlation coefficients for
toluene and its two metabolites were 0.649 for hippuric acid and 0.583 for
o-cresol. The slopes of regression lines for the exposure to benzene
in the presence of toluene were less than half of those obtained when the
workers were exposed to benzene alone;
however, the regression lines for benzene
in mixture versus catechol were out 80% of higher than the lines observed with benzene
as the sole pollutant. The regression lines for toluene in the mixture and
excretion level of hippuric acid and hydroquinone showed reduced metabolic
conversion compared to when exposure was limited to toluene alone.
A retrospective cohort study was conducted in 233 benzene
factories and 83 control factories in 12 cities in China. The benzene
cohort and the control cohort consisted of 28,460 benzene
exposed workers (178,556 person-years in 1972-81) and 28,257 control workers
(199,201 person-years). Thirty cases of leukemia (25 dead and 5 alive) were
detected in the former and four cases (all dead) in the latter. The leukemia
mortality rate was 14/100,000 person-years in the benzene
cohort and 2/100,000 person-years in the control cohort; the standardized
mortality ratio was 5.74 (p less than 0.01 by U test). The average latency of benzene
leukemia was 11.4 years. Most (76.6%) cases of benzene
leukemia were of the acute type. The mortality due to benzene
leukemia was high in organic synthesis plants followed by painting and rubber
synthesis industries. The concentration of benzene
to which patients with a leukemia were exposed ranged from 10 to 1000 mg/cu m
(mostly from 50 to 500 mg/cu m). Of the 25 cases of leukemia, seven had a
history of chronic benzene poisoning
before the leukemia developed.
Cytogenetic and environmental factors in the etiology of acute leukemias in
adults were discussed. Epidemiological aspects of leukemia were considered. The
leukemias currently account for approximately 3% of the total cancer incidence
and 4% of the cancer deaths in the USA. The average annual incidence is eight
cases per 100,000 for females and 11 cases per 100,000 for males. Leukemia is
more common in whites than nonwhites and more common in males. Acute
nonlymphocytic accounts for about 30% of the total leukemia incidence and for
over 85% of the acute leukemia seen in persons over 40 years of age. Recent
mortality data show very little change in leukemia death rates except for acute
nonlymphocytic leukemia which increased by 20% from 1969 to 1977. Genetic and
environmental factors were considered. Chromosome disorders and a family history
may be etiological factors in both acute nonlymphocytic leukemia and lymphocytic
leukemia. Exposures to benzene,
ionizing radiation, and antineoplastic agents are known to cause chromosomal
aberrations and leukemia; however, no evidence of a causal sequence of events
has been obtained. Environmental risk factors such as ionizing radiation,
cigarette smoke, and chemicals were described. Benzene
is considered the best known and most widely occurring human leukemogen. A
number of case reports and cohort studies have linked benzene
exposure and acute leukemias. Benzene
associated relative risk for overall leukemia generally range from 1.5 to 2.0.
Cytogenetic aspects of leukemia were considered. Some studies have shown that
prior chemical exposures are associated with chromosome aberrations in acute
nonlymphocytic leukemic patients. Suggestions for improving epidemiological
studies of leukemia were discussed.
A study of mortality in automobile mechanics and gasoline service station
workers in New Hampshire was conducted. A proportionate mortality ratio analysis
of all deaths occurring among male residents 20 years or older who lived in New
Hampshire between 1975 and 1985 was performed. Occupation, industry, age, and
date and cause of death were obtained from death certificates. A total of 37,426
deaths were recorded. Of these, 453 were automobile mechanics and 134 were
persons who had been employed in the gasoline service station industry.
Automobile mechanics had statistically significant proportionate mortality ratio
elevations for suicide. Nonsignificant increases in proportionate mortality
ratio for leukemia, cancers of the oral cavity, lung, bladder, rectum and
lymphatic tissue, and nonmalignant blood dyscrasias and cirrhosis of the liver
were observed. Workers in the gasoline service station industry had
statistically significant increases in mortality from leukemia and mental and
psychoneurotic and personality disorders, proportionate mortality ratio 328 and
394, respectively; however, the number of deaths was small. Proportionate
mortality ratio increases were also observed for emphysema and suicide. One or
more of the exposures experienced by automobile mechanics and service station
workers presents a carcinogenic risk. The finding of excess mortality from
leukemia in both groups is consistent with exposure to benzene,
a component of gasoline. ... Workers who pump gasoline should be informed of the
potential cancer hazard. Gasoline should not be used as a solvent for removing
grease and cleaning hands, and gasoline should not be siphoned by mouth.
This paper presents a critical review more than 100 references on the
possible leukemogenic (blastomogenic) effects of benzene,
based upon clinical, epidemiological and experimental /studies/. /Evidence
supports the conclusion that/ there exists reliable clinical and epidemiological
/studies/, concerning increased leukemogenic risk on working place with high benzene
concentrations in past years (tens and even hundreds of ppm). Most
epidemiological studies, indicate now that this risk is also elevated in more
favorable working conditions, although practical valuable dose-effect
relationship between benzene
concentrations and rate of leukemogenic risks is still unknown. Results of
experimental investigations on problem of leukemogenic effects of benzene
are contradictory. It was stated recently that there is a lack of adequate
experimental models of benzene
blastomogenesis. Taking into consideration increasing economic significance of benzene
and existence of large contingents of workers dealing with benzene,
it is necessary to continue appropriate experimental and epidemiological
investigations.
The possible association of thinner, a mixture of seven organic solvents used
in the Mexican auto and paint industry, with the frequency of sister chromatid
exchanges in the peripheral lymphocytes of 24 industrial workers was
investigated. The subjects worked in a factory and three workshops in which no
protective measures against inhalation of vapors were taken. A matched
comparison group consisted of 24 administrative and outdoor workers. Use of
cigarettes, alcohol, and medicines, and presence of viral infections within the
3 previous months were determined by questionnaire. Blood was cultured for 72 hr
with phytohemagglutinin, with 5-bromodeoxyuridine added at 24 hr and colchicine
at 70 hr. Sister chromatid exchanges were scored from 50 metaphases from each
individual. Air samples to determine concentrations of thinner components in the
working atmosphere were taken on the day of blood sampling and analyzed by gas
chromatography. Solvent concentrations in the samples from the factory air were
methyl isobutyl ketone 2.4 ppm, methanol 0.6 ppm, isopropanol 3.3 ppm, toluene
3.3 ppm, benzene 6.0 ppm, and hexane
3.3 ppm. The concentrations were below the limits recommended by NIOSH ...
except for benzene which was six times
the NIOSH limit. One way analysis of variance of the sister chromatid exchanges
frequency for the exposed and comparison groups showed no differences for
exposures of either 5 years or less of 6 to 35 years. However, a significant
increase of sister chromatid exchanges was found for tobacco use in the exposed
group but not for the comparison group. The implications of this result were
discussed principally in relation to benzene.
... Working conditions should be improved by a ventilation system and that a benzene
free thinner be substituted for the one being used.
Dose response analyses for a cohort study of chemical workers exposed to benzene
were reported. Exposure information included 8 hour time-weighted averages and
peak exposures and was used to calculate the latency, duration of exposure, and
peak exposure for several types of lymphatic and hematopoietic cancers. The
cohort included 4,602 male chemical workers from seven companies who were
occupationally exposed to benzene for
at least 6 months between 1946 and 1975. A comparison group included 3,074
workers at the same plants who were employed for at least 6 months without
exposure to benzene. Workers exposed
to benzene 5 and 14 years showed an
increased risk of lung cancer with a statistically significant enhancement of
the standardized mortality ratio. Increased in reticulosarcoma and lymphosarcoma
were related to the duration of continuous benzene
exposure. Increased latency was related to a slight enhancement for all cancers
among the exposed workers. Analysis by cumulative exposure demonstrated an
increasing trend for death due to lymphatic and hematopoietic cancer,
lymphosarcoma, reticulosarcoma, and leukemia. Workers with a cumulative exposure
of 180 to 719 ppm month showed a significant increase in lung cancer. No dose
response relation was detected for any other causes of death.
A mortality study of 7,676 male chemical workers occupationally exposed to benzene
was described. The subjects were employed at nine plants belonging to seven
member companies of the Chemical Manufacturers Association. Workers were
classified according to their benzene
exposure into occupationally exposed or comparison groups. Occupationally
exposed workers received at least 6 months of continuous or intermittent job
exposure to benzene between 1946 and
1975. The comparison group comprised workers with at least 6 months of
employment at the same plant with no benzene
exposure. Approximately 40% of the cohort were not occupationally exposed to benzene,
and about 46% of the cohort had received continuous exposure to benzene.
The remaining 14% fell into the intermittent exposure group. The observed
mortality of the cohort was compared with the expected based on the United
States mortality rates appropriately standardized. Standardized mortality ratios
were determined for lymphatic and hematopoietic cancer, leukemia, non Hodgkin's
lymphoma, and non-Hodgkin's lymphopoietic cancer. The number of observed deaths
in the continuous exposure group was slightly but not significantly greater than
expected. Deaths from lymphatic and hematopoietic cancers and from leukemia were
greater than expected in the continuous exposure group. The mortality of the
intermittent exposure group was comparable to the expected mortality. The
standardized mortality ratios of the total group were greater than the
comparison group. Statistically significant associations were demonstrated
between benzene exposure and both
lymphopoietic cancer and leukemia.
Comprehensive comparative studies were conducted on the three groups of 148
male and 167 female workers exposed to benzene,
toluene, or a combination of the two to evaluate subjective symptoms and
hematologic effects of the compounds. Exposed workers were compared to 127
unexposed referents. The exposure intensity of the workers was estimated by
diffusion dosimetry, and their subjective symptoms were obtained from
questionnaires. The workers in the benzene
group were engaged in shoe making and printing; the toluene group was engaged in
shoe making and audio equipment production, and the mixed exposure group was
employed in spray painting in automobile body shops. The mean age of the workers
ranged from 26.7 to 39.0 years. The average 7 hr time weighted exposure to benzene
was 33 and 59 ppm for men and women, respectively; the exposure concentrations
of toluene were 46 and 41 ppm for men and women, respectively. In the mixed
exposure group, men were exposed to 14 ppm of benzene
and 18 ppm of toluene; the female mixed exposure was 18 ppm of benzene
and 21 ppm of toluene. Hematological examinations showed no significant
differences between exposed and nonexposed workers, although leukocytes were
marginally decreased. The prevalence of subjective symptoms was dose related and
statistically significant for both men and women. The number of symptoms per
person during work was at least ten fold higher in the exposed than in the
nonexposed groups. The most frequent symptoms were dizziness, sore throat, and
headache which occurred during work as well as during non work time. This study
provides no indication of pancytopenia, and that both liver and kidney functions
are unchanged under exposure conditions.
Of a total of 528,729 workers exposed to benzene
or benzene mixtures in China, 508,818
(96.23%) were examined. Altogether 2,676 cases of benzene
poisoning were found, a prevalence of 0.15%. A higher prevalence of benzene
poisoning was found in the cities of Hangjou, Hefei, Nanjing, Shenyang, and Xian.
The geometric mean concentration of benzene
in 50,255 workplaces was 18.1 mg/cu m but 64.6% of the workplaces had less than
40 mg/cu m. There was a positive correlation between the prevalence of benzene
poisoning and the concentration in shoemaking factories. The prevalence of benzene
induced aplastic anemia in shoemakers was about 5.8 times that occurring in the
general population. The results of this investigation show the need for a
practicable hygiene standard to prevent benzene
poisoning.
... CYTOGENETIC APPROACHES APPEAR TO BE NEAREST TO ROUTINE SURVEILLANCE IN
DETECTING EARLY BIOLOGIC EFFECTS IN EXPOSED HUMANS. BENZENE
SHOWED CONTRADICTORY RESULTS IN CHROMOSOME ABERRATION TESTS & WAS NEGATIVE
FOR SISTER CHROMATID EXCHANGE.
Investigations on the association between environmental hazards and the
development of various /forms/ of leukemia are reviewed. Regarding acute non-lymphocytic
leukemia exposure to ionizing radiation is a well documented risk factor.
According to several recent studies exposure to strong electronmagnetic fields
may be suspected to be of etiologic importance for acute non-lymphocytic
leukemia. There is evidence that occupational handling of benzene
is a risk factor and other organic solvents may be leukemogenic. Occupational
exposure to petroleum products has been proposed to be a risk factor although
the hazardous substances have not yet been defined. Results of cytogenic studies
in acute non-lymphocytic leukemia suggest that exposure to certain environmental
agents may be associated with relatively specific clonal chromosome aberrations.
These results are of interest because it has been proposed that chromosomal
rearrangements may play a role in the activation of cellular oncogens. Exposure
in utero to ionizing radiation has been proposed to be a risk factor for acute
lymphocytic leukemia in children. Unlike acute non-lymphocytic leukemia there
seems at present to be little evidence that acute lymphocytic leukemia is
related to exposure to some chemicals. Chronic myleoid leukemia may follow
exposure to high doses of ionizing radiation whereas such exposure seems to be
of insignificant importance in the development of chronic lymphocytic leukemia.
According to some studies an abnormally high incidence of chronic lymphocytic
leukemia may be found among farmers in the USA. These results have not been
confirmed in Scandinaavian studies. There seems to be little evidence that
chronic myleoid leukemia or chronic lymphocytic leukemia are related to
occupational handling of some chemicals.
Personal air monitors and breath samples were used to measure benzene
and other volatile compounds in the breath of 200 smokers and 322 nonsmokers in
New Jersey and California during 12 hr sampling periods. The monitor measured
only sidestream and exhaled mainstream smoke. Concentrations were also measured
in a subsample of homes and outdoor air. Compared to nonsmokers, benzene
was significantly higher in the breath of persons who had smoked tobacco the day
they were monitored (p< 0.001); values for smokers were 12 to 16 ug/cu m,
nearly 10 times the breath level of nonsmokers. Values for personal air samplers
were not always significantly higher. Benzene
in breath was related to number of cigarettes smoked. Based on direct
measurements of mainstream smoke, it was calculated that the typical smoker
inhales 2 mg/day compared to the nonsmokers' intake of <0.2 mg/day. Both
smokers and nonsmokers exposed to passive smoking at home or work had increased
levels of benzene compared to
nonsmoking situations (p< 0.05). Indoor air levels in homes with smokers were
significantly greater than in nonsmoking homes in fall and winter but not during
spring and summer.
In both human and animal studies, it appears that benzene-induced
bone marrow depression is a dose-dependent phenomenon.
Toxicities from inhalation /of benzene
include/: irritation of conjunctiva and visual blurring, mucous membranes,
dizziness, headache, unconsciousness, convulsions, tremors, ataxia, delirium,
tightness in chest, irreversible brain damage with cerebral atrophy, fatigue,
vertigo, dyspnea, respiratory arrest, cardiac failure and ventricular
arrhythmias, leukopenia, anemia, thrombocytopenia, petechiae, blood dyscrasia,
leukemia, bone marrow aplasia, fatty degeneration and necrosis of heart, liver,
adrenal glands, fatal overdose. /From table/
Single exposures to concentrations of 66,000 mg/cu m (20,000 ppm) commercial benzene
have been reported to be fatal in man within 5-10 minutes. At lower levels, loss
of consciousness, irregular heart-beat, dizziness, headache and nausea are
observed.
In general, acute symptoms are dependent on both the concentration and
duration of exposure. Exposure to 7500 ppm for 30 min is life-threatening; 1500
ppm for 60 min produces significant symptoms; 50-150 ppm for 5 hr results in
headache and weakness; whereas exposure to 25 ppm or less for 8 hr results in no
demonstrable acute effect.
... Benzene metabolism is a
requirement for bone marrow toxicity.
/Researchers/ examined the blood counts of 161 workers for whom
pre-employment counts were done prior to exposure in the rubber factory. The
results indicated that during the first year of employment in the rubber
factory, employees exposed to benzene
levels higher than the median exposure (estimated at 40-54 ppm) had
significantly lower white and red blood cell counts than employees exposed to benzene
levels below the median exposure.
Leukopenia was observed ... in Chinese workers exposed to 0.69-140 ppm (mean
= 6 ppm) benzene for more than 1 year.
After a fatal occupational exposure to benzene
vapors on a chemical cargo ship for only minutes, autopsy reports on three
victims revealed hemorrhagic respiratory tissues, and second degree burns on the
face, trunk, and limbs.
Skin irritation has been noted at occupational exposures of greater than 60
ppm for up to three weeks.
A retrospective cohort study of incident cases of hematopoietic neoplasms and
related disorders among 74,828 benzene-exposed
workers employed between January 1, 1972 to December 31, 1987 in 672 factories
in 12 Chinese cities was conducted. Workers (35,805) not occupationally exposed
to benzene employed in 109 factories
during the same period were used for comparison. Follow-up of both exposed and
nonexposed workers was carried out using occupational and medical records, and
histopathologic material were reviewed for all patients with hematopoietic
malignancies to ensure correct classification. Among benzene-exposed
workers, 82 patients with hematopoietic neoplasms and related disorders were
diagnosed: 32 (39%) cases of acute leukemia, 9 (11%) aplastic anemia, 7 (9%)
myelodysplastic syndrome, 9 (11%) chronic granulocytic leukemia, 20 (24%)
malignant lymphoma and related disorders, and 5 (6%) others. Among the
nonexposed group, 13 hematologic malignancies were diagnosed: 6 (46%) patients
with acute leukemia, 2 (15%) chronic granulocytic leukemia, 3 (23%) malignant
lymphoma, and 2 (15%) others. The hematopathologic features of acute
nonlymphocytic leukemia associated with benzene
exposure resembled the hematological features following chemotherapy or
radiotherapy. In addition, this study documented myelodysplastic syndrome in
association with benzene exposure.
... Benzene metabolites can
adversely affect human topoisomerases, enzymes involved in DNA replication and
repair. /Benzene metabolites/
Skin, Eye and Respiratory Irritations:
Benzene is irritant to skin.
A severe eye and moderate skin irritant.
Skin irritation has been noted at occupational exposures of greater than 60
ppm for up to three weeks.
Drug Warnings:
Protected intercourse may be prudent following high exposure to benzene.
As well, nursing mothers may be advised to discontinue nursing for 5 days
following high exposure.
Medical Surveillance:
IF INDIVIDUALS ARE KNOWN TO BE EXPOSED TO BENZENE
VAPORS IN THEIR WORKING ENVIRONMENT PROPHYLACTIC MEASURES SHOULD BE TAKEN. ALL
POSSIBLE METHODS SHOULD BE USED TO PROTECT SUCH PERSONS AGAINST BREATHING THE
FUMES. THEY SHOULD HAVE PERIODIC PHYSICAL EXAM, INCL BLOOD STUDIES. IN ADDN THE
URINE SHOULD BE EXAM AT INTERVALS TO DETERMINE EXTENT OF EXCRETION OF BENZENE
CONJUGATION PRODUCTS. ONCE POISONING HAS DEVELOPED, IT IS ESSENTIAL TO PREVENT
FURTHER EXPOSURE.
Assessment of fitness should incl consideration of previous medical ... &
occupational history. Occupational history should take into account any previous
exposure to benzene, radiomimetic
substances or ionizing radiations. Medical exam should incl thorough physical
... & hematological examination. The latter ... should cover hemoglobin
determination, red cell, white cell & platelet counts, white cell
differential count & red cell & leukocyte morphology. Protect young
persons of either sex under 18 yr of age from exposure to benzene
since ... adolescents have lower resistance to bone-marrow poisons. Pregnant
women & nursing mothers should not be exposed ... & special precautions
are necessary where women of childbearing age are exposed to benzene
hazard. ... Subjects with liver diseases & ... microcytemia should /be
protected from exposure/. ... Periodic exam should be carried out in same way as
pre-employment examination. ... Particular attention should be paid to any
hematological abnormalities found during 1st periodic examination. ... Whenever
there is slightest suspicion of leukemia, a bone-marrow biopsy is warranted.
Biological monitoring: Medical surveillance should incl blood pressure check,
lung functions, blood chemistry, hematology, urinalysis & skin exam.
PRECAUTIONS FOR "CARCINOGENS": ... In relation specifically to
cancer hazards, there are at present no health monitoring methods that may
ensure the early detection of preneoplastic lesions or lesions which may
preclude them. Whenever medical surveillance is indicated, in particular when
exposure to a carcinogen has occurred, ad hoc decisions should be taken
concerning additional tests that might become useful or mandatory. /Chemical
Carcinogens/
Populations at Special Risk:
INDIVIDUALS WITH G6PD /GLUCOSE 6-PHOSPHATE DEHYDROGENASE/ DEFICIENCY HAVE ...
BEEN FOUND TO BE MORE SUSCEPTIBLE TO HEMOLYTIC EFFECTS OF ... BENZENE
...
... /It has been observed/ that levels of leukocyte agglutins were elevated
in selected individuals exposed to benzene.
... /This/ suggested that in some people benzene
toxicity may be accounted for in part by an allergic blood dyscrasia.
... Workers with higher activities of /cytochrome P-450(2E1)/ are at more
risk /of benzene hematoxicity/.
... It has been suggested that Thalassemia minor, and presumably other
disorders in which there is increased bone marrow turnover, may predispose a
person to benzene-induced aplastic
anemia.
People living near hazardous waste sites who are chronically exposed to
contaminated air, water, or soil may be at a higher risk for respiratory effects
from exposure to /benzene/ ...
Probable Routes of Human Exposure:
Human populations are primarily exposed to benzene
through inhalation of contaminated ambient air particularly in areas with heavy
traffic and around filling stations. In addition, air close to manufacturing
plants which produce or use benzene
may contain high concentrations of benzene(1,2).
Another source of exposure is from inhalation of tobacco smoke(1). Although most
public drinking water supplies are free of benzene
or contain <0.3 ppb, exposure can be very high from consumption of
contaminated sources drawn from wells contaminated by leaking gasoline storage
tanks, landfills, etc(SRC).
Rough estimates of average ambient ground-level benzene
concentrations over an 8 hour period were calculated based on an emission rate
of 100 g/sec from a manufacturing plant. Benzene
concentrations (in pg/cu m) are estimated to be 11,000 at 0.15 km, 6,100 at 0.3
km, 3,800 at 0.45 km, 2,800 at 0.6 km, 2,100 at 0.75 km, 740 at 1.6 km, 370 at
2.5 km, 220 at 4.0 km, 120 at 6.0 km, 62 at 9.0 km, 34 at 14.0 km, and 20 at
20.0 km distance from the manufacturing plant(1).
NIOSH (NOES Survey 1981-1983) has statistically estimated that 272,275
workers (143,066 of these are female) are potentially exposed to benzene
in the US(1). Occupational exposure to benzene
may occur through inhalation and dermal contact with this compound at workplaces
where benzene is produced or used(SRC).
The general population may be exposed to benzene
via inhalation of ambient air(2-4), ingestion of drinking water(5), and dermal
contact with gasoline products(6) containing benzene(SRC).
Benzene was detected in 3 out of 70
samples taken from 46 spray painting workshops in Sydney, Australia at a concn
of 1 mg/cu m in 1989(1). In a study of in-auto and in-bus exposures to volatile
organic compounds for commutes on an urban-suburban route in Korea from November
21 to December 22, 1994, revealed that mean in-auto concns of benzene
were 30.6 ug/cu m along urban routes and 18.3 ug/cu m along suburban routes
while mean in-bus concns were 20.2 ug/cu m along urban routes and 11.7 ug/cu m
along suburban routes(2). In a 200-trip study of in-vehicle air of Los Angeles
commuters, an avg concn of benzene at
40 ug/cu m during rush hour was detected(3).
Body Burden:
Benzene was detected in all 8
samples of mothers' milk from women living in 4 USA urban areas(1). Breath
samples from persons without specific exposure to benzene
ranged from 8 to 20 ppb(2). Whole blood samples from 250 subjects (121 males,
129 females) ranged from not detected to 5.9 ppb, (mean 0.8 ppb)(3). In FY82,
the National Human Adipose Tissue Survey specimens found that of 46 composite
samples, 96% tested positive to benzene
(concns were >4 ppb for wet tissue) with a max concn of 97 ppb max(4).
In a 1980's study of non-occupational benzene
exposure, it was found that smokers had an avg benzene
body burden about 6 to 10 times that of nonsmokers, and received about 90% of
their benzene exposure from
smoking(1). The mean benzene concn
found in the breath and blood of 1,683 individuals was 13.1 and 131 ng/l,
respectively(1).
Average Daily Intake:
Two recent studies of benzene
levels in foods have confirmed the conclusion that ingesting food and beverages
are an unimportant pathway for benzene
exposure(1). In a study of more than 50 foods, most contained benzene
below 2 ng/g ppbw(1). A Canadian review of benzene
exposures concluded that food and drinking water each contributed only about
0.02 ug/kg benzene per day compared to
a total intake of 2.4 ug/kg per day from airborne exposures (3.3 ug/kg/day if
exposed to cigarette smoke). In a 1980's study of non-occupational benzene
exposure, it was found that more than 99% of the total personal exposure was
through air and that a global avg personal exposure for benzene
was about 15 ug/cu m(1). Roughly half the total benzene
exposure in the United States was borne by smokers(1). For non-smokers, most benzene
exposure ultimately was derived from auto exhaust or gasoline vapor
emissions(1). A series of experiments were conducted in a 290 sq m single-family
residence from June 11-13, 1991 to ascertain the human exposure to benzene
from a contaminated groundwater source(1). It involved an individual taking a 20
min shower with the bathroom door closed, followed by five minutes for drying
and dressing, and then opening the bathroom door and allowing the individual to
leave and have his blood, breath and urine sampled(1). Whole air samples were
collected from the bathroom, shower and living room. The inhalation exposure to benzene
of an individual in the living room avgd 72 ug for the three days(1). The
individual taking the shower had an avg inhalation dose of 113 ug and an avg
dermal dose of 168 ug (exposure = 40% inhalation, 60% dermal)(1). There may be a
large number of cases where well water is contaminated by benzene
at low concns(1). A number of studies have reported finding benzene
at levels on the order of 5 ng/l in surface and well waters(1). However, these
levels correspond to a daily intake of <10 ng benzene,
assuming 2 liters of water drunk daily(1). This amount is only 0.5% of the avg
daily intake for nonsmokers of 200 ng from air(1). Thus, it is concluded that
the effect of contaminated water on total benzene
intake is negligible(1).
Minimum Fatal Dose Level:
Benzene exposure is rapidly fatal
at concentrations approaching 20,000 ppm.
... Probable human oral lethal dose would be between 50-500 mg/kg. Human
inhalation of approximately 20,000 ppm (2% in air) was fatal in 5-10 min.
Estimated oral doses from 9-30 g have proved fatal.
Antidote and Emergency Treatment:
Basic treatment: Establish a patent airway. Suction if necessary. Watch for
signs of respiratory insufficiency and assist ventilations if necessary.
Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary
edema and teat if necessary ... . Monitor for shock and treat if necessary... .
For eye contamination, flush eyes immediately with water. Irrigate each eye
continuously with normal saline during transport ... . Do not use emetics. For
ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution
if the patient can swallow, has a strong gag reflex, and does not drool.
Administer activated charcoal ... . /Benzene
and related compounds.
Advanced treatment: Consider orotracheal or nasotracheal intubation for
airway control in the patient who is unconscious or in respiratory arrest.
Positive-pressure ventilation techniques with a bag-valve-mask device may be
beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... .
Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use
lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid
overload. Consider drug therapy for pulmonary edema ... . Treat seizures with
diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation
... . /Benzene and related compounds/
Animal expt show that benzene
sensitizes the myocardium to epinephrine, so that the endogenous hormone may
precipitate sudden & fatal ventricular fibrillation.
Animal Toxicity Studies:
Evidence for Carcinogenicity:
Classification of carcinogenicity: 1) evidence in humans: sufficient; 2)
evidence in animals: sufficient; Overall summary evaluation of carcinogenic risk
to humans is group 1: The chemical is carcinogenic to humans. /From table/
A2. A1= Confirmed Human Carcinogen (2000)
WEIGHT-OF-EVIDENCE CHARACTERIZATION: Benzene
is classified as a "known" human carcinogen (Category A) under the
Risk Assessment Guidelines of 1986. Under the proposed revised Carcinogen Risk
Asessment Guidelines (USEPA, 1996), benzene
is characterized as a known human carcinogen for all routes of exposure based
upon convincing human evidence as well as supporting evidence from animal
studies. Epidemiologic studies and case studies provide clear evidence of a
causal association between exposure to benzene
and acute nonlymphocytic leukemia and also suggest evidence for chronic
nonlymphocytic leukemia and chronic lymphocytic leukemia. Other neoplastic
conditions that are associated with an increased risk in humans are hematologic
neoplasms, blood disorders such as preleukemia and aplastic anemia, Hodgkin's
lymphoma, and myelodysplastic syndrome. These human data are supported by animal
studies. The experimental animal data add to the argument that exposure to benzene
increases the risk of cancer in multiple species at multiple organ sites (hematopoietic,
oral and nasal, liver, forestomach, preputial gland, lung, ovary, and mammary
gland). It is likely that these responses are due to interactions of the
metabolites of benzene with DNA ...
Recent evidence supports the viewpoint that there are likely multiple
mechanistic pathways leading ... to leukemogenesis from exposure to benzene.
HUMAN CARCINOGENICITY DATA: Benzene is
a known human carcinogen based upon evidence presented in numerous occupational
epidemiological studies. Significantly increased risks of leukemia, chiefly
acute myelogenous leukemia, have been reported in benzene-exposed
workers in the chemical industry, shoemaking and oil refineries. ANIMAL
CARCINOGENICITY DATA:... many experimental animal studies, both inhalation and
oral, also support the evidence that exposure to benzene
increases the risk of cancer in multiple organ systems, including the
hematopoietic system, oral and nasal cavities, liver, forestomach, preputial
gland, lung, ovary, and mammary gland ....
Non-Human Toxicity Excerpts:
Inhalation of air saturated with benzene
vapor resulted in ventricular extrasystole in the cat & primate, with
periods of ventricular tachycardia that occasionally terminated in ventricular
fibrillation. ... In rabbit, sudden death from ventricular fibrillation has also
been observed. ... In acute inhalation by male rats, benzene-induced
resp paralysis occurred, followed by ventricular fibrillation.
... DOGS INHALING BENZENE ...
DEVELOPED HYPERTENSION. THIS WAS SOON FOLLOWED BY PARALYSIS OF VASOMOTOR SYSTEM
DUE TO EFFECT OF BENZENE ON SMOOTH
MUSCLE OF BLOOD VESSELS.
Benzene in rabbit eye is a moderate
irritant, causes conjunctival irritation, & ... transient slight corneal
injury.
IN SERIES OF CHRONIC STUDIES, BILATERAL CATARACTS WERE FOUND IN 50% OF RATS
EXPOSED /TO/ ... 50 PPM FOR 600 HR ...
Rats, guinea-pigs, & rabbits exposed to 80-88 ppm (256-281 mg/cu m) for 7
hr/day for 30-40 wk had incr testicular wt & degeneration of seminiferous
tubules. ... Alteration of estrous cycles has been reported in rats exposed to
1.6 or 9.4 ppm (5 or 30 mg/cu m) for 4 mo ... but there was no effect on their
subsequent fertility or litter size. ... In C3H(JAX) mice whose ovaries were
painted directly ... & which were later mated, a high incidence of sc
hemorrhages & tail defects was observed in offspring, which persisted
through 4 generations.
... STUDIES HAVE DEMONSTRATED THE INDUCTION OF CHROMOSOMAL ABERRATIONS IN
BONE-MARROW CELLS FROM MICE, RATS, AND RABBITS TREATED WITH SINGLE OR MULTIPLE
DAILY DOSES OF BENZENE RANGING FROM
ABOUT 0.2 TO 2.0 ML/KG PER DAY & GIVEN EITHER SC OR IP. MOST OF THE INDUCED
ABERRATIONS WERE BREAKS OR DELETIONS; BUT CHROMOSOME-TYPE ABERRATIONS ALSO
OCCURRED, PARTICULARLY AFTER PROLONGED EXPOSURE, WHEN TOXICITY, MANIFESTED BY A
DROP IN PERIPHERAL BLOOD LEUCOCYTE COUNT, APPEARED. ... A SIGNIFICANT ELEVATED
LEVEL OF ABERRATIONS ARE SEEN UP TO 8 DAYS AFTER A SINGLE IP INJECTION OF 0.5
ML/KG BODY WT IN RATS, WHEREAS ABERRATIONS WERE SIGNIFICANTLY INCR IN MICE 24 HR
BUT NOT 7 DAYS AFTER RECEIVING A SIMILAR DOSE, 0.5 ML/KG BODY WT.
... 30 MALE AKR, DBA2, C3H OR C57BL6 MICE WERE GIVEN WEEKLY SC INJECTIONS OF
0.001 ML BENZENE IN 0.1 ML OLIVE OIL
FOR LIFE. NO TUMORS WERE FOUND IN MICE OF DBA2, C3H OR C57BL6 STRAINS, THE MAX
LIFESPAN BEING 730 DAYS. BETWEEN 7TH & 16TH MO OF TREATMENT 16/30 TREATED
AKR MICE DIED WITH LEUKEMIA, IN ADDITION, 8 DIED BEFORE AGE OF 9 MO WITHOUT
LEUKEMIA. HOWEVER, LEUKEMIA WAS ALSO OBSERVED IN 30/35 AKR UNTREATED MICE WHICH
LIVED, ON AVG, LONGER THAN TEST ANIMALS.
... AFTER 5 TO 8 WK OF 5 HR/DAY, 5 DAYS/WK EXPOSURE AT 44 & 47 PPM, RATS
DEVELOPED A MODERATE DEGREE OF LEUKOPENIA, BUT ... NONE RESULTED FROM 15 TO 31
PPM. ... DECR IN THE WHITE CELL COUNTS OF RATS /WAS OBSERVED/ FOLLOWING 756 HR
OF EXPOSURE AT 50 PPM OF BENZENE ON A
SCHEDULE OF 8 HR/DAY, 5 DAY/WK. REDUCED AMT OF DNA IN THE WHITE CELLS, A
DEPRESSION IN MYELOCYTIC ACTIVITY, & AN INCR IN THE RELATIVE NUMBER OF RED
CELL PRECURSORS IN THE BONE MARROW WERE ALSO OBSERVED.
SPRAGUE-DAWLEY RATS WERE EXPOSED TO 100, 300, & 2200 PPM OF BENZENE
VAPOR IN AIR FOR 6 HR DAILY ON DAYS 6-15 OF GESTATION. THE MEAN BODY WT &
CROWN-RUMP LENGTH WERE LOWER THAN CONTROL GROUPS ONLY AT THE HIGHEST EXPOSURE
LEVEL. SKELETAL EXAM SHOWED AN INCR IN THE NUMBER OF FETUSES WITH DELAYED
OSSIFICATION OF STERNEBRAE IN THE 300- & 2200-PPM GROUPS. THE FEMALE
OFFSPRING APPEARED TO BE AFFECTED TO A GREATER EXTENT THAN MALE FETUSES WITH
RESPECT TO THE INCIDENCE OF DELAYED OSSIFICATION OF STERNEBRAE. LIFETIME
EXPOSURE OF C57BL/6J MICE TO 100 OR 300 PPM (320 OR 958 MG/CU M) BENZENE
PRODUCES ANEMIA, LYMPHOCYTOPENIA & NEUTROPHILIA ASSOC WITH A RELATIVE INCR
IN THE NUMBER OF IMMATURE LEUCOCYTES & DECR IN MATURE LEUCOCYTES IN
CIRCULATION. SC ADMIN BENZENE LED TO A
SELECTIVE DEPRESSION IN B-LYMPHOCYTES IN RABBITS, WHEREAS T LYMPHOCYTES WERE
MORE RESISTANT.
Male Charles River CD-1 mice (number unspecified) were exposed for 6 hr/day,
5 days/wk, for life to atmospheres containing ... levels of 0 (control), 100 ppm
(320 mg/cu m) or 300 ppm (958 mg/cu m). Two mice in high-exposure group develop
myelogenous (myeloid) leukemia. ... There was no evidence of leukemic response
in 45 male 6 wk old Sprague-Dawley rats exposed to ... 900 mg/cu m (300 ppm) ...
for 6 hr/day, 5 days/wk, for life. Exposure was terminated at wk 99 when the
last test animal died. Controls were 27 males of same strain & age. ...
Sprague-Dawley rats & AKR mice exposed to benzene
(300 ppm, 958 mg/cu m) for 6 hr/day, 5 days/wk for life had lymphocytopenia,
with little evidence of anemia. AKR mice were more sensitive to benzene-induced
leucopenia than ... rats. /Mice also displayed agranulocytosis &
reticulocytosis. No evidence of leukemia was reported/.
Single sc injection of 3 ml/kg body wt ... on 1 of days 11-15 of gestation to
CFI mice caused cleft palate, agnathia & micrognathia in offspring ... . (No
controls were used, & it is very likely that these effects were produced by
stress of the injection). Several other studies in pregnant mice exposed to benzene,
(2 & 4 ml/kg body wt sc, 0.3 to 1.0 ml/kg body wt orally or 500 ppm (1597
mg/cu m) by inhalation for 7 hr/day all failed to show any teratogenic effect,
although reduced fetal wt & occasional embryolethality were observed.
Similarly, several inhalation studies in rats have shown embryolethality &
reduced fetal wt but only occasional teratogenic effects: Sprague-Dawley rats
exposed to 10, 50, or 500 ppm (32, 160 & 1600 mg/cu m) for 7 hr/day had low
incidence of brain & skeletal defects but no embryolethality at 50 or 500
ppm, & no abnormality or embryolethality at lower levels ... . No
teratogenic effect was seen in pregnant rats exposed to 10 or 40 ppm (32 or 128
mg/cu m) for 6 hr/day ..., to 313 ppm (1000 mg/cu m) for 24 hr/day or for 6
hr/day ... or to 400 mg/cu m (125 ppm) for 24 hr/day (Tatrai et al 1980). No
teratogenic effect has been reported in rabbits injected sc with 0.25 ml/kg of a
40% benzene soln daily during
pregnancy ... or in rabbits exposed by inhalation to 500 ppm (1600 mg/cu m) for
7 hr/day on days 6-18 of pregnancy.
Rabbits and rats injected subcutaneously with 0.2 mg/kg/day showed an incr
frequency of bone marrow mitoses.
Bone marrow cells from mice orally dosed with 56-2050 mg/kg on two successive
days showed dose-related incr in incidences of chromosomal gaps and single
breaks, multiple breaks at or above 139 mg/kg, pulverization at or above 348
mg/kg, and cytotoxicity at 2050 mg/kg.
Mice orally dosed with 0.22-1.65 g/kg showed a positive dose-related increase
in polychromatic erythrocytes in the micronucleus test.
Rats exposed continuously to 209.7 ppm for 10 days prior to breeding showed a
complete absence of pregnancy. 1/10 rats exposed to 19.8 ppm had resorbed
embryos. Females showed an inverse relationship between dose (0.3-209.7 ppm) and
number of offspring.
Chromosomal abnormalities in bone marrow cells have been reported as a
consequence of experimental benzene
exposure in a number of species including rats, rabbits, mice, and amphibians.
Chromatid deletions in metaphase chromosomes of bone marrow cells have been
found in rats given single doses of subcutaneous benzene
at 2 ml/kg and in rats given 1 g/kg/day for 12 days.
After rats were dosed with 0.5 ml/kg intraperitoneally, no dominant lethality
was found; however, incr chromatid and chromosomal aberrations were reported.
Benzene is a mitotic poison,
producing a decr in DNA synthesis in animal bone marrow cells in vitro.
Weanling male C57BL/6N mice were subcutaneously injected twice weekly for 44
weeks and once weekly for the last 10 weeks, gradually incr the dose from 450
mg/kg to 1.8 g/kg. The mice were killed 104 weeks after the first injection, and
no evidence of carcinogenic activity was found in either the benzene-treated
mice or the negative controls. Butylnitrosourea induced leukemia, lymphomas,
and/or intestinal neoplasms/were observed/ in almost all the positive controls.
TWO GROUPS OF 40 MALE C57BL/6J MICE, 6 WK OLD, WERE EXPOSED TO ATMOSPHERES
CONTAINING 0 OR 900 MG/CU M (300 PPM) BENZENE
FOR 6 HR/DAY, 5 DAYS/WK, FOR LIFE. THE EXPOSURE ENDED AFTER 488 DAYS WITH THE
DEATH OF THE LAST TEST MOUSE. IN ADDN TO ANEMIA, LYMPHOCYTOPENIA, NEUTROPHILIA
& BONE-MARROW HYPERPLASIA, 6 OF 40 MICE EXPOSED ... DEVELOPED LYMPHOCYTIC
LYMPHOMA WITH THYMIC INVOLVEMENT (P< 0.01 FOR LYMPHOMAS, ACCORDING TO PETO'S
LOG-RANK METHOD), 1 PLASMACYTOMA & 1 HEMATOCYTOBLASTIC LEUKEMIA. AVG
SURVIVAL TIME OF THE 8 TUMOR-BEARING MICE WAS 262 DAYS. TWO OF THE 40 CONTROL
ANIMALS DIED FROM LYMPHOCYTIC LYMPHOMA WITH NO THYMIC INVOLVEMENT AFTER 282
& 608 DAYS, RESPECTIVELY. DIFFERENCES IN INCIDENCE & INDUCTION TIME OF
TUMORS BETWEEN THE GROUPS WERE STATISTICALLY SIGNIFICANT (SNYDER ET AL 1980).
(THE WORKING GROUP NOTED THAT THYMUS WAS NOT EXAM ROUTINELY).
THREE GROUPS OF 30 OR 35 MALE & ... FEMALE SPRAGUE-DAWLEY RATS, 13 WK
OLD, RECEIVED 50 OR 250 MG/KG BODY WT BENZENE
(PURITY UNSPECIFIED) DISSOLVED IN PURE OLIVE OIL BY STOMACH TUBE ONCE DAILY ON 4
OR 5 DAYS EACH WK DURING 52 WEEKS. GROUPS OF 30 MALE & 30 FEMALE CONTROLS
RECEIVED OLIVE OIL ONLY. THE RATS WERE ALLOWED TO LIVE UNTIL SPONTANEOUS DEATH
OR WERE KILLED AT 144 WEEKS, THE END OF EXPT; AVG SURVIVAL TIMES WERE
UNSPECIFIED. OF FEMALES OF THE CONTROL, LOW- & HIGH-DOSE GROUPS, 0/30, 2/30
& 8/32, RESPECTIVELY, DEVELOPED ZYMBAL GLAND CARCINOMAS (COCHRAN-ARMITAGE
TEST FOR POS TREND; P= 0.001; FISHER EXACT TEST FOR CONTROL VERSUS HIGH-DOSE
GROUP: P= 0.003); 3/30, 4/30 & 7/32 DEVELOPED MAMMARY GLAND CARCINOMAS;
& 1/30, 2/30 & 1/32 DEVELOPED LEUKEMIAS. NO SUCH TUMORS WERE FOUND IN
MALES, EXCEPT THAT LEUKEMIAS OCCURRED IN 4/32 HIGH-DOSE MALES (COCHRAN-ARMITAGE
TEST FOR POS TREND; P= 0.008; FISHER EXACT TEST: P< 0.069). BACKGROUND
INCIDENCE OF ZYMBAL GLAND CARCINOMAS IN SEVERAL THOUSAND MALE & FEMALE RATS
OF SAME STRAIN ... /WAS/ ABOUT 0.7%. AVG LATENT PERIOD OF MAMMARY GLAND
CARCINOMAS WAS 88 WK IN EACH TEST GROUPS VERSUS 110 WK IN CONTROL ... .
BLUE CRAB JUVENILES WHEN EXPOSED TO SUBLETHAL CONCN OF BENZENE
(0.1 OR 5.0 PPM) IN A STATIC SYSTEM SHOWED AN INCR IN THE TIME NEEDED TO
COMPLETE A MOLT CYCLE (50 DAYS IN CASE OF BENZENE-EXPOSED
CRAB, AS COMPARED TO 33 DAYS FOR CONTROLS), A SLOWER RATE OF GROWTH OF
REGENERATING LIMB BUDS, & A DEPRESSED ACTIVITY OF ATPASE IN MITOCHRONDRIA.
OXYGEN CONSUMPTION BY THE CRAB DECR FROM EXPOSURE TO 1.0 PPM BENZENE.
Toxicity threshold (cell multiplication inhibition test): bacteria
(Pseudomonas putida) 92 mg/l; algae (Microcystis aeruginosa) >1400 mg/l;
green algae (Scenedesmus quadricauda) >1400 mg/l; protozoa (Entosiphon
sulcatum) >700 mg/l, & (Uronema parduczi Chatton-Lwoff) 486 mg/l. Algae
(Chlorella vulgaris) /showed/ 50% reduction of cell numbers versus controls
after 1 day incubation at 20 deg C at 525 ppm. Inhibition of photosynthesis (of
a freshwater, nonaxenic unialgal culture of Selenastrum capricornutum) at 10
mg/l, 95% carbon-14 fixation (versus controls); at 100 mg/l, 84% carbon-14
fixation (versus controls); at 1000 mg/l, 5% carbon-14 fixation (versus
controls). ... Young Coho salmon /showed/ no significant mortalities up to 10
ppm after 96 hr in artificial seawater at 8 deg C ... Mortality /was/ 12/20 at
50 ppm after 24 hr up to 96 hr & 30/30 at 100 ppm after 24 hr in artificial
seawater at 8 deg C. Herring & anchovy larvae (Clupea pallasi &
Engraulis mordex) /studies showed that/ 35-45 ppm caused delay in development of
eggs & /produced/ abnormal larvae; 10-35 ppm caused delay in development of
larvae, decrease in feeding & growth, & increase in respiration.
Groups of 5 to 10 pregnant Swiss-Webster mice were exposed to concentrations
of 0, 5, 10, or 20 ppm benzene from
days 6 through 15 of gestation and offspring of exposed dams were examined for
untoward effects. Litter sizes, fetal weights, numbers of dead, resorbed, or
malformed fetuses were within control limits. In the fetuses (day 16 of
gestation), the number of mature erythroid precursor cells (CFU-E) was decreased
at 20 ppm benzene. In the neonates,
the number of CFU-E cells was increased at 20 ppm benzene.
Granulocytic colony forming cells (GM-CFU-C) were affected by the 2 higher
exposure concentrations. Adult mice treated in utero when re-exposed to benzene
showed a more severe decrease in splenic GM-CFU-C than controls.
The best evidence that benzene must
be metabolized to produce bone marrow depression is based on: 1) the observation
that benzene toxicity is prevented by
coadministration of toluene, which inhibits benzene
metabolism; and 2) that partial hepatectomy (which decreases benzene
metabolism) also decreases benzene
toxicity.
Reports indicate that protection against benzene
toxicity in phenobarbital treated animals reflects the fact that phenobarbital
increased the detoxification rate of benzene
in the liver. Inhibition of metabolism by toluene and by aminotriazole has been
found to protect animals by decreasing the rate of formation of toxic
metabolites.
The principal hydroxy metabolites of benzene,
hydroquinone, catechol and phenol were assayed in tests for mitotic segregation
induction in Aspergillus nidulans diploid strain 19. Hydroquinone was the most
effective chemical, increasing the frequency of mitotic segregants up to 10 fold
at 1-3 mM. Catechol was similarly active at 10-20 mM and phenol was weakly
positive at 15 mM. Genetic characterization of induced abnormal segregating
colonies by replating and complementary assays with haploid strain 35 suggest
that gross chromosomal aberrations, instead of numerical abnormalities, are the
primary genetic damages induced by hydroxybenzenes in Aspergillus. The
protecting activity exerted by L-cysteine against equimolar concentrations of
hydroquinone supports a free radical mechanism for hydroxy metabolite
genotoxicity in Aspergillus nidulans.
Benzene hematotoxicity and
leukemogenesis were investigated to verify epidemiological estimates to the
effect that leukemia had developed in human beings exposed to benzene
for about 15% of their lifetime, and that the levels of exposure reached at
times as high as 250 to 300 ppm for at least a portion of working day. Based on
a review of the literature and ongoing studies, mice were exposed to benzene
vapor for 6 hr/day, 5 days/week for 16 weeks. Exposure of male CBA/Ca mice to
300 ppm benzene proved to be highly
carcinogenic and leukemogenic compared to unexposed controls. Male and female
CBA/Ca mice exposed to 100 ppm benzene,
according to the same schedule, showed 30% mortality as compared to 12% in
controls, while for neoplasms the respective figures were 10% and 1%. In this
case, exposure to benzene reduced the
cellularity of the bone marrow and the number of stem cells, while DNA synthesis
increased. /Data indicates/ that benzene
is carcinogenic in both animals and man and although it is unlikely that the
slope for animals and man would be the same, the investigation of the linearity
of the response would be helpful.
A review of recent advances in the metabolism and toxicity of benzene
was presented. Metabolism of benzene
was discussed including the microsomal metabolism of benzene,
mitochondrial metabolism of benzene,
effect and its metabolites on replication and transcription, and covalent
binding of reactive metabolites of benzene
with macromolecules. The toxicity of benzene,
including genotoxicity, carcinogenicity, hematopoietic toxicity, and
immunotoxicity, was reviewed. Mutagenicity and cytogenic toxicity were also
covered. Effects on stem cells, progenitor cells, and on the stromal
microenvironment were discussed. Cytogenetic effects observed in animals and
humans following exposure to benzene
were reviewed. Myeloclastogenic effects and clastogenic effects were covered.
Leukemias and related diseases in humans, associated with repeated exposure to benzene
at relatively high concentrations, were discussed. Aplastic anemia from benzene
poisoning was also discussed. Progress made in understanding the bioactivation
of benzene and in the elucidation of
metabolites produced in the liver and bone marrow was discussed.
Environmental exposure to benzene
results in both myelotoxicity and immunotoxicity. Although benzene
induced immunotoxicity has been well documented, no studies to date have
addressed the possibility that benzene
toxicity is due in part to altered differentiation of marrow lymphoid cells. The
effect of acute exposure to the benzene
metabolite, hydroquinone, on murine bone marrow B-lymphopoiesis was
investigated. Bone marrow cell suspensions from B6C3F1 (C57BL/6J x C3H/HeJ) mice
were depleted of mature surface IgM+ B cells and cultured for 0, 24, 48, or 72
hr and production of newly formed B cells was assayed both by mature surface
expression and colony formation in soft agar cultures. One hr exposure of bone
marrow cells to hydroquinone before culture reduced the number of mature surface
cells generated in liquid cultures. Small pre-B cells (cytoplasmic mu heavy
chain+, sIgM-) were numerically elevated as compared with control cultures.
Hydroquinone exposure also decreased the number of adherent cells found in
cultures of bone marrow cells. These results suggest that short-term exposure to
hydroquinone, an oxidative metabolite of benzene,
may in some way block the final maturation stages of B cell differentiation.
This apparent differentiation block resulted in reduced numbers of B cells
generated in culture and a corresponding accumulation of pre-B cells. Reduction
of adherent cells in treated cultures may also suggest that toxicity to
regulatory cells for the B lineage may be in part responsible for this aspect of
hydroquinone myelotoxicity.
Benzene is a potent bone marrow
toxin in animals and man. Animal studies have shown that exposure to benzene
can alter lymphocyte functions and decrease the resistance of animals to
Listeria monocytogenes and transplanted tumor cells. Mononuclear phagocytes
participate in host resistance to Listeria and tumor cells. The purpose of the
studies presented here was to determine the effects of benzene
and benzene metabolites on macrophage
functions and the ability of macrophages to be activated for functions which are
important in host defense. Benzene had
no effects on macrophage function or activation for any of the functions tested.
Conversely, metabolites of benzene,
catechol, hydroquinone, benzquinone, and 1,2,4-benzenetriol had potent and
varied effects on macrophage function and activation. Benzoquinone inhibited the
broadest range of functions including release of hydrogen peroxide, Fc
receptor-mediated phagocytosis, interferon gamma priming for tumor cell
cytolysis, and bacterial lipopolysaccharide triggering of cytolysis.
Benzoquinone was also the most potent metabolite causing inhibition at lower
concentrations than the other metabolites. Hydroquinone inhibited hydrogen
peroxide release and priming for cytolysis and 1,2,4-benzenetriol inhibited
phagocytosis and priming for cytolysis. Catechol only inhibited the release of
hydrogen peroxide. None of the compounds tested inhibited the induction of class
II histocompatibililty antigens on the cell surface. All of the effects measured
occurred using concentrations of compounds which did not disrupt the cell
integrity or inhibit general functions such as protein synthesis. Taken together
these data suggest that benzene
metabolites alter macrophage function through several mechanisms including
inhibition of output enzymes and disruption of signal transduction systems.
Female Wistar rats were exposed to various solvent vapors 8 hr/day for 7
days. The leukocyte suspension and serum were prepared from peripheral blood and
utilized for the determination of alkaline phosphatase activity with disodium
phenyl phosphate as a substrate (leukocyte alkaline phosphatase and serum
assay). While the exposure to benzene
at 20 or 50 ppm did not cause significant changes in leukocyte alkaline
phosphatase assay activity, the exposure at 100 to 300 ppm resulted in a
dose-dependent increase of leukocyte alkaline phosphatase assay activity up to
more than 100% over the control. No further increase was observed at 1000 or
3000 ppm. Similar exposure at 300 ppm to either toluene, m-xylene, n-hexane,
trichloroethylene, methyl ethyl ketone, ethyl acetate, or methyl alcohol did not
induce any changes in leukocyte alkaline phosphatase assay activity. Thus, the
increase in leukocyte alkaline phosphatase assay activity was considered to be
specific to benzene exposure. When the
animals were exposed to toluene (300 ppm) in combination with benzene
(300 ppm), not only was the benzene
induced leukopenia alleviated as previously reported, but the benzene
induced increase in leukocyte alkaline phosphatase assay activity was no longer
observed. The parallel inhibitory effects of toluene on benzene
induced increase in leukocyte alkaline phosphatase assay and leukopenia suggest
that a relation may exist between increase in leukocyte alkaline phosphatase
assay activity and leukopenia. No changes in serum alkaline phosphatase assay
activities were observed in the rats under the exposure conditions examined.
A review was presented of data for ... chemicals for which either ovarian
toxicity or carcinogenicity, or both, have been documented in recent studies
/conducted by/ the National Toxicology Program. In most cases, ovarian atrophy
was commonly found after 90 days of exposure, and ovarian hyperplasia and
neoplasia after longer periods. Benzene
administered by gavage produced ovarian atrophy, cysts, hyperplasia and
neoplasia in mice.
Based on literature, the mechanism of multitoxic effects of benzene
and lesions in the peripheral blood of affected animals were postulated. The
effects of chronic benzene poisoning
upon erythrocytes and erythropoiesis, granulocytes and granulopoiesis,
lymphocytes and lymphopoiesis, thrombocytes and thrombopoiesis were presented.
Differences were pointed out in toxic effects of benzene
varying with the kind, concentration and administration route of benzene
and quantitative and qualitative differences in the fodder given to animals
during the experiment.
The effect of a single dose of benzene
(0.5 ml/kg body wt ip) on the heme saturation of tryptophan pyrrolase activity
in liver was examined /in female albino rats/. There was a significant decrease
in the heme saturation of hepatic tryptophan pyrrolase, suggesting depletion of
regulatory heme. After benzene
administration there was significant increase in delta-aminolevulinate
synthetase activity while delta-aminolevulinate dehydratase activity was
significantly decreased, however, ferrochelatase and heme oxygenase activities
were unaltered. Administration of tryptophan to benzene
pretreated rats showed a reversal of benzene
effects on heme synthesizing enzymes: there is an increase in the heme
saturation of tryptophan pyrrolase and decrease in delta-aminolevulinate
synthetase. However, there was no significant alteration in the activity of
delta-aminolevulinate dehydratase.
The effects of five straight alkane petroleum hydrocarbons (nC6 to nC10), as
well as benzene and toluene upon
lysosomal enzymes of the lung were investigated. Pulmonary alveolar macrophages
were obtained from adult male Sprague Dawley rats and from 3 month old
New-Zealand white rabbits by bronchial lavage. These cells were cultured and
subsequently exposed to hydrocarbons in Leighton tubes. All hydrocarbons
examined were cytotoxic to cultured pulmonary alveolar macrophages in a dose
dependent manner, with benzene and
toluene being least toxic. The concentration of hydrocarbon producing death in
50% of treated rat cells was 1.0 millimolar (mM) for nC8, 2.0 mM for nC7, 5 mM
for nC9, and about 10 mM for nC6, nC10, benzene
and toluene. Concentrations of hydrocarbons that killed 50% of rabbit
macrophages were about half those observed in the rat. Cathepsin-D and, to a
lesser extent, cathepsin-B release were stimulated upon addition of hydrocarbons
to the cell media. A similar but more pronounced release of cathepsins was
observed in isolated lysosomes as well. A significant decrease in cell
respiration rate and a time and dose dependent increase in lipid peroxidation
were also observed following exposure of macrophages to the tested hydrocarbons,
particularly nC7 and nC8 alkanes. These results support the concept of an
association between chain length and cytotoxicity of hydrocarbons in pulmonary
alveolar macrophages.
... Under the conditions of these 2 yr gavage studies, there was clear
evidence of carcinogenicity of benzene
for male F344/N rats, for female F344/N rats, for male B6C3F1 mice and for
female B6C3F1 mice. For male rats, benzene
caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas
and squamous cell carcinomas of the oral cavity, and squamous cell papillomas
and squamous cell carcinomas of the skin. For female rats, benzene
caused increased incidences of Zymbal gland carcinomas, squamous cell
papillomas, and squamous cell carcinomas of the oral cavity. For male mice, benzene
caused increased incidences of Zymbal gland squamous cell carcinomas, lymphomas,
alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas
(combined), Harderian gland adenomas, and squamous cell carcinomas of the
preputial gland. For female mice, benzene
caused increased incidences of malignant lymphomas, ovarian granulosa cell
tumors, ovarian benigh mixed tumors, carcinomas and carcinosarcomas of the
mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas,
and Zymbal gland squamous cell carcinomas. ...
In animal models, benzene induces
anemia, lymphocytopenia, and hypoplastic bone marrow. In addition, it has been
suggested recently that this myelotoxicity may be a result of altered
differentiative capacity in bone marrow-derived lymphoid cells.
... Solid tumors have been reported in animals exposed to benzene
by inhalation or orally, suggesting that in mice and rats benzene
may produce tumors in nonhematopoietic organs.
When Sprague-Dawley rats and CD-1 mice of either sex were exposed to benzene
by inhalation 6 hr/day, 5 d/wk for 13 wk at 1, 10, 30, or 300 ppm,
treatment-related pathology was observed in the high-dose (300 ppm) groups of
both species. In mice, hematologic changes included decreased hematocrit, total
hemoglobin, erythrocyte/leukocyte count, platelet count, and myeloid: erythroid
ratio. In rats, decreased lymphocyte count and a relative increase in neutrophil
count were the only exposure-related clinical changes. Histopathological changes
were observed in the testes and ovaries at concentrations below 300 ppm, and
lesions were observed in the thymus, bone marrow, lymph nodes, spleen, ovaries,
and testes in mice inhaling 300 ppm. The alterations were more severe in the
males than in the females. In rats, the only exposure-related pathology was a
slight reduction in femoral marrow cellularity at 300 ppm.
Hematopoietic depression in rodents was observed at benzene
concentrations as low as 103 ppm after a 5 day exposure.
In a lifetime carcinogenicity bioassay in which oral doses of benzene
were administered at 50 and 250 mg/kg body weight/day, 4-5 days per week for 52
weeks, there was a dose-dependent increase in total cancers. The most prominent
rat tumors observed were Zymbal gland carcinomas, mammary carcinomas, and
leukemia. When Wistar rats and Swiss mice were given benzene
at 500 mg/kg/day, 4 days/wk for 104 wk or 5 days/wk for 78 wk, the numbers of
Zymbal gland carcinomas, hemolymphoreticular neoplasias, and total malignant
tumors were increased in the rats; increases in mouse Zymbal gland dysplasia and
carcinomas, mammary carcinomas, pulmonary tumors, and total malignant tumors
were observed.
/Researchers/ conducted an inhalation study in which pregnant Sprague-Dawley
rats were exposed 7 hr/d to benzene at
10, 50, or 500 ppm on days 6 to 15 of gestation. Significant reductions in mean
maternal body weight gain occurred. Mean fetal body weight was reduced. Fetal
crown-to-rump distance was decreased significantly at 500 ppm, and developmental
delay was evidence upon examination of the fetal skeletons. Benzene
was judged ... to be fetotoxic in rats at 50 and 500 ppm and to manifest
teratogenicity at 500 ppm.
/Researchers/ exposed CFLP mice and NZ rabbits 24 hr/day to benzene
at 154 or 308 ppm throughout days 6 to 15 of gestation. Benzene
was detected in fetal blood and in amniotic fluid. At 308 ppm, retarded skeletal
development and reduced fetal body weight were observed in mouse fetuses, and
spontaneous abortions were reported in rabbits.
/Researchers/ found a concentration-dependent increase in DBA/2 mouse bone
marrow lymphocytes after a single 4-hr inhalation study of benzene
at 28-3000 ppm; an increase in SCE was detected at 28 ppm. This response was
strain-dependent because DBA/2 mice were more sensitive than C57BL/6 mice, young
DBA/2 mice (3 mos old) were more sensitive than older mice (10 mos old), and
male mice were more sensitive than female mice. Following intraperitoneal
injection, a linear dose-dependent increase in SCE was observed in DBA/2 mice.
When male DBA/2 mice inhaled benzene
at 0, 10, 100, or 1000 ppm or male Sprague-Dawley rats inhaled benzene
at 0, 0.1, 0.3, 1, 3, 10, or 30 ppm for 6 hr, significant
(concentration-dependent) increases in SCE and micronuclei were observed in mice
at greater than or equal to 10 ppm, and increased SCE and micronuclei were
observed in rats inhaling greater than or equal to 3 ppm and at 1 ppm,
respectively. These data are the lowest concentrations of inhaled benzene
that have been reported to induce genotoxicity.
/Benzene/ has been shown to be
fetotoxic following inhalation exposure in mice (1600 ug/cu m, 7 hr/day,
gestation days 6-15) and in rabbits.
Toluene and benzene administered
concurrently were reported to have an additive effect on induction of
chromosomal aberrations. Toluene reduced the number of sister chromatid
exchanges induced by benzene when both
compounds were administered intraperitoneally to DBA/2 mice and reduced the
clastogenic activity of benzene when
the two compounds were simultaneously administered orally to CD-1 mice,
intraperitoneally to Sprague-Dawley rats, or subcutaneously to NMRI mice.
Rats exposed to 3,526-8,224 ppm of benzene
in a closed chamber for 15 min exhibited an increased number of ectopic
ventricular beats.
Sprague-Dawley SD/Tex rats were exposed to benzene
vapor at 0 or 500 ppm for 5 days per week, 6 hr/day for 3 wk. Blood from the
animals was evaluated for hematologic changes and the bone marrow for the
presence of multinucleated erythroblasts. Animals exposed to 500 ppm showed
decreased lymphocyte and leukocyte counts. Erythrocytes and hemoglobin values
increased. In the bone marrow differential counts, rats showed a relative
decrease in lymphoid and myeloid cells at the 500 ppm dose level and an increase
in erythroid cells. In a companion study, purebred Duroc-Jersey pigs were
exposed to 0, 20, 100, and 500 ppm benzene
vapors 6 hr/day, 5 days/wk for 3 wk.
Granulocytic hyperplasia has been detected in the bone marrow of mice exposed
to 300 ppm benzene in air for 6
hr/day, 5 days/wk for 16 wk, and held 18 mos after the last exposure.
/Researchers/ observed a 26% decrease in spleen weight in male Kunming mice
exposed to 12.52 ppm benzene 2 hr/day,
6 days/wk for 30 days. Examination of the bone marrow showed decreases in
myelocytes, premyelocytes, myeloblasts, and metamyeloblasts at the same dose
level.
Experimental DBA/2 mice were exposed to 300 ppm benzene
for 6 hr/day for 5 days/wk (Regimen 1) or 3 day/wk (Regimen 2) for a duration of
1-13 wk. Polychromatic erythrocytes were affected by benzene
inhalation independent of exposure duration and regimen, while normochromatic
erythrocytes were affected only following Regimen 1 exposure. Males were more
sensitive to benzene inhalation than
females.
Sprague-Dawley rats received a single dose of 950 mg/kg benzene
by gavage and were sacrificed 2 hr after treatment. The control group received
nothing. Brains were dissected ... Results showed that benzene
decreased acetylcholine content of rat hippocampus. 3,4-Dihydroxyphenylalanine
and norepinephrine content decreased in the rat midbrain. Dopamine, serotonin
and 5-hydroxyindoleacetic acid content increased in the rat midbrain. Dopamine,
3,4-dihydroxyphenylacetic acid, norepinephrine, and 5-hydroxyindoleacetic acid
content increased and serotonin content decreased in the rat hypothalamus after
oral administration of benzene.
Increased dopamine, homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, and
serotonin content of rat medulla oblongata was observed. Decreased
norepinephrine and 5-hydroxyindoleacetic acid content of rat medulla oblongata
by benzene treatment was observed.
In /a/ study of cultured rat embryos, /researchers/ evaluated the embryotoxic
effects of benzene and several of its
metabolites. Benzene at 1.6 mM
produced little embryotoxicity, with or without hepatic activating enzymes, but
phenol showed significant embryotoxicity in the presence of hepatic activation
at concentrations as low as 0.01 mM. Trans,trans-muconaldehyde was embryotoxic
at 0.01 mM and embryolethal at 0.05 mM; hydroquinone, catechol, and benzoquinone
were all 100% embryolethal at 0.1 mM.
MICE WERE GIVEN SINGLE DOSES OF BENZENE
SC & ITS EFFECT ON (59)FE UPTAKE WAS EVALUATED. NO SUPPRESSION WAS FOUND
AFTER 1 & 12 HR & ALSO 72 HR, WHEREAS DOSE-DEPENDENT INHIBITION OF
(59)FE UPTAKE WAS OBSERVED 24 HR & 48 HR AFTER TREATMENT WITH 440 OR 2200
MG/KG DOSE. THUS, THE DATA CAN BE INTERPRETED TO SUGGEST THAT (1) BENZENE
DID NOT INTERFERE WITH AN INCORPORATION OF IRON INTO HEME, (2) BENZENE
INTERFERED WITH PROLIFERATION OF NORMOBLASTS & PRONORMOBLASTS, & (3) BENZENE
DID NOT DAMAGE HEMOPOIETIC STEM CELLS WHICH WERE IN THE G0 STATE AT THE TIME OF BENZENE
INJECTION.
When mitochondria are incubated in vitro with 2200 mg/kg of benzene
there is an inhibition of RNA synthesis. Benzene
also caused a dose-dependent inhibition of RNA synthesis in vitro in mitoplasts
derived from cat and rabbit bone marrow mitochondria. Exogenous NADPH is
required for inhibition of mitochondrial RNA synthesis in all these systems
which suggests that benzene must be
bioactivated within the organelle. Toluene does not inhibit RNA synthesis and
the simultaneous addition of equimolar toluene and benzene
results in protection against benzene
inhibition. Both liver and bone marrow mitochondria incubated (3H) with benzene
appear to activate benzene to a
metabolite which can covalently bind to guanine residues of DNA. Benzene
also inhibits mitochondrial translation.
... Benzene hydroxylation was
stimulated when rats were pretreated with phenobarbital and then exposed to
1,000 ppm of benzene vapor for 8
hr/day for 2 wk.
National Toxicology Program Studies:
Two yr toxicology and carcinogenesis studies of benzene
(greater than 99.7% pure) were conducted in groups of 50 F344/N rats and 50
B6C3F1 mice of each sex and for each dose. Doses of 0, 50, 100, or 200 mg/kg
body weight benzene in corn oil (5
ml/kg) were administered by gavage to male rats, 5 days/wk for 103 wk. Doses of
0, 25, 50, or 100 mg/kg benzene in
corn oil were administered by gavage to female rats and to male and female mice
for 103 wk. ... Under the conditions of these 2 yr gavage studies, there was
clear evidence of carcinogenicity of benzene
for male F344/N rats, for female F344/N rats, for male B6C3F1 mice and for
female B6C3F1 mice. For male rats, benzene
caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas
and squamous cell carcinomas of the oral cavity, and squamous cell papillomas
and squamous cell carcinomas of the skin. For female rats, benzene
caused increased incidences of Zymbal gland carcinomas, squamous cell
papillomas, and squamous cell carcinomas of the oral cavity. For male mice, benzene
caused increased incidences of Zymbal gland squamous cell carcinomas, lymphomas,
alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas
(combined), Harderian gland adenomas, and squamous cell carcinomas of the
preputial gland. For female mice, benzene
caused increased incidences of malignant lymphomas, ovarian granulosa cell
tumors, ovarian benigh mixed tumors, carcinomas and carcinosarcomas of the
mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas,
and Zymbal gland squamous cell carcinomas. ...
Non-Human Toxicity Values:
LD50 MOUSE INTRAPERITONEAL 0.34 ML/KG 95% CONFIDENCE LIMITS 0.28 TO 0.42
LD50 Rat oral 3306 mg/kg
LC50 Rat ihl 10,000 ppm/7 hr
LD50 Rat ip 2890 ug/kg
LD50 Mouse oral 4700 mg/kg
LC50 Mouse ihl 9980 ppm
LD50 Mouse ip 340 mg/kg
LD50 Mouse ip 340 mg/kg
Ecotoxicity Values:
LC100 Tetrahymena pyriformis (ciliate) 12.8 mmole/l/24 hr /Conditions of
bioassay not specified/
LC50 Palaemonetes pugio (grass shrimp) 27 ppm/96 hr /Conditions of bioassay
not specified/
LC50 Cancer magister (crab larvae) stage 1, 108 ppm/96 hr /Conditions of
bioassay not specified/
LC50 Crangon franciscorum (shrimp) 20 mg/l/96 hr /Conditions of bioassay not
specified/
LC50 Morone saxatilis (bass) 5.8 to 11 mg/l/96 hr /Conditions of bioassay not
specified/
LC50 Poecilia reticulata (guppy) 63 mg/l/14 days /Conditions of bioassay not
specified/
LC50 Salmo trutta (brown trout yearlings) 12 mg/l/1 hr (static bioassay)
LC50 Ambystoma mexicanum (Mexican axolotl) (3-4 wk after hatching) 370
mg/l/48 hr /Conditions of bioassay not specified/
LC50 Clawed toad (3-4 wk after hatching) 190 mg/l/48 hr /Conditions of
bioassay not specified/
LC50 Carassius auratus (goldfish) 46 mg/l/24 hr /Conditions of bioassay not
specified/
LC50 Lepomis macrochirus (bluegill sunfish) 20 mg/l/24 to 48 hr /Conditions
of bioassay not specified/
LD100 Lepomis macrochirus (bluegill sunfish) 34 mg/l/24 hr /Conditions of
bioassay not specified/
LD100 Lepomis macrochirus (bluegill sunfish) 60 mg/l/2 hr /Conditions of
bioassay not specified/
LC50 Brine shrimp 66-21 mg/l/24-48 hr /Conditions of bioassay not specified/
LC50 Pimephales promelas (fathead minnow) 35 to 33 mg/l/24 hr-96 hr (soft
water) /Conditions of bioassay not specified/
LC50 Pimephales promelas (fathead minnow) 24 to 32 mg/l/24-96 hr (hard water)
/Conditions of bioassay not specified/
LC50 Bluegill 22 mg/l/24-96 hr (soft water) /Conditions of bioassay not
specified/
LC50 Carassius auratus (goldfish) 34.4 mg/l/24-96 hr (soft water) /Conditions
of bioassay not specified/
TLm Lebistes reticulata (guppy) 36 mg/l/24-96 hr (soft water) /Conditions of
bioassay not specified/
LC50 Gambusia affinis (mosquito fish) 395 mg/l/24-96 hr /Conditions of
bioassay not specified/
Ongoing Test Status:
The NTP Toxicology Research and Testing Program releases a Management Status
Report on a quarterly basis. This report gives the status of chemicals studied,
under study, or proposed for study by NTP. The 07/11/2001 issue indicates that
the prechronic study for benzene is
completed, and the chemical is in review for further evaluation. Route: gavage;
Species: transgenic model evaluation II, mice.
TSCA Test Submissions:
An evaluation of fertility was made in female Charles River CD rats
(26/group) exposed by inhalation to benzene
at 0, 1, 10, 30 and 300 ppm for 6 hrs/day, 5 days/week during a 10 week
pre-mating treatment period and ensuing mating period, and continued exposure
for mated females daily for 6 hrs/day during gestation to day 20. Daily exposure
was resumed on day 5 of lactation until weaning (day 21 of lactation). There
were significant differences between treated and control animals in the
following: decrease in pup survival index (for lactation day 4-21 at 10 ppm, no
dose-response), decreased mean pup weights (days 14 and 21 of lactation for
high-dose level), and decreased mean absolute liver weights (high-dose female
pups). There were no significant differences between treated and control animals
in the following: maternal mortality, body weights, in-life observations,
pregnancy rates, mean number dead pups, mean liver weights (male pups at all
levels), mean relative liver weights (female pups at all levels), mean relative
and absolute kidney weights (all female pups), or gross postmortem examinations
of adult females or pups.
Teratogenic effects were evaluated in pregnant female Sprague Dawley rats
(40/group) exposed via inhalation to benzene
at 0 (two groups), 1, 10, 40 and 100 ppm for 6 hrs/day from days 6-15 of
gestation. On day 20 of gestation, the dams were sacrificed and the fetuses
removed by cesarean section. There were significant differences between treated
and control groups only in the decreased mean fetal body weights of fetuses from
dams exposed at the high-dose level. There were no significant differences
between treated and control dams in the following: mortality, clinical
observations, body weight data, maternal gross pathology, pregnancy rates, mean
number of corpora and implantations, or implantation efficiencies. There were no
significant differences between fetuses from treated and control dams in the
following: mean incidence of fetal resorptions, mortality, mean percentage of
male fetuses/litter, mean fetal body lengths, or fetal development.
The mutagenicity of benzene was
evaluated in dominant lethal assay using four groups of 20 male Sprague-Dawley
rats receiving whole body exposures to nominal concentrations of test material
at 1, 10, 30 and 300ppm in a dynamic air flow chamber for 6hours/day, 5days/week
for ten consecutive weeks. Following exposure, each male was mated with two
untreated females per week for two consecutive weeks. There was no effect of
treatment for all dosed male rats as indicated by: mortality, body weight data
and in-life physical observations. Pregnancy rates and implantation efficiency
ratios of females mated to treated males was not significant different from
control group females. Slight increases in the mean number of dead implantations
and mean mutagenic ratios (i.e. no. dead implants/total implants) were noted for
each week of the post treatment mating period for females mated to high dose
males, but these differences were not statistically significant compared to
controls. Males were sacrificed after a 10-week post mating period and
microscopic examination of testis/epididymides revealed two-high dose males with
testicular lesions.
As part of subchronic inhalation study, the ability of benzene
to cause chromosome aberrations was evaluated in bone marrow cells of (50/sex)
CD-1 mice receiving whole body exposures to nominal concentrations of 0, 1, 10,
30 and 300ppm in dynamic air flow chamber for 6hours/day, 5days/week for 13
weeks. Following the last day of exposure, animals received a single
intraperitoneal injection of colchicine and were sacrificed. Bone marrow slides
of mice at the highest concentration (300ppm) exhibited statistically
significant increases chromosome aberrations relative to the control.
As part of subchronic inhalation study, the ability of benzene
to cause chromosome aberrations was evaluated in bone marrow cells of (50/sex)
Sprague Dawley rats receiving whole body exposures to nominal concentrations of
0, 1, 10, 30 and 300ppm in dynamic air flow chamber for 6hours/day, 5days/week
for 13 weeks. Following the last day of exposure, animals received a single
intraperitoneal injection of colchicine and were sacrificed. Bone marrow slides
of female rats at all exposure levels exhibited statistically significant
increases in chromosome aberrations relative to the control. No-exposure related
cytogenic effects were apparent in any of the male rats.
The ability of benzene to increase
the incidence of micronucleated polychromatic erythrocytes was evaluated in male
and female CD-1 mice receiving nominal concentrations of 1, 10, 30 and 300ppm
for 6hours/day, 5days/week for 13 weeks (Micronucleus Test). Groups of 20 mice
(10/sex/sample time) were sacrificed after 0, 15, 30, 60 and 90 days of
exposure. Exposure to 300ppm benzene
caused a significant increases in micronucleated polychromatic erythrocytes
(PCEs) and monochromatic erythrocytes (NCEs) in male and female mice at all
sample times. Male mice exhibited a greater response than female mice. The
frequency of micronucleated PCEs and the frequency micronucleated NCEs achieved
steady state by the 30 day sample time. The rate of erythropoiesis, as measured
by per cent of polychromatic erythrocytes in the peripheral blood, was not
significantly altered by treatment.
The levels of benzene and it's
metabolites in the blood were evaluated in twenty male Sprague-Dawley rats and
eighty male Swiss albino mice receiving nominal concentration of benzene
at 300ppm in a dynamic air flow chamber. Sixteen mice and four rats were removed
from the chamber after 1, 2, 4, 8 and 12 hours for eye bleeding. The mean levels
of benzene in the rat blood were <
1.0, 4.7, 4.8, 5.7, 5.3, and 7.1ppm at intervals of 0, 1, 2, 4, 8 and 12 hours
respectively. No free metabolites (phenol, catechol & hydroquinone) were
detected at any of the time intervals in rats. The mean levels of benzene
in mouse blood were < 1.0, 3.7, 3.0, 2.4, 3.0 and 1.3ppm at intervals of 0,
1, 2, 4, 8 and 12 hours, respectively. The mean levels of free phenol in mouse
blood were 2.0, 2.4, 2.2, 2.3, 2.5 and 2.3ppm at respective intervals. No free
catechol or hydroquinone were detected at any of the time intervals in mice.
Also determined were levels of conjugates in rat and mouse blood. The mean
levels of conjugated phenol in rat blood were < 1.0, 3.0, 5.3, 4.2, 7.1 and
4.7ppm and the mean levels in the mouse blood were 2.7, 7.2, 8.7, 8.4, 9.1, and
3.7 at intervals 0, 1, 2, 4, 8 and 12 hours, respectively. No conjugated
catechol or hydroquinone were detected at any of the time intervals in rats or
mice. It was concluded, that its takes approximately one hour to achieve a
steady state level of benzene in rat
and mouse blood.
The levels of benzene and its's
metabolites in blood were evaluated in male Sprague Dawley rats (4/group) and
male Swiss albino mice (16/group) receiving nominal concentrations of benzene
at 0, 3, 30, 300 or 1000ppm in dynamic air flow chamber for 6 hours. The mean
levels of benzene in rat blood were
< 1.0, < 1.0, < 1.0, 8.3 and 33.6ppm at exposure levels 0, 3, 30, 300
and 1000ppm, respectively. No free metabolites (phenol, catechol &
hydroquinone) were detected at any exposure level in rat blood. The mean levels
of benzene in the mouse blood were
< 1.0, < 1.0, < 1.0, 1.44 and 29.5ppm at exposure levels 0, 3, 30, 300
and 1000ppm, respectively. A mean level of 1.2ppm of free phenol was only
detected at the high dose level in mice. No free catechol or hydroquinone were
detected in mouse blood. Also determined were the levels of conjugates in rat
and mouse blood. The mean level of conjugated phenol in rat blood were < 1.0,
< 1.0, 1.7, 6.0 and 6.3ppm and the mean levels of conjugated phenol in mouse
blood were < 1.0, 1.1, 2.9, 7.9 and 15.5ppm at exposure levels of 0, 30, 300
and 1000ppm, respectively. No conjugated catechol or hydroquinone were detected
at any exposure level in rats or mice. It was concluded that there was a direct
correlation between increased exposure to benzene
and increased blood concentration levels of benzene
and conjugated phenol. Mice exposed to 1000ppm benzene
had double the concentration of conjugated phenol in the blood relative to the
300ppm mice. In contrast, this effect was not observed in rats.
The concentration of benzene and
it's metabolites were determined after 12, 24, 48 and 72 hours in the urine of
five exposed male Sprague Dawley rats and 25 male Swiss albino mice which
received a nominal concentration of benzene
at 300ppm in dynamic air flow chamber for 6 hours. No level of benzene
at or above the detection limit (1.0ppm) were detected in rat and mice urine at
any of the sampling intervals. The level of free phenol in the rat urine were
2.0, 2.2, 1.7 and 3.2ppm and in mouse urine were 15.6, 4.7, 5.8 and 4.3ppm at
12, 24, 48 and 72 hours, respectively. The mean levels of free catechol in rat
urine were < 2.0, 0.46, 0.32 and < 2.0ppm and in mouse urine were 1.09,
1.29, 1.56 and 7.76ppm at 12, 24, 48 and 72 hours, respectively. No free
hydroquinone at or above the detection limit were determined in rat urine at any
sampling time. The mean levels of free hydroquinone in mouse urine were 12.87,
1.49, 1.46 and 0.31ppm at 12, 24, 48 and 72 hours, respectively. The expired air
of rats was bubbled through dichloromethane and the mean total levels of benzene
detected were 440.6, 101.4, not detected and 22.2ug/sampling interval ending at
6, 12, 24 and 48 hours, respectively. Benzene
in expired air of mice was only detected at the 48 hour sampling interval.
The in vitro percutaneous absorption of 14C-benzene
was evaluated in mammalian skin samples maintain in a dynamic culture system.
C3H Mice (primary test subject), HRS mice, rabbit and guinea pig (strain not
specified) dorsal skin, and human skin from elective surgery were all placed in
culture medium chamber for penetration analysis. 14C-Benzene
(20ul) was topically applied to cultured C3H mouse skin samples and
radioactivity was detected in the effluent medium 15 minutes following treatment
with no apparent lag phase. Penetration was linear and the rates were 2.97 +/-
0.03 and 3.70 +/- 0.03%/hr for metabolically viable (fresh skin) and nonviable
skin (frozen skin), respectively. Analysis of the effluent medium indicated
negligible conversion of benzene to
phenol. Different rates of in vitro skin permeation were observed between male
and female C3H mice, however this difference was not observed between sexes in
similar studies with hairless HRS mice. In vitro penetration of benzene
in hairless mice skin (2.44 +/- 0.07%) was lower than C3H mice. Additional in
vitro penetration studies with 14C-benzene
(20ul) were preformed with metabolically viable guinea pig, rabbit and human
skin with rates of penetration of 0.04 +/- 0.01, 0.55 +/- 0.02 and 0.23 +/-
0.04%/hr, respectively. The lag phase of these additional studies were between
45-60 minutes and two hours from application followed by linear radioactivity.
Toluene and unleaded gasoline containing 14C-benzene
(20ul) produced rates of permeation of 2.32 +/- 0.04 and 2.81 +/- 0.4%/hr,
respectively in C3H mice which appeared linear.
The benzene uptake rate was
evaluated in five male Sprague Dawley rats and twenty five male Swiss albino
mice receiving benzene at a nominal
concentration of 300ppm in a dynamic air flow chamber for 6 hours. Five
individual rats were determined to have an internal mean benzene
uptake rate of 152ml/min prior to conducting the six hour test and an mean
pretest respiratory minute volume of 145ml/min. The mean benzene
uptake rates as compared to pretest values for rats decreased to 33, 22 and 9%
of the mean test value 1, 3 and 6 hours after administration, respectively. The
mean minute volume for rats decreased to 85, 78 and 66% of the pretest at 1, 3
and 6 hours after administration, respectively. Rats had an estimated retained
dose of 56mg/kg. Mice (5/group) had a mean total pretest benzene
uptake rate of 188ml/min and a mean pretest total respiratory minute volume of
189ml/min. The mean total benzene
uptake for the mice decreased 65, 76 and 81% of the pretest value, after 1, 3
and 6 hours of exposure, respectively. The mean total minute volume for groups
of mice decreased 96, 84 and 69% of the pretest after 1, 3 and 6 hours,
respectively. The mean total retained dose per mice was estimated to be
377mg/kg.
The dermal absorption of benzene
vapor was examined in 2 Rhesus monkeys exposed to the test article at saturated
concentrations for 30 minutes using a hydration controlled chamber which was
held tightly against the skin of the back. The radioactivity measured in the
urine was used to determined absorption rate. A correction factor was included
to account for radioactivity excreted by other routes. Under the 2 skin
conditions, of 40% hydration and 100% hydration, the absorption rates were
determined to be 0.02 microliter/sq cm and .15 microliter/sq cm, respectively.
Total absorption was found to be 7.5-fold higher from a 100% relative humidity
environment than from a 40% relative humidity environment. In a benzene
liquid exposure experiment, the concentration of benzene
was given by its density of 0.8787 gm/cu cm and the dermal absorption was 5.4
microliter/sq cm. The authors suggested that benzene
absorption from the liquid state was less than expected due to a dehydrating
effect on the stratum corneum.
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
... In human system /benzene/ is
metabolized through a variety of major & minor pathways. The primary site of
action is liver, where benzene is
oxidized to phenol (hydroxybenzene), catechol (1,2-dihydroxybenzene), or quinol
(1,4-dihydroxybenzene). Phenol is subsequently conjugated with inorganic sulfate
to phenylsulfate, the other hydroxybenzenes are conjugated to a lesser extent,
& all excreted in urine. Minor pathways incl further oxidation of catechol
to hydroxyhydroquinol (1,2,4-trihydroxybenzene) or catabolism to cis, cis- or
trans, trans-muconic acids, & phenol conjugation with glucuronic acid to
form glucuronides, or with cysteine to produce 2-phenylmercapturic acid.
METABOLIC PRODUCTS IN RAT ... ARE PHENOL, HYDROQUINONE, CATECHOL,
HYDROXYHYDROQUINONE, & PHENYLMERCAPTURIC ACID. CONJUGATED PHENOLS HAVE BEEN
REPORTED ... EXCEPT FOR A SMALL AMT OF FREE PHENOL, ALL THE PHENOLIC METABOLITES
WERE EXCRETED IN CONJUGATED FORM. WHEN (3)H-BENZENE
WAS ADMIN TO MICE, (3)H2O WAS ALSO RECOVERED FROM URINE.
YIELDS N-ACETYL-S-PHENYL-CYSTEINE IN RAT. YIELDS BENZYL ALCOHOL IN GUINEA
PIGS. ... YIELDS CIS-1,2-DIHYDRO-1,2-DIHYDROXYBENZENE IN PSEUDOMONAS. PHENOL IN
PSEUDOMONAS & ACHROMOBACTER. YIELDS CIS,CIS-MUCONIC ACID IN RABBIT. /FROM
TABLE/
In the rabbit, the major hydroxylation product of benzene
was phenol, which along with some catechol and hydroquinone, was found in the
urine conjugated with ethereal sulfate or glucuronic acid.
Unconjugated phenol has been found in mouse and rat urine after benzene
administration.
The formation of benzene oxide, an
epoxide of benzene is involved in the
metabolism of benzene. This highly
unstable intermediate rearranges non-enzymatically to form phenol. This step
accounts for the occurrence of phenol as the major metabolite of benzene
in urine. Catechol formation is thought to result from the hydration of benzene
oxide by the enzyme epoxide hydratase followed by oxidation to catechol. It
appears that catechol and phenol are formed by two distinctly different
metabolic pathways. Hydroquinone is thought to result from a second passage of
phenol through the mixed function oxidases.
The metabolism of benzene in vitro
can be altered by the use of enzyme inducers administered to animals prior to
sacrifice or by the addition of inhibitors to the mixtures. Benzene,
phenobarbital, 3-methylcholanthrene and dimethyl sulfoxide are all microsomal
stimulants for the metabolism of benzene.
Benzene metabolism in vitro can be
inhibited by carbon monoxide, aniline, metyrapone, SKF-525A /proadifen/,
aminopyrine, cytochrome c, aminotriazole, or toluene.
Benzene, when administered sc at
880 mg/kg twice daily for 3 days, decreased erythropoiesis much more markedly in
DBA/2 mice than in C57BL/6 mice. Total urinary benzene
metabolites and the % of the dose excreted in the urine were the same in both
strains. Although the metabolic profile differed between the two strains, it was
very similar when equitoxic doses of benzene
were administered. The levels of both free and covalently bound benzene
were higher in all organs of the DBA/2 mice. Phenol, hydroquinone, resorcinol,
and catechol had no effect on erythopoiesis.
The urinary metabolites isolated by DEAE Sephadex A-24 anion-exchange
chromatography from mice treated with radiolabeled benzene
included phenol as the major component, as well as catechol, hydroquinone, and
phenylmercapturic acid. The phenolic metabolites were excreted primarily as
glucronides with the exception of a small amount of free phenol.
Benzene reduced the incorporation
of (59)Fe into red cells by 75% at the higher dose when administered at 440 or
880 mg/kg to mice pretreated with (59)Fe 48 hr earlier. However, when toluene
was administered simultaneously with benzene
in a ratio of 2:1, the depression of (59)Fe uptake was prevented. Toluene
reduced the appearance of benzene
metabolites to 45% of controls at the higher dose and 30% at the lower dose.
Thus toluene appears to inhibit benzene
metabolism and by so doing, alleviates its toxicity.
A sensitive high performance liquid chromatography method is described which
separates urinary metabolites from benzene-treated
male CD-1 mice. Phenol, trans, trans-muconic acid and quino in the 48 hr urine,
accounted, respectively for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the orally
administered single dose of benzene
(880, 440, and 220 mg/kg body wt). Catechol occurred in trace amounts. Trans,
trans-muconic acid was identified and was unique to benzene
as none was detected in urine of mice dosed orally with phenol, catechol, or
quinol. The potential existence of a toxic metabolite in the form of an aldehyde
precursor of muconic acid in vivo is discussed.
In humans, phenol sulfate is the major metabolite of benzene
until 400 mg/l levels are reached in the urine. Beyond than level, glucuronide
conjugates are also present in the urine.
Male Wistar rats were tested to determine the effect of enzymes with
different kinetic characteristics on the metabolism of benzene,
in vitro. Kinetic analysis of the enzymes in the liver of rats fed a normal diet
revealed the presence of two benzene
hydroxylases with low Michaelis constant values of 0.01 millimolar and 0.07
millimolar, respectively. After 1 day of food deprivation, the isozyme with a
constant equal to 0.01 millimolar disappeared while the activity of the second
isozyme increased. Following the administration of phenobarbital there was
evidence of a third benzene
metabolizing enzyme in the liver of the animals exposed to benzene
in concentrations ranging from 0.0055 to 6.25 millimolar, in vitro; the value of
the Michaelis constant for this enzyme was equal to 4.5 millimolar and was not
evident in control animals. Treatment with phenobarbital failed to affect the
activity of the other low Michaelis constants of benzene
hydroxylases identified in the liver of normal rats. Treatment with ethanol
resulted in significant increase in the activity of both normally occurring benzene
hydroxylases in the normal liver.
Mitoplasts (mitochondria with the outer membrane removed) from the bone
marrow of rabbits were incubated sequentially with (3)H-labeled deoxyguanosine
triphosphate and (14)C-labeled benzene
to study the DNA adducts formed from benzene
metabolites in mitochondria. Following isolation and isopycnic density gradient
centrifugation in CsCl, the doubly labeled DNA was hydrolyzed to
deoxynucleosides and separated on a Sephadex LH 20 column. At least seven
deoxyguanosine adducts and one deoxyadenine adduct were present.
Primary metabolism of benzene
occurs predominantly in the liver via cytochrome P-450, the principal product
being phenol. Phenol, in turn, undergoes further oxidation via cytochrome P-450
to produce the polyphenolic metabolites of benzene
(principally hydroquinone), or alternatively, oxidation via peroxidases in
extrahepatic tissues to form biphenols, hydroquinone, and its terminal oxidation
product, p-benzoquinone. Muconic acid /is/ ... a minor urinary metabolite of benzene
...
... Literature identifies the following metabolites after incubation of benzene
with mouse liver microsomes: phenol, hydroquinone, trans,trans-muconaldehyde,
6-oxo-trans,trans-2,4-hexadienoic acid, 6-hydroxy-trans,trans,2-4,-hexadienal,
and 6-hydroxy-trans,trans-2,4-hexadienoic acid. Beta-hydroxymuconaldehyde, a new
metabolite, was also identified.
Data produced in vitro by mouse and rat liver microsomes ... indicate species
differences in benzene metabolism.
Quantitation of metabolites from the microsomal metabolism of benzene
indicated that after 45 min, mouse liver microsomes from male B6C3F1 mice had
converted 20% of the benzene to
phenol, 31% to hydroquinone, and 2% to catechol. In contrast, rat liver
microsomes from male Fischer 344 rats converted 23% to phenol, 8% to
hydroquinone, and 0.5% to catechol. Mouse liver microsomes continued to produce
hydroquinone and catechol for 90 min, whereas rat liver microsomes had ceased
production of these metabolites by 90 min. Muconic acid production by mouse
liver microsomes was <0.04 and <0.2% from phenol and benzene,
respectively, after 90 min.
Subjects who inhaled concentrations of 340 mg/cu m (106 ppm) benzene
in air for 5 hr excreted 29% as phenol, 3% as catechol and 1% as hydroquinone in
the urine, mostly as ethereal sulfates.
Absorption, Distribution & Excretion:
BENZENE IS READILY ABSORBED VIA
LUNG, & ABOUT 40-50% IS RETAINED. ... IT IS TAKEN UP PREFERENTIALLY BY FATTY
& NERVOUS TISSUES, & ABOUT 30-50% ... IS EXCRETED UNCHANGED VIA LUNG; A
3-PHASE EXCRETION PATTERN IS SEEN AT ... /APPROX/ 0.7-1.7 HR, 3-4 HR, &
20-30 HR.
When benzene was placed on skin
under closed cup it was absorbed at rate of 0.4 mg/sq cm/hr (Hanke et al 1961)
...
MICE TREATED SC WITH 2 ML (3)H-LABELED BENZENE/KG
CONTAINED IRREVERSIBLY BOUND RADIOACTIVITY WITH DECREASING BINDING MAGNITUDE IN
THE FOLLOWING ORGANS: LIVER, BRAIN, KIDNEY, SPLEEN, FAT. MICE TREATED WITH 2
DAILY SC DOSES OF 0.5 ML (3)H-BENZENE/KG
FOR 1-10 DAYS SHOWED A RADIOACTIVITY BINDING WITH LIVER & BONE MARROW
RESIDUES WHICH INCREASED WITH TREATMENT DURATION, EXCEPT IN THE CASE OF BINDING
TO BONE MARROW WHICH DECREASED AFTER DAY 6.
When administered to mice subcutaneously, 72% of dose is recovered in expired
air.
Rats were exposed to 500 ppm benzene
for 30 min to eight hr. Benzene
concentrations reached steady state within four hr in blood (steady-state concn=
11.5 ug/g), six hr in fat (concn= 164.4 ug/g), and two hr in bone marrow (concn=
37.0 ug/g). Lesser concn were detected in the kidney, lung, liver, brain, and
spleen.
Benzene is absorbed from the
gastrointestinal tract when ingested.
BENZENE CROSSES THE HUMAN PLACENTA,
& LEVELS IN CORD BLOOD ARE SIMILAR TO THOSE IN MATERNAL BLOOD. ... THE MOST
FREQUENT ROUTE BY WHICH HUMANS ARE EXPOSED TO BENZENE
IS VIA INHALATION. TOXIC EFFECTS IN HUMANS HAVE BEEN ATTRIBUTED TO COMBINED
EXPOSURE BY BOTH RESPIRATION & THROUGH THE SKIN ... IT IS ELIMINATED
UNCHANGED IN EXPIRED AIR ... IN MEN & WOMEN EXPOSED TO 52-62 PPM (166-198
MG/CU M) BENZENE FOR 4 HR, A MEAN OF
46.9% WAS TAKEN UP, 30.2% WAS RETAINED & THE REMAINING 16.8% EXCRETED AS
UNCHANGED BENZENE IN EXPIRED AIR. ...
WHEN HUMANS WERE EXPOSED TO 100 PPM (300 MG/CU M) BENZENE,
IT WAS DETECTED IN EXPIRED AIR 24 HR LATER, SUGGESTING THAT IT IS POSSIBLE TO
BACK-EXTRAPOLATE TO THE BENZENE
CONCENTRATION IN THE INSPIRED AIR.
... In female & male rats with large body fat content, benzene
was eliminated more slowly & stored longer than in lean animals. ...
Distribution in rabbit was highest in adipose tissue, high for bone marrow,
& lower for brain, heart, kidney, lung, & muscle, although direct
binding was higher in liver than in bone marrow.
The solubility characteristics of benzene
are such that it is easily taken up by the stratum corneum. Once in the stratum
corneum, it does not meet many restraining forces to impede its movement and
diffuses easily. The permeability constant for benzene,
as determined in vitro, is higher than that of many other small molecules,
particularly those having one or more polar groups. ... Even though these
uncertainties exist, and more data are needed to support the ... conclusion that
there is good overall agreement between in vitro and in vivo data. ... An adult
working in ambient air containing 10 ppm of benzene,
with 100 cm of glaborous skin in contact with gasoline containing 5% benzene,
and his entire skin (2 sq m) in contact with ambient air, will absorb in an hr,
7.5 ul of benzene from inhalation, 7.0
ul from contact with gasoline, and 1.5 ul from body exposure to ambient air.
Since ... in vitro techniques measure the penetration of benzene
through strongly hydrated stratum corneum, the calculated flux may be higher
than under some in vivo conditions. Nevertheless, it seems that unless good
hygiene is maintained and care is taken to prevent lengthy exposure to solvents
containing benzene, significant
amounts of benzene may enter the body
through the skin.
Subjects who inhaled concentrations of 340 mg/cu m (106 ppm) benzene
in air for 5 hr excreted 29% as phenol, 3% as catechol and 1% as hydroquinone in
the urine, mostly as ethereal sulfates. Most of the phenol and catechol was
excreted within 24 hr, and the hydroquinone within 48 hr.
In men and women exposed to 52-62 ppm (166-198 mg/cu m) benzene
for 4 hr, a mean of 46.9% was taken up, 30.2% was retained and the remaining
16.8% excreted as unchanged benzene in
expired air.
In animals, expired air is the main route of elimination of unmetabolized benzene,
while urine is the major route of excretion of benzene
metabolites (with very little fecal excretion).
In a series of experiments conducted in a single-family residence from June
11 to 13, 1991, exposure to benzene
through contaminated residential water was monitored. The residential water was
contaminated with benzene and other
hydrocarbons in 1986. Exposure was monitored for a person taking a 20-min shower
and for people in other parts of the house during and after the shower. An
average dermal dose of 168 ug was calculated for a 20-min shower using this
water. The total benzene dose
resulting from the shower was estimated to be approximately 281 ug (40% via
inhalation, 60% via dermal), suggesting a higher potential exposure to benzene
via dermal contact from the water than through vaporization and inhalation. This
exposure was 2-3.5 times higher than the mean 6-hr inhalation dose received by
the sampling team members in other parts of the house.
In Sprague-Dawley rats administered a single dose of 0.15, 1.5, 15, 150, or
500 mg/kg of 14C-benzene by gavage, benzene
was rapidly absorbed and distributed to various organs and tissues within 1 hr
of administration. One hour after rats were dosed with 0.15 or 1.5 mg/kg of benzene,
tissue distribution of benzene was
highest in liver and kidney, intermediate in blood, and lowest in the Zymbal
gland, nasal cavity tissue, and mammary gland. At higher doses, beginning with
15 mg/kg, benzene disproportionately
increased in the mammary glands and bone marrow. Bone marrow and adipose tissue
proved to be depots of benzene at the
higher dose levels. The highest tissue concentrations of benzene's
metabolite hydroquinone 1 hr after administration of 15 mg/kg of benzene
were in the liver, kidney, and blood, while the highest concentrations of the
metabolite phenol were in the oral cavity, nasal cavity, and kidney. The major
tissue sites of benzene's conjugated
metabolites were blood, bone marrow, oral cavity, kidney, and liver for phenyl
sulfate and hydroquinone glucuronide; muconic acid was also found in these
sites. Additionally, the Zymbal gland and nasal cavity were depots for phenyl
glucuronide, another conjugated metabolite of benzene.
The Zymbal gland is a specialized sebaceous gland and a site for benzene-induced
tumors. Therefore, it is reasonable to expect that lipophilic chemicals like benzene
would partition readily into this gland. However, benzene
did not accumulate in the Zymbal gland; within 24 hr after administration,
radiolabel derived from 14C-benzene in
the Zymbal gland constituted less than 0.0001% of the administered dose.
Monkeys were dosed intraperitoneally with 5-500 mg/kg radiolabeled benzene,
and urinary metabolites were examined. The proportion of radioactivity excreted
in the urine decreased with increasing dose, whereas the dose increased, more benzene
was exhaled unchanged. This indicated saturation of benzene
metabolism at higher doses. Phenyl sulfate was the major urinary metabolite.
Hydroquinone conjugates and muconic acid in the urine decreased as the dose
increased.
Biological Half-Life:
The excretion of unchanged benzene
from the lung of rats was reported to be biphasic, suggesting a two-compartment
model for distribution and a half-life of 0.7 hr. This agreed with experimental
half-life values for various tissues that ranged from 0.4 to 1.6 hr.
... The half-time of benzene in
/high lipid content/ tissues is approximately 24 hours.
Mechanism of Action:
COVALENT INTERACTION OF A BENZENE
METABOLITE WITH DNA WAS SHOWN IN VIVO, BUT NO INFORMATION WAS GIVEN ABOUT THE
CHEM NATURE OF THIS METABOLITE. A LIKELY INTERMEDIATE IN BENZENE
METABOLISM IS BENZENE OXIDE. IN
NEUTRAL AQ MEDIA IT REARRANGES ONLY SLOWLY TO THE PHENOL SO THAT ITS LIFETIME
COULD BE LONG ENOUGH FOR DIFFUSION FROM THE SITE OF ACTIVATION TO THE DNA.
ALTERNATIVELY, THE METABOLIC APPEARANCE OF POLYHYDROXY DERIVATIVES SUGGESTS THE
FORMATION OF A PHENOL EPOXIDE, SO THAT THE REACTIVE MOLECULE COULD BE A
SECONDARY METABOLITE.
THE AVAILABLE EVIDENCE SUPPORTS THE CONCEPT THAT BENZENE
TOXICITY IS CAUSED BY ONE OR MORE METABOLITES OF BENZENE.
... BENZENE METABOLITES CONTAINING 2
OR 3 HYDROXYL GROUPS INHIBITED MITOSIS. TOLUENE, WHICH INHIBITS BENZENE
METABOLISM, PROTECTED ANIMALS AGAINST BENZENE-INDUCED
MYELOTOXICITY. BENZENE TOXICITY COULD
BE CORRELATED WITH THE APPEARANCE OF BENZENE
METABOLITES IN BONE MARROW. ALTHOUGH IT IS CLEAR THAT BENZENE
CAN BE METABOLIZED IN BONE MARROW, THE OBSERVATION THAT PARTIAL HEPATECTOMY
PROTECTS AGAINST BENZENE TOXICITY
SUGGESTS THAT A METABOLITE FORMED IN LIVER IS ESSENTIAL FOR BENZENE
TOXICITY.
... IMPORTANCE OF POLYHYDROXYLATED DERIVATIVES OF BENZENE
& THEIR SEMIQUINONES. ... /IT HAS BEEN/ SHOWN THAT HYDROQUINONE INHIBITS RAT
BRAIN MICROTUBULE POLYMERIZATION; THAT HYDROQUINONE & PARA-BENZOQUINONE ARE
THE MOST POTENT INHIBITORS OF T- & B-LYMPHOCYTE FUNCTION, AS MEASURED IN
MOUSE SPLEEN CELLS IN CULTURE; THAT HYDROQUINONE INHIBITS LECTIN-STIMULATED
LYMPHOCYTE AGGLUTINATION IN RAT SPLEEN PREPN IN VITRO; & THAT
PARA-BENZOQUINONE IS THE METABOLITE MOST LIKELY TO BE RESPONSIBLE FOR
SUPPRESSION OF LYMPHOCYTE TRANSFORMATION & MICROTUBULE ASSEMBLY IN RAT
SPLEEN CELLS IN CULTURE. HOWEVER, ADMIN OF THESE CMPD TO ANIMALS DOES NOT
PRODUCE THE TYPICAL PICTURE OF BENZENE
TOXICITY ... ADMIN /OF/ MAJOR METABOLITES OF BENZENE
TO MICE ... FAILED TO ... DECR ... RED BLOOD CELL PRODUCTION, USING THE (59)FE
UPTAKE TECHNIQUE ... /IT'S BEEN/ SUGGESTED THAT RING-OPENING PRODUCTS MAY PLAY A
ROLE IN BENZENE TOXICITY. ... IN MICE BENZENE
TREATMENT SUPPRESSED SUBSEQUENT COLONY FORMING UNIT-C FORMATION FROM BONE-MARROW
CELLS IN VITRO. TREATING THE ANIMALS WITH PHENOL, HYDROQUINONE OR BENZENE
DIHYDRODIOL FAILED TO SUPPRESS COLONY FORMING UNIT-C. THUS, THE TOXIC
METABOLITES OF BENZENE HAVE YET TO BE
IDENTIFIED.
... RADIOACTIVITY /HAS BEEN DEMONSTRATED/ IN A NUCLEIC ACID FRACTION FROM RAT
LIVER FOLLOWING ADMIN OF EITHER (3)H- OR (14)C-LABELLED BENZENE.
IT HAS BEEN SHOWN THAT BENZENE BINDS
COVALENTLY TO PROTEIN IN LIVER, BONE MARROW, KIDNEY, LUNG, SPLEEN, BLOOD, &
MUSCLE. LESS COVALENT BINDING WAS OBSERVED TO THE PROTEIN OF BONE MARROW, BLOOD,
& SPLEEN OF C57BL/6 MICE, WHICH ARE MORE RESISTANT TO THE BENZENE-INDUCED
EFFECTS ON RED CELL PRODUCTION, THAN TO THAT OF SENSITIVE DBA/2 MICE. ...
COVALENT BINDING OF BENZENE TO PROTEIN
IN PERFUSED BONE-MARROW PREPN /HAS BEEN DEMONSTRATED/. ... A METABOLITE OF
PHENOL BINDS TO LIVER PROTEIN MORE EFFICIENTLY THAN DOES BENZENE
OXIDE, & THEY HAVE ELECTROPHORETICALLY SEPARATED HEPATIC PROTEINS TO WHICH BENZENE
PREFERENTIALLY BINDS. ... COVALENT BINDING TO MITOCHONDRIA IS A PROMINENT
FEATURE OF BENZENE METABOLISM. ...
THERE IS RELATIVELY MORE RADIOACTIVITY IN A NUCLEIC ACID-RICH FRACTION OF A BENZENE
METABOLITE ISOLATED FROM MOUSE BONE-MARROW CELLS THAN IN A SIMILAR FRACTION FROM
LIVER.
EVIDENCE INDICATES THAT BENZENE
MUST BE METABOLICALLY ACTIVATED IN ORDER TO EXERT ITS CHARACTERISTIC TOXICITY ON
BONE MARROW. SOME OF THE HYDROXYLATED BENZENE
METABOLITES, PHENOL, CATECHOL, HYDROQUINONE, RESORCINOL & SOME
TRIHYDROXYLATED DERIVATIVES IN URINE OF RABBITS ARE SUGGESTED TO BE THE TOXIC
METABOLITES.
THE MECHANISM OF BENZENE
OXYGENATION IN LIVER MICROSOMES & IN RECONSTITUTED ENZYME SYSTEMS FROM
RABBIT LIVER WAS INVESTIGATED. THE RESULTS INDICATE THAT THE MICROSOMAL
CYTOCHROME P450 DEPENDENT OXIDATION OF BENZENE
IS MEDIATED BY HYDROXYL RADICALS FORMED IN A MODIFIED HABER-WEISS REACTION
BETWEEN HYDROGEN PEROXIDE & SUPEROXIDE ANIONS & SUGGEST THAT ANY
CELLULAR SUPEROXIDE-GENERATING SYSTEM MAY BE SUFFICIENT FOR THE METABOLIC
ACTIVATION OF BENZENE &
STRUCTURALLY RELATED COMPOUNDS.
Animal expt show that benzene
sensitizes the myocardium to epinephrine, so that the endogenous hormone may
precipitate sudden & fatal ventricular fibrillation.
The protective effects of pyridine and xylene against benzene,
benzo(a)pyrene, or cyclophosphamide clastogenicity were studied in mice.
Swiss-ICR mice were treated orally with 220 to 880 mg/kg benzene,
150 mg/kg benzo(a)pyrene, or intraperitoneally with 50 mg/kg cyclophosphamide
with or without 0 to 500 mg/kg pyridine or xylene. The mice were killed 24 to 72
hours later and the femurs were removed. The bone marrow was isolated and
assayed for micronuclei. Xylene inhibited the induction of micronuclei of benzene
only when given at an equimolar dose or greater. No delay in the peak
micronuclei response was seen. Pyridine at 60 mg/kg completely blocked the
induction of micronuclei by 880 mg/kg benzene
of 24 hours. Pyridine at 25 mg/kg completely blocked the clastogenic effect of
440 mg/kg benzene at 36 to 76 hours
and partially blocked micronuclei induction at 24 hours. The clastogenicity of
benzo(a)pyrene was inhibited by pyridine only at doses of 100 mg/kg or more.
Pyridine showed no protective effect against micronuclei induction by
cyclophosphamide at any concn; micronuclei formation was enhanced by 60 to 260
mg/kg pyridine. Since the results suggested that the biological activation of benzene
was due to different cytochrome p450 isozymes than the ones activating
benzo(a)pyrene or cyclophosphamide, DBA/2 mice (aryl hydrocarbon hydrolase
noninducible) and C57B1/6 mice with or without pretreatment with
methylcholanthrene were dosed once or three times with benzene
and the effects on bone marrow micronuclei were examined as before. Micronuclei
formation was greater in DBA/2 mice. The effect was potentiated by
methylcholanthrene. The cytochrome p450 isozyme involved in activating benzene
is one of the enzymes induced by methylcholanthrene, independent of the high
affinity aryl hydrocarbon hydrolase receptor.
Interactions:
DMSO pretreatment enhances benzene
metabolism and toxicity in male Wistar rats.
BENZENE & ETHANOL INDUCED A
COMMON CYTOCHROME P450 SPECIES IN RABBIT LIVER SPECIFICALLY EFFECTIVE IN
HYDROXYL RADICAL-MEDIATED OXYGENATION OF ETHANOL. BENZENE
OXIDATION BY THE BENZENE-INDUCIBLE
FORM OF CYTOCHROME P450 WAS ALMOST COMPLETELY INHIBITED BY CATALASE, SUPEROXIDE
DISMUTASE, DMSO, & MANNITOL.
Simultaneous treatments with both benzene
and toluene, or benzene and piperonyl
butoxide, increased the excretion of unchanged benzene
in the expired air. These compounds apparently act by inhibiting benzene
metabolism.
Toluene, Aroclor 1254, phenobarbital, acetone, and ethanol are known to alter
the metabolism and toxicity of benzene.
SKF-525A inhibited benzene
metabolism in the rat. Injection of 80 mg/kg of SKF-525A in rats resulted in a
depression of phenol excretion. It also prolonged phenol excretion and
interfered in the conversion of benzene
to glucuronides and free phenols.
Carbon monoxide, aniline, aminopyrine, cytochrome C, and metyrapone inhibited
benzene metabolism in vitro by mouse
liver microsomes.
Pharmacology:
Therapeutic Uses:
MEDICATION (VET): HAS BEEN USED AS A DISINFECTANT. /FORMER USE/
Drug Warnings:
Protected intercourse may be prudent following high exposure to benzene.
As well, nursing mothers may be advised to discontinue nursing for 5 days
following high exposure.
Interactions:
DMSO pretreatment enhances benzene
metabolism and toxicity in male Wistar rats.
BENZENE & ETHANOL INDUCED A
COMMON CYTOCHROME P450 SPECIES IN RABBIT LIVER SPECIFICALLY EFFECTIVE IN
HYDROXYL RADICAL-MEDIATED OXYGENATION OF ETHANOL. BENZENE
OXIDATION BY THE BENZENE-INDUCIBLE
FORM OF CYTOCHROME P450 WAS ALMOST COMPLETELY INHIBITED BY CATALASE, SUPEROXIDE
DISMUTASE, DMSO, & MANNITOL.
Simultaneous treatments with both benzene
and toluene, or benzene and piperonyl
butoxide, increased the excretion of unchanged benzene
in the expired air. These compounds apparently act by inhibiting benzene
metabolism.
Toluene, Aroclor 1254, phenobarbital, acetone, and ethanol are known to alter
the metabolism and toxicity of benzene.
SKF-525A inhibited benzene
metabolism in the rat. Injection of 80 mg/kg of SKF-525A in rats resulted in a
depression of phenol excretion. It also prolonged phenol excretion and
interfered in the conversion of benzene
to glucuronides and free phenols.
Carbon monoxide, aniline, aminopyrine, cytochrome C, and metyrapone inhibited
benzene metabolism in vitro by mouse
liver microsomes.
Minimum Fatal Dose Level:
Benzene exposure is rapidly fatal
at concentrations approaching 20,000 ppm.
... Probable human oral lethal dose would be between 50-500 mg/kg. Human
inhalation of approximately 20,000 ppm (2% in air) was fatal in 5-10 min.
Estimated oral doses from 9-30 g have proved fatal.
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Benzene's production, existence in
gasoline, and use in the production of ethylbenzene and styrene as well as many
other chemicals may result in its release to the environment through various
waste streams. Benzene is found in
volcanoes, as a constituent of crude oil, from forest fires, and as a plant
volatile. If released to air, a vapor pressure of 94.8 mm Hg at 25 deg C
indicates benzene will exist solely as
a vapor in the ambient atmosphere. Vapor-phase benzene
will be degraded in the atmosphere by reaction with photochemically-produced
hydroxyl radicals; the half-life for this reaction in air is estimated to be 13
days. Vapor-phase benzene is also
degraded by ozone radicals and nitrate found in the atmosphere but at such low
rates as to not be important. Since benzene
is very water soluble, it may be removed from the atmosphere by rain. If
released to soil, benzene is expected
to have high mobility based upon a Koc of 85. Volatilization from moist soil
surfaces is expected to be an important fate process based upon a Henry's Law
constant of 5.56X10-3 atm-cu m/mole. Benzene
may volatilize from dry soil surfaces based upon its vapor pressure. Benzene
is expected to biodegrade in soils based on a biodegradation study in a
base-rich para-brownish soil where 20 ppm benzene
was 24% degraded in 1 week, 44% in 5 weeks, and 47% in 10 weeks. If released
into water, benzene is not expected to
adsorb to sediment and suspended solids in water based upon the Koc.
Volatilization from water surfaces is expected to be an important fate process
based upon this compound's Henry's Law constant. Estimated volatilization
half-lives for a model river and model lake are 1 hr and 3.5 days, respectively.
Biodegradation of benzene in water is
expected based on an experiment using an enriched aerobic bacterial culture in
which benzene began to degrade 12 hrs
after incubation in an aqueous (soil-free) solution with 50% of benzene
degrading after 60 hrs and almost complete degradation within 90 hrs. In aqueous
solution, benzene will react with
hydroxyl radical (OH radical ave concn = 1.0X10-17 molec/cu cm) at a reaction
rate of 7.8X10+9 L/mol sec which results in an estimated half-life of 103 days.
A BCF ranging from 1.1-20 suggests bioconcentration in aquatic organisms is low.
Hydrolysis is not expected to occur due to the lack of hydrolyzable functional
groups. Occupational exposure to benzene
may occur through inhalation and dermal contact with this compound at workplaces
where benzene is produced or used. The
general population may be exposed to benzene
via inhalation of ambient air, ingestion of drinking water, and dermal contact
with gasoline products containing benzene.
Benzene is widely detected in
atmospheric samples due to its presence in gasoline. (SRC)
Probable Routes of Human Exposure:
Human populations are primarily exposed to benzene
through inhalation of contaminated ambient air particularly in areas with heavy
traffic and around filling stations. In addition, air close to manufacturing
plants which produce or use benzene
may contain high concentrations of benzene(1,2).
Another source of exposure is from inhalation of tobacco smoke(1). Although most
public drinking water supplies are free of benzene
or contain <0.3 ppb, exposure can be very high from consumption of
contaminated sources drawn from wells contaminated by leaking gasoline storage
tanks, landfills, etc(SRC).
Rough estimates of average ambient ground-level benzene
concentrations over an 8 hour period were calculated based on an emission rate
of 100 g/sec from a manufacturing plant. Benzene
concentrations (in pg/cu m) are estimated to be 11,000 at 0.15 km, 6,100 at 0.3
km, 3,800 at 0.45 km, 2,800 at 0.6 km, 2,100 at 0.75 km, 740 at 1.6 km, 370 at
2.5 km, 220 at 4.0 km, 120 at 6.0 km, 62 at 9.0 km, 34 at 14.0 km, and 20 at
20.0 km distance from the manufacturing plant(1).
NIOSH (NOES Survey 1981-1983) has statistically estimated that 272,275
workers (143,066 of these are female) are potentially exposed to benzene
in the US(1). Occupational exposure to benzene
may occur through inhalation and dermal contact with this compound at workplaces
where benzene is produced or
used(SRC). The general population may be exposed to benzene
via inhalation of ambient air(2-4), ingestion of drinking water(5), and dermal
contact with gasoline products(6) containing benzene(SRC).
Benzene was detected in 3 out of 70
samples taken from 46 spray painting workshops in Sydney, Australia at a concn
of 1 mg/cu m in 1989(1). In a study of in-auto and in-bus exposures to volatile
organic compounds for commutes on an urban-suburban route in Korea from November
21 to December 22, 1994, revealed that mean in-auto concns of benzene
were 30.6 ug/cu m along urban routes and 18.3 ug/cu m along suburban routes
while mean in-bus concns were 20.2 ug/cu m along urban routes and 11.7 ug/cu m
along suburban routes(2). In a 200-trip study of in-vehicle air of Los Angeles
commuters, an avg concn of benzene at
40 ug/cu m during rush hour was detected(3).
Body Burden:
Benzene was detected in all 8
samples of mothers' milk from women living in 4 USA urban areas(1). Breath
samples from persons without specific exposure to benzene
ranged from 8 to 20 ppb(2). Whole blood samples from 250 subjects (121 males,
129 females) ranged from not detected to 5.9 ppb, (mean 0.8 ppb)(3). In FY82,
the National Human Adipose Tissue Survey specimens found that of 46 composite
samples, 96% tested positive to benzene
(concns were >4 ppb for wet tissue) with a max concn of 97 ppb max(4).
In a 1980's study of non-occupational benzene
exposure, it was found that smokers had an avg benzene
body burden about 6 to 10 times that of nonsmokers, and received about 90% of
their benzene exposure from
smoking(1). The mean benzene concn
found in the breath and blood of 1,683 individuals was 13.1 and 131 ng/l,
respectively(1).
Average Daily Intake:
Two recent studies of benzene
levels in foods have confirmed the conclusion that ingesting food and beverages
are an unimportant pathway for benzene
exposure(1). In a study of more than 50 foods, most contained benzene
below 2 ng/g ppbw(1). A Canadian review of benzene
exposures concluded that food and drinking water each contributed only about
0.02 ug/kg benzene per day compared to
a total intake of 2.4 ug/kg per day from airborne exposures (3.3 ug/kg/day if
exposed to cigarette smoke). In a 1980's study of non-occupational benzene
exposure, it was found that more than 99% of the total personal exposure was
through air and that a global avg personal exposure for benzene
was about 15 ug/cu m(1). Roughly half the total benzene
exposure in the United States was borne by smokers(1). For non-smokers, most benzene
exposure ultimately was derived from auto exhaust or gasoline vapor
emissions(1). A series of experiments were conducted in a 290 sq m single-family
residence from June 11-13, 1991 to ascertain the human exposure to benzene
from a contaminated groundwater source(1). It involved an individual taking a 20
min shower with the bathroom door closed, followed by five minutes for drying
and dressing, and then opening the bathroom door and allowing the individual to
leave and have his blood, breath and urine sampled(1). Whole air samples were
collected from the bathroom, shower and living room. The inhalation exposure to benzene
of an individual in the living room avgd 72 ug for the three days(1). The
individual taking the shower had an avg inhalation dose of 113 ug and an avg
dermal dose of 168 ug (exposure = 40% inhalation, 60% dermal)(1). There may be a
large number of cases where well water is contaminated by benzene
at low concns(1). A number of studies have reported finding benzene
at levels on the order of 5 ng/l in surface and well waters(1). However, these
levels correspond to a daily intake of <10 ng benzene,
assuming 2 liters of water drunk daily(1). This amount is only 0.5% of the avg
daily intake for nonsmokers of 200 ng from air(1). Thus, it is concluded that
the effect of contaminated water on total benzene
intake is negligible(1).
Natural Pollution Sources:
... Benzene has been reported to be
a natural constituent of fruits, vegetables, meats, and dairy products with
concentrations ranging from 2 ug/kg in canned beef to 2100 ug/kg for eggs.
Benzene is found naturally in the
environment from volcanoes, as a natural constituent of crude oil, from forest
fires and as a plant volatile(1,2). Benzene
concns range from 100-200 parts per trillion over the Pacific and Atlantic
Oceans due to seepage and spillage of oil into the oceans(3).
Artificial Pollution Sources:
Benzene enters the environment from
production, storage, transport, venting, and combustion of gasoline; and from
production, storage, and transport of benzene
itself. Other sources result from its use as an intermediate in the production
of other chemicals, and as a solvent, from spills, including oil spills; from
its indirect production in coke ovens; from nonferrous metal manufacture, ore
mining, wood processing, coal mining and textile manufacture, and from cigarette
smoke(1,2).
Benzene's production and use in the
production of ethylbenzene/styrene (53%), cumene/phenol (22%), cyclohexane
(12%), nitrobenzene/aniline (5%), detergent alkylate (3%), chlorobenzenes and
other products (5%) may result in its release to the environment through various
waste streams(SRC). Benzene has been
detected in cigarette smoke ranging from 47-64 ppm(2). The world wide release of
benzene into the environment is
estimated to be 4-5 Tg/yr with 0.6 Tg/yr coming from the United States alone(3).
Leachate from landfills is also a source of benzene
in the environment(4).
Environmental Fate:
TERRESTRIAL FATE: Based on a classification scheme(1), a Koc value of 85(2),
indicates that benzene is expected to
have high mobility in soil(SRC). Volatilization of benzene
from moist soil surfaces is expected to be an important fate process(SRC) given
a Henry's Law constant of 5.56X10-3 atm-cu m/mole(3). The potential for
volatilization of benzene from dry
soil surfaces may exist(SRC) based upon a vapor pressure of 94.8 mm Hg(4). Benzene
is expected to biodegrade in soils based on a biodegradation study in a
base-rich para-brownish soil where 20 ppm benzene
was 24% degraded in 1 week, 44% in 5 weeks, and 47% in 10 weeks(5). Anaerobic
degradation of benzene in soil is not
expected to be an important loss process based on various studies(6,7). In one
study of chemical biotransformation under nitrate- and sulfate-reducing
conditions, benzene was found to be
stable for 60 days(6). In a related study, benzene
did not undergo biodegradation in situ nor in laboratory controlled soil samples
under denitrifying conditions(7).
AQUATIC FATE: Based on a classification scheme(1), a Koc value of 85(2),
indicates that benzene is not expected
to adsorb to sediment and suspended solids in water(SRC). Volatilization from
water surfaces is expected(3) based upon a Henry's Law constant of 5.56X10-3
atm-cu m/mole(4). Using this Henry's Law constant and an estimation method(3),
volatilization half-lives for a model river and model lake are 1 hr and 3.5
days, respectively(SRC). Anaerobic degradation of benzene
in water is not expected to be an important loss process based on various
studies(5). In one study of chemical biotransformation under nitrate- and
sulfate-reducing conditions, benzene
was found to be stable for 60 days(5). In aqueous solution, benzene
will react with hydroxyl radical at a reaction rate of 7.8X10+9 L/mol sec; using
the average OH radical concentration (1.0X10-17 molec/cu cm), benzene
would have a half-life of 103 days(6). According to a classification scheme(7),
a BCF ranging from 1.1-20(8) suggests the potential for bioconcentration in
aquatic organisms is low.
AQUATIC FATE: Evaporation was the primary loss mechanism in winter in a
mesocosm experiment which simulated a northern bay where the half-life was 13
days(1). In spring and summer the half-lives were 23 and 3.1 days,
respectively(1). In these cases biodegradation plays a major role and takes
about 2 days(1). However, acclimation is critical and this takes much longer in
the colder water in spring(1). According to one experiment, benzene
has a half-life of 17 days due to photodegradation(2) which could contribute to benzene's
removal. In situations of cold water, poor nutrients, or other conditions less
conducive to microbial growth, photolysis will play a important role in
degradation(SRC). The half-life of benzene
in sea water is about 5 hrs(3) based on its high Henry's Law constant of
5.56X10-3 atm-cu m/mole(4).
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of
semivolatile organic compounds in the atmosphere(1), benzene,
which has a vapor pressure of 94.8 mm Hg at 25 deg C(2), is expected to exist
solely as a vapor in the ambient atmosphere. Vapor-phase benzene
is degraded in the atmosphere by reaction with photochemically-produced hydroxyl
radicals(SRC); the half-life for this reaction in air is estimated to be 13
days(SRC), calculated from its rate constant of 1.23X10-12 cu cm/molecule-sec at
25 deg C(3). The half-life in polluted atmospheres which contain nitrogen oxides
or sulfur dioxide has been observed to shorten to 4-6 hrs(4). Vapor-phase benzene
is also degraded in the atmosphere by atmospheric ozone radicals at an extremely
slow rate; the half-life for this reaction in air is estimated to be 170,000
days(5). The reaction rate of benzene
with nitrate radical in the atmosphere is estimated to be less than 0.3X10-16 cu
cm/molecule sec at 25 deg C(3); the half-life for this reaction in air is
estimated to be greater than or equal to 111 days based on an average
concentration of nitrate radicals of 2.4X10+8 molec/cu cm(6). Benzene
has a maximum absorbance frequency of 253 nm suggesting that direct photolysis
will not be an important degradation process(7). Due to benzene's
high water solubility, it may be removed from the atmosphere by rainfall(8).
Environmental Biodegradation:
No degradation of benzene as
measured by BOD was reported in coarse-filtered (through 1 cm cotton layer)
Superior harbor water incubated at 21 deg C for 12 days(1). Biodegradation
half-lives of 28 and 16 days were reported in die-away tests for degradation of
up to 3.2 ul/l benzene using
groundwater and water from Lester River, Minnesota, respectively, under aerobic
conditions(2). The half-life in estuarine water was 6 days as measured by
radiolabeled C02 produced(3). In a base-rich para-brownish soil, 20 ppm benzene
was 24% degraded in 1 week, 44% in 5 weeks, and 47% in 10 weeks(4). In a marine
ecosystem biodegradation occurred in 2 days after an acclimation period of 2
days and 2 weeks in the summer and spring, respectively, whereas no degradation
occurred in winter(5).
Benzene, in a mixture with toluene
and xylenes, is readily biodegraded (total degradation of 7.5 ppm total mixture)
in shallow ground water in the presence of oxygen in the unconfined sand aquifer
at Canada Forces' Base Borden, Ontario; laboratory batch experiments
demonstrated that the degradation could be attributed to biodegradation(1).
Complete biodegradation in 16 days was reported under simulated aerobic
groundwater conditions at 20 deg C(2). Reported metabolites of benzene
using pure cultures of microorganisms include phenol and unidentified
phenols(3), catechol and cis-1,2-dihydroxy-1,2-dihydrobenzene(4).
Benzene at 50 ppm was 90% degraded
by industrial wastewater seed incubated at 23 deg C for 6 hrs(1). Benzene
inhibited industrial seed at concn of 100 ppm and above and municipal seed at 50
ppm and above(1). In a bench scale activated-sludge reactor with an 8 hour
retention time, complete degradation occurred with 0.5% of the benzene
being lost by air stripping(2). In laboratory systems, low concentrations of benzene
are degraded in 6-14 days(3,4). 44-100% removal occurred at a sewage treatment
plant; percentage by evaporation and biodegradation were not determined(5).
AEROBIC: Benzene present at 100
mg/l, reached 39-41% of its theoretical BOD in 2 weeks using an activated sludge
inoculum at 30 mg/l and the Japanese MITI test(1). Benzene
reached 24% of its theoretical oxygen demand in a non-acclimated microbial
population after 15 days(2). Benzene
is metabolized by the avocado fruit and grapes to carbon dioxide(3). Aerobic
biodegradation of benzene was studied
in pre-equilibrated soil-water slurry microcosms(4). Using an enriched aerobic
bacterial culture, benzene began to
degrade 12 hrs after incubation in an aqueous(soil-free) solution with 50% of benzene
degrading after 60 hrs and almost complete degradation within 90 hrs(4). Using a
pre-equilibrated soil-water slurry microcosm, benzene
did not begin to degrade until 3 days after application and reached complete
degradation after about 12 days(4). The decrease in biodegradation is based on benzene's
sorption to soil and organic particles(4).
ANAEROBIC: Benzene was degraded
under methanogenic conditions in an enrichment culture fed ferulic acid for five
years. It was also degraded under sulfate-reducing conditions in microcosms
containing benzene-contaminated
aquifer sediment(1). The biotransformation of benzene
in aquifer sediment down gradient of the Wilder's Grove sanitary landfill near
Raleigh, NC U.S.A. was studied under anaerobic conditions(1). According to the
study, benzene was not found to
biodegrade(1). In a study of chemical biotransformation under nitrate- and
sulfate-reducing conditions, benzene
was found to be stable under these anaerobic conditions for 60 days(2). In a
related study, benzene did not undergo
biodegradation in situ nor in laboratory controlled soil samples under
denitrifying conditions(3). Although benzene
appears to be recalcitrant under anaerobic conditions, there was one experiment
in which benzene underwent degradation
under methanogenic conditions. The microbial inoculum employed in the study
originally had been enriched from anaerobic municipal sludge(4). Benzene
was transformed into phenol by the microbial inoculum by using water as a source
of oxygen(4).
Environmental Abiotic Degradation:
While benzene is considered to be
relatively unreactive in photochemical smog situations (in the presence of
nitrogen oxides), its rate of degradation is accelerated with about 16% decrease
in concentration in 5 hr(1). A typical experiment in the presence of active
species such as NOx and SO2 showed that benzene
photodegradation was considerably accelerated above that in air alone(2). Its
half-life in the presence of active species was 4-6 hr with 50% mineralization
to CO2 in approximately 2 days(3). Products of degradation include phenol,
2-nitrophenol, 4-nitrophenol, 2,4-dinitrophenol, 2,6-dinitrophenol,
nitrobenzene, formic acid, and peroxyacetyl nitrate(4-6). Hydrolysis is not a
significant process for benzene due to
the lack of hydrolyzable functional groups(7).
The rate constant for the vapor-phase reaction of benzene
with photochemically-produced hydroxyl radicals is 1.23X10-12 cu
cm/molecule-sec(1). This corresponds to an atmospheric half-life of about 13
days at an atmospheric concn of 5X10+5 hydroxyl radicals per cu cm(1). The
half-life in polluted atmospheres which contain nitrogen oxides or sulfur
dioxide has been observed to shorten to 4-6 hrs(2). Vapor phase benzene
is also degraded in the atmosphere by atmospheric ozone radicals at an extremely
slow rate; the half-life for this reaction in air is estimated to be 170,000
days(3). Reaction of benzene with
nitrate radical is estimated to be <0.3X10-16 cu cm/molecule sec at 25 deg
C(1); the half-life for this reaction in air is estimated to be greater than or
equal to 111 days based on an average concentration of nitrate radicals of
2.4X10+8 molec/cu cm in the ambient atmosphere(4). Benzene
is not expected to undergo hydrolysis in the environment due to the lack of
hydrolyzable functional groups(5) nor to directly photolyze since benzene
has a maximum absorbance frequency of 253 nm(6). However, slight shifts in
wavelength of absorption might be expected in more representative environmental
media, such as water(7); eg, a half-life of 16.9 days was reported for
photolysis of benzene dissolved in
deionized water saturated with air exposed to sunlight(8). Benzene
has an estimated lifetime under photochemical smog conditions in southeastern
England of 28 hrs(3). Benzene has an
estimated global life-time of 16 days and 4.8 days in the tropics(9). Global
conditions were considered as having an average temperature of 2 deg C, OH
radical concentration of 6.0X10+5 molecule/cu cm and an ozone radical
concentration of 7.4X10+11 molecule/cu cm; while tropical conditions were
considered as having an average temperature of 25 deg C, OH radical
concentration of 2.0X10+6 molecule/cu cm and an ozone radical concentration of
7.4X10+11 molecule/cu cm(9). In aqueous solution, benzene
will react with hydroxyl radical at a reaction rate of 7.8X10+9 L/mol sec; using
the average OH radical concentration(1.0X10-17 molec/cu cm), benzene
would have a half-life of 103 days(10).
Environmental Bioconcentration:
Benzene has a BCF ranging from
1.1-20(1). According to a classification scheme(2), this BCF suggests the
potential for bioconcentration in aquatic organisms is low. The uptake and
elimination rate constants for benzene
in fathead minnows were studied(3). Fathead minnows were found to have an avg
uptake rate of 7 L/kg/hr with an avg elimination rate of 0.384/hr which
corresponds to a BCF of 19(3). In a study of BCF values for various aquatic
species, benzene was found to have a
BCF value of 3.5 in eels(4), 4.4 in pacific herring(5), and 4.3 in goldfish(6).
Soil Adsorption/Mobility:
An experimentally derived log Koc of 1.93 (Koc = 85) was obtained via reverse
phase HPLC (High Performance Liquid Chromatography) with a cyanopropyl column
and a mobile phase of water(1). According to a classification scheme(2), this
estimated Koc value suggests that benzene
is expected to have high mobility in soil. The sorption equilibrium for benzene
in a soil/water mixture (ratio soil/water 0.12 kg/l) took 72 hrs(3). The Koc for
benzene has also been experimentally
determined to be 79(4).
Volatilization from Water/Soil:
The Henry's Law constant for benzene
is 5.56X10-3 atm-cu m/mole(1). This Henry's Law constant indicates that benzene
is expected to volatilize rapidly from water surfaces(2). Based on this Henry's
Law constant, the volatilization half-life from a model river (1 m deep, flowing
1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 1 hr(SRC). The
volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind
velocity of 0.5 m/sec)(2) is estimated as 3.5 days(SRC). Benzene's
Henry's Law constant(1) indicates that volatilization from moist soil surfaces
may occur(SRC). The potential for volatilization of benzene
from dry soil surfaces may exist(SRC) based upon a vapor pressure of 94.8 mm
Hg(3).
Environmental Water Concentrations:
GROUNDWATER: Benzene was the
dominant dissolved organic compound in groundwater contaminated by gasoline in
the Swan Coastal Plain near Perth, Western Australia at a concn around 15,000
ug/l at depths greater than 4.5 m below ground surface(1). At a distance of 210
m from a petrol storage area, a chalk aquifer, located in the United Kingdom,
contained benzene ranging from 1-10
ppb; at 120 m from the petrol storage area it contained benzene
concns greater than 250 ppb; and at 10 m from the petrol storage area, benzene
concns rose to 1250 ppb(2). Benzene
occurs in both groundwater and surface public water supplies with higher levels
occurring in groundwater supplies. Based upon U.S. Federal drinking water
surveys, approximately 1.3% of all groundwater systems are estimated to contain benzene
at levels greater than 0.5 ug/l. The highest level reported in the surveys for
groundwater was 80 ug/l(3).
DRINKING WATER: Out of 113 public drinking water supplies in 1976, 7 sites
tested positive for benzene with an
avg concn of <0.2 ppb(1). Of five US cities from 1974-5, benzene
concns ranged from 0-0.3 ppb in drinking water supplies(2). Contaminated
drinking water wells in NY, NJ, and CT ranged from 30-300 ppb; the highest benzene
concns in drinking water were derived from surface water sources at 4.4 ppb(3).
In three separate surveys of community water supplies: 0 of 111 samples tested
positive for benzene; 7 of 113 samples
tested positive with a mean concn of 4 ppb; and 4 of 16 samples tested positive
with a benzene max concn of 0.95
ppb(4). In a USA Groundwater Supply Survey (GWS, 1982, finished drinking water),
out of 466 samples selected at random from a 1000 sample survey, 0.6% tested
positive for benzene at a median value
of 3 ppb and max of 15 ppb(5). In a study of Wisconsin drinking water wells
(data through Jun 1984), of 1174 community wells sampled, 0.34% tested positive
for benzene while of 617 private
wells, 2.9% tested positive(6).
DRINKING WATER: There may be a large number of cases where well water is
contaminated by benzene at low
concns(1). A number of studies have reported finding benzene
at levels on the order of 5 ng/l in surface and well waters(1).
SURFACE WATER: Surface water samples taken from 14 heavily industrialized
areas with water basins between 1975-1976, contained benzene
in 20% of the samples at concns ranging from 1-7 ppb(1). Benzene
concns in Lake Erie from 1975-6, ranged from 0-1 ppb(2). Benzene
concns in Lake Michigan from 1975-6, ranged from 0-7 ppb(2). Out of 700 random
surface water sites throughout the US in 1975, benzene
had an avg concn of 5.4 ppb(3). In the US EPA STORET database, out of 1,271
surface water samples, 15.0% tested positive for benzene
with a median concn of 5.0 ppb(4). Benzene
concns in seawater taken from the Gulf of Mexico in 1977, ranged from 5-15 parts
per trillion in unpolluted areas and 5-175 parts per trillion in areas affected
by anthropogenic activities(5). Approximately 3% of all surface water drinking
systems are estimated to be contaminated at levels higher than 0.5 ug/l(6).
RAIN/SNOW/FOG: Benzene was detected
in rainwater in Japan and in the UK at a concn of 87.2 ppb(1,2).
Effluent Concentrations:
Industries in which mean or max levels of benzene
in raw wastewater exceeded 1 ppm are (number of samples, percent pos, mean, max,
in ppm): raw wastewater: auto and other laundries (20 samples, 70% pos, <1.4
ppm mean, 23 ppm max), iron and steel manufacturing (mfg) (9 samples, 77.8% pos,
<8.0 mean, 46 max), aluminum forming (32 samples, 56.2% pos, 0.70 mean, 2.1
max), photographic equipment/supplies (48 samples, 54.2% pos, 0.16 mean, 2.1
max), pharmaceutical mfg (9 samples, 100% pos, 12 mean, 87 max), organic
chemical/plastics mfg (number of samples not reported (NR), 63 detections, 22,
NR), paint and ink formulation (36 samples, 63.9% pos, 1.2 mean, 9.9 max),
petroleum refining (11 samples, number of pos NR, <0.10, 2.4), rubber
processing (4 samples, 100% pos, 0.60 mean, 3.4 max), timber products processing
(14 samples, 92.9% pos, 0.2 mean, 2.8 max); treated wastewater: auto and other
laundries (4 samples, 50% pos, 0.1 ppm mean, 0.2 ppm max), iron and steel
manufacturing (mfg) (13 samples, 76.9% pos, <14 mean, 120 max), aluminum
forming (21 samples, 81.0% pos, <0.0058 mean, 0.040 max), photographic
equipment/supplies (4 samples, 100% pos, 0.016 mean, 0.021 max), pharmaceutical
mfg (6 samples, 100% pos, 1.8 mean, 10 max), organic chemical/plastics mfg
(number of samples not reported (NR), 42 detections, 26, max NR), paint and ink
formulation (24 samples, 62.5% pos, 0.39 mean, 3.8 max), petroleum refining (13
samples, NR, NR, 0.012), rubber processing (5 samples, 100% pos, <0.0077
mean, 0.010 max), timber products processing (5 samples, 60% pos, 0.010 mean,
0.033 max)(1).
Wastewater from coal preparation plants ranged from 0.3-48 ppb while
wastewater from plants which manufacture or use benzene
ranged from <1-179 parts per trillion(1). Stack emissions from coking plants
located in Czechoslovakia contained benzene
ranging from 15-50 ppm(2). In 11.2% of groundwater samples taken from 178 CERCLA
hazardous waste sites, benzene was
detected(3). In the US EPA STORET database, out of 1,474 effluent samples, 16.4%
tested positive for benzene at a
median concn of 2.50 ppb(4).
Benzene was emitted by pre-catalyst
cars at 114-153 mg/mile while with catalyst cars emissions dropped to 5-32
mg/mile(1). In 4 municipal landfill gases in Southern Finland (1989-1990 data), benzene's
avg concn ranged from 0.17-9 mg/cu m with a max concn of 11 mg/cu m(1). Benzene
emissions were studied from seven Swedish incineration plants before and after
air pollution control systems (APCS) were introduced(2). Benzene
concns emitted from plant A (3 incinerators) without APCS were 1.93, 1.95, and
21.16 ug/cu nm and with APCS were 2.46, 0.83 and 1.81 ug/cu nm, respectively.
Plant B (3 incinerators) benzene
levels were 21.23, 10.81, and 1.63 ug/cu nm before APCS and 14.37, 444.20, and
0.14 ug/cu nm after APCS, respectively(2). Oddly, benzene
levels rose on an incinerator after APCS. At the third plant, benzene
concns were 2.57 ug/cu nm before APCS and 0.79 ug/cu nm after APCS(2). At the
fourth plant, benzene concns were 3.44
ug/cu nm before APCS and 1.32 ug/cu nm after APCS(2). At the fifth plant, benzene
concns were 0.82 ug/cu nm before APCS and 0.37 ug/cu nm after APCS(2). At the
sixth plant, benzene concns were 2.92
ug/cu nm before APCS and 1.64 ug/cu nm after APCS(2). At the seventh plant (3
incinerators) benzene concns were
4.31, 8.30 and 5.13 ug/cu nm before APCS and 1.49, 1.02, and 11.36 ug/cu nm
after APCS, respectively(2).
Sediment/Soil Concentrations:
SOIL: Soil near factories where benzene
was used or produced contained benzene
ranging from 2-191 ug/kg(1). SEDIMENT: Surface sediments taken from Walvis Bay
(off Capetown, South Africa) contained benzene
ranging from 0-20 ppb(2). In the US EPA STORET database, out of 355 samples, 9%
tested positive for benzene at a
median concn of <5.0 ppb(3).
Atmospheric Concentrations:
SUBURBAN/URBAN: Air samples taken in the US from 1977-1980, had an avg benzene
concn of 2.8 ppb in 2292 samples(1). Avg benzene
concns were 13 ppb (98 ppb max) in Toronto, Canada 1971(2). Avg benzene
concns in Los Angeles, California 1966 avgd 15 ppb (57 ppb max)(2). In 24 hr
sampling periods conducted in US cities in 1979, benzene
concns in Los Angeles, CA in April ranged from 0.72-27.87 ppb(mean 6.04 ppb), in
Phoenix, AZ from April-May benzene
ranged from 0.39-59.89 ppb (mean 4.74 ppb), in Oakland, CA from June-July benzene
ranged from 0.06-4.63 ppb (mean 1.55 ppb)(3). Atmospheric benzene
concns were studied in New Jersey in 1978 with the following cities reporting
detections: Rutherford, out of 149 samples, 3.8 ppb mean concn with 107 ppb max,
Newark, out of 110 samples, 2.6 ppb mean concn with 24 ppb max,
Piscataway/Middlesex, out of 18 samples, 1.0 ppb mean concn with 1.9 ppb max,
Somerset county, out of 30 samples, 5.6 mean concn with 33 ppb max, Bridgewater
Township, out of 22 samples, 1.4 ppb mean concn with 7.9 ppb max(4). In general,
the avg concn of benzene in the urban
atmosphere is estimated at 0.02 ppm(5).
URBAN/SUBURBAN: Benzene has been
detected in urban air samples in London, U.K., Southampton, U.K., Budapest,
Hungary, Oslo, Norweigh, St. Petersburg, Russia, Boston, Chicago, Los Angeles,
Houston, Sydney, Australia, and Tokyo, Japan at 9,16, 27, 18, 30, 1, 1.3, 2.7,
18, 2.6, and 1.8 ppbv, respectively(1). The median concn of benzene
in 39 U.S. cities from 1984-1985 was 12.6 ppb(2). Benzene's
ambient concn was highest at night-time and lowest by mid-day due to deep
convective mixing and chemical loss by OH radicals(2). Since the 1960's, the
ambient atmospheric concn of benzene
has declined(2). Benzene concns were
reported for 586 ambient air samples collected from 10 Canadian cities(3). The
overall mean was 4.4 ug/cu m, with Ottawa and Montreal ranging between 5.1 and
7.6 ug/cu m(3). Benzene concns in a
traffic tunnel in London, that was poorly ventilated, ranged from 0.010-0.21
ppb(4).
INDOOR: In a recent benzene
exposure study, day and night 12-hr avg concns of benzene
were measured for 58 residents of Valdez, Alaska(1). The mean benzene
concns in the personal, indoor, and outdoor samples were 20, 16, and 5 ug/cu m
during the summer, and 28, 25, and 11 ug/cu m during the winter,
respectively(1). In a nationwide Canadian study which measured the 24-hr indoor
air concns of benzene in 754 randomly
selected homes, benzene had a mean
indoor air concn of 6.39, 5.60, 2.72, and 6.98 ug/cu m in the winter, spring,
summer, and fall seasons, respectively(1). Indoor and outdoor 48-hr avg concns
of benzene were measured at 161 homes
throughout much of California in which indoor samples had a mean concn of 8.3
ug/cu m compared to 6.1 ug/cu m outdoor samples(1). Concns of benzene
emitted from tobacco smoke in 5 workplaces located in Finland, 1995 ranged from
1.5-8 ug/cu m(2). Gasoline leaking from an underground storage tank near an
elementary school in the Midwest United States (location not specified) created
elevated levels of benzene concns
within the school property(3). Benzene
was detected in air samples collected from the classrooms,
offices/libraries/corridors, boiler room, crawl space beneath floor,
soil/duct/floor interface, and outdoor/background at 0-5 ppb, 3-4 ppb, 4 ppb,
approx 2600 ppb, 70-80 ppb, and 0-3 ppb, respectively(3). A series of
experiments were conducted in a 290 sq m single-family residence from June
11-13, 1991 to ascertain the human exposure to benzene
from a contaminated groundwater source(4). It involved an individual taking a 20
min shower with the bathroom door closed, followed by five minutes for drying
and dressing, and then opening the bathroom door and allowing the individual to
leave and have his blood, breath and urine sampled(4). Whole air samples were
collected from the bathroom, shower and living room. Mean concn of benzene
coming from the shower head for the three days was 292 ug/l(4). Peak benzene
levels were measured in the shower stall at 18-20 mins (758-1670 ug/cu m), in
the bathroom at 10-25 mins (366-498 ug/cu m), in the bedroom at 25.5-30 mins
(81-146 ug/cu m), and in the living room at 36-70 mins (40-62 ug/cu m)(4).
RURAL/REMOTE: In 100 rural air samples taken within the US from 1977-1980,
the avg concn of benzene was 1.4 ppb
avg(1). Ambient air samples taken from Barrows, Alaska in 1967 contained benzene
at 0.16 ppb over a 24 hr avg in 5 of 25 samples(2). Avg benzene
concn in rural areas range from 0.1-17 ppb(3). Multilatitude background concns
of benzene (ppb/deg North): Atlantic
Ocean 0.07/35 deg N, Pacific Ocean 0.23/45 deg N, Niwot Ridge (Colorado Rockies)
0.16-0.24 ppb(4). Benzene concns in
the Pacific Ocean ranged from 0.05 ppb in the Northern hemisphere to 0.01 ppb in
the Southern hemisphere(5). Pacific Ocean, 0.581, Pullman, WA, 0.226, Cape
Meares, OR, 0.230, Norwegian Arctic, 0.066(5). In 5 remote tropical sites, benzene
concns ranged from not detected to 1.8 ppb; avg concns from the 5 sites ranged
from 0.07-0.65 ppb(6).
RURAL/REMOTE: Benzene was measured
at 35 ug/cu m in the plume of a forest fire at a distance of 6 km of the seat of
the fire(1). The median concn of benzene
in the Southern Appalachian Mountains was 1.1 ppb(2). Benzene
concns range from 100-200 parts per trillion over the Pacific and Atlantic
Oceans due to seepage and spillage of oil into the oceans(2). Rural sampling for
benzene in Canada found concns ranging
from 0.6-1.2 ug/cu m(3). Benzene was
detected (concn not specified) in ambient air samples taken from Witaker's
Forest/Sierra Nevada Mountains, California from June 20-June 22, 1990(4).
Measurements were performed in midsummer at high ambient temperatures and under
stable meteorological conditions with high solar radiation(4). Although the area
was very remote, the air samples could have been influenced by emissions from
California's Central Valley and even from the San Francisco Bay area(4).
SOURCE DOMINATED: Atmospheric benzene
concns were studied throughout the USA between 1977-1980 in which out of 487
samples taken, benzene was found at an
avg concn of 3.0 ppb(1). The concn of benzene
near USA chemical factories where benzene
is used ranged from 0.6-34 ppb, near service stations 0.0003-3.2 ppm, and in
cigarette smoke 57-64 ppm(2).
Food Survey Values:
Benzene was found in both heat
treated and canned beef at 2 ug/kg; in Jamaican rum at 120 ug/kg; in eggs
ranging from 500-1900 ug/kg; and it was detected (concns not specified) in
fruits, nuts, vegetables, dairy products, meat, fish, poultry, eggs, and
beverages(1).
In 1990, benzene was detected in
fruit flavored mineral waters at concns greater than 5.0 ug/kg in Canada(1).
When an investigation of benzene
concns in beverages was performed, benzene
was found at an avg concn of 0.042, 0.67, 0.056, 0.14, 0.29, 0.12, 0.95, 0.062,
0.79, and 0.55 ug/kg in freshly squeezed fruit, retail juice (wth benzoate
additive), retail juice (without benzoate), fruit drinks (with benzoate), fruit
drinks (with cranberry, without benzoate), fruit drinks (excluding cranberry,
without benzoate), cranberry drinks (without benzoate), carbonated soft drinks
(without benzoate), carbonated soft drinks (with benzoate), and ice tea (with
benzoate), respectively(1). These data suggest the natural occurrence of benzene
in fruits and fruit juices, especially from cranberies(1). Benzene
is a volatile organic compound emitted by both common and pineapple guava at a
concn of 0.10 ug/g(2).
Plant Concentrations:
Benzene has been detected as a
plant volatile(1). Benzene has been
detected from 2 species of macroalgae at 20 ppb(2).
Fish/Seafood Concentrations:
Benzene was detected in 5 oyster
samples from the Inner Harbor Navigational Canal in Lake Pontchartrain, LA at
220 ppb wet weight(1). Composite clam samples from Chef Menteur Pass in Lake
Pontchartain, LA contained benzene at
260 ppb wet weight; however clam samples from The Rigolets did not contain benzene(1).
Milk Concentrations:
Benzene was detected in all 8
samples of mothers milk from women in 4 US urban areas(1).
Other Environmental Concentrations:
In private homes, benzene levels in
the air have been shown to be higher in homes with attached garages, or where
inhabitants smoke inside the house.
Environmental Standards & Regulations:
FIFRA Requirements:
Benzene is exempted from the
requirement of a tolerance when used as a solvent or cosolvent in accordance
with good agricultural practice as inert (or occasionally active) ingredients in
pesticide formulations applied to growing crops only.
Acceptable Daily Intakes:
Insufficient data are available to calculate a one-day Health Advisory for benzene.
The Ten-day Health Advisory (0.235 mg/l) is considered to be adequately
protective for a one-day exposure as well. ... Longer-term Health Advisories
have not been calculated because of the carcinogenic potency of benzene.
CERCLA Reportable Quantities:
Persons in charge of vessels or facilities are required to notify the
National Response Center (NRC) immediately, when there is a release of this
designated hazardous substance, in an amount equal to or greater than its
reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is
(800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The
rule for determining when notification is required is stated in 40 CFR 302.4
(section IV. D.3.b).
RCRA Requirements:
D018; A solid waste containing benzene
may or may not become characterized as a hazardous waste when subjected to the
Toxicity Characteristic Leaching Procedure listed in 40 CFR 261.24, and if so
characterized, must be managed as a hazardous waste.
F005; When benzene is a spent
solvent, it is classified as a hazardous waste from a nonspecific source (F005),
as stated in 40 CFR 261.31, and must be managed according to State and/or
Federal hazardous waste regulations.
U019; As stipulated in 40 CFR 261.33, when benzene,
as a commercial chemical product or manufacturing chemical intermediate or an
off-specification commercial chemical product or a manufacturing chemical
intermediate, becomes a waste, it must be managed according to Federal and/or
State hazardous waste regulations. Also defined as a hazardous waste is any
residue, contaminated soil, water, or other debris resulting from the cleanup of
a spill, into water or on dry land, of this waste. Generators of small
quantities of this waste may qualify for partial exclusion from hazardous waste
regulations (40 CFR 261.5).
Atmospheric Standards:
National emission standard for equipment leaks (fugitive emission sources) of
benzene prohibit detectable benzene
emissions from processing equipment (eg, pumps, valves) that contains materials
which have a benzene concn of 10% or
more by wt.
This action promulgates standards of performance for equipment leaks of
Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing
Industry (SOCMI). The intended effect of these standards is to require all newly
constructed, modified, and reconstructed SOCMI process units to use the best
demonstrated system of continuous emission reduction for equipment leaks of VOC,
considering costs, non air quality health and environmental impact and energy
requirements. Benzene is produced, as
an intermediate or a final product, by process units covered under this subpart.
Benzene has been designated as a
hazardous air pollutant under section 112 of the Clean Air Act.
The actual standards, if applicable, are contained in 40 CFR Part 61 Subpart
V (61.240-61.247), National Emission Standards for Equipment Leaks (Fugitive
Emission Sources) and refer to standards of operation of process equipment. EPA
regulations establish a national emission standard for equipment leaks of benzene.
They apply to pumps, compressors, pressure relief devices, sampling connecting
systems, open-ended valves or lines, valves, flanges and other connectors,
product accumulator vessels, and control devices, or systems required by this
subpart.
Listed as a hazardous air pollutant (HAP) generally known or suspected to
cause serious health problems. The Clean Air Act, as amended in 1990, directs
EPA to set standards requiring major sources to sharply reduce routine emissions
of toxic pollutants. EPA is required to establish and phase in specific
performance based standards for all air emission sources that emit one or more
of the listed pollutants. Benzene is
included on this list.
Clean Water Act Requirements:
Toxic pollutant designated pursuant to section 307(a)(1) of the Federal Water
Pollution Control Act and is subject to effluent limitations.
Benzene is designated as a
hazardous substance under section 311(b)(2)(A) of the Federal Water Pollution
Control Act and further regulated by the Clean Water Act Amendments of 1977 and
1978. These regulations apply to discharges of this substance. This designation
includes any isomers and hydrates, as well as any solutions and mixtures
containing this substance.
The maximum contaminant level (MCL) set forth by the National Revised Primary
Drinking Water Regulations for the organic contaminant benzene
in community and non-transient, non-community water systems is 0.005 mg/l.
Federal Drinking Water Standards:
EPA 5 ug/l
State Drinking Water Standards:
(CA) CALIFORNIA 1 ug/l
(FL) FLORIDA 1 ug/l
(NJ) NEW JERSEY 1 ug/l
State Drinking Water Guidelines:
(AZ) ARIZONA 1.3 ug/l
(CT) CONNECTICUT 1 ug/l
(ME) MAINE 5 ug/l
(MN) MINNESOTA 10 ug/l
FDA Requirements:
Benzene is an indirect food
additive for use only as a component of adhesives.
Allowable Tolerances:
Benzene is exempted from the
requirement of a tolerance when used as a solvent or cosolvent in accordance
with good agricultural practice as inert (or occasionally active) ingredients in
pesticide formulations applied to growing crops only.
Chemical/Physical Properties:
Molecular Formula:
C6-H6
Molecular Weight:
78.11
Color/Form:
Clear, colorless liq
RHOMBIC PRISMS
Colorless to light-yellow liquid [Note: A solid below 42 degrees F].
Odor:
Aromatic odor.
Gasoline-like odor; rather pleasant aromatic odor. Odor threshold = 4.68 ppm.
Taste:
Taste threshold in water is 0.5-4.5 mg/l.
Boiling Point:
80.1 deg C
Melting Point:
5.5 deg C
Critical Temperature & Pressure:
Critical temperature: 288.9 deg C; critical pressure: 48.6 atm
Density/Specific Gravity:
0.8787 @ 15 deg C/4 deg C
Heat of Combustion:
-3275.3 KJ/mol
Heat of Vaporization:
33.83 KJ/mol @ 25 deg C
Octanol/Water Partition Coefficient:
log Kow= 2.13
Solubilities:
Miscible with alcohol, chloroform, ether, carbon disulfide, acetone, oils,
carbon tetrachloride, & glacial acetic acid
Miscible in most organic solvents.
In water, 1.79X10+3 mg/l @ 25 deg C.
Spectral Properties:
MAX ABSORPTION (ALCOHOL): 243 NM (LOG E= 2.2), 249 NM (LOG E= 2.3), 256 NM
(LOG E= 2.4), 261 NM (LOG E= 2.2); SADTLER REF NUMBER: 6402 (IR, PRISM), 1765
(UV)
Index of Refraction: 1.50108 @ 20 deg C/D
UV: 198 (Sadtler Research Laboratories Spectral Collection)
MASS: 102 (Atlas of Mass Spectral Data, John Wiley & Sons, New York)
IR: 136 (Sadtler Research Laboratories IR Grating Collection)
NMR: 3429 (Sadtler Research Laboratories Spectral Collection)
Intense mass spectral peaks: 78 m/z
Surface Tension:
28.22 mN/m @ 25 deg C
Vapor Density:
2.8 (air= 1)
Vapor Pressure:
94.8 mm Hg @ 25 deg C
Relative Evaporation Rate:
2.8 (ether= 1)
Viscosity:
0.604 mPa.s @ 25 deg C
Other Chemical/Physical Properties:
Conversion factors: 1 ppm= 3.26 mg/cu m
SPECIFIC DISPERSION 189.6; DENSITY OF SATURATED VAPOR-AIR MIXT AT 760 MM HG
(AIR= 1) IS 1.22 AT 26 DEG C; PERCENT IN SATURATED IN AIR AT 760 MM HG IS 13.15
AT 26 DEG C
Blood/air partition coefficient is 7.8
Sublimes -30 to 5 deg C
Heat of fusion= 9.95 KJ/mol
Heat capacity: 135.6 (liquid), 81.6 (gas) J/mol deg K at 1 atm (to convert to
calories/mol-K multiply by 0.2390057)
Vapors burn with smoky flame
Very useful compilations of the thermodynamic properties of benzene
are given by Rossini & co-workers, Selected Values of Physical and
Thermodynamic Properties of Hydrocarbons and Related Compounds, Amer Petrol Res
Proj 44, Carnegie Press, Pittsburgh, PA (1953); and in American Petroleum
Institute Project 44, data sheets, API Data Distribution Office, A&M Press,
College Station, Texas
A comprehensive collection of general properties of benzene,
thermodynamic & transport properties, & benzene
in binary multicomponent systems is contained in Hancock & co-workers, Benzene
and Its Industrial Derivatives, John Wiley & Sons, Inc, New York, 1975
pp.97-117
Henry's Law constant= 5.56X10-3 atm-cu m/mol @ 25 deg C
Hydroxyl radical rate constant= 1.23X10-12 cu cm/molecule-sec @ 25 deg C
Chemical Safety & Handling:
DOT Emergency Guidelines:
Fire or explosion: Highly flammable: Will be easily ignited by heat, sparks
or flames. Vapors may form explosive mixtures with air. Vapors may travel to
source of ignition and flash back. Most vapors are heavier than air. They will
spread along ground and collect in low or confined areas (sewers, basements,
tanks). Vapor explosion hazard indoors, outdoors or in sewers. Some may
polymerize (P) explosively when heated or involved in a fire. Runoff to sewer
may create fire or explosion hazard. Containers may explode when heated. Many
liquids are lighter than water.
Health: May cause toxic effects if inhaled or absorbed through skin.
Inhalation or contact with material may irritate or burn skin and eyes. Fire
will produce irritating, corrosive and/or toxic gases. Vapors may cause
dizziness or suffocation. Runoff from fire control or dilution water may cause
pollution.
Public safety: Call Emergency Response Telephone Numbers. ... Isolate spill
or leak area immediately for at least 50 to 100 meters (160 to 330 feet) in all
directions. Keep unauthorized personnel away. Stay upwind. Keep out of low
areas. Ventilate closed spaces before entering.
Protective clothing: Wear positive pressure self-contained breathing
apparatus (SCBA). Structural firefighters' protective clothing will only provide
limited protection.
Evacuation: Large spill: Consider initial downwind evacuation for at least
300 meters (1000 feet). Fire: If tank, rail car or tank truck is involved in a
fire, isolate for 800 meters (1/2 mile) in all directions; also, consider
initial evacuation for 800 meters (1/2 mile) in all directions.
Fire: Caution: All these products have a very low flash point: Use of water
spray when fighting fire may be inefficient. Small fires: Dry chemical, CO2,
water spray or regular foam. Large fires: Water spray, fog or regular foam. Do
not use straight streams. Move containers from fire area if you can do it
without risk. Fire involving tanks or car/trailer loads: Fight fire from maximum
distance or use unmanned hose holders or monitor nozzles. Cool containers with
flooding quantities of water until well after fire is out. Withdraw immediately
in case of rising sound from venting safety devices or discoloration of tank.
Always stay away from the ends of tanks. For massive fire, use unmanned hose
holders or monitor nozzles; if this is impossible, withdraw from area and let
fire burn.
Spill or leak: Eliminate all ignition sources (no smoking, flares, sparks or
flames in immediate area). All equipment used when handling the product must be
grounded. Do not touch or walk through spilled material. Stop leak if you can do
it without risk. Prevent entry into waterways, sewers, basements or confined
areas. A vapor suppressing foam may be used to reduce vapors. Absorb or cover
with dry earth, sand or other non-combustible material and transfer to
containers. Use clean non-sparking tools to collect absorbed material. Large
spills: Dike far ahead of liquid spill for later disposal. Water spray may
reduce vapor; but may not prevent ignition in closed spaces.
First aid: Move victim to fresh air. Call emergency medical care. Apply
artificial respiration if victim is not breathing. Administer oxygen if
breathing is difficult. Remove and isolate contaminated clothing and shoes. In
case of contact with substance, immediately flush skin or eyes with running
water for at least 20 minutes. Wash skin with soap and water. Keep victim warm
and quiet. Effects of exposure (inhalation, ingestion or skin contact) to
substance may be delayed. Ensure that medical personnel are aware of the
material(s) involved, and take precautions to protect themselves.
Odor Threshold:
BENZENE HAS DISTINCTIVE /SRP:
AROMATIC/ ODOR ... HOWEVER /WARNING PROPERTIES/ ARE INADEQUATE SINCE 100 PPM HAS
IRRITATION RATING OF 0 & ODOR INTENSITY BETWEEN 1 & 2.
4.68 PPM
In air: 4.9 mg/cu m (characteristic odor), in water: 2.0 mg/l.
Skin, Eye and Respiratory Irritations:
Benzene is irritant to skin.
A severe eye and moderate skin irritant.
Skin irritation has been noted at occupational exposures of greater than 60
ppm for up to three weeks.
Fire Potential:
A dangerous fire hazard when exosed to heat or flame. ... Ignites on contact
with sodium peroxide + water, dioxygenyl tetrafluoroborate, iodine
heptafluoride, and dioxygen difluoride.
NFPA Hazard Classification:
Health: 2. 2= Materials that, on intense or continued (but not chronic)
exposure, could cause temporary incapacitation or possible residual injury,
including those requiring the use of respiratory protective equipment that has
an independent air supply. These materials are hazardous to health, but areas
may be entered freely if personnel are provided with full-face mask
self-contained breathing apparatus that provides complete eye protection.
Flammability: 3. 3= This degree includes Class IB and IC flammable liquids
and materials that can be easily ignited under almost all normal temperature
conditions. Water may be ineffective in controlling or extinguishing fires in
such materials.
Reactivity: 0. 0= This degree includes materials that are normally stable,
even under fire exposure conditions, and that do not react with water. Normal
fire fighting procedures may be used.
Flammable Limits:
Lower flammable limit: 1.2% by volume; Upper flammable limit: 7.8% by volume
Flash Point:
12 DEG F (-11 DEG C) CLOSED CUP
Autoignition Temperature:
928 deg F
Fire Fighting Procedures:
Approach fire from upwind to avoid hazardous vapors. Use water spray, dry
chemical, foam, or carbon dioxide. Use water spray to keep fire-exposed
containers cool.
If material on fire or involved in fire: Do not extinguish fire unless flow
can be stopped or safely confined. Use water in flooding quantities as fog.
Solid streams of water may spread fire. Cool all affected containers with
flooding quantities of water. Apply water from as far a distance as possible.
Use foam, dry chemical, or carbon dioxide.
Firefighting Hazards:
VAPORS ARE HEAVIER THAN AIR AND MAY TRAVEL TO A SOURCE OF IGNITION &
FLASH BACK. LIQUID FLOATS ON WATER AND MAY TRAVEL TO A SOURCE OF IGNITION AND
SPREAD FIRE.
Explosive Limits & Potential:
LOWER 1.4%, UPPER 8.0%
Hazardous Reactivities & Incompatibilities:
Reacts violently with iodine pentafluoride.
Hydrogenation of benzene to
cyclohexane was effected in a fixed bed reactor at 210-230 deg C, but a fall in
conversion was apparent. Increasing the bed temp by 10 deg C & the hydrogen
flow led to a large increase in reaction rate which the interbed cooling coils
could not handle, & an exotherm to 280 deg C developed, with a hot spot
around 600 deg C which bulged the reactor wall.
Benzene ... ignites in contact with
/iodine heptafluoride/ gas ...
Dioxygenyl tetrafluoroborate is a very powerful oxidant, addition of a small
particle to small samples of benzene
... at ambient temp ... /caused/ ignition.
... A 2% solution /dioxygen difluoride/ in hydrogen fluoride ignites solid benzene
at -78 deg C.
Simultaneous contact of sodium peroxide with ... benzene
... causes ignition, (equivalent to contact with concn hydrogen peroxide).
Interaction /of uranium hexafluoride/ with benzene
... is very vigorous, with separation of carbon ...
Benzene ignites in contact with
powdered chromic anhydride.
AN EXPLOSION OF BENZENE VAPORS
& CHLORINE (INADVERTENTLY MIXED) WAS INITIATED BY LIGHT.
Reacts explosively with bromine pentafluoride, chlorine, chlorine
trifluoride, diborane, nitric acid, nitryl perchlorate, oxygen (liquid), ozone,
silver perchlorate.
Interaction of the pentafluoride & methoxide /from arsenic pentafluoride
& potassium methoxide/ proceeded smoothly in trichlorotrifluoroethane at
30-40 deg C, whereas in benzene as
solvent repeated explosions occurred.
The effects of the presence of moisture or benzene
vapor in air on the spontaneously explosive reaction /of diborane/ have been
studied.
Silver perchlorate forms solid complexes with aniline, pyridine, toluene, benzene
& many other aromatic hydrocarbons. A sample of the benzene
complex exploded violently on crushing in a mortar.
Interaction /of nitryl perchlorate/ with benzene
gave a slight explosion & flash. ...
The solution of permanganic acid (or its explosive anhydride, dimanganese
heptoxide) produced by interaction of permanganates & sulfuric acid, will
explode on contact with benzene ... .
Large-scale addition of too-cold nitrating acid to benzene
without agitation later caused an uncontrollably violent reaction to occur when
stirring was started. The vapor-air mixture produced was ignited by interaction
of benzene & nitric acid at
100-170 deg C & caused an extremely violent explosion.
Peroxodisulfuric acid ... /is/ a very powerful oxidant; uncontrolled contact
with ... benzene ... may cause
explosion.
Mixtures of /liquid oxygen &/ benzene
are specifically described as explosive.
During ozonization of rubber dissolved in benzene,
an explosion occurred. This seems unlikely to have been ... /due/ to formation
of benzene triozonide (which separates
as a gelatinous precipitate after prolonged ozonization), since the solution
remained clear. A rubber ozonide may have been involved, but the benzene-oxygen
system itself has high potential for hazard.
Mixtures /of peroxomonosulfuric acid/ with ... benzene
... explodes.
Certain metal perchlorates recrystallized from benzene
or ethyl alcohol can explode spontaneously.
Strong oxidizers, many fluorides & perchlorates, nitric acid.
Vigorous or incandescent reaction with hydrogen + Raney nickel (above 210 deg
C) ... and bromine trifluoride. Can react vigorously with oxidizing materials,
such as ... CrO3, oxygen, NClO4, ozone, perchlorates, (AlCl3 + FClO4), (sulfuric
acid + permanganates), K2O2, (AgClO4 + acetic acid) ...
Explodes on contact with diborane, bromine pentafluoride, permanganic acid,
peroxomonosulfuric acid, and peroxodisulfuric acid. Forms sensitive, explosive
mixtures with iodine pentafluoride, silver perchlorate, nitryl perchlorate,
nitric acid, liquid oxygen, ozone, arsenic pentafluoride + potassium methoxide
(explodes above 30 deg C). ... Moderate explosion hazard when exposed to heat or
flame.
Prior History of Accidents:
/On June 30, 1992/ a derailed tank car fell 135 feet from a trestle cracking
open and spilling most of its 26,200 gallons of benzene
solution into the Nemadji River in Wisconsin. /This accident/ resulted in a 10
hr evacuation of more than 50,000 people. About 25 persons went to hospitals in
Superior, WI and Duluth, MN complaining of dizziness, headaches, and burning
eyes and skin, after a noxious gas cloud enveloped low-lying areas. The vapor
was dispersed later that day by wind and rain.
Immediately Dangerous to Life or Health:
NIOSH has recommended that benzene
be treated as a potential human carcinogen.
Protective Equipment & Clothing:
Protective clothing consisting of coveralls or other full body clothing
should be worn and changed at least twice weekly.
Where there is a possibility of benzene
contact to eyes or skin, safety showers, eye-wash fountains, and cleansing
facilities shall be installed and maintained.
WHERE HIGH VAPOR CONCN ARE UNAVOIDABLE, FORCED AIR MASKS SHOULD BE USED.
LIFELINE ATTENDED BY ... PERSON OUTSIDE CONTAMINATED ENCLOSURE IS MANDATORY. IF
SKIN CONTACT IS UNAVOIDABLE, NEOPRENE GLOVES MUST BE WORN.
HYDROCARBON VAPOR CANISTER, SUPPLIED AIR OR A HOSE MASK; HYDROCARBON
INSOLUBLE RUBBER OR PLASTIC GLOVES; CHEMICAL GOGGLES OR FACE SPLASH SHIELD;
HYDROCARBON-INSOLUBLE APRON SUCH AS NEOPRENE.
PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent
/should be available./ ... Safety pipettes should be used for all pipetting. ...
In animal laboratory, personnel should ... wear protective suits (preferably
disposable, one-piece & close-fitting at ankles & wrists), gloves, hair
covering & overshoes. ... In chemical laboratory, gloves & gowns should
always be worn ... however, gloves should not be assumed to provide full
protection. Carefully fitted masks or respirators may be necessary when working
with particulates or gases, & disposable plastic aprons might provide addnl
protection. ... Gowns ... /should be/ of distinctive color, this is a reminder
that they are not to be worn outside the laboratory. /Chemical Carcinogens/
Performance data: For butyl rubber, natural rubber, neoprene, neoprene,
neoprene/natural rubber, nitrile rubber, polyethylene, chlorinated polyethylene,
polyurethane, and polyvinyl chloride give breakthrough times less (usually
significantly less) than one hour reported by (normally) two or more testers.
Vendor Recommendations: C or D ratings from three or more (apparently
independent) vendors.
Wear appropriate personal protective clothing to prevent skin contact.
Wear appropriate eye protection to prevent eye contact.
Eyewash fountains should be provided in areas where there is any possibility
that workers could be exposed to the substance; this is irrespective of the
recommendation involving the wearing of eye protection.
Facilities for quickly drenching the body should be provided within the
immediate work area for emergency use where there is a possibility of exposure.
[Note: It is intended that these facilities should provide a sufficient quantity
or flow of water to quickly remove the substance from any body areas likely to
be exposed. The actual determination of what constitutes an adequate quick
drench facility depends on the specific circumstances. In certain instances, a
deluge shower should be readily available, whereas in others, the availability
of water from a sink or hose could be considered adequate.]
Recommendations for respirator selection. Condition: At concentrations above
the NIOSH REL, or where there is no REL, at any detectable concentration.
Respirator Class(es): Any self-contained breathing apparatus that has a full
facepiece and is operated in a pressure-demand or other positive pressure mode.
Any supplied-air respirator that has a full face piece and is operated in
pressure-demand or other positive pressure mode in combination with an auxiliary
self-contained breathing apparatus operated in pressure-demand or other positive
pressure mode.
Recommendations for respirator selection. Condition: Escape from suddenly
occurring respiratory hazards: Respirator Class(es): Any air-purifying,
full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted
organic vapor canister. Any appropriate escape-type, self-contained breathing
apparatus.
Preventive Measures:
Contact lenses should not be worn when working with this chemical.
SRP: The scientific literature for the use of contact lenses in industry is
conflicting. The benefit or detrimental effects of wearing contact lenses depend
not only upon the substance, but also on factors including the form of the
substance, characteristics and duration of the exposure, the uses of other eye
protection equipment, and the hygiene of the lenses. However, there may be
individual substances whose irritating or corrosive properties are such that the
wearing of contact lenses would be harmful to the eye. In those specific cases,
contact lenses should not be worn. In any event, the usual eye protection
equipment should be worn even when contact lenses are in place.
SRP: Local exhaust ventilation should be applied wherever there is an
incidence of point source emmissions or dispersion of regulated contaminants in
the work area. Ventilation control of the contaminant as close to its point of
generation is both the most economical and safest method to minimize personnel
exposure to airborne contaminants.
VENTILATION CONTROL: WHEREVER POSSIBLE, PLANT SHOULD BE TOTALLY ENCLOSED ...
ENCLOSURES SHOULD BE SUPPLEMENTED BY EXHAUST VENTILATION ... ATMOSPHERE ...
SHOULD BE TESTED PERIODICALLY ...
PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage
of food or of food & beverage containers or utensils, & the application
of cosmetics should be prohibited in any laboratory. All personnel should remove
gloves, if worn, after completion of procedures in which carcinogens have been
used. They should ... wash ... hands, preferably using dispensers of liq
detergent, & rinse ... thoroughly. Consideration should be given to
appropriate methods for cleaning the skin, depending on nature of the
contaminant. No standard procedure can be recommended, but the use of organic
solvents should be avoided. Safety pipettes should be used for all pipetting.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel
should remove their outdoor clothes & wear protective suits (preferably
disposable, one-piece & close-fitting at ankles & wrists), gloves, hair
covering & overshoes. ... Clothing should be changed daily but ... discarded
immediately if obvious contamination occurs ... /also,/ workers should shower
immediately. In chemical laboratory, gloves & gowns should always be worn
... however, gloves should not be assumed to provide full protection. Carefully
fitted masks or respirators may be necessary when working with particulates or
gases, & disposable plastic aprons might provide addnl protection. If gowns
are of distinctive color, this is a reminder that they should not be worn
outside of lab. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth
& purification ... should be carried out under well-ventilated hood.
Analytical procedures ... should be carried out with care & vapors evolved
during ... procedures should be removed. ... Expert advice should be obtained
before existing fume cupboards are used ... & when new fume cupboards are
installed. It is desirable that there be means for decreasing the rate of air
extraction, so that carcinogenic powders can be handled without ... powder being
blown around the hood. Glove boxes should be kept under negative air pressure.
Air changes should be adequate, so that concn of vapors of volatile carcinogens
will not occur. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological
safety cabinets may be used for containment of in vitro procedures ... provided
that the exhaust air flow is sufficient to provide an inward air flow at the
face opening of the cabinet, & contaminated air plenums that are under
positive pressure are leak-tight. Horizontal laminar-flow hoods or safety
cabinets, where filtered air is blown across the working area towards the
operator, should never be used ... Each cabinet or fume cupboard to be used ...
should be tested before work is begun (eg, with fume bomb) & label fixed to
it, giving date of test & avg air-flow measured. This test should be
repeated periodically & after any structural changes. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or
biochem lab also apply to microbiological & cell-culture labs. ... Special
consideration should be given to route of admin. ... Safest method of
administering volatile carcinogen is by injection of a soln. Admin by topical
application, gavage, or intratracheal instillation should be performed under
hood. If chem will be exhaled, animals should be kept under hood during this
period. Inhalation exposure requires special equipment. ... Unless specifically
required, routes of admin other than in the diet should be used. Mixing of
carcinogen in diet should be carried out in sealed mixers under fume hood, from
which the exhaust is fitted with an efficient particulate filter. Techniques for
cleaning mixer & hood should be devised before expt begun. When mixing
diets, special protective clothing &, possibly, respirators may be required.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to
skin, animals should be kept in cages with solid bottoms & sides &
fitted with a filter top. When volatile carcinogens are given, filter tops
should not be used. Cages which have been used to house animals that received
carcinogens should be decontaminated. Cage-cleaning facilities should be
installed in area in which carcinogens are being used, to avoid moving of ...
contaminated /cages/. It is difficult to ensure that cages are decontaminated,
& monitoring methods are necessary. Situations may exist in which the use of
disposable cages should be recommended, depending on type & amt of
carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ...
contamination in lab could build up during conduct of expt, periodic checks
should be carried out on lab atmospheres, surfaces, such as walls, floors &
benches, & ... interior of fume hoods & airducts. As well as regular
monitoring, check must be carried out after cleaning-up of spillage. Sensitive
methods are required when testing lab atmospheres for chem such as nitrosamines.
Methods ... should ... where possible, be simple & sensitive. ... /Chemical
Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination
has occurred, such as spillage, should be decontaminated by lab personnel
engaged in expt. Design of expt should ... avoid contamination of permanent
equipment. ... Procedures should ensure that maintenance workers are not exposed
to carcinogens. ... Particular care should be taken to avoid contamination of
drains or ventilation ducts. In cleaning labs, procedures should be used which
do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner
equipped with high-efficiency particulate filter on exhaust, which are avail
commercially, should be used. Sweeping, brushing & use of dry dusters or
mops should be prohibited. Grossly contaminated cleaning materials should not be
re-used. ... If gowns or towels are contaminated, they should not be sent to
laundry, but ... decontaminated or burnt, to avoid any hazard to laundry
personnel. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where
carcinogens are used ... should be marked distinctively with appropriate labels.
Access ... limited to persons involved in expt. ... A prominently displayed
notice should give the name of the Scientific Investigator or other person who
can advise in an emergency & who can inform others (such as firemen) on the
handling of carcinogenic substances. /Chemical Carcinogens/
SRP: Contaminated protective clothing should be segregated in such a manner
so that there is no direct personal contact by personnel who handle, dispose, or
clean the clothing. Quality assurance to ascertain the completeness of the
cleaning procedures should be implemented before the decontaminated protective
clothing is returned for reuse by the workers.
The worker should immediately wash the skin when it becomes contaminated.
Work clothing that becomes wet should be immediately removed due to its
flammability hazard.
Evacuation: If material leaking (not on fire) consider evacuation from
downwind area based on amount of material spilled, location and weather
conditions.
Personnel protection: Avoid breathing vapors. Keep upwind. ... Do not handle
broken packages unless wearing appropriate personal protective equipment. Wash
away any material which may have contacted the body with copious amounts of
water or soap and water.
If material not on fire and not involved in fire: Keep sparks, flames, and
other sources of ignition away. Keep material out of water sources and sewers.
Build dikes to contain flow as necessary. Attempt to stop leak if without undue
personnel hazard. Use water spray to knock-down vapors.
Shipment Methods and Regulations:
No person may /transport,/ offer or accept a hazardous material for
transportation in commerce unless that person is registered in conformance ...
and the hazardous material is properly classed, described, packaged, marked,
labeled, and in condition for shipment as required or authorized by ... /the
hazardous materials regulations (49 CFR 171-177)./
The International Air Transport Association (IATA) Dangerous Goods
Regulations are published by the IATA Dangerous Goods Board pursuant to IATA
Resolutions 618 and 619 and constitute a manual of industry carrier regulations
to be followed by all IATA Member airlines when transporting hazardous
materials.
The International Maritime Dangerous Goods Code lays down basic principles
for transporting hazardous chemicals. Detailed recommendations for individual
substances and a number of recommendations for good practice are included in the
classes dealing with such substances. A general index of technical names has
also been compiled. This index should always be consulted when attempting to
locate the appropriate procedures to be used when shipping any substance or
article.
PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt
... should be avoided. To avoid spilling, carcinogens should be transported in
securely sealed glass bottles or ampoules, which should themselves be placed
inside strong screw-cap or snap-top container that will not open when dropped
& will resist attack from the carcinogen. Both bottle & the outside
container should be appropriately labelled. ... National post offices, railway
companies, road haulage companies & airlines have regulations governing
transport of hazardous materials. These authorities should be consulted before
... material is shipped. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the
following procedure must be adopted. The carcinogen should be enclosed in a
securely sealed, watertight container (primary container), which should be
enclosed in a second, unbreakable, leakproof container that will withstand chem
attack from the carcinogen (secondary container). The space between primary
& secondary container should be filled with absorbent material, which would
withstand chem attack from the carcinogen & is sufficient to absorb the
entire contents of the primary container in the event of breakage or leakage.
Each secondary container should then be enclosed in a strong outer box. The
space between the secondary container & the outer box should be filled with
an appropriate quantity of shock-absorbent material. Sender should use fastest
& most secure form of transport & notify recipient of its departure. If
parcel is not received when expected, carrier should be informed so that
immediate effort can be made to find it. Traffic schedules should be consulted
to avoid ... arrival on weekend or holiday. ... /Chemical Carcinogens/
Storage Conditions:
KEEP IN WELL CLOSED CONTAINERS IN A COOL PLACE & AWAY FROM FIRE.
PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as
practicable to lab in which carcinogens are to be used, so that only small
quantities required for ... expt need to be carried. Carcinogens should be kept
in only one section of cupboard, an explosion-proof refrigerator or freezer
(depending on chemicophysical properties ...) that bears appropriate label. An
inventory ... should be kept, showing quantity of carcinogen & date it was
acquired ... Facilities for dispensing ... should be contiguous to storage area.
/Chemical Carcinogens/
Cleanup Methods:
For spills on water, contain with booms or barriers, use surface acting
agents to thicken spilled materials. Remove trapped materials with suction
hoses.
Small spills of benzene can be
taken up by sorption on carbon or synthetic sorbent resins. Flush area with
water. For large quantities, if response is rapid, benzene
can be skimmed off the surface. Straw may be used to mop slicks.
PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate
arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in
exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal
rooms. ... Filter housing that is designed so that used filters can be
transferred into plastic bag without contaminating maintenance staff is avail
commercially. Filters should be placed in plastic bags immediately after
removal. ... The plastic bag should be sealed immediately. ... The sealed bag
should be labelled properly. ... Waste liquids ... should be placed or collected
in proper containers for disposal. The lid should be secured & the bottles
properly labelled. Once filled, bottles should be placed in plastic bag, so that
outer surface ... is not contaminated. ... The plastic bag should also be sealed
& labelled. ... Broken glassware ... should be decontaminated by solvent
extraction, by chemical destruction, or in specially designed incinerators.
/Chemical Carcinogens/
Eliminate all ignition sources. Stop or control the leak, if this can be done
without undue risk. Use water spray to cool and disperse vapors, protect
personnel, and dilute spills to form nonflammable mixtures. Absorb in
noncombustible material for proper disposal. Control runoff and isolate
discharged material for proper disposal.
Environmental considerations - Air spill: Apply water spray or mist to knock
down vapors.
Environmental considerations - Water spill: Use natural barriers or oil spill
control booms to limit spill travel. Use surface active agent (e.g., detergent,
soaps, alcohols), if approved by EPA. Inject "universal" gelling agent
to solidify encircled spill and increase effectiveness of booms. If dissolved,
in region of 10 ppm or grater concentration, apply activated carbon at ten times
the spilled amount. Remove trapped material with suction hoses. Use mechanical
dredges or lifts to remove immobilized masses of pollutants and precipitates.
Environmental considerations - Land spill: Dig a pit, lagoon, holding area to
contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons,
soak holes, or holding areas should be sealed with an impermeable flexible
membrane liner./ Dike surface flow using soil, sand bags, foamed polyurethane,
or foamed concrete. Absorb bulk liquid with fly ash, cement powder, or
commercial sorbents. Apply appropriate foam to diminish vapor and fire hazard.
Disposal Methods:
Generators of waste (equal to or greater than 100 kg/mo) containing this
contaminant, EPA hazardous waste number F005, must conform with USEPA
regulations in storage, transportation, treatment and disposal of waste.
Generators of waste (equal to or greater than 100 kg/mo) containing this
contaminant, EPA hazardous waste number U019, must conform with USEPA
regulations in storage, transportation, treatment and disposal of waste.
Generators of waste (equal to or greater than 100 kg/mo) containing this
contaminant, EPA hazardous waste number D018, must conform with USEPA
regulations in storage, transportation, treatment and disposal of waste.
Biodegradation, incineration: Benzene
is biodegradable. Diluted aqueous soln, therefore, are drained into sewage
treatment plants and decomposed there by anaerobic bacteria. Solvent mixtures
and sludges of higher concn are burnt in special waste incinerators if a
recovery process is uneconomical.
This flammable liquid burns with a very smoky flame. Dilution with alcohol or
acetone is suggested to minimize smoke. Recommendable methods: Use as boiler
fuel, incineration. Not recommendable: Landfill, discharge to sewer.
Incinerate or dispose of via a licensed solvent recycling or disposal
company.
PRECAUTIONS FOR "CARCINOGENS": There is no universal method of
disposal that has been proved satisfactory for all carcinogenic compounds &
specific methods of chem destruction ... published have not been tested on all
kinds of carcinogen-containing waste. ... Summary of avail methods &
recommendations ... /given/ must be treated as guide only. /Chemical
Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Total destruction ... by
incineration may be only feasible method for disposal of contaminated laboratory
waste from biological expt. However, not all incinerators are suitable for this
purpose. The most efficient type ... is probably the gas-fired type, in which a
first-stage combustion with a less than stoichiometric air:fuel ratio is
followed by a second stage with excess air. Some ... are designed to accept ...
aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb
soln onto suitable combustible material, such as sawdust. Alternatively, chem
destruction may be used, esp when small quantities ... are to be destroyed in
laboratory. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate
arrestor) filters ... can be disposed of by incineration. For spent charcoal
filters, the adsorbed material can be stripped off at high temp &
carcinogenic wastes generated by this treatment conducted to & burned in an
incinerator. ... LIQUID WASTE: ... Disposal should be carried out by
incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses
of lab animals, cage litter & misc solid wastes ... should be disposed of by
incineration at temp high enough to ensure destruction of chem carcinogens or
their metabolites. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some
carcinogens can be destroyed using chem reactions ... but no general rules can
be given. ... As a general technique ... treatment with sodium dichromate in
strong sulfuric acid can be used. The time necessary for destruction ... is
seldom known ... but 1-2 days is generally considered sufficient when freshly
prepd reagent is used. ... Carcinogens that are easily oxidizable can be
destroyed with milder oxidative agents, such as sat soln of potassium
permanganate in acetone, which appears to be a suitable agent for destruction of
hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn
or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating,
arylating or acylating agents per se can be destroyed by reaction with
appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols &
thiosulfate. The reactivity of various alkylating agents varies greatly ...
& is also influenced by sol of agent in the reaction medium. To facilitate
the complete reaction, it is suggested that the agents be dissolved in ethanol
or similar solvents. ... No method should be applied ... until it has been
thoroughly tested for its effectiveness & safety on material to be
inactivated. For example, in case of destruction of alkylating agents, it is
possible to detect residual compounds by reaction with
4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/
Chemical Treatability of Benzene;
Concentration Process: Biological Treatment; Chemical Classification: Aromatic;
Scale of Study: Full Scale; Type of Wastewater Used: Industrial Wastewater;
Results of Study: 90-100% reduction; (treated by aerated lagoon).
Chemical Treatability of Benzene;
Concentration Process: Biological Treatment; Chemical Classification: Aromatic;
Scale of Study: Full Scale; Type of Wastewater Used: Industrial Wastewater;
Results of Study: 95-100% reduction; (completely mixed activated sludge
process).
Chemical Treatability of Benzene;
Concentration Process: Biological Treatment; Chemical Classification: Aromatic;
Scale of Study: Respirometer Study; Type of Wastewater Used: Domestic
Wastewater; Results of Study: 1.44-1.45 g of oxygen utilized/g of substrate
added after 72 hr of oxidation.
Chemical Treatability of Benzene;
Concentration Process: Biological Treatment; Chemical Classification: Aromatic;
Scale of Study: Respirometer Study; Type of Wastewater Used: Domestic
Wastewater; Results of Study: Oxygen uptake of 34 ppm oxygen/hr for 50 ppm
chemical and 37 ppm oxygen/hr for 500 ppm chemical.
Chemical Treatability of Benzene;
Concentration Process: Biological Treatment; Chemical Classification: Aromatic;
Scale of Study: Full Scale; Type of Wastewater Used: Industrial Wastewater;
Results of Study: 95-100% reduction; (Activated sludge process).
Chemical Treatability of Benzene;
Concentration Process: Stripping; Chemical Classification: Aromatic; Scale of
Study: Literature Review; Type of Wastewater Used: Unknown; Results of Study:
Air and steam strippable.
Chemical Treatability of Benzene;
Concentration Process: Stripping; Chemical Classification: Aromatic; Scale of
Study: Continuous Flow, Pilot Scale; Type of Wastewater Used: Synthetic
Wastewater; Results of Study: 95-99% reduction by steam stripping; (estimated
cost of $3.35/1000 gal based on 0.03 MGD).
Chemical Treatability of Benzene;
Concentration Process: Solvent Extraction; Chemical Classification: Aromatic;
Scale of Study: Literature Review; Type of Wastewater Used: Unknown; Results of
Study: Extractable with suitable solvent.
Chemical Treatability of Benzene;
Concentration Process: Solvent Extraction; Chemical Classification: Aromatic;
Scale of Study: Laboratory Scale, Continuous Flow; Type of Wastewater Used:
Industrial Wastewater; Results of Study: 290 ppm @ 3 gal/hr, 97% reduction;
(Extraction of wastewater from styrene manufacture using isobutylane (S/W=
0.107), RDC extractor used).
Chemical Treatability of Benzene;
Concentration Process: Solvent Extraction; Chemical Classification: Aromatic;
Scale of Study: Laboratory Scale, Continuous Flow; Type of Wastewater Used:
Industrial Wastewater; Results of Study: 71 ppm @ 4.6 gal/hr, 96% reduction;
(extraction of ethylene quench wastewater using isobutylene (S/W= 0.101) RDC
extractor used).
Chemical Treatability of Benzene;
Concentration Process: Solvent Extraction; Chemical Classification: Aromatic;
Scale of Study: Laboratory Scale, Continuous Flow; Type of Wastewater Used:
Industrial Waste; Results of Study: 81 ppm @ 4.6 gal/hr, 97% reduction;
(extraction of ethylene quench wastewater using isobutane (S/W= 0.097) RDC
extractor used).
Chemical Treatability of Benzene;
Concentration Process: Activated Carbon; Chemical Classification: Aromatic;
Scale of Study: Pilot Scale, Continuous Flow; Type of Wastewater Used: Hazardous
Material Spill Results of Study: 90% removal (to 0.1 ppb effluent conc) achieved
in 8.5 min contact time; (Spilled material treated using EPA's mobile treatment
trailer).
Chemical Treatability of Benzene;
Concentration Process: Activated Carbon; Chemical Classification: Aromatic;
Scale of Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results
of Study: 0.7 mg/g carbon capacity.
Chemical Treatability of Benzene;
Concentration Process: Activated Carbon; Chemical Classification: Aromatic;
Scale of Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results
of Study: Isotherm kinetics were as follows: Carbon: K= 26.8, l/n= 1.305;
Filtrasorb: K= 18.5 l/n= 1.158; carbon dose (mg/l) required to reduce 1 mg/l to
0.1 mg/l; Daro-678 Filtrasorb-705.
Chemical Treatability of Benzene;
Concentration Process: Activated Carbon; Chemical Classification: Aromatic;
Scale of Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results
of Study: 95% reduction, 21 ppm final concn, 0.080 g/g carbon capacity; (Carbon
dose with 5 g/l Westvaco Nuchar).
Chemical Treatability of Benzene;
Concentration Process: Activated Carbon; Chemical Classification: Aromatic;
Scale of Study: Literature Review; Type of Wastewater Used: Industrial
Wastewater; Results of Study: Effluent concn of 30 ppm TOC achieved; 98%
removal; (at contact time of 55 min 0.15 MGD flow; pretreatment including pH
adjustment).
Chemical Treatability of Benzene;
Concentration Process: Activated Carbon; Chemical Classification: Aromatic;
Scale of Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results
of Study: Effluent Character (ppm): 500, 95% removal; 250, 91% removal; 50, 60%
removal; (24 hr contact time, carbon dose was 10 times chemical concn).
Chemical Treatability of Benzene;
Concentration Process: Activated Carbon; Chemical Classification: Aromatic;
Scale of Study: Literature Review; Type of Wastewater Used: Unknown; Results of
Study: 95% removal at 0.5% carbon dose.
A good candidate for liquid injection incineration at a temperature range of
650 to 1,600 deg C and a residence time of 0.1 to 2 seconds. A good candidate
for rotary kiln incineration at a temperature range of 820 to 1,600 deg C and
residence times of seconds for liquids and gases, and hours for solids. A good
candidate for fluidized bed incineration at a temperature range of 450 to 980
deg C and residence times of seconds for liquids and gases, and longer for
solids.
Full-scale activated carbon column treatment: Influent concn: 28,000 ug/l;
Effluent concn: 1) < 10 ug/l with +99% removal, 2) 73 ug/l with 48-80%
removal.
Occupational Exposure Standards:
OSHA Standards:
The employer shall assure that no employee is exposed to an airborne
concentration of benzene in excess of
one part of benzene per million parts
of air (1 ppm) as an 8 hr TWA. The employer shall assure that no employee is
exposed to an airborne concentration of benzene
in excess of 5 ppm as averaged over any 15 min period.
Permissible Exposure Limit: Table Z-2 8-hr Time Weighted Avg: 10 ppm. (Note:
This standard applies to the industry segments exempt from the 1 ppm 8 hr TWA
and 5 ppm STEL of the benzene standard
at 1910.1028)
Permissible Exposure Limit: Table Z-2 Acceptable Ceiling Concentration: 25
ppm. (Note: This standard applies to the industry segments exempt from the 1 ppm
8 hr TWA and 5 ppm STEL of the benzene
standard at 1910.1028).
Permissible Exposure Limit: Table Z-2 Acceptable maximum peak above the
acceptable ceiling concentration for an 8-hour shift. Concentration: 50 ppm.
Maximum Duration: 10 minutes. (Note: This standard applies to the industry
segments exempt from the 1 ppm 8 hr TWA and 5 ppm STEL of the benzene
standard at 1910.1028.)
Threshold Limit Values:
8 hr Time Weighted Avg (TWA) 0.5 ppm; 15 min Short Term Exposure Limit
(STEL): 2.5 ppm, skin.
BEI (Biological Exposure Indices): S-Phenylmercapturic acid in urine (end of
shift): 25 ug/g creatinine. t,t-Muconic acid in urine (end of shift): 500 ug/g
creatinine. These two determinants are usually present in a significant amt in
biological specimens collected from subjects who have not been occupationally
exposed. Such background levels are incl in the BEI value.
NIOSH Recommendations:
NIOSH recommends that benzene be
regulated as a potential human carcinogen.
NIOSH usually recommends that occupational exposures to carcinogens be
limited to the lowest feasible concn.
Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 0.1 ppm.
Recommended Exposure Limit: 15 Min Short-Term Exposure Limit: 1 ppm.
Immediately Dangerous to Life or Health:
NIOSH has recommended that benzene
be treated as a potential human carcinogen.
Other Occupational Permissible Levels:
Belgium: TWA (skin) 30 mg/cu m, 10 ppm (1978); Czechoslovakia: TWA 50 mg/cu
m, Ceiling 80 mg/cu m/10 min (1976); Finland: TWA (skin) 32 mg/cu m, 10 ppm
(1975); Hungary: TWA 20 mg/cu m, may be exceeded 5 times/shift as long as avg
does not exceed value (1974); Poland: Ceiling (skin) 30 mg/cu m (1976); Romania:
Maximum (skin) 50 mg/cu m (1975); Switzerland: TWA (skin) 6.5 mg/cu m, 2 ppm
(1978); USSR: Ceiling (skin) 5 mg/cu m (1980); Yugoslavia: Ceiling (skin) 50
mg/cu m, 15 ppm (1971).
Emergency Response Planning Guidelines (ERPG): ERPG(1) 50 ppm (no more than
mild, transient effects) for up to 1 hr exposure; ERPG(2) 150 ppm (without
serious, adverse effects) for up to 1 hr exposure; ERPG(3) 1000 ppm (not life
threatening) up to 1 hr exposure.
Australia: 5 ppm, Category 1, established human carcinogen (1990); Commission
of the European Communities: 0.5 ppm (corresponding to estimated lifetime risk
of 0.25-3.3 excess leukemia cases per 1000 workers); Federal Republic of
Germany: no MAK, Group A1 carcinogen, capable of inducing malignant tumors in
humans, skin, Technical Guiding Concentration (TRK), 1 ppm (1996); Sweden: 0.5
ppm, short-term value, 3 ppm, 15 min, skin, carcinogenic (1991); United Kingdom:
5 ppm (1997).
Manufacturing/Use Information:
Major Uses:
Manuf of industrial chemicals such as polymers, detergents, pesticides
pharmaceuticals, dyes, plastics, resins. Solvent for waxes, resins, oils,
natural rubber, etc. Gasoline additive /Use as solvent is now discouraged/
Used for printing and lithography, paint, rubber, dry cleaning, adhesives and
coatings, detergents
Extraction and rectification; preparation and use of inks in the graphic arts
industries; as a thinner for paints; as a degreasing agent
CHEM INT FOR ETHYLBENZENE, CUMENE, CYCLOHEXANE, NITROBENZENE, MALEIC
ANHYDRIDE, CHLOROBENZENES, DETERGENT ALKYLATE, ANTHRAQUINONE, BENZENE
HEXACHLORIDE, BENZENE SULFONIC ACID,
BIPHENYL, HYDROQUINONE, & RESORCINOL
Benzol (Benzene)
Discontinued by Crowly Tar Products Co.
... In the tire industry and in shoe factories, ... benzene
was used extensively.
Used primarily as a raw material in the synthesis of styrene (polystyrene
plastics and synthetic rubber), phenol (phenolic resins), cyclohexane (nylon),
aniline, maleic anhydride (polyester resins), alkylbenzenes (detergents),
chlorobenzenes, and other products used in the production of drugs, dyes,
insecticides, and plastics.
Therap Cat (VET): Has been used as a disinfectant
Manufacture of explosives, PCB gasoline, tanning; nylon intermediates; food
processing; photographic chemicals.
Uses: Ethylbenzene/styrene 53%; cumene/phenol 22%; cyclohexane 12%;
nitrobenzene/aniline 5%; detergent alkylate 3%; chlorobenzenes and other uses 5%
In the past benzene has been used
in the shoe and garment industry as a solvent for natural rubber. Benzene
has also found limited application in medicine for the treatment of certain
blood disorders, such as polythemia and malignant lymphoma. Benzene,
along with other light high octane aromatic hydrocarbons such as toluene and
xylene, is used as a component of motor gasoline. Although this use has been
largely reduced in the U.S., benzene
is still used extensively in many countries for the production of commercial
gasoline.
Manufacturers:
Chevron Chemical Company, 6001 Bollinger Canyon Rd, San Ramon, CA 94583,
(925)842-5500; U.S. Chemicals Division, 1301 McKinney St. PO Box 3766, Houston,
TX 77253 (713)754-2000; Production sites: Pascagoula, MI 39567; Port Arthur, TX
77640; Richmond, CA 94802
Hess Oil Virgin Islands Corp., Kings Hill Rd., P.O. Box 127, Kingshill, VI
00851-0127, (340)778-4000; Production site: St Croix, Virgin Islands 00851
Fina Oil and Chemical Co., P.O. Box 2159, Dallas, TX 75221, (214)750-2400;
Production site: Port Arthur, TX 77640
Amoco Corp, Hq, 200 E Randolph Dr, Chicago, IL 60601, (312) 856-6111;
Production site: Texas City, TX 77590
Coastal Eagle Point Oil Co., P.O. Box 1000, U.S. Route 130 & I-295,
Westville, NJ 08093, (609)853-3100; Production site: Westville, NJ 08093
Coastal Refining and Marketing, Inc.,, 9 Greenway Plaza, Houston, TX 77046,
(713)877-7174; Production site: Corpus Christi, TX 78403
BP America, Inc, Hq.,, 200 Public Sq, Cleveland, OH 44114-2375,
(440)586-4141; Production sites: Lima, OH 45804; Alliance, LA 70037
Citgo Petroleum Corp.,, Hq, 6130 S Yale St., Tulsa, OK 74136, (918) 495-4000;
Production sites: Lake Charles, LA 70601; Corpus Cristi, TX 78469; Lemont, IL
60439-3659
Dow Chemical USA, Hq, 2020 Dow Center, Midland, MI 48674, (517) 636-1000;
Production sites: Freeport, TX 77541; Plaquemine, LA 70765
Equistar Chemicals, LP, One Houston Center, 1221 McKinney St., Suite 1600,
Houston, TX 77010, (713)652-7300; Production sites: Alvin, TX 77511;
Channelview, TX 77530; Corpus Christi, TX 78410
Exxon Chemical Company, 13501 Katy Freeway, Houston, TX 77079, (281)870-6000;
Exxon Chemical Americas, P.O. Box 3272, Houston, TX 77253-3272, (281)870-6000;
Production sites: Baton Rouge, LA 70821; Baytown, TX 77520
Huntsman Corp., 3040 Post Oak Blvd., Houston, TX 77056, (713)235-6000;
Production sites: Bayport, TX 77062; Port Arthur, TX 77640
Koch Refining Co., P.O. Box 2256, Wichita, KS 67201, (316) 828-5500;
Production site: Corpus Christi, TX 78403
Lyondell-Citgo Refining Company Ltd., 12000 Lawndale, Houston, TX 77017,
(713)321-4111; Production site: Houston, TX 77252
Marathon Ashland Petroleum LLC, 539 Sourth Main Street, Findlay, OH
45840-3295, (419)422-2121; Production sites: Catlettsburg, Kentucky 41129; Texas
City, Texas 77592-1191
Mobil Chemical Company, 3225 Gallows Road, Rairfax, VA 22037-0001,
(703)846-3000; Petrochemicals Division, Intercontinental Center, Suite 906,
15600 JF Kennedy Boulevard, Houston, TX 77032-2343, (281)590-7700; Production
sites: Beaumont, TX 77704-2295; Chalmette, LA 70043
Phillips Petroleum Co., Phillips Bldg, Bartlesville, OK 74004, (918)661-6600,
Chemicals Division Olefins and Cyclics Branch; Production site: Sweeny, TX 77480
Phillips Puerto Rico Core Inc., Road No. 3, Route 710, Barrio Las Mareas,
P.O. Box 10003, Guayama, PR 00785, (787)864-1515; Production site: Guayama,
Puerto Rico 00784
Shell Chemical Company, Hq, One Shell Plaza, PO Box 2463, Houston, TX
77252-2463, (713) 241-6161; Production sites: Deer Park, TX 77536 (Houston
Plant); Wood River, IL 62095
Sun Company, Inc., 1801 Market Street, Philadelphia, PA 19103, (800)825-3535;
Production sites: Marcus Hook, PA 19061; Toledo, OH 43693; Tulsa, OK 74102;
Philadelphia, PA 19145
Star Enterprise, 12700 Northborough Dr., Houston, TX 77067, (281) 874-7000;
Production site: Delaware City, DE 19706
Texaco Refining and Marketing Inc., 10 Universal City Plaza, Universal City,
CA 91608-1097, (818)505-2000; Production site: El Dorado, KA 67042
Ultramar Diamond Shamrock Corp., 6000 N. Loop 1604, W, San Antonio, TX
78249-1112, (210)592-2000; Production site: Three Rivers, TX 78071
Valero Energy Corp., San Antonio Valero Towers, 7990 West IH 10, San Antonio,
TX 78229-4718, (210)370-2000; Production site: Houston, TX 77012-2408
Methods of Manufacturing:
Worldwide, approximately 30% of commercial benzene
is produced by catalytic reforming, a process in which aromatic molecules are
produced from the dehydrogenation of cycloparaffins, dehydroisomerization of
alkyl cyclopentanes, and cyclization and subsequent dehydrogenation of
paraffins. The benzene product is most
often recovered from the reformate by solvent extraction techniques.
The production of benzene by
reforming-separation processes is assoc with the production of toluene and
xylene (BTX plants). The relative production of the various aromatic
hydrocarbons is a function of the feedstock, reactor conditions, catalyst, and,
primarily, of the boiling range of the prod fraction subjected to solvent
extraction. ... In reforming processes, cycloparaffins, such as cyclohexane,
methylcyclohexane, and dimethylcyclohexanes are converted to benzene
by dehydrogenation or by dehydrogenation and dealkylation, and
methylcyclopentane and dimethylcyclpentanes are converted to benzene
by isomerization, dehydrogenation, and dealkylation. Straight-chain paraffins
such as hexane are converted to benzene
by cyclodehydrogenation. The process conditions & the catalyst determine
which reaction predominate and their kinetics (Hydrocarbon Process 55 (9): 171-8
(1976); and P Bonnifay and co-workers, Oil Gas J 74 (3): 48 (1976)).
Two molecules of toluene are converted into one molecule of benzene
and one molecule of mixed xylene isomers in a sequence called transalkylation or
disproportionation. Economic feasibility of the process strongly depends on the
relative prices of benzene, toluene,
and xylene. Operation of a transalkylation unit is practical only when there is
an excess of toluene and a strong demand for benzene.
In recent years, xylene and benzene
prices have generally been higher than toluene prices so transalkylation is
presently an attractive alternative to hydrodealkylation.
Benzene has been recovered from
coal tar. The lowest boiling fraction is extracted with caustic soda to remove
tar acids. The base washed oil is then distilled and further purified by
hydrodealkylation.
Benzene is produced from the
hydrodemethylation of toluene under catalytic or thermal conditions. The main
catalytic hydrodealkylation processes are Hydeal and DETOL. Two widely used
thermal processes are HDA and THD. These processes contribute 25-30% of the
world's total benzene supply.
The steam cracking of heavy naphthas or light hydrocarbons such as propane or
butane to produce ethylene yields a liquid by-product rich in aromatic content
called pyrolysis gasoline, dripolene, or drip oil. A typical pyrolysis gasoline
contains up to about 65% aromatics, about 50% of which is benzene.
Approximately 30-35% of benzene
produced worldwide is derived from pyrolysis gasoline.
Purification by washing with water: British patent 863,711 (1961 to
Schloven-Chemie and Koppers gmbh), Chem Abstr 55: 16971f (1961). Lab prepn from
aniline: Gattermann-Wieland, Praxis des Organischen Chemikers (de Gruyter,
Berlin, 40th ed: 247 (1961)).
General Manufacturing Information:
Benzene is a component of gasoline;
European concn 5-16%, USA concn 0.3-2.0% averaging 0.8%.
Benzene was first isolated by
Michael Faraday in 1825 from the liquid condensed by compressing oil gas. He
proposed the name bicarburet of hydrogen for the new compound. In 1833, Eilhard
Mischerlich synthesized bicarburet of hydrogen by distilling benzoic acid,
obtained from gum benzoin, with lime and suggested the name benzin for the
compound. In 1845, A.W. Hoffman and C. Mansfield found benzene
in light oil derived from coal tar. The first practical industrial process for
recovery of benzene from coal tar was
reported by Mansfield in 1849. Coal tar soon became the largest source of benzene.
Soon afterward, benzene was discovered
in coal gas and this initiated the recovery of coal gas light oil as a source of
benzene. Until the 1940's, light oil
obtained from the destructive distillation of coal was the principal source of benzene.
Benzene is the simplest and most
important member of the aromatic hydrocarbons and should not be confused with
benzine, a low boiling petroleum fraction composed chiefly of aliphatic
hydrocarbons. The term benzole, which denotes commercial products that are
largely benzene, is not common in the
United States, but is still used in Europe.
The Comission of European Communities ... prohibit the use of benzene
in products intended for use as toys (eg, children's balloons).
... Benzene has been banned as
ingredient in products intended for use in the home.
The 16th highest-volume chemical produced in USA (1995).
Benzene is a major constituent of
the gas phase of the mainstream smoke of unfiltered cigarettes. It makes up
12-50 ug of a cigarette. /From table/
/Benzene/ is one of the largest
volume organic chemicals, with the United States being the largest producer. Benzene
is the source of a variety of organic chemicals, many of which are intermediates
for the production of a host of commercial products...The commercial sources of benzene...are
coal and petroleum.
Formulations/Preparations:
Nitration grade > 99% purity.
"Benzol 90" contains
80-85% benzene, 13-15% toluene, 2-3%
xylene.
Commercial grades of benzene:
Refined benzene-535 (free of H2S and
SO2, 1 ppm max thiophene, 0.15% max nonaromatics); Refined benzene-485,
Nitration-grade (free of H2S and SO2); Industrial-grade benzene
(free of H2S and SO2)
Grade: crude, straw color; motor; industrial pure (2C); nitration (1C);
thiophene-free; 99 mole%; 99.94 mole%; nanograde.
Impurities:
Major impurities are toluene and xylene, others: phenol, thiophene, carbon
disulfide, acetylnitrile, and pyridine.
Consumption Patterns:
Consumption by chemical industry in USA, 1977: 1.4 billion gallons annually.
CHEM INT FOR ETHYLBENZENE, 49.1%; CHEM INT FOR CUMENE, 18.4%; CHEM INT FOR
CYCLOHEXANE, 15.1%; CHEM INT FOR NITROBENZENE, 4.5%; CHEM INT FOR MALEIC
ANHYDRIDE, 2.8%; CHEM INT FOR CHLOROBENZENES, 2.5%; CHEM INT FOR DETERGENT
ALKYLATE, 2.4%; EXPORTS, 2.7%; OTHER USES, 2.5% (1981 NON-GASOLINE USES)
Demand: (1980) 1,586 Million Gal; /Projected demand for/ (1984): 1,708
Million Gal
BENZENE RANKED 17TH IN 1981 &
1982 IN THE TOP 50 CHEMICAL PRODUCTION: BILLIONS OF LB: 7.87 (1982), 9.61
(1981).
Ethylbenzene/styrene, 52%; cumene/phenol, 22%; clyclohexane, 15%;
nitrobenzene/aniline, 4.5%; detergent alkylate, 2.5%; chlorobenzenes, maleic
anhydride and other, 3%; exports, 1% (1984)
USA benzene demand /is projected
to/ climb /from/ 3.8% in 1987, to 5.7 million tons, and reach 6 million tons in
1990 (1987 and 1990)
In future, coal will increasingly replace petroleum and natural gas as a
source of hydrocarbons both for fuel and petrochemicals. Processes such as USA
Steel Corporation's Clean Coke process, which yields 38% coke and 20% chemical
by-products compared to 73% coke and 2% chemical by-products in conventional
coking technology, should soon be used commercially. New coking, liquefaction,
and gasification processes for coal are all potential sources of benzene.
CHEMICAL PROFILE: Benzene.
Ethylbenzene/styrene, 55%; cumene/phenol, 21%; cyclohexane, 14%;
nitrobenzene/aniline, 5%; detergent alkylate, 3%; chlorobenzenes, exports and
others, 2%.
CHEMICAL PROFILE: Benzene. Demand:
1986: 1,603 million gal; 1987: 1,667 million gal; 1991 /projected/: 1,790
million gal. (Includes imports; 155 million gal were imported in 1986.)
World benzene production rose to
6X10+6 tons (1.8X10+9 gallons) in 1988. The United States is the largest
producer of benzene and accounts for
about 30% of world production.
U.S. demand: 2,000 million gallons in 1995; 1,900 million gallons 1996;
predicted 2,100 million gallons 2000.
U. S. Production:
(1967) 9.6X10+8 gal (data reported by tar distillers are not included)
(1977) 4.80X10+12 G
(1980) 1.5X10+9 gal (data reported by tar distillers are not included)
(1981) 4.3X10+11 GRAMS
(1981) 1.3X10+9 gal (all grades produced from light-oil distillates of tar
and tar crudes)
(1982) 3.55X10+12 G
(1983) 1.227X10+8 gallons
(1984) 1.312X10+8 gallons
(1988) 1.776X10+8 gallons (from petroleum), 5.25X10+7 gallons (from coal)
(1985) 3.74X10+9 g (98-100% pure from petroleum and natural gas)
(1985) 5.16X10+8 g (90-97.9% pure from petroleum and natural gas)
(1986) 4.39X10+11 g
(1986) 1.39X10+9 gal
(1987) 1.59X10+9 gal (est)
(1989) 5,414,072,000 kg (all grades)
Benzene ranks 16th in production
volume for chemicals produced in the USA, with approx 9.9 billion lb being
produced in 1984, 9.1 billion lb in 1983, and 7.8 billion lb in 1982.
(1990) 12.45 billion lb
(1991) 11.49 billion lb
(1992) 11.27 billion lb
(1993) 12.32 billion lb
U. S. Imports:
(1978) 2.26X10+11 G
(1979) 1.6 billion kg
(1983) 4.93X10+11 G
(1985) 4.96X10+11 g
(1986) 4.72X10+11 g
(1986) 1.56X10+8 lb
Imports in 1987 were estimated to total 175 million gallons.
U. S. Exports:
(1978) 1.52X10+11 G
(1983) 3.66X10+10 G
(1979) 1.3 million lb
(1985) 3.77X10+10 g
Exports were thought to be less than 10 million gallons.
Laboratory Methods:
Clinical Laboratory Methods:
Volatile cmpd such as benzene are
separated from blood or tissue homogenate directly on gas-chromatographic column
& detected using a flame ionization detector. High volatility permits gas
chromatograph to be operated at relatively low temp. The nonvolatile & high
boiling components of the biological matrix are left behind in the injection
port. This insures long column life & requires only occasional cleaning of
the injection chamber: Baker RN et al; Toxic volatiles in alcoholic coma; Bull
Los Angles County Neurol Soc 33: 140 (1968); Wallace JE, Dahl EV; Rapid vapor
phase method for determining ethanol in blood & urine by gas chromatography;
Am J Clin Pathol 46: 152 (1966).
GLC & colorimetric (phenol metabolite) methods are used to determine benzene
in serum, urine, & breath. Conventional reference range: >1.0 mg/l (toxic
concn) for serum; <10.0 mg/l as phenol, >75.0 mg/l (toxic concn) as phenol
for urine. Internationally recommended conc reference range is: >13 umol/l
(toxic concn) for serum; <106 umol/l as phenol, >795 umol/l (toxic concn)
as phenol for urine. Substances producing phenol as a metabolite can interfere
with color assay.
GC/MS method to determine benzene
in adipose tissue, brain, kidney, liver, lung, muscle, pancreas, & spleen;
treat sample with chlorobenzene, ethanol & water at 60 deg C; inject vapor
phase into gas chromatograph: Nagata T et al; Koenshu-lyo Masu Kenkyukai 3:
77-82 (1978), (Chem Abstr 92: 192082X).
The urinary metabolites isolated by DEAE Sephadex A-24 anion-exchange
chromatography from mice treated with radiolabeled benzene
included phenol as the major component, as well as catechol, hydroquinone, and
phenylmercapturic acid.
A sensitive HPLC method is described which separates urinary metabolites from
benzene-treated male CD-1 mice phenol,
trans, trans-muconic acid and quinol in the 48 hr urine, accounted, respectively
for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the orally administered single dose of benzene
(880, 440, and 220 mg/kg body wt).
Analytic Laboratory Methods:
VAPOR-PHASE ORGANICS IN AMBIENT AIR NEAR INDUSTRIAL COMPLEXES & CHEMICAL
WASTE DISPOSAL SITES WERE CHARACTERIZED BY CAPILLARY GAS CHROMATOGRAPHY/MASS
SPECTROMETRY/COMPUTER. /VAPOR-PHASE ORGANICS/
A SIMPLE METHOD BASED ON A SINGLE DILUTION STEP & QUANTIFICATION BY
HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) HAS BEEN DEVELOPED FOR
DETERMINATION OF BENZENE IN GASOLINE.
THIS STUDY INDICATES THAT APART FROM BEING FASTER & DEMANDING LESS
PRETREATMENT, THE HPLC METHOD IS LESS EXPOSED TO INTERFERENCES THAN THE
HIGH-RESOLUTION CAPILLARY GAS CHROMATOGRAPHY (HRGC) METHOD.
GC/FID method to determine benzene
in landfill vapors & soil. Adsorb landfill vapors on carbon in glass tubes;
desorb with carbon disulfide: (Colenutt BA, Davies DN; Int J Environ Anal Chem
7: 223-9 (1980)). Sparge soil sample with nitrogen; trap in Tenax GC tube; limit
of detection 0.1 ug/kg. (Fentiman AF et al; Environmental Monitoring Benzene
(PB-295 641) - prepared for USEPA by Battelle Columbus Lab, Springfield, Va,
Natl Tech Info Ser, pp 9-15, 26-110 (1979)).
Analyte: Benzene; Matrix: air;
Procedure: Gas chromatography (portable), photoionization detector; Range: 0.1
to 500 ppm; Est LOD: 0.15 ng/injection (0.05 ppm for a 1 ml injection);
Precision: 0.127; Interferences: any compound having the same or nearly the same
retention time as benzene on the
column in use.
EPA Method 8020: Aromatic Volatile Organics. For the detection of aromatic
volatile organics, a representative sample (solid or liquid) is collected in a
standard 40 ml glass screw-cap VOA vial equipped with a Teflon-faced silicone
septum. Sample agitation, as well as comtamination of the sample with air, must
be avoided. Two vials are filled per sample location, then placed in separate
plastic bags for shipment and storage. Samples may be analyzed by direct
injection or purge-and-trap using gas chromatography, with detection achieved by
a photo-ionization detector (PID). A temperature program is used in the gas
chromatograph to separate the organic compounds. Column 1 is a 6-ft by 0.082-in
ID #304 stainless steel or glass column packed with 5% SP-1200 and 1.75%
Bentone-34 on 100/120 mesh Supelcort or equivalent. Column 2 is an 8-ft by
0.1-in stainless steel or glass column packed with 5%
1,2,3-Tris(2-cyanoethoxy)propane on 60/80 mesh Chromosorb W-AW or equivalent.
Under the prescribed conditions, benzene
has a detection limit of 0.2 ug/l, an average recovery range of four
measurements of 10.0-27.9 ug/l, and a limit for the standard deviation of 4.1
ug/l.
EPA Method 8240: Gas Chromatography/Mass Spectrometry for Volatile Organics
Method 8240 can be used to quantify most volatile organic commpounds that have
boiling points below 200 C (vapor pressure is approximately equal to mm Hg @ 25
C) and that are insoluble or slightly soluble in water, including the title
compound. Volatile water-soluble compounds can be included in this analytical
technique, however, for the more soluble compounds, quantitation limits are
approximately ten times higher because of poor purging efficiency. The method is
also limited to compounds that elute as sharp peaks from a GC column packed with
graphitized carbon lightly coated with a carbowax (6-ft by 0.1-in ID glass,
packed with 1% SP-1000 on Carbopack-B (60/80 mesh) or equivalant). This gas
chromatography/mass spectrometry method is based on a purge-and-trap procedure.
The practical quantitation limit (PQL) for Method 8240 for an individual
compound is approximately 5 ug/kg (wet weight) for wastes and 5 ug/l for ground
water. PQLs will be proportionately higher for sample extracts and samples that
require dilution or reduced sample size to avoid saturation of the detector. A
representative sample (solid or liquid) is collected in a standard 40 ml glass
screw-cap VOA vial equipped with a Teflon-faced silicone septum. Sample
agitation, as well as contamination of the sample with air, must be avoided. Two
vials are filled per sample location, then placed in separate plastic bags for
shipment and storage. Under the prescribed conditions, benzene
has an average recovery range for four samples of 15.2-26.0 ug/l with a limit
for the standard deviation of 6.9 ug/l and a retention time of 17.0 min.
EPA Method 602 A purge and trap gas chromatography method for the
determination of benzene in municipal
and industrial discharges consists of a stainless steel column, 6 ft x 0.85 in
ID, packed with Supelcoport (100/120) coated with 5% SP-1200/1.75% Bentone-34,
with photoionization detection and helium as the carrier gas at a flow rate of
36 ml/min. A sample volume of 5.0 ml is used, the column temperature is held at
50 deg C for two minutes, then programmed at 6 deg C/min to a final temperature
of 90 deg C. This method has a detection limit of 0.2 ug/l, an overall precision
of 0.21 times the average recovery + 0.56 over a working range of 2.1 to 550
ug/l.
EPA Method 624 - Purgeables: Grab samples of water in industrial and
municipal discharges must be collected in glass containers and extracted with
methylene chloride. Analysis is performed by a purge and trap gas
chromatography/mass spectrometry method. Using this procedure, benzene
has a method detection limit of 4.4 ug/l and an overall precision of 0.25 times
the average recovery - 1.33, over a working range of 5 to 600 ug/l.
EPA Method 1624 - Volatile Organic Compounds By GC/MS: Grab samples in
municipal and industrial discharges are collected. If residual chlorine is
present, add sodium thiosulfate. Extraction is performed by a purge and trap
apparatus. An isotope dilution gas chromatography/ mass spectrometry method for
the determination of volatile organic compounds in municipal and industrial
discharges is described. Unlabeled benzene
has a minimum level of 10 ug/l and a mean retention time of 1212 sec. This
method has an initial precision of 9.0 ug/l, an accuracy of 13.0-28.2 ug/l, and
a labeled compound recovery of >0-196%.
NIOSH Method 1500. Determination of Hydrocarbons with the Boiling Point Range
of 36 to 126 C, by Gas Chromatography with Flame Ionization Detection.
NIOSH Method 1501. Determination of Aromatic Hydrocarbons by Gas
Chromatography with Flame Ionization Detection.
NIOSH Method 3700. Determination of Benzene
by Portable Gas Chromatography with a Photoionization Detector.
EPA Method 5021. Volatile Organic Compounds in Soils and Other Solid Matrices
Using Equilibrium Headspace Analysis.
EPA Method 8021. Analysis of Halogenated and Aromatic Volatiles By Gas
Chromatography using Electrolytic Conductivity and Photoionization Detectors in
Series: Capillary Column Technique.
EPA Method 5041. Analysis of Sorbent Cartridges From Volatile Organic
Sampling Train by using the Wide-Bore Capillary Column Technique.
Sampling Procedures:
ANALYTE: BENZENE; MATRIX: AIR;
RANGE: 13 TO 51.8 PPM; PROCEDURE: ADSORPTION ON CHARCOAL, DESORPTION WITH CARBON
DISULFIDE, GC. PRECISION: COEFFICIENT OF VARIATION 0.059 FOR TOTAL ANALYTICAL
& SAMPLING METHOD IN RANGE OF 13 TO 51.8 PPM.
Analyte: Benzene by portable GC;
Matrix: air; Sampler: air bag (Tedlar); Flow rate: 0.02 to 0.05 l/min or higher;
Stability: approx 4 hr
Analyte: Benzene; Matrix: air;
Sampler: Solid sorbent tube (coconut shell charcoal, 100 mg/50 mg); Flow rate:
approx 0.20 l/min; Vol: max: 30 l; Stability: at least 2 wk; Bulk sample: 1 to
10 ml, ship in separate containers from samples.
Analyte; Benzene; Matrix: air;
Sampler: Solid sorbent tube (coconut shell charcoal, 100 mg/50 mg); Flow rate:
approx 0.20 l/min; Vol: max: 30 l; Stability: not determined; Bulk sample: 1 to
10 ml, ship in separate containers from samples.
Special References:
Special Reports:
DHHS/NTP; Toxicology & Carcinogenesis Studies of Benzene
in F344/N Rats and B6C3F1 Mice (Gavage Studies) Technical Report Series No. 289
(1986) NIH Publication No. 86-2545
DHHS/ATSDR; Toxicological Profile for Benzene
(Update) TP-92/03 (1993)
WHO; Environmental Health Criteria 150: Benzene
(1993)
U.S. Environmental Protection Agency's Integrated Risk Information System
(IRIS) for Benzene (71-43-2)
Toxicological Review in Adobe PDF. Available from:
http://www.epa.gov/ngispgm3/iris on the Substance File List as of October 16,
1998.
U.S. Department of Health & Human Services/National Toxicology Program;
9th Report on Carcinogens. National Institute of Environmental Health Sciences,
Research Triangle Park, NC. (2000)
Synonyms and Identifiers:
Related HSDB Records:
Synonyms:
AI3-00808
**PEER REVIEWED**
(6)ANNULENE
**PEER REVIEWED**
BENZEEN (DUTCH)
**PEER REVIEWED**
BENZEN (POLISH)
**PEER REVIEWED**
BENZOL
**PEER REVIEWED**
Benzol 90
**PEER REVIEWED**
BENZOLE
**PEER REVIEWED**
BENZOLO (ITALIAN)
**PEER REVIEWED**
BICARBURET OF HYDROGEN
**PEER REVIEWED**
Caswell no 077
**PEER REVIEWED**
COAL NAPHTHA
**PEER REVIEWED**
CYCLOHEXATRIENE
**PEER REVIEWED**
EPA pesticide chemical code 008801
**PEER REVIEWED**
FENZEN (CZECH)
**PEER REVIEWED**
NCI-C55276
**PEER REVIEWED**
PHENE
**PEER REVIEWED**
PHENYL HYDRIDE
**PEER REVIEWED**
Polystream
**PEER REVIEWED**
PYROBENZOL
**PEER REVIEWED**
PYROBENZOLE
**PEER REVIEWED**
Formulations/Preparations:
Nitration grade > 99% purity.
"Benzol 90" contains
80-85% benzene, 13-15% toluene, 2-3%
xylene.
Commercial grades of benzene:
Refined benzene-535 (free of H2S and
SO2, 1 ppm max thiophene, 0.15% max nonaromatics); Refined benzene-485,
Nitration-grade (free of H2S and SO2); Industrial-grade benzene
(free of H2S and SO2)
Grade: crude, straw color; motor; industrial pure (2C); nitration (1C);
thiophene-free; 99 mole%; 99.94 mole%; nanograde.
Shipping Name/ Number DOT/UN/NA/IMO:
UN 1114; Benzene
IMO 3.2; Benzene
Standard Transportation Number:
49 081 10; Benzene
EPA Hazardous Waste Number:
U019; A toxic waste when a discarded commercial chemical product or
manufacturing chemical intermediate or an off-specification commercial chemical
product or a manufacturing chemical intermediate.
F005; A hazardous waste from nonspecific sources when a spent solvent.
D018; A waste containing benzene
may or may not be characterized as a hazardous waste following testing by the
Toxicity Characteristic Leaching Procedure as prescribed by the Resource
Conservation and Recovery Act (RCRA) regulations.
RTECS Number:
NIOSH/CY1400000
Administrative Information:
Hazardous Substances Databank Number: 35
Last Revision Date: 20020531
Last Review Date: Reviewed by SRP on 1/29/2000