ETHYLENE OXIDE
ETHYLENE OXIDEEvidence for Carcinogenicity:
A2. A2= Suspected human carcinogen. (1984)
Evaluation: There is limited evidence in
humans for the carcinogenicity of ethylene oxide. There
is sufficient evidence in experimental animals for the carcinogenicity of ethylene
oxide. In making the overall evaluation, the Working Group took into
consideration the following supporting evidence. Ethylene
oxide is a directly acting alkylating agent that: (1) induces a
sensitive, persistent dose-related increase in the frequency of chromosomal
aberrations and sister chromatid exchange in peripheral lymphocytes and
micronuclei in bone marrow cells of exposed workers; (2) has been associated
with malignancies of the lymphatic and hematopoietic system in both humans and
experimental animals; (3) induces a dose related increase in the frequency of
hemoglobin adducts in exposed humans and dose related increases in the numbers
of adducts in DNA and hemoglobin in exposed rodents; (4) induces gene mutations
and heritable translocations in germ cells of exposed rodents; and (5) is a
powerful mutagen and clastogen at all phylogenetic levels. Overall evaluation: Ethylene
oxide is carcinogenic to humans (Group 1).
Human Toxicity Excerpts:
INHALATION CAUSES NAUSEA, VOMITING,
NEUROLOGICAL DISORDERS, & EVEN DEATH. TRACES OF GAS IN GLOVES OR CLOTHING
MAY CAUSE BURNS. ... RESIDUES IN VASCULAR CATHETERS CAN CAUSE THROMBOPHLEBITIS;
IN ENDOTRACHEAL TUBES, TRACHEITIS.
... A pulmonary irritant if inhaled
... MAY BE DESCRIBED AS A CENTRAL DEPRESSANT,
AN IRRITANT ... CONTACT WITH ... DILUTE SOLN MAY CAUSE IRRITATION & NECROSIS
OF EYES ... BLISTERING ... & NECROSIS OF SKIN. EXCESSIVE EXPOSURE MAY CAUSE
IRRITATION OF ... LUNGS, & CENTRAL DEPRESSION.
Conjunctivitis, dyspnea, cough, vertigo,
nausea and vomiting, abdominal pain, parasystole, arrhythmia, pulmonary edema,
and paralysis.
The incidence of spontaneous abortions among
hospital staff who used ethylene oxide, glutaral (glutaraldehyde)
and formaldehyde for the chemical sterilization of instruments was studied using
data from a questionnaire and a hospital discharge register. Results showed that
the frequency of spontaneous abortions was 11.3% for the sterilizing staff and
10.6% for the nursing auxiliaries (controls). When the staff were concerned in
sterilizing during their pregnancy the frequency was 16.7% compared with 5.6%
for the nonexposed pregnancies. The incr frequency ... correlated with exposure
to ethylene oxide but not with exposure to glutaral or
formaldehyde.
Accidental exposure of a person to an
estimated concn of 500 ppm in air for 2-3 min was enough to cause temporary
unconsciousness and seizures, but apparently did not produce ocular symptoms.
A report of 1st to 3rd degree burns occurring
postoperatively or postpartum in 19 women. The gowns and sheets used were found
to contain 16-50 times the safe residual concn of ethylene
oxide.
Workers who had been employed for more than
one year by a company producing ethylene oxide had been
studied from 1960-1961. No significant differences had been found between
workers permanently working in the ethylene oxide manufacturing
area, those who had previously worked in this area, those working there
intermittently and a further group who had never worked in ethylene
oxide production. However, a subgroup of individuals with high exposure
had decreased hemoglobin concn and signficant lymphocytosis. When workers were
followed up from 1961-1977, those who had been exposed full-time to ethylene
oxide production showed a considerably excess mortality, this being
mainly due to an increased incidence of leukemia, stomach cancer and diseases of
the circulatory system. Although malignancies could not be linked to any
particular chemical associated with ethylene oxide production
it was considered that ethylene oxide and ethylene
dichloride, possibly together with ethylene chlorohydrin or ethylene, were the
causative agents.
The permeation of ethylene
oxide through human skin was determined in vitro. Permeation studies were
performed with excised skin in diffusion cells. Ethylene oxide
shows that it permeated quickly. The health hazard involved in the use of
ethylene oxide in sterilization of medical goods is
discussed.
Chronic ethylene oxide poisoning
occurred collectively in four sterilizing workers of a factory manufacturing
medical appliances in Izumo, Japan. All the patients presented with symptoms of
multiple neuropathy, of which the chief complaints were sensory disturbance of
the lower limbs and gait disturbance. One of the patients presented with
delirium and visual hallucinations. ... Clinical observations of the poisoning
/were analyzed/ and the causal factors from the standpoint of industrial
epidemiology and safety measures for the future /were discussed/.
Chromosome aberration frequencies in 61
employees potentially exposed to ethylene oxide were
compared with those in unexposed control groups. Three worksites /were studied/
with differing historical ambient levels of ethylene oxide. Within
worksites, groups were classified as high potential exposed, low potential
exposed, or controls. Further control groups including an off-site community
control group were added to give a total of 304 control individuals. Blood
samples were drawn several times over a 24-month period. Aberrations were
analyzed in 100 cells per sample after culture for 48-51 hours. Worksites I, II,
and III respectively represented increasing levels of potential ethylene
oxide exposure. At worksites I and II, no consistent differences in
aberration frequencies were found among groups. At worksite III aberration
frequencies in potentially exposed individuals were significantly increased
compared with controls. The frequencies of cells with aberrations were 5.6% for
the 2 individuals in the high potential exposure category and 2.6% for 23
persons in the low potential exposure group. The overall frequency of cells with
aberrations in the matched control individuals was 1.4%. In the total control
group of 304 individuals, ... significant increases in aberrations associated
with smoking and increasing age /were found/.
A retrospective cohort study was performed on
a group of 664 male workers employed for at least one month during the period
1942-1979 in a chemical factory. Both established and suspected carcinogens had
been handled in the plant, primarily piperazine, but also urethane, ethylene
oxide, formaldehyde, and organic solvents. A significantly increased
mortality, compared with the regional death rate, was observed in the cohort.
The increase was mainly due to violent deaths and cardiovascular diseases. A
statistically significant increase in cancer morbidity was observed for
malignant lymphoma/myelomatosis when an induction latency time /minimum/ of 10
years was used. Furthermore, an increase in bronchial cancer was noted, but it
was statistically significant only when an induction-latency time /minimum of/
15 years was used.
Samples of blood were collected from a group
of plant workers engaged in the manufacture of ethylene oxide for
periods of up to 14 yr, and also from a group of control personnel matched by
age and smoking habits. Peripheral blood lymphocytes were cultured for
cytogenetic analysis. Selected immune and hematological parameters were also
investigated. The results of these studies showed no statistically significant
difference between the group of plant workers and the control group in respect
to any of the biological parameters investigated in this study. Nevertheless,
duration of employment in ethylene oxide manufacturing
was positively correlated (p< 0.05) with the frequency of chromosome breaks
and with the percentage of neutrophils in a differential white blood cell count,
and negatively correlated (p< 0.05) with the percentage of lymphocytes. As
the values of these parameters remained within the normal limits of control
populations, the correlations were considered to have no significance for
health. The amount of alkylation (2-hydroxyethyl groups) of the Nt atom of
histidinyl residues in hemoglobin was also measured in an attempt to gauge
recent individual exposures to ethylene oxide. Variable
but, in most instances, readily measurable amounts of Nt- (2'-hydroxyethyl)-L-histidine
(Nt represents the N3 atom of histidine) were found in the hemoglobin of plant
workers and in the control group who had not knowingly been exposed to an
exogenous source of ethylene oxide. There was no
statistically significant difference between the results obtained in the control
group and in the group of plant workers.
A study was made of the effects of ethylene
oxide on the health of sterilizer workers and other personnel exposed
while using ethylene oxide for sterilization of
disposable medical devices. The only significant findings were obtained by
chromosomal analysis of cultured lymphocytes harvested from the workers. There
were significant differences in the numbers and types of chromosomal aberrations
between the exposed workers and the nonexposed controls. Quadriradial and
triradial chromosomal forms, which were rarely found in nonexposed populations,
were increased in exposed workers. Increased numbers of sister chromatid
exchanges was found in the cultured lymphocytes of some, but not all, exposed
persons during the 2 yr of study. Workers (13) were removed from exposure in
1979 because of increased numbers of aberrant cells. Follow-up over 4 yr did not
show a significant improvement, except for a moderate reduction in sister
chromatid exchanges. Recommendations were given for a surveillance of persons
working with or exposed to ethylene oxide.
... Dialyzer hypersensitivity syndrome
presents as an acute anaphylactoid reaction, the symptoms of which may range
from mild to life threatening in severity. The cause of this syndrome is
unknown, but affected patients appear to have a high incidence of positive
radioallergosorbent tests to a conjugate of human serum albumin and ethylene
oxide, suggesting that ethylene oxide, a
substance used to dry sterilize artificial kidneys, may be an offending
allergen.
Samples of peripheral blood were collected
from 33 men who were employed in the manufacture of ethylene
oxide for between 1 and 14 yr, and from 32 men from other parts of the
same plant who were used as controls. Their lymphocytes were analyzed for
chromosome damage. There were low frequencies of polyploidy, chromatid
aberrations and chromosome breaks in the cells of the 65 men. A slightly higher
frequency of chromatid aberrations was observed in the cells of the ethylene
oxide workers than in those of the controls. There was a positive
correlation between length of employment in the ethylene oxide
group and the numbers of aberrations in the cultures of each individual.
This trend was not solely attributable to the age of the men. The levels of
chromatid and chromosome damage observed in this study are consistent with those
in humans who were not recently exposed to known chromosome-breaking agents.
EXPOSURE TO LOW VAPOR CONCN OFTEN RESULTS IN
DELAYED NAUSEA AND VOMITING. HIGHER CONCN PRODUCE IRRITATION OF EYES, NOSE, AND
THROAT; HIGH CONCN MAY CAUSE EDEMA OF LUNGS. CONTACT WITH SKIN CAUSES BLISTERING
AND BURNS.
Concern about the possible adverse influence
of the workplace environemnt on reproduction now extends to women health
professionals. ... A postal survey of all women who graduated from US veterinary
schools during the period 1970-1980 (n = 2,997; response rate = 90.2%) /was
conducted/. Occupational and reproductive histories were obtained, and
spontaneous abortion risks were estimated with respect to self-reported exposure
to radiation, ethylene oxide, halothane and other
anesthetic gases, and pesticides. Of the 2,174 pregnancies among cohort members
who had one veterinary job at the time of conception, 83.3% of the conceptions
occurred while the veterinarian held a job that involved exposure to pesticides,
63.2% involved exposure to radiation, 61.9% to anesthetic gases other than
halothane, 50.7% to halothane, and 14.0% to ethylene oxide. Agent-specific
spontaneous abortion risks were estimated for the exposed/unexposed pregnancies,
and risk ratios adjusted for gravidity, history of spontaneous abortion, age and
alcohol and tobacco use were derived by means of logistic regression. Estimated
risk ratios were close to 1.0, and no effect was seen for hours worked per week,
a measure of exposure intensity. Despite no apparent influence of the exposures
on spontaneous abortion risk, caution must be exercised in interpretation of
these results because of potential exposure misclassification. Importantly, the
results emphasize the extent to which women veterinarians may be exposed to
reproductive hazards while pregnant.
Eight hospital workers with chronic ethylene
oxide exposure were age-sex matched with eight nonexposed controls with
no significant differences in educational backgrounds and vocabulary scores. The
exposed group performed more poorly on all eight measures of cognition, memory,
attention, and coordination, with 71.3% less accuracy on the Hand-Eye
Coordination Test. There was a dose-response relationship between exposure and
the following: Continuous Performance Test and sural velocity. These findings
suggest that neurologic dysfunction may result from long-term low-dose exposure
to ethylene oxide, and that these effects may occur at
exposure levels common in hosptial sterilizer operations.
Ethylene oxide is an
alkylating agent and a model direct-acting mutagen and carcinogen. This study
has evaluated a panel of biologic markers including ethylene
oxide-hemoglobin adducts, sister-chromatid exchanges, micronuclei,
chromosomal aberrations, DNA single-strand breaks and an index of DNA repair
(ratio of unscheduled DNA synthesis to NA-AF-DNA binding) in the peripheral
blood cells of 34 workers at a sterilization unit of a large university hospital
and 23 controls working in the univer library. Comprehensive environmental
histories were obtained on each subject including detailed occupational and
smoking histories. Industrial hygiene data obtained prior to the study and
personal monitoring during the 8 years preceding the study showed that workers
were subject to low level exposure near or below the current Occupational Safety
and Health Administration (OSHA) standard of 1 ppm (TWA). Personal monitoring
data obtained during 2 weeks prior to blood sampling were uniformly less than
0.3 ppm (TWA). After adjusting for smoking, ethylene oxide workplace
exposure was significantly (p< 0.001) associated with ethylene
oxide hemoglobin (a carcinogen protein adduct) and 2 measures of sister
chromatid (the average number of sister chromatid exchanges/cell (SCE50) and the
number of high frequency cells (SCEHFC). There was an apparent suppression of
DNA repair capacity in ethylene oxide exposed
individuals as measured by the DNA repair index; ie, the ratio of unscheduled
DNA synthesis and NA-AAF-DNA binding (p< 0.01). No association of DNA repair
index with smoking was found. Another important finding of this study is the
highly significant correlation between ethylene oxide-hemoglobin
adduct levels and SCEHFC (p< 0.01) and sister-chromatid exchanges (p<
0.02) which provides evidence of a direct link between a marker of biologically
effective dose and markers of genotoxic response. In contrast, micronuclei,
chromosomal aberrations and single-strand breaks were not significantly elevated
in the workers. The activity of the u-isoenzyme of glutathione-S-transferase was
measured as a possible genetic marker of susceptibility and a modulator of
biomarker formation. However, possibly because of confounding by age, no
significant relationships were found between glutathione-S-transferase and any
of the exposure-related markers by ANOVA or among other independent variables by
regression.
A multicenter cohort study was carried out to
study the possible association between exposure to ethylene
oxide and cancer mortality. The cohort consisted of 2658 men from eight
chemical plants of six chemical companies in the Federal Republic of Germany who
had been exposed to ethylene oxide for at least one
year between 1928 and 1981. The number of subjects in the separate plants varied
from 98 to 604. By the closing date of the study (31 December 1982) 268 had
died, 68 from malignant neoplasms. For 63 employees who had left the plant
(2.4%) the vital status remained unknown. The standardized mortality ratio for
all causes of death was 0.87 and for all malignancies 0.97 compared with
national rates. When local state rates were used the standardized mortality
ratio were slightly lower. Two deaths from leukemia were observed compared with
2.35 expected standardized = 0.85). Standardized mortality ratios for carcinoma
of the esophagus (2.0) and carcinoma of the stomach (1.38) were raised but not
significantly. In one plant an internal "control group" was selected
matched for age, sex, and date of entry into the factory and compared with the
exposed group. In both groups a "healthy worker effect" was observed.
The total mortality and mortality from malignant neoplasms was higher in the
exposed than in the control group; the differences were not statistically
significant. There were no deaths from leukemia in the exposed group and one in
the control group.
We have applied the micronucleus assay to
exfoliated cells of buccal and nasal cavities to monitor the genotoxic risk in a
group of workers exposed to chromic acid and in another group exposed to ethylene
oxide. The first group comprised 16 subjects working in a hard type
chrome plating factory showing increased chromium absorption and chromium
induced rhinopathy. The second group comprised 9 subjects working in a
sterilization unit, exposed to ethylene oxide concentrations
lower than 0.38 ppm as timed weighted average for a working shift; 3 of them
were involved in a acute exposure too. The frequency of micronucleus in buccal
mucosa was within the norm for exposure both to chromium and to ethylene
oxide. The micronucleus frequency in nasal mucosa was not altered in
chromium platers, whereas a significant increase (p less than 0.01) in
micronucleus was found in 2 out of 3 subjects involved in the accidental ethylene
oxide leakage and a non-significant increase in micronucleus was found in
the group chronically exposed to ethylene oxide.
Work practices as well as personal and
environmental exposure levels were reported among ethylene
oxide sterilizer operators in health care facilities in the province of
Alberta, Canada. A survey was undertaken between October of 1985 and September
of 1986 concerning the use of and exposure to ethylene oxide in
174 hospitals. The first part of the survey considered all hospitals with ethylene
oxide sterilizers, inquiring about their use at the facility. The second
part of the survey queries workers (14 men and 151 women) concerning their work
history and health status. While no detectable levels of ethylene
oxide were found in environmental samples, over half of the respondents
stated they could smell ethylene oxide at work. While
sampling results never indicated concentrations above the provincial 15 minute
time weighted average short term exposure limit of 50 ppm, personal exposure
concentrations and the use of portable sterilizers were positively associated
with short term symptoms such as irritations of the mucous membranes and skin.
Life style behavior and exposure to other chemical irritants were not considered
in the course of this study.
A retrospective cohort study was conducted to
examine the mortality experience of 2174 men employed between 1940 and 1978 by a
large chemical company and who had been assigned to a chemical production
department that used or produced ethylene oxide. Comparisons
were made with the general United States population, the regional population,
and with a group of 26,965 unexposed men from the same plants. Comparisons with
general United States death rates showed fewer deaths than expected in the ethylene
oxide group due to all causes and for total cancers. There was no
statistically significant excess of deaths due to any cause. Seven deaths each
due to leukemia and pancreatic cancer were observed with 3.0 and 4.1 deaths
expected. Among the subcohort of men who worked where both average and peak
exposure levels were probably highest, however, one death due to pancreatic
cancer (0.9 expected) and no deaths due to leukemia were observed. Four of the
seven who died from leukemia and six of the seven died from pancreatic cancer
had been assigned to the chlorohydrin department where the potential for
exposure to ethylene oxide is judged to have been low.
The relative risk of death due to each disease was strongly related to duration
of assignments to that department. When men who worked in the chlorohydrin
department were excluded, there was no evidence for an association of exposure
to ethylene oxide with pancreatic cancer or leukemia.
Together with the failure to show independent ethylene oxide associations,
the chlorohydrin department results suggest that leukemia and pancreatic cancer
may have been associated primarily with production of ethylene chlorohydrin or
propylene chlorohydrin, or both. These results emphasize the importance of
examing additional concurrent asynchronous exposures among human populations
exposed to ethylene oxide.
An epidemiological study was conducted in 55
subjects (mean age: 41) in hospitals to determine the prevalence of lens
opacities and cataracts in workers exposed to ethylene oxide in
six sterilization units. The relation between occupational exposure to ethylene
oxide and white blood cell concentrations was also investigated. Lens
opacities were observed in 19 of the 55 exposed. No link was found between the
characteristics of the lens opacities and the characteristics of exposure. For
cataracts, their prevalence differed significantly between the exposed (six of
21) and the non-exposed (0 of 16); there was no relation between their existence
and overexposures. The risk of lens opacifications by ethylene
oxide could also exist during chronic exposure to low concentrations.
Linear relations were found between the logarithm of the cumulative exposure
index and the logarithms of blood concentrations of polymorphoneutrophils.
A cohort study was carried out of mortality
among 2876 men and women exposed to ethylene oxide during
its manufacture and use in England and Wales. The study cohort included
employees from three companies producing ethylene oxide and
derivative compounds such as polyethylene glycols and ethoxylates, from one
company that manufactured alkoxides from ethylene oxide and
from eight hospitals with ethylene oxide sterilizing
units. While industrial hygiene data were not available before 1977, since then
the time weighted average exposures have been less than 5 ppm in almost all jobs
and less than 1 ppm in many. Past exposures were probably somewhat higher. In
contrast to other studies, no clear excess of leukemia was noted (three deaths
occurred versus 2.09 expected), and no increase in the incidence of stomach
cancer (five deaths occurred versus 5.95 expected) was observed. This lack of
consistency with the results of earlier studies may be due to differences in
exposure levels. Total cancer mortality was similar to that expected from
national and local death rates from this disease. Small excesses were noted in
some specific cancers, but their relevance to ethylene oxide exposure
was doubtful. No excess of cardiovascular disease was found. While the results
of this study did not exclude the possibility that ethylene
oxide is a human carcinogen, they suggested that any risk of cancer from
currently permitted occupational exposures is small.
Ethylene oxide is
widely used to sterilize heat-sensitive materials. Acute and chronic neurogenic
effects to the central and peripheral nervous system in man and animals have
been described. A cross-sectional study of 25 hospital central supply workers
exposed to low levels of ethylene oxide and 24
unexposed control workers was conducted. Subjects were tested with a
neuropsychological screening battery by examiners blinded to exposure status.
Results were reviewed independently by 2 neuropsychologists without knowledge of
exposure. Subject status was categorized as normal, impaired, or disagreement
(between the two neuropsychologists). There were more subjects concordantly
judged as impaired in the exposed group than in the control group. Although
limited by the cross-sectional study design and the global categorization, these
findings suggest that central nervous system dysfunction and cognitive
impairment may result from chronic ethylene oxide exposure
in hospital central supply units.
Ethylene oxide is
used to chemically sterilize heat-sensitive materials in hospitals. Neurotoxic
effects of ethylene oxide have been described in
animals and humans; cognitive deficits may be associated with chronic low level ethylene
oxide exposure. In this study, hospital workers with chronic ethylene
oxide exposure were compared with a non-exposed control group to detect
neurological and neuropsychological abnormalities. Ethylene
oxide breathing zone levels of up to 250 ppm in exposed subjects were
reported. The exposed group had lower P300 amplitude in electroencephalographic
(EEG) tests, bilaterally hypoactive distal deep tendon reflexes and poorer
performance on neuropsychological tests involving psychomotor speed. Exposed
subjects acknowledge more symptoms and higher levels of depression and anxiety.
Nerve conduction velocities and EEG spectral analysis were simialr in both
exposed and control groups as were scores on most psychological tests.
A 43 yr old female licensed practical nurse,
while sterilizing heat sensitive medical items, accidentally dropped and broke
an ampule containing 17 gm epoxyethane. While disposing
of the broken ampule, she began to experience nausea and stomach spasms. The
exposure was estimated to have been of 2-3 min duration and not to have exceeded
500 ppm. Upon leaving the contaminated room, she became pale, lightheaded, and
passed out for approximately 3-4 min. Convulsive movements of her arms and legs
were noted during a 1-min period of apnea. She was given oxygen, began
breathing, and awoke instantly without confusion or nausea. Approximately 3 min
later she again felt nausea, stomach spasms, and lightheadedness and became
apneic and passed out. Twitching of the extremities occurred and she was given
oxygen again. Arterial blood gases, chest X rays, and routine laboratory
measurements performed at that time were normal. During the 24 hr following
discharge she continued to complain of random muscle twitches, nausea, and
malaise.
The presence of ethylene
oxide in dialysis tubing has been suggested as a possible cause of
allergic reactions in some patients. Ethylene oxide also
is a pulmonary irritant when inhaled. It is too toxic to be applied topically as
an antiseptic.
Three cases of hematopoietic cancer that had
occurred been 1972 and 1977 /were reported/ in workers at a Swedish factory
where 50% ethylene oxide and 50% methyl formate had
been used since 1968 to sterilize hospital equipment. Attention had been drawn
to the case cluster by the factory safety committee. One woman with chronic
myeloid leukaemia and another with acute myelogenous leukaemia had worked in a
storage hall where they were exposed for 8 hr per day to an estimated 20 plus or
minus 10 (SD) ppm (36 plus or minus 18 mg/cu m) ethylene
oxide. The third case was that of a man with primary macroglobulinemia (morbus
Waldenstrom) who had been manager of the plant since 1965 and had been exposed
to ethylene oxide for an estimated 3 hr per week. (The
Working Group noted that Waldenstrom's macroglobulinemia is classified in ICD
/International Classification of Diseases codes/ 10 as a malignant
immunoproliferative disease.)
Two hundred and three workers employed for at
least one year at /a Swedish factory where 50% ethylene oxide and
50% methyl formate had been used since 1968 to sterilize hospital equipment/
were subsequently followed up for mortality. During 1978-82, five deaths
occurred (4.9 expected), of which four were from cancer (1.6 expected). Two of
the deaths were from lymphatic and hematopoietic cancer (0.13 expected), but one
of these decedents had been part of the original case cluster that had prompted
the study.
A retrospective cohort study /was reported/ of
767 men employed at a chemical plant in eastern Texas, USA, between 1955 and
1977 where ethylene oxide was produced. All of the men
had worked at the factory for at least five years and were potentially exposed
to the compound. Potential exposure to ethylene oxide was
determined by personnel at the company on the basis of work histories. In an
industrial hygiene survey in all samples taken in the ethylene
oxide production area contained less than 10 ppm (18 mg/cu m). Vital
status was ascertained for more than 95% of cohort members from a combination of
plant records, personal knowledge and telephone follow-up. Altogether, 46 deaths
were recorded, whereas 80 were expected on the basis of US vital statistics.
Death certificates were obtained for 42 of the 46 deceased subjects. Eleven
deaths were from cancer (15.2 expected), and nonsignificant excesses were seen
of cancers of the pancreas (3/0.8) and brain and central nervous system (2/0.7)
and of Hodgkin's disease (2/0.4); no death from leukaemia was found.
18,254 employees at 14 US industrial plants
where ethylene oxide had been used to sterilize medical
supplies or spices or in the testing sterilizing equipment /were followed/. The
plants were selected because they held adequate records on personnel and
exposure and their workers had accumulated at least 400 person-years at risk
before 1978. Only workers with at least three months of exposure to ethylene
oxide were included in the cohort. Forty five percent of the cohort were
male, 79% were white, 1,222 were sterilizer operators and 15,750 were employed
before 1978. Analysis of 627 8 hr personal samples indicated that average
exposure during 1976-85 was 4.3 ppm (7.7 mg/cu m) for sterilizer operators; the
average level for other exposed workers, on the basis of 1,888 personal samples,
was 2.0 ppm (3.6 mg/cu m). Many companies began to install engineering controls
in 1978, and exposures before that year were thought to have been higher. There
was no evidence of confounding exposure to other occupational carcinogens. The
cohort was followed to 1987 through the national death index and records of the
Social Security Administration, the Internal Revenue Service and the US Postal
Service, and 95.5% were traced successfully. The expected numbers of deaths were
calculated from rates in the US population, stratified according to age, race,
sex and calendar year. In total, 1,177 cohort members had died (1,454.3
expected), including 40 for whom no death certificate was available. There were
343 deaths from cancer (380.3 expected). The observed and expect numbers of
deaths were 36/33.8 from all lymphatic and hematopoietic cancer, including 8/5.3
from lymphosarcoma-reticulosarcoma (ICD9 200), 4/3.5 from Hodgkin's disease,
13/13.5 from leukaemia, 8/6.7 from non-Hodgkin's lymphoma (ICD9 202) and 3/5.1
from myeloma; 6/11.6 from cancer of the brain and nervous system; 11/11.6 from
cancer of the stomach; 16/16-9 from cancer of the pancreas; 8/7.7 from cancer of
the oesophagus; and 13/7.2 from cancer of the kidney. Mortality ratios for
subjects first exposed before 1978 were virtually identical to those for the
full cohort. No significant trend in mortality was observed in relation to
duration of exposure, but the mortality ratios for leukaemia (1.79 based on five
deaths) and non-Hodgkin's Lymphoma (1.92 based on five deaths) were higher after
allowance for a latency of more than 20 years. Among the sterilizer operators,
mortality ratios (and observed numbers of deaths) were 2.78 (two) for leukaemia
and 6.68 (two) for lymphosarcoma/reticulosarcoma; no death from stomach cancer
was seen.
Repeat plasma donors were studied to determine
whether there was a relationship between allergic-type reactions during
plasmapheresis and IgE-dependent sensitization to ethylene
oxide gas used for sterilization of disposable fluid administration sets.
Serums from 32 donors with allergic-type reactions and 84 donors who had no
reactions but were exposed to the same materials and served as controls were
tested for IgE antibodies to ethylene oxide. The
results, expressed as an IgE ethylene oxide index, were
greater than 2 in 78% of serums from donors with allergic and 12% of serums from
controls. This association was significant (p< 0.0001). Reactivity of the
antibodies was directed against an ethylene oxide-human
serum albumin conjugate and not against human serum albumin carrier protein. IgG
antibodies with ethylene oxide specificity also were
present in the serums of repeat plasmapheresis donors. Each of seven rabbits
immunized with an ethylene oxide-protein conjugate
responded with a high serum level of antibody with ethylene
oxide specificity. It was concluded that the residual ethylene
oxide in fluid administration sets is immunogenic and may cause allergic
reactions in plasma donors.
Chromosomal aberrations and micronuclei in
lymphocytes were measured in workers exposed to propylene oxide in a factory
producing alkylated starch, and in workers exposed to ethylene
oxide in connection with sterilization of medical equipment. Adduct
levels in hemoglobin were determined as a measure of in vivo doses of the two
compounds. The levels of hydroxypropylvaline in propylene oxide exposed workers
were correlated in estimated exposure doses. The levels of this adduct in the
unexposed group were close to the detection limit of the method. The levels of
hydroxyethylvaline, recorded in the propylene oxide-exposed group were
consistent with earlier data on hemoglobin alkylation in occupationally
unexposed subjects. The adduct measurements revealed increased levels of
hydroxyethylvaline in the two subgroups of ethylene oxide-exposed
workers, ie, assemblers with a low and sterilizers with a high exposure.
According to expectation the subgroups differed in adduct levels. The results of
the cytogenetic study showed that the clastogenic potency of propylene oxide was
lower than that of ethylene oxide, since the propylene
oxide-exposed individuals had lower frequencies of micronuclei and chromosomal
breaks compared to the assemblers despite a lower adduct level in the last
group.
Cases of human ethylene
oxide (EtO) neuropathy were reviewed and the clinical features
characterized. ... The 12 patients with EtO toxicity selected for review were
each engaged ln sterilizing work with EtO in the factory or hospital.
Sensorimotor neuropathy developed in two patients within 3 and 5 months of
exposure. They had been repeatedly exposed to EtO for up to several hundred ppm.
Complaints included muscle weakness hypesthesia and a tingling sensation in
distal lower limbs although distal upper limbs were also sometimes involved. Ten
of the 12 demonstrated muscle weakness in neurological examinations. Needle EMG
revealed neurogenic changes in eight. Histological studies of the sural nerve
biopsied in three patients demonstrated mild abnormalities. Cerebrospinal fluid
studies showed elevated protein in two of six patients. ...
Mortality from cancer among workers exposed to
ethylene oxide (EtO) has been studied in 10 distinct
cohorts that include about 29800 workers and 2540 deaths. This paper presents a
review and meta-analysis of these studies, primarily for leukemia, nonHodgkin's
lymphoma, stomach cancer, pancreatic cancer, and cancer of the brain and nervous
system. The magnitude and consistency of the standardized mortality ratios (SMRs)
were evaluated for the individual and combined studies, as well as trends by
intensity or frequency of exposure, by duration of exposure, and by latency
(time since first exposure). Exposures to other workplace chemicals were
examined as possible confounder variables. Three small studies ... initially
suggested an association between EtO and leukemia, but ln seven subsequent
studies the SMRs for leukemia have been much lower. For the combined studies the
SMR = 1.06 (95% confidence interval (95% CI) 0.73-1.48). There was a slight
suggestion of a trend by duration of exposure (p = 0-19) and a suggested incr
with longer latency (p = 0.07), but there was no overall trend in risk of
leukemia by intensity or frequency of exposure; nor did a cumulative exposure
analysis in the largest study indicate a quantitative association. There was
also an indication that ln two studies with Increased risks the workers had been
exposed to other potential carcinogens. For non-Hodgkin's lymphoma there was a
suggestive risk overall (SMR = 1.35, 95% CI 0.93-1.90). Breakdowns by exposure
intensity or frequency, exposure duration, or latency did not indicate an
association, but a positive trend by cumulative exposure (p = 0.05) was seen In
the largest study. There was a suggested incr ln the overall SMR for stomach
cancer (SMR = 1.28, 95% CI 0.98-1.65 (CI 0.73-2.26 when heterogeneity among the
risk estimates was taken Into account)), but analyses by intensity or duration
of exposure or cumulative exposure did not support a causal association for
stomach cancer. The overall SMRs and exposure-response analyses did not indicate
a risk from EtO for pancreatic cancer (SMR = 0.98), brain and nervous system
cancer (SMR = 0.89), or total cancer (SMR = 0.94). Although the current data do
not provide consistent and convincing evidence that EtO causes leukemia or
non-Hodgkin's lymphoma, the issues are not resolved and await further studies of
exposed populations.
Ethylene oxide (EtO)
induced mutations in the hypoxanthine-guanine phosphoribosyltransferase (HPRT)
gene were characterized in 28 independently derived 6-thioguanine resistant
human diploid fibroblast clones using polymerase chain reaction based techniques
and Southern blot analysis. Sequence analysis revealed one single base pair
deletion and 13 base substitutions nine of which were transversions: five AT-TA
three GC-TA and one GC-CG. Four mutants were found to have GC-AT transitions.
Seven of the point mutations caused splicing errors. Six occurred in splice site
sequences and one created a new splice acceptor site 16 bp upstream of exon 9.
Three splice mutations were localized at the same site in the splice donor
sequence of intron 8. Fourteen mutants had large HPRT gene deletions. In seven
mutants the entire HPRT gene was deleted. The remaining deletion mutants had a
truncated HPRT gene where one or several exons were lost. These results show
that EtO induces many different kinds of HPRT mutations, among which as many as
50% are large deletions.
A cohort of 1971 chemical workers licensed to
handle ethylene oxide was followed up retrospectively
from 1940 to 1984 and the vital status of each subject was ascertained. No
quantitative information on exposure was available and therefore cohort members
were considered as presumably exposed to ethylene oxide. The
cohort comprised 637 subjects allowed to handle only ethylene
oxide and 1334 subjects who obtained a license valid for ethylene
oxide as well as other toxic gases. Potential confounding arising from
the exposure to these other chemical agents was taken into consideration. Causes
of death were found from death certificates and comparisons of mortality were
made with the general population of the region where cohort members were
resident. Seventy six deaths were reported whereas 98.8 were expected; the
difference was statistically significant. The number of malignancies for any
site exceeded the expected number (standardized mortality ratio (SMR) = 130; 43
observed deaths; 95% confidence interval (95% CI) 94-175) and approached
statistical significance. For all considered cancer sites the SMRs were higher
than 100 but the excess was only significant p < 0.05, two sided test for
lymphosarcoma and reticulosarcoma ICD-9 = 200; SMR = 682; four observed deaths;
(95% CI 186-1745) The excess of cases for all cancers of hematopoietic tissue
(ICD-9)= 200-208) also approached statistical significance (SMR = 250; six
observed deaths; 95% CI 91-544).
Human Toxicity Values:
No effect level: 5-10 ppm, during 10 yr;
severe toxic effects: 60 min 250 ppm= 450 mg/cu m; symptoms of illness: 100 ppm=
180 mg/cu m; unsatisfactory >10 ppm= 18 mg/cu m
Skin, Eye and Respiratory Irritations:
Ethylene oxide is
irritating to the eyes, respiratory tract, and skin.
Aqueous solutions of ethylene
oxide or solutions formed when the anhydrous cmpd comes in contact with
moist skin are irritating and may lead to a severe dermatitis with blisters,
blebs and burns. It is also absorbed by leather and rubber and may produce burns
or irritation. Allergic eczematous dermatitis has also been reported. Exposure
to the vapor in high concn leads to irritation of the eyes. Severe eye damage
may result if the liquid is splashed in the eyes. Large amounts of ethylene
oxide evaporating from the skin may cause frostbite.
Medical Surveillance:
Biological monitoring of ethylene
oxide exposure by analysis of alveolar air and blood was studied in 10
workers employed in a hospital sterilizer unit. Environmemtal air, alveolar air,
and venous blood were sampled during and at the end of an 8 hr workshift. The
mean environmental concentration of ethylene oxide was
5.4 mg/cu m air and the mean alveolar ethylene oxide concentration
was 1.2 mg/cu m alveolar air. Regression analysis showed that blood ethylene
oxide concentrations were higher than environmental ethylene
oxide concentrations by a mean ratio of 3 and higher than alveolar ethylene
oxide concentrations by a mean ratio of 12.
PRECAUTIONS FOR "CARCINOGENS":
Whenever medical surveillance is indicated, in particular when exposure to a
carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic
and/or other/ tests that might become useful or mandatory. /Chemical
Carcinogens/
The 1984 OSHA standard for ethylene
oxide (EtO) mandates medical surveillance under various circumstances.
When performed medical surveillance for EtO must include a complete blood count
(CBC) with differential leukocyte count. This requirement is based on reports of
EtO associated absolute lymphocytosis and other hematologic effects. This paper
describes experiences in providing EtO medical surveillance for a 300 bed
hospital over a 6 year period. An apparent relative lymphocytosis which
persisted over 3-4 years in sterilization workers with documented TWA personal
EtO exposures averaging 0.07 ppm /was observed/. In addition three workers had a
history of acutely toxic overexposure to EtO as a result of a sterilizer
malfunction. These workers became symptomatic following the high accidental
overexposure but did not show absolute lymphocytosis or altered patterns in the
relative lymphocytosis. Finally a cross-sectional comparison of the CBC data
from the EtO exposed workers to data from non-EtO exposed hospital workers
showed no significant differences ruling out an association of the relative
lymphocytosis with EtO exposure. These observations led us to review the basis
for the inclusion of the CBC in routine EtO medical surveillance. /Such/
experience, review of the literature on EtO associated lymphocytosis and anemia,
and review of the literature on the use of the CBC with differential as
screening test suggest that the leukocyte differential may not be useful in
routine medical surveillance for EtO exposure.
In a study on workers in a chemical plant where ethylene oxide
(EtO) is manufactured and partly used for ethylene glycol production,
exposure to EtO was monitored during annual periodic health assessments In
January 1988, December 1988, and March 1990 by the determination of the level of
2-hydroxyethylvaline in hemoglobin. The 2-hydroxyethylvaline levels in workers
corresponded with the potential EtO exposures. The highest level was found in
December 1988, in blood samples collected 1-2 months after a shut down,
maintenance, and start up program. The range of adduct levels found in the three
examinations indicated that average EtO exposures during the 4 months preceding
blood sampling were below 0.5 ppm. It was demonstrated that the method allows
for the accurate monitoring of low levels of EtO exposure and provides
personalized time integrated exposure data with great discriminative power. In
addition, the method may serve to identify unexpected personal exposures, which
may lead to targeted exposure control measures.
Populations at Special Risk:
Ethylene oxide is a
suspected occupational toxicant of the male reproductive system indigenous to
the occupation of hospital sterilizers. /From table/
Industrial and occupational exposure is
generally the result of inhalation of ethylene oxide vapor
released from leaking or faulty equipment, valves, or fittings.
/Hospital workers/ operating a defective ethylene
oxide sterilizer.
Probable Routes of Human Exposure:
Exposure to ethylene oxide is
primarily occupational via inhalation. (SRC)
OSHA estimates that approximately 80,000 and 144,000 workers are directly and
indirectly exposed to ethylene oxide in ethylene
oxide production, chemical synthesis by ethoxylation, health care
facilities (sterilization), medical products (sterilization) and miscellaneous
manufacturers (e.g., spice sterilization)(1). The number of workers exposed
directly (indirectly) in the various industries are: production and synthesis
3676; sterilization - health care facilities 62,370 (25,000); sterilization -
medical products manufacture 14,000 (116,900); sterilization - spice
manufacturers 160(1). Typical exposures are usually high during short periods in
which sterilizer doors are opened, typically 5-10 ppm for 20 minutes(1). Some
typical survey results are: Medical products manufactures 0.1.1-2.0 ppm 8 hr TWA;
Hospital sterilizer chamber operators 2.5 ppm TWA; 121 use sites in Southern
California <5 ppm (TWA) in 114/121 sites; 2 hospitals 3-6 ppm and <5 ppm
resp; survey of 27 hospitals TWA exposures less than or equal to 1, <4 and
>10 ppm in 9/27, 16/27 and 5/27, respectively(1). Union Carbide production
plant in Texas City 5-33 ppm and 7.25 and 10.25 ppm avg in 2 control rooms and
0-56 ppm, 11.6 ppm avg throughout plant(2). In-depth survey of 2 Union Carbide
production facilities in West Virginia- 2 of 48 and 4 of 41 samples positive,
TWA exposure of positive samples 1.5-82 ppm(4,5). Production and maintenance
workers in the 1960's avg exposure levels 0.6-60 ppm(3).
NIOSH (NOES Survey 1981-1983) has
statistically estimated that 50,132 workers are exposed to ethylene
oxide in the USA(2). The personal 8-hr TWA exposure in 12 hospitals
ranged from ND to 6.3 ppm for sterilizer operators and ND to 6.7 ppm for folders
and packers. Short term (2 to 30 min) exposure levels for sterilizer operators
ranged from ND to 103 ppm(1). Lower exposure levels were correlated with
effective engineering controls and good work practices, rather than with the
size of the hospital, or number or location of sterilizers.
Animal Toxicity Studies:
Evidence for Carcinogenicity:
A2. A2= Suspected human carcinogen. (1984)
Evaluation: There is limited evidence in
humans for the carcinogenicity of ethylene oxide. There
is sufficient evidence in experimental animals for the carcinogenicity of ethylene
oxide. In making the overall evaluation, the Working Group took into
consideration the following supporting evidence. Ethylene
oxide is a directly acting alkylating agent that: (1) induces a
sensitive, persistent dose-related increase in the frequency of chromosomal
aberrations and sister chromatid exchange in peripheral lymphocytes and
micronuclei in bone marrow cells of exposed workers; (2) has been associated
with malignancies of the lymphatic and hematopoietic system in both humans and
experimental animals; (3) induces a dose related increase in the frequency of
hemoglobin adducts in exposed humans and dose related increases in the numbers
of adducts in DNA and hemoglobin in exposed rodents; (4) induces gene mutations
and heritable translocations in germ cells of exposed rodents; and (5) is a
powerful mutagen and clastogen at all phylogenetic levels. Overall evaluation: Ethylene
oxide is carcinogenic to humans (Group 1).
Non-Human Toxicity Excerpts:
Perturbations in bone marrow and peripherial
blood elements of mice exposed to ethylene oxide were
evaluated. Mice exposed to 225 ppm ethylene oxide for 6
hr/day were removed for analysis 1, 2, 4, 8, and 14 days and 4, 6, 8, and 10 wk
(5 day/week). Blood analysis included blood cell counts, hemoglobin
determination, and hematocrit. Bone marrow evaluation included stem-cell assay (CFU-S)
or flow cytometry analysis, cell cycle and B-cell analysis. Perturbations of
peripheral leukocytes occurred after one exposure. After multiple exposures,
hematocrit, red cell number, and hemoglobin were generally depressed, with
transient compensatory bursts, and bone marrow cellularity and CFU-S were below
normal. White cell numbers fluctuated dramatically during the exposure period.
There was a shift in the numbers of granulocytes in the bone marrow followed by
replacement and relative lymphocyte deficit, especially pronounced at 10 wk.
Female mice of hybrid stocks (C3H x C57BL)F1
and (SEC x C57BL)F1 were exposed to 300, 1200, or 1800 ppm of ethylene
oxide for various exposure periods. Exposed females were either mated
before or after treatment to male mice (C3H x C57BL)F1 and killed on the 17th
day after observation of a vaginal plug. Fetal abnormalities and mortality were
observed in both treatment groups. Early developmental stages of the zygote
appears to be more sensitive to the action of ethylene oxide than
later stages.
... REPEATED EXPOSURES OF RATS @ 400 PPM
CAUSED RESP IRRITATION, WT LOSS, WEAKNESS & DEATH. ... REPEATED EXPOSURES OF
DOGS, RATS & MICE @ 100 PPM FOR SIX MONTHS CAUSED NO SIGNIFICANT EFFECTS;
HOWEVER, THERE WAS A SLIGHT ANEMIA IN DOGS.
... THERE WAS IRRITATION OF RESP PASSAGES,
INCLUDING THE LUNGS, IN ANIMALS REPEATEDLY EXPOSED TO 204, 357 & 841 PPM ...
IN ADDITION THERE WERE GROWTH DEPRESSIONS, ORGAN WT CHANGES & ORGANIC INJURY
TO THE LIVERS, KIDNEYS, ADRENALS, & TESTES OF RATS & GUINEA PIGS.
Exposure of animals to high concn of the gas
has caused lacrimation in cats, and inflammation of the conjunctiva and clouding
of the cornea in dogs, cats, rabbits, and especially guinea pigs.
30 8-WK OLD FEMALE ICR/HA SWISS MICE WERE
PAINTED THRICE WEEKLY ON CLIPPED DORSAL SKIN WITH APPROX 0.1 ML OF 10% SOLN ...
IN ACETONE FOR LIFE. MEDIAN SURVIVAL TIME WAS 493 DAYS; NO SKIN TUMORS WERE
OBSERVED.
12 RATS RECEIVED MAX TOTAL DOSES OF 1 G/KG
BODY WT ... IN ARACHIS OIL BY SC INJECTION ... PERIOD OF TREATMENT WAS 94 DAYS.
ANIMALS WERE OBSERVED FOR LIFETIME; NO LOCAL SARCOMAS WERE OBSERVED.
... 86 FEMALE SWISS-WEBSTER MICE, GERM-FREE
& INBRED, WERE EXPOSED TO ... ETHYLENE OXIDE TREATED
GROUND-CORNCOB BEDDING FOR 150 DAYS & THEN TO UNTREATED BEDDING FOR LIFESPAN
(MAXIMAL, 900 DAYS); 63 MICE DEVELOPED TUMORS @ VARIOUS SITES. NO TUMORS WERE
REPORTED IN 83 FEMALE MICE, 100-600 DAYS OLD, WHICH WERE NOT EXPOSED TO TREATED
BEDDING ... (THIS OBSERVATION DOES NOT ALLOW AN EVALUATION OF THE
CARCINOGENICITY OF ETHYLENE OXIDE).
EXPOSURE OF MALE LONG-EVANS RATS FOR 4 HR TO
1.83 G/CU M (1000 PPM) ETHYLENE OXIDE PRODUCED DOMINANT
LETHAL MUTATIONS; CHROMOSOME ABERRATIONS WERE OBSERVED IN BONE-MARROW CELLS OF
MALE LONG-EVANS RATS EXPOSED TO 0.45 G/CU M (250 PPM) ETHYLENE
OXIDE FOR 7 HR PER DAY FOR 3 DAYS.
TERATOGENIC POTENTIAL OF IV ADMIN WAS ASSESSED
IN CD-1 MOUSE @ DOSE 0, 75, & 150 MG/KG @ 4 PERIODS DURING GESTATION.
RESULTS INDICATE TERATOGENICITY @ LEVELS 500-5000 TIMES ABOVE EXPOSURE LIMITS
CURRENTLY PROPOSED BY FDA FOR ETO RESIDUES IN MEDICAL DEVICES.
Ethylene oxide was
reported positive for mutagenicity test performed on bacteria, Neurospora,
Drosophila, mammalian cells.
Statistically significant increases in
mononuclear cell leukemia in female Fischer rats increased linearly with dose.
Among male Fischer 344 rats in the same experiment, ethylene
oxide induced peritoneal mesothelioma which originated in the testicular
mesothelium.
Rats and mice exposed to ethylene
oxide had significantly increased numbers of polychromatic erythrocytes
containing micronuclei.
/Ethylene oxide/ was
injected iv on several days during organogenesis in the mouse. Skeletal
malformations occurred in fetuses whose mother received 150 mg/kg which produced
maternal toxicity. Doses of 75 mg/kg caused no defects. Rats /were/ exposed on
days 6-15 of gestation for 6 hr daily to 10-100 ppm. At the highest dose, fetal
growth retardation occurred but there was no increase in congenital defects.
Ethylene oxide was
administered intragastrically by gavage at 2 dosages, 30 and 7.5 mg/kg body
weight to groups of 50 female Sprague-Dawley rats twice weekly for a period of
nearly 3 years using salad oil as the solvent. It induced local tumors, mainly
squamous cell carcinomas of the forestomach, dependent on the dosage. The first
tumor occurred in the 79th week. The following tumor rates resulted 62 and 16%.
In addition carcinomata in situ, papillomas and reactive changes of the squamous
epithelium of the forestomach were observed in other animals, but ethylene
oxide did not induce tumors at sites away from the point of
administration.
Groups of F344 rats of each sex were exposed
to either ethylene oxide vapor (concentrations of 100,
33 or 10 ppm) or to room air 6 hr daily, 5 days/wk, for up to 2 yr. Three
representative sections of the brain from each rat were evaluated. Of 23 primary
brain tumors which were found, 2 were in control animals. Increased numbers of
brain tumors were seen in 100 ppm and 33 ppm ethylene oxide exposed
male and female rats. Significant trend analyses were found for both males and
females, indicating that ethylene exposure > 10 ppm was related to the
development of these brain tumors.
In a dose-response study, male mice were
exposed to inhalation of ethylene oxide for 4
consecutive days. Mice were exposed for 6 hr per day to 300 ppm, 400 ppm, or 500
ppm ethylene oxide for a daily total of 1,800, 2,400,
or 3,000 ppm per hr, respectively. In the dose-rate study, mice were given a
total exposure of 1,800 ppm per hr per day delivered either at 300 ppm in 6 hr,
600 ppm in 3 hr, or 1,200 ppm in 1.5 hr. Quantitation of dominant-lethal
responses was made on matings involving sperm exposed as late spermatids and
early spermatozoa, the most sensitive stages to ethylene
oxide. In the dose-response study, a dose related increase in
dominant-lethal mutations were observed, the dose-response curve proved to be
nonlinear. In the dose-rate study, increasing the exposure concentrations
resulted in increased dominant-lethal responses.
The offspring of DBA/2J male mice exposed to ethylene
oxide (ETO) by inhalation had an increased incidence of both dominant
visible and electrophoretically detected mutations over that found in control
populations. The progeny at risk were obtained from matings during the exposure
period and were the products of germ cells that were exposed throughout the
entire spermatogenic process. Apparently, male germ cells repeatedly exposed to ethylene
oxide during spermatogenesis are susceptible to ethylene
oxide induced transmissible damage.
Ethylene oxide at 357
ppm 35 hr/week for 12 weeks produced a sensorimotor neuropathy in rats, rabbits,
and monkeys, but not guinea pigs or mice. Continued exposure resulted in
paralysis and muscle atrophy of the hindlimbs. At 204 ppm, 35 hr/wk for 32
weeks, rabbits and monkeys, but not guinea pigs, rats, or mice, developed a
clinical neuropathy. The monkeys had decreased tendon reflexes, loss of
withdrawal from superficial pain over the hindquarters, partial paralysis, and
muscle atrophy indicative of toxic axonopathy. A positive Babinski reflex in
these monkeys indicated that upper motor neurons or their axons were also
affected. Dogs showed occasional tremors, transient weakness, atrophy and fatty
replacement of skeletal muscle following ethylene oxide exposures
of 292 ppm, 30 hr/week for 6 weeks. Levels of about 100 ppm repeatedly were
without neurotoxicity in rats, rabbits, guinea pigs, mice, dogs, and monkeys.
The results of efforts to identify and
quantify macromolecular adducts of ethylene oxide, to
determine the source and significance of background levels of these adducts, and
to generate molecular dosimetry data on these adducts are reviewed. A
time-course study was conducted to investigated the formation and persistence of
7-(2-hydroxyethyl) guanine in various tissues of rats exposed to ethylene
oxide by inhalation, providing information necessary for designing
investigations on the molecular dosimetry of adducts of ethylene
oxide. Male F344 rats were exposed 6 hr/day for up to 4 weeks (5 days/wk)
to 300 ppm ethylene oxide by inhalation. Another set of
rats was exposed for 4 weeks to 300 ppm ethylene oxide, and
then killed 1-10 days cessation of exposures. DNA samples from control and
treated rats were analyzed for 7-(2-hydroxyethyl)guanine using neutral thermal
hydrolysis, HPLC separation, and fluorescence detection. The adduct was
detectable in all tissues of treated rats following 1 day of ethylene
oxide exposure and increased approximately linearly for 3-5 days before
the rate of increase began to level off. Concentrations of
7-(2-hydroxyethyl)guanine was greatest in brain, but the extent of formation was
similar in all tissues studied. The adduct disappeared slowly from DNA, with an
apparent half-life of approx 7 days. The shape of the formation curve and the in
vivo half-life indicate that 7-(2-hydroxyethyl)guanine will approach
steady-state concentrations in rat DNA by 28 days of ethylene
oxide exposure. The similarity in 7-(2-hydroxyethyl)guanine formation in
target and nontarget tissues indicates that the tissue specificity for tumor
induction is due to factors in addition to DNA-adduct.
The utility of hemoglobin as a DNA monitor in
cases of exposure to ethylene oxide was investigated in
rats via use of an inhalation system with dynamically generated test
atmospheres. Animals were exposed to atmospheres containing 1, 10, or 33 ppm
radiolabeled ethylene oxide for 6 hours. After
exposure, the animals were sacrificed and the organs removed for isolation of
DNA. DNA hydrolysates and adducts were further analyzed by high pressure liquid
chromatography. Globin was isolated from pooled erythrocytes. The relationship
between inhalation doses of ethylene oxide and
alkylation DNA and globin was described in terms of moles of adduct per gram of
DNA or globin. Linear relationships were observed between formation of
hydroxyethyl adducts in both DNA and hemoglobin and the exposure concentration
of radiolabeled ethylene oxide. Alkylation frequencies
of DNA were similar in all tissues studied with exception of testis;
corresponding alkylation in hemoglobin was not significantly different. Results
indicate that the results support the suggestion that, in the case of ethylene
oxide exposure, determination of the hemoglobin dose in vivo is a valid
indicator of the dose delivered to DNA.
Exposure of female mice to ethylene
oxide by inhalation 1 or 6 hr after mating produced not only
multitemporal death of conceptuses but also high rates of abnormalities among
surviving fetuses. In contrast, only marginal effects were observed when females
were exposed 9 or 25 hr after mating. The abnormalities found among 17 day
gestation live fetuses were predominated by hydrops and eye defects, which,
together, constitute 54% of all anomalies. Most of the remaining anomalies were
distributed among 5 other types: small size, cleft palate, and cardiac,
abdominal wall, or extremity and/or tail defects. In a follow-up study the
fetuses of females treated 6 hr postmating were examined at 11-15 days gestation
and the progression of fetal death and of malformations was studied. Results
indicate that the expression of most fetal anomalies does not become apparent
until late in gestation. Several of these induced anomalies are similar to
common human sporadic birth defects. This new class of experimentally induced
fetal anomalies provides a new avenue for investigating zygotic biology and a
system for studying the progression of aberrant development.
Wistar male and female rats were exposed to ethylene
oxide at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17
weeks simultaneously, and the sex difference of anemia induced by ethylene
oxide was investigated. Hemoglobin concentrations of both the male and
female exposed groups were decreased when compared with each control group, and
the anemia in the female exposed group was more severe than that in the male
exposed group. Absolute spleen weight increased only in the female exposed
group. We have already reported that a decrease of the glutathione reductase
activity in the erythrocyte plays an important role in the ethylene
oxide induced anemia. In the present study, the activity in both male and
female exposed groups decreased when compared with each control group, and there
was no sex difference in the degree of the decrease. From these observations,
/it was/ concluded that there was a sex difference in the ethylene
oxide induced anemia.
The effect of chronic inhalation of ethylene
oxide on urinary coproporphyrin and delta- aminolevulinic acid were
studies. When Wistar male rats were exposed to 500 ppm ethylene
oxide three times a week, daily urine volume was increased by 200-300%
from the first week to the fifth week of the experimental period. After
exposure, daily coproprorphyrin excretion and urinary coproporphyrin per mg of
creatinine increased by 250% and 141%, respectively. On the other hand, daily
excretion of delta-aminolevulinic acid in urine tended to increase but did not
increase significantly by creatinine correction. This /may be/ the first report
of ethylene oxide induced experimental porphyria.
Male Wistar rats were exposed to ethylene
oxide at concentrations of 50, 100, or 250 ppm for six hours a day, on
five days a week for 13 weeks. Dose effect relations of inhaled ethylene
oxide on spermatogenesis were evaluated from testicular and epididymal
weights, histopathological changes and lactate dehydrogenase X (LDH X) activity
in the testis, and sperm counts and sperm head abnormalities in the epididymis.
At 250 ppm, a decrease in epididymal weights, slight degenerations in the
seminiferous tubules, decreased sperm counts, and increased numbers of abnormal
sperm heads in the tail of the epididymis were found; these were not seen at
lower doses. When the abnormal sperm heads were classified into immature types
and teratic types, the number of immature heads increased only at 250 ppm. On
the other hand, the teratic type had increased at doses of 50 and 100 ppm ethylene
oxide when compared with the control group. Hence, subchronic inhalation
of ethylene oxide at low concentrations affects
spermatogenesis in rats.
The effects of systemic toxicity including
reproductive toxicity of ethylene oxide on female rats
were studied. When Wistar female rats were exposed to 250 ppm of ethylene
oxide for six hours a day, five days a week for ten weeks, they showed
inhibition of body weight gain and paralysis of the hindlegs. Hematogological
examination revealed macrocytic and normochromic anemia with high reticulocyte
counts. The estrus cycle of the exposed group was prolonged and the percentage
of the diestrus stage increased. There was no atrophy in the ovary or the
uterus. However, the activity of glutathione reductase in the ovary decreased by
18% and that of glutathione-S-transferase increased by 30%. These results
indicate that ethylene oxide has a similar effect on
both female and male rats and that the female reproductive system is also
affected.
The toxic effects of residual ethylene
oxide, a frequently used gas-sterilant, on embryos either frozen for
long-term purposes or stored acutely for 30 min to 9 hr in a fresh condition in
0.25 ml straw containers were evaluated. In Experiment 1, fresh embryos were
frozen (using conventional technology) in straws previously aerated for 0 hr to
8 mo after ethylene oxide sterilization. With the
exception of the 8 mo group in which survival and quality ratings were
depressed, embryo viability was not affected significantly by short-term
prefreeze and post-thaw exposure to ethylene oxide residues.
Experiment 2 was conducted to analyze the influence of prefreeze exposure to ethylene
oxide residues on embryo development in vitro for embryos temporarily
stored in previously sterilized straws aerated for different intervals. Compared
to non-ethylene oxide sterilized control straws, the
development, quality, and viability of embryos exposed to ethylene
oxide-treated straws were compromised (p less than 0.05) as the aeration
interval decreased and the exposure interval increased. The combined results of
both experiments indicate that ethylene oxide-treated
straws can be used to cryopreserve gametes efficiently, but only if the aeration
interval is greater than or equal to 72 hr and the prefreeze duration of
exposure is less than or equal to 3 hr.
Thirty B6C3F1 mice of both sexes that were
exposed at ethylene oxide vapor concentrations of 1,
10, 50, 100, or 250 ppm, 6 hours/day, 5 days/week for 10 to 11 weeks showed no
effects on survival, body weight, or histologic sections of various organs.
Neuromuscular toxicity was observed at the three highest exposure levels, and
both sexes in the 250 ppm exposure group had a statistically significant
increase in hunched posture, reduced locomotion, and righting reflex. These
symptoms were also observed in some animals of both sexes exposed at 50 or 100
ppm. Neuromuscular effects appeared to be the most sensitive indicator of
exposure to ethylene oxide in this study.
When ethylene oxide/saline
solutions of varied concentrations (0.1% to > 20%) were applied repeatedly
over a 6-hour period to the eyes of rabbits, a dose-dependent increase in
congestion, swelling, discharge, iritis, and corneal cloudiness was observed.
These effects were an indication of the irritating effect of ethylene
oxide on mucous membranes and corneal epithelium. The 0.1% ethylene
oxide concentration was the maximum, nondamaging concentration of this
chemical for the 6 hour exposure period.
Infusion of ethylene oxide into
the aorta of rats caused a significant decrease (approximately 30%) in kidney
glomerular filtration rates, resulting in kidney dysfunction.
Pathological examination of tissues from mice,
rats, and guinea pigs that died after lethal exposure to ethylene
oxide revealed adverse effects that included lung congestion, hyperemia
of the liver and kidneys, and gray discoloration of the liver. Animals that
experienced delayed death had emphysema of the lungs, fatty degeneration of the
liver, cloudy swelling of the kidney tubules, and congestion of the spleen and
brain, all believed to be a cause or contributing to these deaths.
Mice, rats, guinea pigs, rabbits, and dogs
exposed to lethal concentrations of ethylene oxide had
symptoms of mucous membrane irritation, central nervous system (CNS) depression,
lacrimation, nasal discharge, salivation, nausea, vomiting, diarrhea,
respiratory irritation, incoordination, and convulsions. Surviving animals
showed subsequent bronchitis, pneumonia, and loss of appetite with delayed
symptoms of apathy, dyspnea, vomiting, paralysis (particularly of the
hindquarters), and periodic convulsions, followed eventually by death. Rapid
deaths were usually associated with lung edema; delayed deaths frequently
resulted from secondary infections in the lungs, although general systemic
intoxication is also believed to be associated with these delayed deaths.
... Fischer 344 rats, 120 rats/sex/group,
/were exposed/ at 10, 30, or 100 ppm ethylene oxide vapor,
6 hours/day, 5 days/week for 2 years. Two groups of controls were exposed to
untreated air under similar conditions. Ten animals each at 6 and 12 months and
20 animals at 18 months were sacrificed to determine possible treatment-related
effects. Both interim and terminal evaluations included hematology, serum
clinical chemistry, urinalysis, body weight, organ weight, bone marrow
cytogenicity studies, and gross and histologic examinations. Histopathologic
examinations of rat tissue from the 100 ppm ethylene oxide exposed
animals and the control group were performed at 6, 12, and 18 month necropsy
intervals. At the 24 month sacrifice, histopathologic examination was made on
all tissues of the 100 ppm exposed rats as well as controls and on potential
target tissues, other selected tissues, and tissues with gross lesions in the 10
and 33 ppm exposed animals. The six types of tumors found in the ethylene
oxide exposed rats that appear to be treatment related are subcutaneous
fibroma, peritoneal mesothelioma, pancreatic adenoma, pituitary adenoma, brain
neoplasm, and mononuclear cell leukemia. In this 2-year study, a dose-related
increased incidence of mononuclear cell leukemia was found in both sexes. It was
significant in the 100 and 33 ppm exposed females from the 18th or 19th month
onward. A trend test revealed a treatment-related response in both sexes. An
increased incidence of peritoneal mesotheliomas originating from the testicular
mesothelium was found in males exposed at 33 and 100 ppm from the 23rd month
onwards and an increased incidence of subcutaneous fibroma in males surviving
the 24-month, 100 ppm exposures. There was no increased incidence of pituitary
tumors, although they appeared earlier in the 100 ppm exposed group.
No specific testicular damage was seen in test
animals exposed at nontoxic doses of ethylene oxide. When
maternally toxic doses of ethylene oxide were
administered intravenously in mice, embryo and fetal toxicity were found.
Pregnant rats inhaling ethylene oxide had a reduction
in fetal weight but no teratogenic effects.
Earlier studies ... revealed that ethylene
oxide or ethyl methanesulfonate induced high frequencies of midgestation
and late fetal deaths and of malformations among some of the surviving fetuses
when female mice were exposed at the time of fertilization of their eggs or
during the early pronuclear stage of the zygote. Effects of the two mutagens are
virtually identical. Thus ln investigating the mechanisms responsible for the
dramatic effects ln the early pronuclear zygotes the two compounds were used
interchangeably in the experiments. First a reciprocal zygote-transfer study was
conducted in order to determine whether the effect is directly on the zygotes or
Indirectly through maternal toxicity. And second cytogenetic analyses of
pronuclear metaphases early cleavage embryos and midgestation fetuses were
carried out. The zygote transplantation experiment rules out maternal toxicity
as a factor ln the fetal maldevelopment. Together with the strict stage
specifically observed in the earlier studies this result points to a genetic
cause for the abnormalities. However the cytogenetic studies failed to show
structural or numerical chromosome aberrations. Since intragenic base changes
and deletions may also be ruled out it appears that the lesions in question
induced In zygotes by the two mutagens are different from conventional ones and
therefore could be a novel one ln experimental mammalian mutagenesis.
A ... 2-year carcinogenic study involved male
Fischer 344 rats (80 in each group) and 12 Cynomolgus-monkeys per group exposed
at either 50 or 100 ppm ethylene oxide 7 hours/day, 5
days/week for 24 months. Rats exposed at 50 ppm had a significantly increased
incidence of mononuclear cell leukemia. The absence of a dose-response
relationship was attributed to an increased mortality rate for the rats exposed
at 100 ppm. Peritoneal mesotheliomas originating from the testicular mesothelium
and mixed cell gliomas in the brain were found in a dose related increased
incidence that was statistically significant for the 100 ppm exposure group.
Exposures at the 50 and 100 ppm concentrations also reduced body weight gain and
had an adverse effect upon the survival rate of the rats compared to the
controls. Mortality was dose-dependent. Peritoneal mesotheliomas and gliomas are
tumor types that can be found in humans. The 50 or 100 ppm exposed monkeys did
not show any significant changes in hematological, clinical or urine chemistry,
or ophthalmological parameters. At 100 ppm, nerve conduction velocities were
decreased, and evidence of neurotoxicity and demyelination was noted in the 50
ppm and 100 ppm exposure groups. Sperm counts and motility were also reduced,
and both exposure concentrations caused significant increases in the incidence
of sister-chromatid exchanges (SCE) and chromosomal aberrations.
... Monkeys /were exposed/ at 50 or 100 ppm ethylene
oxide for 7 hours/day, 5 days/week for 2 years. ... Data /were collected/
in 1987 for sister chromatid exchanges (SCE) in peripheral blood lymphocytes and
compared these data with those generated immediately prior to cessation of the 2
year exposure in 1981. Ethylene oxide induced SCE
persisted at levels significantly higher than those of the nonexposed controls.
These findings indicate that long lived lymphocytes may not be efficient with
repair of the ethylene oxide induced lesions which
produce SCE.
Male mice were exposed to ethylene
oxide for 6 hours/day on 4 consecutive days at 300, 400, or 500 ppm for a
daily total of 1800, 2400, or 3000 ppm hours (total exposures of 7200, 9600, and
12,000 ppm hours), respectively. A dose related increase in dominant-lethal
mutations was observed; the dose response curve proved to be nonlinear. In a
dose rate study, mice were given a total exposure of 1800 ppm hours per day for
4 consecutive days. This exposure was delivered at 300 ppm for 6 hours, 600 ppm
for 3 hours, or 1200 ppm for 1.5 hours. Increasing the exposure concentrations
resulted in increased dominant lethal responses even when the total dose was the
same.
When freshly prepared aqueous solutions (2 to
5 percent) were injected intravenously into dogs, the LD50 was found to be about
125 mg/kg. A dose of 30 mg/kg or more usually caused vomiting and defecation for
about 2 hr, followed by weakness and flaccidity, usually apparent in the hind
limbs first. Doses up to 100 mg/kg in dogs under barbiturate anesthesia caused
no apparent changes in blood pressure or cardiac rate. Respiration is adequate
until terminal stages, when it becomes labored and cyanosis develops. Tonic
extensor spasm may precede respiratory cessation. Since the heart usually beats
after all reflexes disappear, death is believed due to respiratory failure .
... In aqueous solution the maximum
concentration that could be applied externally to the ... /eyes of rabbits/, one
drop every 10 minutes for 6 hours, without causing damage to the conjunctiva was
0.1%, to the cornea was 1%, and to the lens or retina was 20%. ... /Also/ if the
aqueous humor was replaced once with an aqueous solution of ethylene
oxide the maximum nondamaging concentration for the iris and lens was
0.1%, and for the cornea was 1%. At higher concentrations, damage consisted of
irreversible opacities of cornea and lens.
Ethylene oxide is a
classical mutagen and a carcinogen based on evidence from studies in
experimental animals. Chinese hamster V79 cells were treated for 2 hr with
gaseous ethylene oxide, in sealed treatment chambers,
and assayed for survival and mutagenic response by analysis of induced
resistance to 6-thioguanine or ouabain. Significant numbers of mutants were
produced at both genetic markers by 1,250-7,500 ppm ethylene
oxide. Similarly, primary Syrian hamster embryo cells were treated for 2
or 20 hr with gaseous ethylene oxide in sealed
treatment chambers and subsequently assayed for survival and increased
sensitivity to SA7 virus transformation. Treatment concentrations extended from
toxic to several nontoxic concentrations. After 2 hr ethylene
oxide treatment at 625-2,500 ppm a significant enhancement of virus
transformation was observed. At 20 hr after treatment no enhancement was
observed. Treatment of hamster cells with ethylene oxide in
both bioassay systems yielded concentration-related, quantitative results.
In mice exposed by inhalation for 5 hr/day, 5
days/week, for 10 weeks to 250, 100, 50, 10, or 0 ppm epoxyethane
in air, clinical significant pathological findings were limited to the group
exposed to 250 ppm. These findings included minimal decreases in red blood cell
count, packed cell volume, and hemoglobin; decreased testicular and spleen
weights; and increased liver weight. Abnormal pinch and righting reflexes,
posture, and locomotion were also observed in mice exposed to 250 ppm. However,
histological sections of the liver, testis, bone marrow, brain, and spleen taken
from these mice were normal.
Groups of 120 male and 120 female Fischer 344
rats, eight weeks of age, were exposed by inhalation to ethylene
oxide (purity, > 99.9%) vapor at 10, 33 or 100 ppm (18, 59 or 180
mg/cu m) for 6 hr per day on five days per week for two years. Two control
groups, each of 120 male and 120 female rats, were exposed in inhalation
chambers to room air. All animals that died or were killed when moribund and
those killed at scheduled intervals of 6, 12, 18 an 24-25 months were examined.
During month 15 of exposure, mortality increased in both treated and control
groups due to a viral sialodacryoadenitis. Mortality was higher in the groups
inhaling 33 and 100 ppm ethylene oxide than in the
other groups and was more frequent in females than in males near the fifteenth
month. Up to 18 months of exposure, no significant increase in tumor incidence
was observed. In treated rats killed after 18 months, the incidence of tumors in
the brain classified as gliomas, malignant reticulosis and granular-cell tumors
was increased for animals of each sex. The incidences of glioma among rats
killed at 18 and 24-25 months were: males: 1/181 (controls), 0/92 (10 ppm), 3/86
(33 ppm) and 6/87 (100 ppm) (p < 0.05, trend analysis and Fisher's exact test
for high dose versus control); and females: 0/187 (controls), 1/94 (10 ppm),
2/90 (33 ppm) and 2/78 (100 ppm) (p < 0.05, trend analysis). In females
killed after 24 months of exposure mononuclear-cell leukaemia was found in 5/60
(control I), 6/56 (control II), 11/54 (10 ppm), 14/48 (33 ppm) and 15/26 (100
ppm) animals; the incidence of leukaemia was reported ... to be significantly
increased in the 100 ppm group (p < 0.001) and in a mortality adjusted trend
test (p < 0.005). In males, mononuclear-cell leukaemia was found in 5/48
(control I), 8/49 (control II), 9/51 (10 ppm), 12/39 (33 ppm) and 9/30 (100 ppm)
animal (p < 0.05 in a mortality adjusted trend test). Peritoneal
mesotheliomas originating in the testicular serosa were found in 1/48 (control
I), 1/49 (control II), 2/51 (10 ppm), 4/39 (33 ppm) and 4/30 (100 ppm) males (p
< 0.005 trend test). The incidence of subcutaneous fibromas in male rats of
the high-dose group was also significantly increased: 1/48 (control I) 2/49
(control II), 9/51 (10 ppm), 1/39 (33 ppm) and 11/30 (100 ppm) (p < 0.001).
The effects of repeated exposure to ethylene
oxide on lipid peroxidation and glutathione metabolism in both rat liver
and brain were examined. Increased levels of malondialdehyde in the liver were
observed after 6 and 13 weeks of exposure to ethylene oxide. The
increased level of malondialdehyde observed in the hepatic homogenates of the
treated rats reflected that of the microsomal fraction. On the other hand, no
change in the level of malondialdehyde was detected in the brain of rats either
at a 6- or 13-week treatment. Glutathione reductase activity was found to
decrease at 6 or 13 weeks in liver and brain of treated rats. Both reduced and
oxidized forms of glutathione in homogenates of liver and brain obtained from
treated rats were, however, similar to those of the control at 40 hr after the
last exposure in individual experiments. To elucidate the cause of lipid
peroxidation, the time course of glutathione content after exposure with ethylene
oxide were studied in more detail. Significant decreases in both GSH and
GSSG content in these organs were detected shortly after exposure to ethylene
oxide and their levels recovered gradually with time and reached the
control values at 40 hr in the liver, although the changes were less significant
in the brain as compared with those in the liver. These results suggest that
enhancement of lipid peroxidation in the microsomal fraction of the liver after
repeated exposure to ethylene oxide may possibly arise
from repeated depletions of glutathione to certain critical levels and less
removal of lipid peroxidation.
This paper describes a dominant neurological
mutation identified among the progeny of a male parent treated with ethylene
oxide. The defects observed in the heterozygous mutant include: head
tossing, poor limb coordination, and corneal clouding. Both the behavior and
ocular manifestations of the mutant syndrome worsen progressively as the
affected animals grow older. The mutant animals swim poorly, although they do
orient themselves in reference to the surface of the water. Breeding in general
is poor. Very small litter sizes result when heterozygous animals of either sex
are mated to normal mice. Many male carriers are functionally sterile. All
mutant animals had abnormal karyotypes. The original carrier mouse had a
translocation between chromosomes 4 and 17, which was also present in all but
one mutant animal. The exceptional animal, which showed all mutant behavior
characteristics, had 41 chromosomes, which included two normal 4 and 17 homologs
and the small 417 translocation chromosome. Karyotypes of unaffected siblings of
mutants were normal. ...
Male Fischer and B6C3Fl mice
(10/species/group) were exposed to ethylene 6 hr/day, 5 days/week, for 4 weeks.
The ethylene target concentrations were 0, 40, 1000, and 3000 ppm. An ethylene
oxide (EO) control group for each species was exposed under the same
conditions at a target concentration of 200 ppm. Bone marrow was collected
approximately 24 hr after the final exposure. Polychromatic erythrocyte (PCE) to
normochromatic erythrocyte (NCE) ratios were determined and 2000 PCE/animal were
scored for the presence of micronuclei. Ethylene did not produce statistically
significant, exposure-related increases in the frequency of micronucleated PCE (MNPCE)
in the bone marrow of either rats or mice when compared to air exposed control
animals. As expected, EO exposure resulted in significant increases in the
frequencies of MNPCE in both species.
... Conclusions: Under the conditions of these
2 yr inhalation studies, there was clear evidence of carcinogenic activity for
B6C3F1 mice as indicated by dose related incr incidences of benign or malignant
neoplasms of the lung and benign neoplasms of the harderian gland in both male
and female B6C3F1 mice following exposure to ethylene oxide vapors
at 50 and 100 ppm. In female mice, ethylene oxide caused
additional malignant neoplasms of the uterus, mammary gland, and hematopoietic
system (lymphoma).
National Toxicology Program Studies:
... Toxicology and carcinogenesis studies of ethylene
oxide (greater than 99% pure) were conducted by exposing groups of 50
B6C3F1 mice of each sex to air containing 0, 50, or 100 ppm ethylene
oxide, 6 hours per day, 5 days per week for 102 wk. ... Conclusions:
Under the conditions of these 2 yr inhalation studies, there was clear evidence
of carcinogenic activity for B6C3F1 mice as indicated by dose related incr
incidences of benign or malignant neoplasms of the lung and benign neoplasms of
the harderian gland in both male and female B6C3F1 mice following exposure to ethylene
oxide vapors at 50 and 100 ppm. In female mice, ethylene
oxide caused additional malignant neoplasms of the uterus, mammary gland,
and hematopoietic system (lymphoma).
Non-Human Toxicity Values:
LC50 Rat 1460 ppm (Exposure: 882-2298 ppm/4
hr). Effects were ocular and respiratory irritation, diarrhea, increased
activity. /From table/
LC50 Mouse 835 ppm (Exposure: 533-1365 ppm/4
hr). Effects were ocular and respiratory irritation, increased activity. /From
table/
LD50 Rat oral 330 mg/kg
LC50 Rat inhalation 1462 ppm/4 hr
LC50 Mouse inhalation 836 ppm/4 hr
LC50 Dog inhalation 973 ppm/4 hr
LD50 Guinea pig oral 270 mg/kg
TSCA Test Submissions:
Chronic toxicity was evaluated in rats from
the Army Chemical Center's Chemical Corps Medical Laboratories colony (20
animals) exposed to 100 ppm ethylene oxide via
inhalation for 6 hrs/day for 6 months. The exposed animals showed no toxic
signs. No significant effects were observed in weight gain, rectal temperature,
EKG's, blood calcium and urea, or bilirubin. Mortalities for exposed and control
rats were 3 out of 20 and 3 out of 20, respectively.
Chronic toxicity was evaluated in mice from
the Army Chemical Center's Chemical Corps Medical Laboratories colony (30
animals) exposed to 100 ppm ethylene oxide via
inhalation for 6 hrs/day for 6 months. The exposed animals showed no toxic
signs. No significant effects were observed in weight gain, rectal temperature,
EKG's, blood calcium and urea, or bilirubin. Mortalities for exposed and control
mice were 8 out of 30 and 4 out of 30, respectively.
In a one-generation teratology study, pregnant
female Fischer 344 rats (21-22/group) were exposed to ethylene
oxide by inhalation at nominal concentrations of 0, 10, 33 or 100 ppm for
6 hrs on gestation days (GD) 6-15. The only treatment-related effect noted was a
significant decrease in male and female fetal body weight relative to fetuses in
control groups. No significant differences between treated and control animals
were observed in the following: maternal and fetal survival, number of
implantation and resorption sites, number of preimplantation losses,
crown-to-rump length, the results of examination of all the fetuses for gross
external abnormalities and half of each litter for visceral abnormalities and
the other half for skeletal abnormalities.
Chronic toxicity and oncogenicity were
evaluated in groups of male and female Fischer 344 rats (120/sex/group) exposed
to ethylene oxide via inhalation at 0, 10, 33 and 100
ppm for 6 hrs/day, 5 days/week for approximately 2 yrs. There was a
statistically significant difference between treated animals and controls in the
following: mortality (increased for both sexes at 100 ppm), body weight
(decreased in males at 100 ppm and females at 100 and 33 ppm), mononuclear cell
leukemia (increased in all treated female groups), peritoneal mesothelioma
(increased in males at 100 and 33 ppm), cumulative percentage of pituitary
adenoma (increased in females at 100 ppm), number of neoplasms/neoplasm bearing
rats (increased for all treated rats, especially females), and number of rats
with malignant neoplasms (increased in females at 100 and 33 ppm). There were no
statistically significant differences in the following: chromosomal aberrations,
ophthalmic lesions, urinalysis, hematology, serum clinical chemistry, or
histopathology of the testes in males.
As part of a chronic inhalation study, the
ability of ethylene oxide to cause chromosome
aberrations was evaluated in bone marrow cells of Fischer 344 rats receiving
nominal concentrations of the test material at 0 or 100ppm in a dynamic air flow
chamber for 6hours/day, 5days/week for 12 months [also see OTS0206201; final
report]. After exposure, a minimum of 5 animals/sex/group were sacrificed and at
least 50 bone marrow cells/animal were collected. No statistically significant (Wilcoxon
Sum of Ranks Test) increase in the frequency of chromosome aberrations was
observed in bone marrow cells of rats exposed to 100ppm of ethylene
oxide compared to the controls.
The fate of ethylene oxide (EO)
was evaluated in preexposed male Fischer 344 rats and their respective controls
(2 preexposed to 100ppm EO for 8 weeks plus 2 controls/ 2 preexposed to 100ppm
EO for 10 weeks plus two controls) receiving a nominal concentration of 14C-EO
at 100ppm for six hours in a closed cycle, recirculating inhalation chamber.
Urine, feces and expired air were collected during and 18 hours after exposure
to 14C-EO. There were no significant differences between the non-preexposed or
preexposed animals in the routes of elimination or in metabolic profiles. There
were no significant differences in the concentration of radioactivity in either
group of animals, except that the radioactivity associated with the RBC was 1.3
times greater in the non-preexposed animals. The data indicates that prolonged
exposure of rats to EO has little effect on the metabolism of the chemical.
The disposition of ethylene
oxide (EO) was evaluated in male Fischer 344 rats (4/exposure) receiving
nominal concentrations of 14C-EO at 10, 100 or 1000ppm for six hours in a closed
cycle, recirculating, inhalation metabolism chamber. Urine, feces and carbon
dioxide was collected during exposure and in Roth metabolism cages for 18 hours
following exposure. The mean estimated absorbed dose was 2.7, 20.2 and 106.8mg
EO/kg body weight for the 10, 100 and 1000ppm exposure, respectively. For all
exposures the primary route of elimination was urine (mean value of 59%
recovered 14C-activity), followed by CO2 (12%), feces (4.5%), and expired EO
(1%). The highest concentrations of 14C-activity was found in the urinary
bladder, liver, packed blood cells and adrenal glands, with the lowest
concentration found in the fat. The increase in radioactivity concentration in
tissue associated with increased exposure level of EO appeared to have a
non-linear component. Analysis of urine obtained 18 hours post exposure was
characterized by four radioactive metabolites. A significant increase in
radioactivity was observed in two metabolites, a significant decrease in one and
no difference in the fourth metabolite at 1000ppm relative to urinary
metabolites in the other exposed rats.
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
... ABSORBED INTO THE CELL WHERE IT UNDERGOES
HYDROLYSIS TO ETHYLENE GLYCOL ...
In adult male Sprague-Dawley rats, male Swiss
CD-1 mice, and male rabbits, 20 or 60 mg/kg ethylene oxide as
a solution in distilled water was injected into the caudal vein in rats and mice
or in the marginal vein in rabbits. Some animals were exposed to 200 ppm ethylene
oxide in inhalation chambers. The animals were housed in metabolism
cages, and urine samples were collected at 0-6 hr and 6-24 hr. The urine samples
were analyzed for 2-hydroxyethylmercapturic acid, N-acetyl-S-carboxy-methyl-L
cysteine, S-(2-hydroxyethyl)-L-cysteine, S-carboxymethyl-L-cysteine, and
ethylene glycol. Species-related differences in the metabolic disposition of ethylene
oxide were observed. Excretion product patterns did not differ
significantly between injected doses. Rats (n= 5) eliminated 37% of ethylene
oxide as 2-hydroxyethylmercapturic acid (31%) and ethylene glycol (6%);
mice (n= 10) converted 19.3% of the ethylene oxide to
2-hydroxyethylmercapturic acid (8.3%), S-2-hydroxyethyl-L-cysteine (5.8%), S-carboxymethyl-L-cysteine
(1.9%), and ethylene glycol (3.3%). The rabbits (n= 3) excreted only 2% of the ethylene
oxide, primarily as ethylene glycol. In rats, larger amounts of
2-hydroxyethylmercapturic acid were excreted in the 6-24 hr period, and larger
amounts of ethylene glycol were excreted in the 0-6 hr period. In mice, equal
amounts of 3-hydroxyethylmercapturic acid were excreted in the two collection
periods and larger amounts of ethylene glycol were excreted in the 6-24 hr
period. No urine was voided by the rabbits in the 0-6 hr period. No qualitative
differences in urinary metabolite excretion of ethylene oxide were
observed relative to the method of exposure.
After fumigation of coca powder with ethylene
oxide, several derivatives were isolated. Using IR and MS, these
compounds have been identified as
N,N-bis-(di-ethoxy-O-hydroxyethyl)isoleucylalanyl-cysteine, and N-(ethoxy-O-hydroxyethyl)tyrosine.
Absorption, Distribution & Excretion:
AFTER EXPOSURE OF MICE TO MIXT OF 1,2-(3)H-ETHYLENE
OXIDE VAPOR IN AIR FOR 75 MIN, 90-95% OF RADIOACTIVITY WAS ELIMINATED IN
24 HR. HIGHEST CONCN OF RESIDUAL RADIOACTIVITY WERE FOUND IN PROTEIN FRACTIONS
OF SPLEEN; SMALLER AMT OCCURRED IN LIVER, KIDNEY, LUNG & TESTIS.
Iv injection of (14)C-labeled ethylene
oxide indicated that (14)C concn in the testicle, epididymis and other
organs were higher than those in the blood when measured 20 min to 4 hr after
exposure. Radioactivity was still present in the epididymis 24 hr after exposure
had ended.
Biological monitoring of ethylene
oxide exposure by analysis of alveolar air and blood was studied in 10
workers employed in a hospital sterilizer unit. Environmental air, alveolar air,
and venous blood were sampled during and at the end of an 8-hr workshift. The
mean environmental concentration of ethylene oxide was
5.4 mg/cu m air and the mean alveolar ethylene oxide concentration
was 1.2 mg/cu m alveolar air. Regression analysis showed that blood ethylene
oxide concentrations were higher than environmental ethylene
oxide concentrations by a mean ratio of 3 and higher than alveolar ethylene
oxide concentrations by a mean ratio of 12.
... Rats /were exposed/ for 6 hours at
airborne concentrations of 1800, 180, or 18 ug/l of (14)C labeled ethylene
oxide. The assimilated doses of ethylene oxide were
107 20, and 2.7 mg/kg, respectively.
The distribution of radioactivity following
the incubation of human blood with radio-labelled ethylene oxides was
investigated in vitro. After incubation, the individual blood samples were
separated into lymphocytes and high (Mr greater than 10,000) and low (Mr less
than 10,000) molecular fractions of erythrocyte cytoplasm and blood plasma. The
radioactivity was determined in each sample by liquid scintillation counting. In
erythrocyte cytoplasm, the distribution of radioactivity showed marked
interindividual differences and two distinct groups could be distinguished. The
coincidence of these groups with conjugators and non-conjugators, in terms of
the enzymatic conjugation of methyl halides to glutathione in erythrocytes,
suggests a common principle, such as enzyme polymorphism. Such polymorphism has
been described for glutathione S-transferase mu in the human liver, an enzyme
that efficiently conjugates epoxides. In the other blood compartments, the
interindividual differences were either less significant or were not detectable.
Binding products with various macromolecules in blood, such as hemoglobin or
lymphocyte DNA, are being discussed as biological monitors for occupational
exposure to ethylene oxide. The observation that
erythrocytes exhibit interindividual differences as described above make binding
products with hemoglobin less suitable for biological monitoring of ethylene
oxide exposure than, for example, DNA adducts in lymphocytes.
Inhaled epoxyethane
is well absorbed. The absorption of inhaled epoxyethane
was limited by alveolar ventilation in resting rats and mice. In mice, the
highest concn of radioactivity were found in the liver and kidneys following a
75-min inhalation exposure to 2.2 ppm 14(C) epoxyethane.
Concentrations of radioactivity in the testes, spleen, lungs, and brain were
approximately equal to level expected if 14(C) epoxyethane
was evenly distributed in the body. The radioactivity was rapidly cleared from
the tissue and eliminated in the urine.
Ethylene oxide is
readily taken up by the lungs. A study on workers exposed to ethylene
oxide revealed an alveolar retention of 75-80%, calculated from hourly
determinations of ethylene oxide concentrations in
environmental air ranging from 0.2 to 22.5 mg/cu m (0.11-12.3 ppm) and in
alveolar air from 0.05 to 7 mg/cu m (0.03-3.8 ppm). At steady state, therefore,
20-25% of inhaled ethylene oxide reaching the alveolar
space is exhaled as unchanged compound and 75-80% is taken up by the body and
metabolized. Blood samples taken from workers 4 hours after the work shift and
later gave venous blood:alveolar air coefficients of 12-17 and venous
blood:environmental air coefficients of 2.5-3.3. The difference from the value
of 90 determined from the blood:air partition coefficient in vitro was explained
by incomplete saturation of tissues and limitation of the metabolic rate by the
lung uptake rate.
Mechanism of Action:
Ethylene oxide is a
carcinogenic compound which is also an ethylene metabolite. Ethylene
oxide forms macromolecular adducts with proteins and nucleic acids.
Targets in proteins are the amino acids cysteine, histidine and valine (if
N-terminal, as in hemoglobin). The major DNA adduct is
7-(2-hydroxyethyl)-guanine.
Mechanisms underlying the production of fetal
anomalies subsequent to exposure of zygotes to ethylene oxide or
ethyl methanesulfonate were investigated in (C3HxC57BL)F1-mice. Female mice were
injected with ethyl methanesulfonate ip at 250 mg/kg, 6 hours after mating, or
were exposed to ethylene oxide at 1,200 ppm for 1.5
hours, starting 6 hours after mating. A reciprocal zygote transfer study was
conducted to determine if the induced response was direct property of exposed
zygotes or an indirect effect due to maternal toxicity. Cytogenetic analyses of
pronuclear metaphases, early cleavage embryos, and midgestation fetuses were
also carried out to explore the nature of the genetic damage. The zygote
transplantation experiment ruled out maternal toxicity as a factor in fetal
maldevelopment and pointed to a genetic cause for the abnormalities. The
cytogenetic studies, however, failed to uncover structural or numerical
chromosome aberrations. The authors conclude that while the lesions induced in
zygotes by the two mutagenic compounds are likely to be genetic in nature, they
are different from conventional ones; they could be novel lesions in
experimental mammalian mutagenesis, or the mechanisms responsible for their
production could involve a nonmutational imprinting process that causes changes
in gene expression.
Interactions:
Cell transformation in vitro of C3H/10T1/2
cells, using gamma-radiation and ethylene oxide, in
both the absence and presence of the cancer promoter,
12-O-tetradecanoylphorbol-13- acetate, was studied.
12-O-tetradecanoylphorbol-13-acetate promotes transformation of C3H/10T1/2 cells
to the same extent. In the dose ranges studied the average enhancement of the
transformation frequency was 2.4 and 2.5 for ethylene oxide and
gamma-radiation, respectively. The rad-equivalence of ethylene
oxide in the presence of 12-O-tetradecanoylphorbol-13-acetate was
calculated to be 75 + or - 52 rad/mMh (95% confidence interval) which is
consistent with the value 78 + or - 14 rad/mMh (95% confidence interval)
obtained without 12-O-teradecanoylphorbol-13-acetate treatment.
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Ethylene oxide will
primarily enter the atmosphere in association with its production and use as a
chemical intermediate as well as its relatively minor use as a sterilant and
fumigant. From its industrial use, some ethylene oxide will
be discharged into water. Once in the atmosphere it will degrade very slowly by
reaction with hydroxyl-radicals (estimated half-life 211 days). Releases into
water will be removed by volatilzation, hydrolysis and to a lesser extent,
biodegradation. The volatilization half-lives for its removal from a model river
and model lake are 5.9 hr and 3.8 days, respectively. Ethylene
oxide will not adsorb strongly to soil or bioconcentrate in fish,
although its presence in some food items may result from its use as a fumigant
and sterilant. Major human exposure will be from occupational atmospheres. (SRC)
Probable Routes of Human Exposure:
Exposure to ethylene oxide is
primarily occupational via inhalation. (SRC)
OSHA estimates that approximately 80,000 and
144,000 workers are directly and indirectly exposed to ethylene
oxide in ethylene oxide production, chemical
synthesis by ethoxylation, health care facilities (sterilization), medical
products (sterilization) and miscellaneous manufacturers (e.g., spice
sterilization)(1). The number of workers exposed directly (indirectly) in the
various industries are: production and synthesis 3676; sterilization - health
care facilities 62,370 (25,000); sterilization - medical products manufacture
14,000 (116,900); sterilization - spice manufacturers 160(1). Typical exposures
are usually high during short periods in which sterilizer doors are opened,
typically 5-10 ppm for 20 minutes(1). Some typical survey results are: Medical
products manufactures 0.1.1-2.0 ppm 8 hr TWA; Hospital sterilizer chamber
operators 2.5 ppm TWA; 121 use sites in Southern California <5 ppm (TWA) in
114/121 sites; 2 hospitals 3-6 ppm and <5 ppm resp; survey of 27 hospitals
TWA exposures less than or equal to 1, <4 and >10 ppm in 9/27, 16/27 and
5/27, respectively(1). Union Carbide production plant in Texas City 5-33 ppm and
7.25 and 10.25 ppm avg in 2 control rooms and 0-56 ppm, 11.6 ppm avg throughout
plant(2). In-depth survey of 2 Union Carbide production facilities in West
Virginia- 2 of 48 and 4 of 41 samples positive, TWA exposure of positive samples
1.5-82 ppm(4,5). Production and maintenance workers in the 1960's avg exposure
levels 0.6-60 ppm(3).
NIOSH (NOES Survey 1981-1983) has
statistically estimated that 50,132 workers are exposed to ethylene
oxide in the USA(2). The personal 8-hr TWA exposure in 12 hospitals
ranged from ND to 6.3 ppm for sterilizer operators and ND to 6.7 ppm for folders
and packers. Short term (2 to 30 min) exposure levels for sterilizer operators
ranged from ND to 103 ppm(1). Lower exposure levels were correlated with
effective engineering controls and good work practices, rather than with the
size of the hospital, or number or location of sterilizers.
Natural Pollution Sources:
Since ethylene oxide is
a product of combustion of hydrocarbon fuels, it is likely that ethylene
oxide would be produced during the combustion of naturally-occurring
hydrocarbons.(SRC)
Artificial Pollution Sources:
In vent gas and fugitive emission from its
production and use as a chemical intermediate in the manufacture of ethylene
glycol, ethoxylates, glycol ethers and ethanolamines(1). Aqueous effluent
associated with its production and use as a chemical intermediate. Fugitive
emissions from its use as a fumigant and sterilant of food, cosmetics and
hospital supplies(1,3-4); auto and diesel exhaust - combustion product of
hydrocarbon fuels(1,2); tobacco smoke(1). While its use as a fumigant and
sterilant constitute only 2% of its use, emissions from these uses are
proportionately higher than other uses and result in greater exposure(3,4).
Environmental Fate:
TERRESTRIAL FATE: When released on land, ethylene
oxide would tend to volatilize rapidly. It is miscible in water and
poorly adsorbed to soil so leaching is likely to occur. Although experimental
data are lacking, hydrolysis in soil is probable. (SRC)
AQUATIC FATE: When released into water ethylene
oxide will primarily be lost by three processes: volatilization,
hydrolysis and biodegradation in that order of importance. Volatilization will
depend on wind and mixing conditions and would be expected to occur in hours to
days. The volatilization half-lives of ethylene oxide in
a model river and lake are 5.9 hr and 3.8 days, respectively. The half-life for
hydrolysis is 9-14 days leading to biodegradable products. Because of the
limited data, it is difficult to estimate the rate of biodegradation; the
available data would suggest that the biodegradation rate is slower than the
volatilization and hyrdrolysis rates. Ethylene oxide would
not tend to adsorb to sediment. In groundwater, ethylene oxide
will degrade due to hydrolysis. (SRC)
ATMOSPHERIC FATE: Ethylene
oxide will degrade in the atmosphere primarily by reaction with
photochemically produced hydroxyl radicals. Assuming a hydroxyl radical concn of
5X10+5 radicals/cu cm, the half-life of ethylene oxide in
the atmosphere will be 211 days(1,SRC). Data suggests that neither rain out nor
adsorption into aqueous aerosols in the air should remove much of this
compound(2).
Environmental Biodegradation:
Based on limited data, ethylene
oxide biodegrades at a reasonable rate after a period of acclimation. In
a dilution bottle test, there was 3-5% degradation after 5 days and 52%
degradation after 20 days(1,2). Since ethylene oxide hydrolyzes
to ethylene glycol which is readily biodegraded, there is a fair amount of
uncertainty in the biodegradability measurements(2). In a river die-away test,
the rate of degradation was not significantly different than for hydrolysis(2). Ethylene
oxide biodegradation rate constants measured at a full-scale wastewater
treatment plant were 0.38 and 0.59 ug/min-g biomass(3). These rate constants
would imply that a system with a 6 day residence time operated with mixed liquor
suspended solids of 2500 mg/L would effectively biodegrade 8.2 and 12.7 mg/L of ethylene
oxide, respectively(SRC).
Environmental Abiotic Degradation:
Ethylene oxide hydrolyzes
slowly in fresh and salt water to give ethylene glycol and ethylene
chlorohydrin(1). The half-life for this reaction is 12-14 days for pH's between
5-7 in fresh water(1,2,3) and 9-11 days in salt water(1). The ratio of
chlorohydrin to glycol formed was found to be 0.11 and 0.23 in 1% and 3% sodium
chloride solutions respectively(1). The hydrolysis rate is increased
considerably in acidic or basic solutions(2). In the atmosphere, ethylene
oxide reacts with photochemically-produced hydroxyl radicals with a rate
constant of 7.6X10-14 cu cm/molecule-s at(1). Assuming a hydroxyl radical concn
of 5X10+5 radicals/cu cm, the half-life of ethylene oxide in
the atmosphere would be 211 days(SRC). Earlier smog chamber experiments with
both natural and artificial illumination are consistent with a slowly degrading
compound(6). In one of these, 20% of the ethylene oxide degraded
in 5.3 hr(4).
Environmental Bioconcentration:
Although no studies of bioconcentration for ethylene
oxide were found in the literature, one would not expect it to
bioconcentrate due to its low octanol/water partition coefficient (log Kow=
-0.3)(1).(SRC)
Soil Adsorption/Mobility:
No data could be found concerning the
adsorption of ethylene oxide to soil. One would not
expect a very high adsorptivity due to its low octanol/water partition
coefficient (log Kow = -0.3)(1). Based on a regression analysis with the log
octanol/water partition coefficient(2), one would calculate a KOC of 16(SRC).
Volatilization from Water/Soil:
The half-life for evaporation of ethylene
oxide from water is 1 hr with no wind and 0.8 hr with a 5 m/sec wind as
determined in a laboratory experiment(1). The Henry's law constant for ethylene
oxide is 1.48X10-4 atm-cu m/mole(1). Using this value of the Henry's Law
constant, one would estimate a volatilization half-life of 5.9 hr for ethylene
oxide from a model river 1 m deep with a 1 m/s current and a 3 m/s
wind(3,SRC). Similarly, its half-life from a model lake 1 m deep with a 0.05 m/s
current and 0.5 m/s wind is 3.8 days. Although no data on the volatilization of ethylene
oxide from soil could be found, a study of the dissipation of ethylene
oxide from fumigated commodities gave half-life values of 4 hr to 17.5
days(2).
Effluent Concentrations:
Detected, not quantified in an effluent sample
in Brandenburg, KY in Feb 1974, at a production facility(1,2). It is estimated
that in ethylene oxide production, between 0.25 and
47.5 kg of ethylene oxide is emitted to the air for
each kg produced(3).
Environmental Standards & Regulations:
FIFRA Requirements:
A tolerance is established for residues of the
antimicrobial agent and insecticide ethylene oxide, when
used as a postharvest fumigant in or on the following raw agricultural
commodities: black walnut meats, copra, whole spices.
Ethylene oxide may be
safely used as a fumigant for the control of microorganisms and insect
infestation in ground spices and other processed natural seasoning materials,
except mixt to which salt has been added ... Tolerances are established for
residues of ethylene oxide in ground spices from both
postharvest application to the raw agricultural commodity whole spices and
application to the ground spices.
As the federal pesticide law FIFRA directs,
EPA is conducting a comprehensive review of older pesticides to consider their
health and environmental effects and make decisions about their future use.
Under this pesticide reregistration program, EPA examines health and safety data
for pesticide active ingredients initially registered before November 1, 1984,
and determines whether they are eligible for reregistration. In addition, all
pesticides must meet the new safety standard of the Food Quality Protection Act
of 1996. Ethylene oxide is found on List A, which
contains most food use pesticides and consists of the 194 chemical cases (or 350
individual active ingredients) for which EPA issued registration standards prior
to FIFRA, as amended in 1988. Case No: 2275; Pesticide type: insecticide,
fungicide, rodenticide, antimicrobial; Case Status:In Pre-Special Review. The
pesticide is in or has completed the reregistration process and, meanwhile, is
also the subject of an in-depth Special Review.; Active ingredient (AI): Ethylene
oxide; Data Call-in (DCI) Date(s): 05/24/91; AI Status: The producers of
the pesticide has made commitments to conduct the studies and pay the fees
required for reregistration, and are meeting those commitments in a timely
manner.
TSCA Requirements:
Pursuant to section 8(d) of TSCA, EPA
promulgated a model Health and Safety Data Reporting Rule. The section 8(d)
model rule requires manufacturers, importers, and processors of listed chemical
substances and mixtures to submit to EPA copies and lists of unpublished health
and safety studies. Oxirane is included on this list.
Section 8(a) of TSCA requires manufacturers of
this chemical substance to report preliminary assessment information concerned
with production, use, and exposure to EPA as cited in the preamble of the 51 FR
41329.
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).
Releases of CERCLA hazardous substances are
subject to the release reporting requirement of CERCLA section 103, codified at
40 CFR part 302, in addition to the requirements of 40 CFR part 355. Ethylene
Oxide is an extremely hazardous substance (EHS) subject to reporting
requirements when stored in amounts in excess of its threshold planning quantity
(TPQ) of 1,000 lbs.
RCRA Requirements:
U115; As stipulated in 40 CFR 261.33, when ethylene
oxide, 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:
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. Ethylene
oxide is produced, as an intermediate or a final product, by process
units covered under 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. Ethylene
oxide is included on this list.
Allowable Tolerances:
A tolerance of 50 ppm is established for
residues of the antimicrobial agent and insecticide ethylene
oxide, when used as a postharvest fumigant in or on the following raw
agricultural commodities: Black walnut meats, copra, whole spices.
Residues of ethylene oxide in
ground spices from both postharvest application to the raw agricultural
commodity whole spices and application to the ground spices shall not exceed the
established tolerance of 50 ppm for residues in whole spices.
Chemical/Physical Properties:
Molecular Formula:
C2-H4-O
Molecular Weight:
44.06
Color/Form:
COLORLESS GAS @ ORDINARY ROOM TEMP &
PRESSURE; LIQUID BELOW 12 DEG C
Colorless gas or liquid (below 51 degrees F)
...
Odor:
Sweet
ETHER-LIKE ODOR
Reminiscent of bruised apples
... Ether-like odor.
Boiling Point:
10.7 DEG C @ 760 MM HG
Melting Point:
-111 DEG C
Critical Temperature & Pressure:
Critical temperature = 469.15 K; Critical
pressure = 7.1941X10+6 Pa
Density/Specific Gravity:
0.882 @ 10 DEG C/10 DEG C
Heat of Combustion:
1280.9 kJ/mol (liquid); 1306.1 kJ/mol (gas)
Heat of Vaporization:
24.75 kJ/mol @ 25 deg C
Octanol/Water Partition Coefficient:
log Kow= -0.30
Solubilities:
... Miscible in all proportions with water,
alcohol, ethers, and most organic solvents
SOL IN BENZENE, ACETONE
MISCIBLE WITH CARBON TETRACHLORIDE
Spectral Properties:
MAX ABSORPTION (GAS): 169 NM (LOG E= 3.58);
171 NM (LOG E= 3.57)
INDEX OF REFRACTION: 1.3597 @ 7 DEG C/D
IR: 1109 (Sadtler Research Laboratories Prism
Collection)
MASS: 12 (Atlas of Mass Spectral Data, John
Wiley & Sons, New York)
Surface Tension:
Liquid: 24.3 dynes/cm= 0.0243 N/m at 20 deg C.
Vapor Density:
1.49
Vapor Pressure:
1314 MM HG AT 25 DEG C (calculated from
experimentally derived coefficients)
Viscosity:
9.45x10-3 mPa.s (25 deg C, gas) and 0.254
mPa.s (10 deg C, liquid)
Other Chemical/Physical Properties:
LIQ IS LIGHTER THAN WATER, VAPOR IS HEAVIER
THAN AIR
Heat of solution in water: 142.57 kJ/kg @ 25
deg C
CAN REACT WITH OXIDIZING MATERIALS
Ratio of specific heats of vapor (gas): 1.212
Chemical oxygen demand: 1.74 Nederlands norm (dutch
standard test method) 3235 - 5.3 sublimation: 24.9 K/mole at 25 deg C
Heat of fusion: 28.07 cal/g
Ionization potential: 10.56 eV
Standard Enthalpy of Formation: -77.8 kJ/mol
/liquid/; -52.6 kJ/mol (gas)
Heat of fusion: 5.1714 J/k mol
Coefficient of thermal expansion:
1.51x10-3/deg C
Chemical Safety & Handling:
DOT Emergency Guidelines:
Health: TOXIC; may be fatal if inhaled or
absorbed through skin. Contact with gas or liquefied gas may cause burns, severe
injury and/or frostbite. Fire will produce irritating, corrosive and/or toxic
gases. Runoff from fire control may cause pollution.
Fire or explosion: Flammable; may be ignited
by heat, sparks or flames. May form explosive mixtures with air. Some may
polymerize (P) explosively when heated or involved in a fire. Vapors from
liquefied gas are initially heavier than air and spread along ground. Vapors may
travel to source of ignition and flash back. Some of these materials may react
violently with water. Containers may explode when heated. Ruptured cylinders may
rocket. Runoff may create fire or explosion hazard.
Public safety: CALL Emergency Response
Telephone Number on Shipping Paper first. If Shipping Paper not available or no
answer, refer to appropriate telephone number listed on the inside back cover.
Isolate spill or leak area immediately for at least 100 to 200 meters (330 to
660 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Many
gases are heavier than air and will spread along ground and collect in low or
confined areas (sewers, basements, tanks). Keep out of low areas. Ventilate
closed spaces before entering.
Protective clothing: Wear positive pressure
self-contained breathing apparatus (SCBA). Wear chemical protective clothing
which is specifically recommended by the manufacturer. It may provide little or
no thermal protection. Structural firefighters' protective clothing is
recommended for fire situations ONLY; it is not effective in spill situations.
Evacuation: Spill: See the Table of Initial
Isolation and Protective Action Distances for highlighted substances. For
non-highlighted substances, increase, in the downwind direction, as necessary,
the isolation distance shown under "PUBLIC SAFETY". Fire: If tank,
rail car or tank truck is involved in a fire, ISOLATE for 1600 meters (1 mile)
in all directions; also, consider initial evacuation for 1600 meters (1 mile) in
all directions.
Fire: DO NOT EXTINGUISH A LEAKING GAS FIRE
UNLESS LEAK CAN BE STOPPED. Small fires: Dry chemical, CO2, water spray or
alcohol-resistant foam. Large fires: Water spray, fog or alcohol-resistant foam.
FOR CHLOROSILANES, DO NOT USE WATER; use AFFF alcohol-resistant medium expansion
foam. Move containers from fire area if you can do it without risk. Damaged
cylinders should be handled only by specialists. Fire involving tanks: 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. Do
not direct water at source of leak or safety devices; icing may occur. Withdraw
immediately in case of rising sound from venting safety devices or discoloration
of tank. ALWAYS stay away from the ends of tanks.
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. Fully encapsulating, vapor
protective clothing should be worn for spills and leaks with no fire. Do not
touch or walk through spilled material. Stop leak if you can do it without risk.
Do not direct water at spill or source of leak. Use water spray to reduce vapors
or divert vapor cloud drift. FOR CHLOROSILANES, use AFFF alcohol-resistant
medium expansion foam to reduce vapors. If possible, turn leaking containers so
that gas escapes rather than liquid. Prevent entry into waterways, sewers,
basements or confined areas. Isolate area until gas has dispersed.
First aid: Move victim to fresh air. Call
emergency medical care. Apply artificial respiration if victim is not breathing.
Do not use mouth-to-mouth method if victim ingested or inhaled the substance;
induce artificial respiration with the aid of a pocket mask equipped with a
one-way valve or other proper respiratory medical device. 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. In case of contact with liquefied gas, thaw
frosted parts with lukewarm water. Keep victim warm and quiet. Keep victim under
observation. Effects of contact or inhalation may be delayed. Ensure that
medical personnel are aware of the material(s) involved, and take precautions to
protect themselves.
Initial Isolation and Protective Action
Distances: Small Spills (from a small package or small leak from a large
package): First, ISOLATE in all Directions 60 meters (200 feet); then, PROTECT
persons Downwind during DAY 0.2 kilometers (0.1 miles) and NIGHT 0.3 kilometers
(0.2 miles). LARGE SPILLS (from a large package or from many small packages):
First, ISOLATE in all Directions 125 meters (400 feet); then, PROTECT persons
Downwind during DAY 0.3 kilometers (0.2 miles) and NIGHT 1.0 kilometers (0.6
miles). /Ethylene oxide; Ethylene oxide with nitrogen/
Odor Threshold:
50 ppm
Recognition: 1.5 mg/cu m= 0.8 ppm, mean
detection concn: 700 ppm; absolute perception limit: 260 ppm; 50% recognition:
500 ppm; 100% recognition: 500 ppm
Low: 520 mg/cu m; High: 1400 mg/cu m
300 ppm in air
Skin, Eye and Respiratory Irritations:
Ethylene oxide is
irritating to the eyes, respiratory tract, and skin.
Aqueous solutions of ethylene
oxide or solutions formed when the anhydrous cmpd comes in contact with
moist skin are irritating and may lead to a severe dermatitis with blisters,
blebs and burns. It is also absorbed by leather and rubber and may produce burns
or irritation. Allergic eczematous dermatitis has also been reported. Exposure
to the vapor in high concn leads to irritation of the eyes. Severe eye damage
may result if the liquid is splashed in the eyes. Large amounts of ethylene
oxide evaporating from the skin may cause frostbite.
Fire Potential:
Flammable liquid
NFPA Hazard Classification:
Health: 3. 3= Materials that, on short
exposure, could cause serious temporary or residual injury, including those
requiring protection from all bodily contact. Fire fighters may enter the area
only if they are protected from all contact with the material. Full protective
clothing, including self-contained breathing apparatus, coat, pants, gloves,
boots, and bands around legs, arms, and waist, should be provided. No skin
surface should be exposed.
Flammability: 4. 4= This degree includes
flammable gases, pyrophoric liquids, and Class IA flammable liquids. The
preferred method of fire attack is to stop the flow of material or to protect
exposures while allowing the fire to burn itself out.
Reactivity: 3. 3= This degree includes
materials that, in themselves, are capable of detonation, explosive
decomposition, or explosive reaction, but require a strong initiating source or
heating under confinement. This includes materials that are sensitive to thermal
and mechanical shock at elevated temperatures and pressures and materials that
react explosively with water. Fires involving these materials should be fought
from a protected location.
Flammable Limits:
Lower flammable limit: 3%; Upper flammable
limit: 100%
Flash Point:
<0 deg F (Open cup)
Autoignition Temperature:
804 DEG F
Fire Fighting Procedures:
Fire extinguishing agents: water.
Stop flow of gas if possible. Combat fires
from behind barrier, with unmanned hose holder or monitor nozzle. Flood
discharge area with water. Cool exposed containers and protect men effecting
shut off with water.
Carbon dioxide and dry-chemical extinguishers
are useful against small fire.
If material on fire or involved in fire: Do
not extinguish fire unless flow can be stopped. Use water in flooding quantities
as fog. Solid streams of water may be ineffective. Cool all affected containers
with flooding quantities of water. Apply water from as far a distance as
possible. Use "alcohol" foam, dry chemical or carbon dioxide.
Evacuation: If fire is prolonged and material
is confined in the container consider evacuation of one (1) mile radius. If fire
becomes uncontrollable or container is exposed to direct flame, consider
evacuation of one (1) mile radius.
Toxic Combustion Products:
Irritating vapors generated when heated.
Firefighting Hazards:
Vapor is heavier than air and may travel
considerable distance to a source of ignition and flash back.
Explosive Limits & Potential:
LOWER EXPLOSIVE LIMIT: 3.0%, UPPER EXPLOSIVE
LIMIT: 100%. EXPLOSION HAZARD: SEVERE, WHEN EXPOSED TO FLAME.
GAS IS EXPLOSIVE IN CONCN ABOVE 3% & MUST
BE MIXED WITH CARBON DIOXIDE OR FLUOROCARBONS.
Decompostion products are explosive.
VAPOR FORMS EXPLOSIVE MIXTURES WITH AIR OVER A
WIDE RANGE.
Hazardous Reactivities & Incompatibilities:
Metal fittings containing copper, silver,
mercury, or magnesium should not be used in ethylene oxide service,
since traces of acetylene could produce explosive acetylides capable of
detonating ethylene oxide vapor.
INCOMPATIBILITIES: BECAUSE OF HIGH CHEMICAL
REACTIVITY ... IT REACTS WITH MANY PHARMACEUTICAL SUBSTANCES & WITH
VITAMINS, AMINO ACIDS, & OTHER FOOD CONSTITUENTS. ...
Accidental contamination of a large ethylene
oxide feed-cylinder by reaction liquor containing trimethylamine caused
the cylinder to explode 18 hr later. Contamination was possible because of a
faulty pressure gauge and suck-back of froth above the liquid level.
Highly reactive! Hazardous polymerization may
occur especially if contaminated. Reacts with acids, alkalies, salts,
combustible materials. Ethylene oxide and water may
form stratified layers. May undergo runaway reaction with water. Many materials
may accelerate this reaction.
It reacts with chloride and water to produce
two active germicides, 2-chloroethanol and ethylene glycol.
Strong acids, alkalis & oxidizers;
chlorides of iron, aluminum & tin; oxides of iron & aluminum; water.
Hazardous Decomposition:
Liquid ethylene oxide is
not detonable, but the vapor may be readily initiated into explosive
decomposition.
Hazardous Polymerization:
Precautions designed to prevent explosive
polymerization of ethylene oxide are discussed,
including rigid exclusion of acids, covalent halides such as aluminium, iron
(III), and tin (IV) chloride, basic materials like alkali hydroxides, ammonia,
amines, metallic potassium, and catalytically active solids such as aluminium or
iron oxides or rust.
POLYMERIZATION IS CATALYZED BY A NUMBER OF
MATERIALS, SUCH AS ACIDS, ALKALIS, SOME CARBONATES, OXIDES OF IRON &
ALUMINUM, & CHLORIDES OF IRON, TIN, ALUMINUM, & BORON. NO ACETYLIDE-FORMING
METALS SUCH AS COPPER OR COPPER ALLOYS SHOULD BE IN CONTACT WITH ETHYLENE
OXIDE.
Accidental contamination of an ethylene
oxide feed tank by ammonia caused violently explosive polymerization.
Prior History of Accidents:
A Chessie System freight train derailed in a
wooded, rural area near Woodland Park, Michigan in February 1978. Four tank cars
were damaged, spilling approx 300,000 lb of vinylidene chloride, 330,000 lb of
phenol, and 125,000 lb of ethylene oxide. Most of the
phenol, which had solidified on the surface, was removed by a cleanup contractor
although residual phenol remained in the soil. The ethylene
oxide vaporized, posing no groundwater contamination problems. The
vinylidene chloride percolated through the sandy soils into the groundwater
about 50 ft below the ground surface. Vinylidene chloride concentrations as high
as 300 mg/l were found in monitoring wells near the derailment site. The
groundwater cleanup program was completed over a three yr period. ...
Immediately Dangerous to Life or Health:
NIOSH considers ethylene
oxide to be a potential occupational carcinogen.
Protective Equipment & Clothing:
AIR-SUPPLIED MASK; GOGGLES OR FACE SHIELD;
RUBBER SHOES & COVERALLS.
Wear neoprene gloves, safety glasses, plastic
protective clothing and self-contained breathing apparatus.
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/
A study was conducted to evaluate protective
clothing garment materials used by emergency response personnel and to determine
their effectiveness when combating ammonia or ethylene oxide in
gaseous form. Data were collected using an automated permeation test system for
13 garment materials representing 11 types of total encapsulating suit materials
and two glove materials. For the study neat (100%) and 2000 ppm (0.2%) gas were
chosen as challenge concentrations. A closed loop test system was chosen for the
study using an infrared detector. Breakthrough times and steady state permeation
rates were determined. The results indicated suitable garment materials were
found to protect workers against 100% anhydrous ammonia for an extended time
period and there was also a large selection of materials for 0.2% ammonia.
Surgical latex was not recommened for protection against ammonia. While several
materials offered resonable working time protection against 100% ethylene
oxide, only two of the 17 materials were useful for extended time
periods. The semiautomated test system expedited chemical permeation resistance
testing and proved to be effective in securing the needed data.
Wear appropriate personal protective clothing
to prevent skin contact. /Liquid/
Wear appropriate eye protection to prevent eye
contact. /Liquid/
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
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.] /Liquid/
Recommendations for respirator selection. Max
concn for use: 5 ppm. Respirator Class(es): Any air-purifying, full-facepiece
respirator (gas mask) with a chin-style, front- or back-mounted canister
providing protection against the compound of concern. End of service life
indicator (ESLI) required. Any self-contained breathing apparatus with a full
facepiece. Any supplied-air respirator with a full facepiece.
Recommendations for respirator selection.
Condition: Emergency or planned entry into unknown concn or IDLH conditions:
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 facepiece and is operated in a
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 canister providing protection against the
compound of concern. End of service life indicator (ESLI) required. Any
appropriate escape-type, self-contained breathing apparatus.
Preventive Measures:
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 disperse
vapors and dilute standing pools of liquid.
Personnel protection: Avoid breathing vapors.
Keep upwind. Avoid bodily contact with the material. 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.
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.
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. ...
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/
Substantial quantities of ethylene
oxide may remain in treated materials after gas sterilization.
Consequently,, safe use of ethylene oxide in hospitals
and health instrument manufacture requires an aeration phase, the length of
which depends on the material being treated.
The worker should immediately wash the skin
when it becomes contaminated. /Liquid/
Work clothing that becomes wet should be
immediately removed due to its flammability hazard.
Stability/Shelf Life:
HYDROLYZES SLOWLY IN AQ SOLN
STABLE IN WATER
Storage Conditions:
Temperature: ambient
Protect containers against physical damage,
check for leakage intermittently. Store in distant outdoor tank or container
protected from direct sunlight, lined with insulating material, equipped with an
adequate refrigeration and water system. Indoor storage should be restricted to
small quantities. Place material in a combustible liquid cabinet which is
fireproof in conformity with regulations.
PRECAUTIONS FOR "CARCINOGENS":
Storage site should be as close as practical 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:
Shut off ignition sources and call fire dept.
Stop /flow/ if possible. Stay upwind and use water spray to "knock
down" vapor. Isolate and remove discharged material. Notify local health
and pollution control agencies.
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/
Disposal Methods:
Generators of waste (equal to or greater than
100 kg/mo) containing this contaminant, EPA hazardous waste number U115, must
conform with USEPA regulations in storage, transportation, treatment and
disposal of waste.
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.
Evaporation & open burning: A) Place on
ground in an open area. Evaporate or burn by igniting from a safe distance. B)
Dissolve in benzene, petroleum ether or higher alcohol such as butanol. Dispose
by burning the soln. Recommendable method: Incineration. Peer review: Ethylene
oxide boils @ 11 deg C, therefore burning in an incinerator can cause
difficulties unless a gas feed can be arranged. It is soluble in water or
alcohol and these soln can be burned. (Peer-review conclusions of an IRPTC
expert consultation (May 1985))
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": ...
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 saturated 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/
Occupational Exposure Standards:
OSHA Standards:
The employer shall ensure that no employee is
exposed to an airborne concentration of ethylene oxide in
excess of 1 ppm as an 8-hr TWA. The employer shall ensure that no employee is
exposed to an airborne concentration of ethylene oxide in
excess of 5 ppm as averaged over a sampling period of 15 min.
Threshold Limit Values:
8 hr Time Weighted Avg (TWA) 1 ppm
A2. A2= Suspected human carcinogen.
NIOSH Recommendations:
Recommended Exposure Limit: 10 Hr
Time-Weighted Avg: <0.1 ppm (<0.18 mg/cu m).
Recommended Exposure Limit: 10 min/day ceiling
value: 5 ppm (9 mg/cu m).
NIOSH considers ethylene
oxide to be a potential occupational carcinogen.
NIOSH usually recommends that occupational
exposures to carcinogens be limited to the lowest feasible concn.
Immediately Dangerous to Life or Health:
NIOSH considers ethylene
oxide to be a potential occupational carcinogen.
Other Occupational Permissible Levels:
Germany: 5 ppm; USSR: 0.5 ppm.
Emergency Response Planning Guidelines (ERPG):
ERPG(1) Not appropriate; ERPG(2) 50 ppm (without serious, adverse effects) for
up to 1 hr exposure; ERPG(3) 500 ppm (not life threatening) up to 1 hr exposure.
Manufacturing/Use Information:
Major Uses:
RIPENING AGENT FOR FRUITS, FUNGISTAT
INACTIVATES KREB'S ASCITES TUMOR CELLS
ROCKET PROPELLANT
FUMIGANT FOR FOODSTUFFS & TEXTILES; IN
ORGANIC SYNTHESIS; STERILIZE SURGICAL INSTRUMENTS; AGRICULTURAL FUNGICIDE
STARTING MATERIAL FOR MFR OF ACRYLONITRILE AND
NONIONIC SURFACTANTS.
... USEFUL FOR FUMIGATING INSECTS IN PACKAGED
CEREALS, BAGGED RICE, TOBACCO, & CLOTHING & FURS IN VAULTS. ... IT IS
ALSO USED IN VAULTS FOR FUMIGATING VALUABLE PACKAGED DOCUMENTS.
... FOR TREATMENT BY FUMIGATION OF BOOKS;
DENTAL, PHARMACEUTICAL, MEDICAL & SCIENTIFIC EQUIPMENT & SUPPLIES, ...
DRUGS; LEATHER; MOTOR OIL; PAPER; SOIL; BEDDING FOR EXPERIMENTAL ANIMALS; ...
FURNITURE; & TRANSPORTATION VEHICLES ... .
Formation of diethylene glycol, the
cellosolves and carbitols, dioxane, ethylene chlorohydrin and polymer (carbowax);
intermediate for polyethylene terephthalate polyester fiber.
STERILANT & SPOROCIDE-EG, IN HEALTH CARE
INDUST
Used as a fumigation agent on ... beehives
(empty and diseased), beekeeping equipment ... .
Used on hospital equipment including:
hypodermic needles/syringes, surgical prosthetic parts, heart and lung machines,
dental, hospital and laboratory instruments, heat labile materials, moisture
labile materials, oral and inhalation equipment, diagnostic
instruments/equipment, hospital critical rubber, plastic items, hospital
critical equipment, thermometers, laboratory equipment, pharmaceutical
equipment, stainless steel surfaces; and on hospital fabrics, materials, paper
products, sheeting, grooming instruments.
Chemical intermediate for ethylene glycols,
ethanolamines, glycol ethers & surfactants.
Methods of Manufacturing:
CATALYTIC OXIDATION OF ETHYLENE; PREPARED FROM
ETHYLENE CHLOROHYDRIN & POTASSIUM HYDROXIDE.
Direct oxidation ... utilizes the catalytic
oxidation of ethylene with oxygen over a silver-based catalyst ... .
The process involves the reaction of ethylene
with hypochlorous acid followed by dehydrochlorination of the resulting
chlorohydrin with lime .... . /Chlorohydrin process/
General Manufacturing Information:
A variety of new process concepts for ethylene
oxide-ethylene glycol are being developed based on such raw materials as
synthesis gas and ethanol.
The compatibility of polycarbonate with ethylene
oxide was studied. The polycarbonate devices can be safely exposed to 3 ethylene
oxide cycles. Polycarbonates are compatible with ethanol at 73-158 deg F.
The chlorohydrin process is not economically
competitive, and was quickly replaced by the direct oxidation process as the
dominant technology. At the present time, all ethylene oxide production
in the world is achieved by the direct oxidation process.
Formulations/Preparations:
/ETHYLENE OXIDE/ IS
MIXED WITH EITHER CARBON DIOXIDE OR FLUOROCARBON 12 ... TO ELIMINATE
FLAMMABILITY ... . CARBOXIDE IS NONFLAMMABLE MIXTURE OF 10% BY WT ETHYLENE
OXIDE IN CARBON DIOXIDE ... STERILANT 12 IS NONFLAMMABLE MIXT OF 12% BY
WT ... IN FLUOROCARBON 12 ... .
Grades or purity: commercial: 100% must
contain no acetylene.
GRADES: TECHNICAL; PURE (99.7%).
Specifications: 0.002 wt % acidity, max
(calculated as acetic acid), 0.003 wt % aldehydes, max (calculated as
acetaldehyde), 0.03 wt % water, max.
Consumption Patterns:
CHEM INT FOR ETHYLENE GLYCOL, 60.5%; CHEM INT
FOR NONIONIC SURFACTANTS (ACYCLIC), 7.1%; CHEM INT FOR NONIONIC SURFACTANTS
(CYCLIC), 4.6%; CHEM INT FOR GLYCOL ETHERS, 7.2%; CHEM INT FOR ETHANOLAMINES,
7.1%; CHEM INT FOR DIETHYLENE GLYCOL, 5.1%; CHEM INT FOR TRIETHYLENE GLYCOL,
2.1%; CHEM INT FOR POLYETHYLENE GLYCOL, 1.6%; OTHER, 4.7% (1981)
Monoethylene glycol, 59%; higher glycols, 15%;
ethoxylates, 10%; ethanolamines, 6%; glycol ethers, 5%; miscellaneous, 5% (1984)
CHEMICAL PROFILE: Ethylene
oxide. Ethylene glycol, 59%; nonionic surfactants, 14%; ethanolamines,
8%; glycol ethers, 6%; diethylene glycol, 6%, triethylene glycol, 2%;
miscellaneous, including polyethylene glycol, urethane polyols and exports, 5%.
CHEMICAL PROFILE: Ethylene
oxide. Demand: 1986: 5.7 billion lb; 1987: 5.8 billion lb; 1991
/projected/: 6.4 billion lb.
CHEMICAL PROFILE: Ethylene
oxide. Ethylene glycol, 59%; nonionic surfactants, 13%; ethanolamines,
8%; glycol ethers, 6%; diethylene glycol, 6%, triethylene glycol, 2%;
miscellaneous, including polyethylene glycol, urethane polyols and exports, 6%.
Synonyms and Identifiers:
Related HSDB Records:
168
[ETHYLENE] (Metabolic Precursor)
Synonyms:
E O
**PEER REVIEWED**
AETHYLENOXID (GERMAN)
**PEER REVIEWED**
AI3-26263
**PEER REVIEWED**
Amprolene
**PEER REVIEWED**
ANPROLENE
**PEER REVIEWED**
Anproline
**PEER REVIEWED**
Caswell no 443
**PEER REVIEWED**
DIHYDROOXIRENE
**PEER REVIEWED**
DIMETHYLENE OXIDE
**PEER REVIEWED**
ENT-26263
**PEER REVIEWED**
EPA pesticide chemical code 042301
**PEER REVIEWED**
Epoxyethane
**PEER REVIEWED**
1,2-EPOXYETHANE
**PEER REVIEWED**
ETO
**PEER REVIEWED**
ETYLENU TLENEK (POLISH)
**PEER REVIEWED**
Fema no 2433
**PEER REVIEWED**
T-GAS
**PEER REVIEWED**
NCI-C50088
**PEER REVIEWED**
OXACYCLOPROPANE
**PEER REVIEWED**
OXANE
**PEER REVIEWED**
OXIDOETHANE
**PEER REVIEWED**
ALPHA,BETA-OXIDOETHANE
**PEER REVIEWED**
OXIRAAN (DUTCH)
**PEER REVIEWED**
OXIRAN
**PEER REVIEWED**
OXIRANE
**PEER REVIEWED**
OXIRENE, DIHYDRO-
**PEER REVIEWED**
OXYFUME
**PEER REVIEWED**
OXYFUME 12
**PEER REVIEWED**
Formulations/Preparations:
/ETHYLENE OXIDE/ IS
MIXED WITH EITHER CARBON DIOXIDE OR FLUOROCARBON 12 ... TO ELIMINATE
FLAMMABILITY ... . CARBOXIDE IS NONFLAMMABLE MIXTURE OF 10% BY WT ETHYLENE
OXIDE IN CARBON DIOXIDE ... STERILANT 12 IS NONFLAMMABLE MIXT OF 12% BY
WT ... IN FLUOROCARBON 12 ... .
Grades or purity: commercial: 100% must
contain no acetylene.
GRADES: TECHNICAL; PURE (99.7%).
Specifications: 0.002 wt % acidity, max
(calculated as acetic acid), 0.003 wt % aldehydes, max (calculated as
acetaldehyde), 0.03 wt % water, max.
Standard Transportation Number:
49 201 08; Ethylene oxide
EPA Hazardous Waste Number:
U115; 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.
RTECS Number:
NIOSH/KX2450000
Administrative Information:
Hazardous Substances Databank Number: 170
Last Revision Date: 20020531
Last Review Date: Reviewed by SRP 11/1/1994
http://www.osha-slc.gov/SLTC/ethyleneoxide/
EtO possesses several physical and health hazards that merit special attention.
EtO is both flammable and highly reactive. Acute exposures to EtO gas may result
in respiratory irritation and lung injury, headache, nausea, vomiting, diarrhea,
shortness of breath, and cyanosis. Chronic exposure has been associated with the
occurrence of cancer, reproductive effects, mutagenic changes, neurotoxicity,
and sensitization.
http://www.osha-slc.gov/pls/oshaweb/owadisp.show
_document?p_table=FACT_SHEETS&p_id=168
Both human and animal studies suggest that EtO is a potential occupational
carcinogen, causing leukemia and other cancers. EtO has also been linked to
reproductive damage, including spontaneous abortions; cytogenetic damage;
neurological effects ranging from nausea and dizziness to peripheral paralysis;
and tissue irritation.
Communication of EtO hazards to employees. Information must be provided to workers through signs and labels clearly indicating EtO's carcinogenic and reproductive hazards. Information and training must be given initially to workers who may be exposed at or above the action level or excursion limit and at least annually thereafter.
http://www.cdc.gov/niosh/81130_35.html?
TABLE OF CONTENTS
Background
Epidemiologic Evidence
for Cancer in Humans
Evidence of
Carcinogenicity in Experimental Animals
Evidence of Mutagenic
and Reproductive Effects
Exposure Standards and Guides
Recommendations
References
Appendix I - Guidelines for Minimizing Worker Exposure to
Ethylene Oxide
Appendix II - Major Manufacturers of Ethylene Oxide
Appendix III - Identifiers and Synonyms
http://www.cdc.gov/niosh/75218.html?
Human data: Other than temporary, slight irritation, no aftereffects were
reported in 4 men after intentional exposure to 2,500 ppm for a brief
period; definite nasal irritation was reported after 10 seconds of exposure
to 12,500 ppm [Walker and Greeson 1932]. Exposures to concentrations above
2,000 ppm have resulted in headache, nausea, vomiting, dyspnea,
hematological abnormalities, and respiratory irritation [NRC 1986].
Based on acute inhalation toxicity data in humans [Clayton and Clayton 1981; NRC 1986; Walker and Greeson 1932] the original IDLH for ethylene oxide (800 ppm) is not being revised at this time. [Note: NIOSH recommends as part of its carcinogen policy that the "most protective" respirators be worn for ethylene oxide at concentrations above 5 ppm. OSHA currently requires in 29 CFR 1919.1047 that workers be provided with and required to wear and use the "most protective" respirators in concentrations exceeding 2,000 ppm (2,000 × the PEL).]
http://www.cdc.gov/niosh/ipcs/ipcs0155.html?
ETHYLENE OXIDE
1,2-Epoxyethane
Oxirane
Dimethylene oxide
(cylinder)
C2H4O
Molecular mass: 44.1
Gas/air mixtures are explosive. Risk of fire and explosion as a result of violent decomposition when heated.
EXPOSURE: STRICT HYGIENE! AVOID ALL CONTACT! IN ALL CASES CONSULT A DOCTOR!
INHALATION: Cough. Dizziness. Drowsiness. Headache. Nausea. Sore throat. Vomiting. Weakness Symptoms may be delayed.
SKIN: MAY BE ABSORBED! Dry skin. Redness. Burning sensation. Pain. Blisters. ON CONTACT WITH LIQUID: FROSTBITE.
EYES: Redness.
Pain.
Blurred vision.
PHYSICAL STATE; APPEARANCE:
COLOURLESS COMPRESSED LIQUEFIED GAS.
PHYSICAL DANGERS: The gas is heavier than air and may travel along
the ground; distant ignition possible.
CHEMICAL DANGERS: The substance may polymerize
due to heating,
under the influence of acids, bases, metal chlorides and metal oxides
with fire or explosion hazard. The substance decomposes on heating above 500°C
, causing fire and explosion hazard. Reacts violently with many compounds.
Metal fittings containing silver, copper, mercury, or magnesium should not be
used since they may react with impurities in the gas to form explosive
compounds.
ROUTES OF EXPOSURE: The substance can be absorbed into the body by
inhalation and through the skin in water solution.
INHALATION RISK: A harmful concentration of this gas in the air will be reached very quickly on loss of containment.
EFFECTS OF SHORT-TERM EXPOSURE:
The substance irritates the eyes,
the skin and
the respiratory tract.
Inhalation of very high concentrations may cause lung oedema (see Notes).
Water solutions may cause skin burns.
Rapid evaporation of the liquid may cause frostbite.
The substance may cause effects on the eyes , resulting in delayed development
of cataract.
EFFECTS OF LONG-TERM OR REPEATED
EXPOSURE: Repeated
or prolonged contact with skin may cause dermatitis in water solutions.
Repeated or prolonged contact may cause skin sensitization.
The substance may have effects on the nervous system.
This substance is carcinogenic to humans.
May cause heritable genetic damage in humans.
The symptoms of lung oedema often do not become manifest until a few hours have passed and they are aggravated by physical effort. Rest and medical observation are therefore essential. Immediate administration of an appropriate spray, by a doctor or a person authorized by him/her, should be considered. The odour warning when the exposure limit value is exceeded is insufficient. Turn leaking cylinder with the leak up to prevent escape of gas in liquid state.
http://pmep.cce.cornell.edu/facts-slides-self/facts/gen-posaf-health.html
CHEMICAL FAMILY:
METHYL BROMIDE, ETHYLENE OXIDE AND PROPYLENE OXIDE
Pesticide
Human Health Effects
PESTICIDE HEALTH EFFECTS ON HUMANS. ... Type of Pesticide:
Fumigants. CHEMICAL FAMILY:
METHYL BROMIDE, ETHYLENE OXIDE AND PROPYLENE OXIDE. ...
http://pmep.cce.cornell.edu/facts-slides-self/facts/gen-posaf-health.html
More Results From: pmep.cce.cornell.edu
OSH
Answers: Ethylene Oxide
CCOHS Homepage, Français, Ethylene Oxide. Basic Information on Ethylene
Oxide.
First Aid for Exposure to Ethylene Oxide. Health Effects
of Ethylene Oxide. ...
http://www.ccohs.ca/oshanswers/chemicals/chem_profiles/ethylene_oxide/
More Results From: www.ccohs.ca
Health
Effects of Ethylene Oxide
Health Effects of Ethylene Oxide. 3.1 Overview. A
handler of EO should be familiar
with the Occupational Safety and Hygiene Act [1] standards contained in 29 CFR ...
http://www.ethyleneoxide.com/html/body_health_effects.html
More Results From: www.ethyleneoxide.com
ATSDR
- Toxicological Profile: Ethylene Oxide
... Toxicological Profile for. Ethylene Oxide. CAS ...
The ATSDR toxicological profile succintly
characterizes the toxicologic and adverse health effects ...
http://www.atsdr.cdc.gov/toxprofiles/tp137.html
More Results From: www.atsdr.cdc.gov
Health
Care Facilities
... This NIOSH report reviews current scientific information on health
effects associated
with ... Ethylene Oxide: Ethylene Oxide
Sterilizers in Health ...
http://www.osha.gov/SLTC/healthcarefacilities/
More Results From: www.osha.gov
Ethylene
Oxide
... Health effects: Ethylene oxide is
classified by the Occupational Safety and Health
Administration (OSHA) as an occupational carcinogen and as a "de minimis ...
http://www.nsc.org/library/chemical/Ethylen0.htm
More Results From: www.nsc.org
NIOSH
Current Intelligence Bulletins (CIBs)
... 89-111, CIB-51 - Carcinogenic Effects of Exposure to Propylene
Oxide (July 1989),
PB 90-142589. 89-115, CIB-52 - Ethylene Oxide Sterilizers in Health
Care ...
http://www.cdc.gov/niosh/cibs2.html
More Results From: www.cdc.gov
Information
for personnel (PDF)
... Page 4. n Air monitoring n Health effects of ethylene
oxide n The OSHA ethylene oxide
standard 2FFXSDWLRQDO +\JLHQH 3URJUDPV 2FFXSDWLRQDO DQG (QYLURQPHQWDO 6DIHW ...
http://www.safety.duke.edu/OccSafetyHyg/Ethylene_oxide_Infosheet.pdf
More Results From: www.safety.duke.edu
Regulatory
Advocacy - Regulatory Advocacy - Appendix to ...
... Unlike ethylene oxide ... Substances and Disease
Registry and Sax's Dangerous Properties
of Industrial Materials, there are adverse health effects ...
http://www.aha.org/ar/comment/appendixocc.asp
Adverse Reproductive
and Developmental Health Effects Where Used ... (PDF)
... MI AG/P, CF, HG/P Ethylene Dibromide MI CW, WP/S, IP Ethylene
Oxide C ... banned in US)
Phthalates H, MI, SA, SBD CP, CF, CW, IP Key Health Effects ...
http://www.igc.org/psr/GBPSRPhysNat.pdf
More Results From: www.igc.org
Matheson
Tri-Gas MSDS Ethylene Oxide (1-10%), Blance Nitrogen
... COMPRESSED GAS CAS NUMBER: 7727-37-9 EC NUMBER (EINECS): 231-783-9
PERCENTAGE:
90-99 COMPONENT: ETHYLENE OXIDE CAS ... POTENTIAL HEALTH
EFFECTS ...
http://www.matheson-trigas.com/msds/EthyleneOxideBalanceNitrogen.htm
More Results From: www.matheson-trigas.com
CRC
Press: ATSDR Online
... mitigation of health effects, data gaps, and all
available health ... Rigorously peer-reviewed,
this work covers the toxicological effects of ... ETHYLENE OXIDE
...
http://www.atsdr.net/default.asp?cc=69
More Results From: www.atsdr.net
Technical
Information for CRHA Employee Ethylene Oxide (PDF)
... and moisture sterilization techniques No suitable substitute to ethylene
oxide ... studies
have shown that there are no significant health effects ...
http://www.crha-health.ab.ca/supp/ohs/etosurv.PDF
Ethylene
Oxide Probabilistic Risk Assessment
... It is well established that ethylene oxide can induce
cancer, along with
genetic, reproductive, developmental, and acute health effects. ...
http://biowww.dfci.harvard.edu/~corrigan/Envirostats/williams_ethyleneoxide.html
More Results From: biowww.dfci.harvard.edu
DOW
Oxides and Glycols Safe Handling: Health and Toxicity
... Inhalation Ethylene oxide has a sweet smell at
concentrations of 250 - 700 ppm. However,
these levels are above the 50 ppm level that may cause health effects.
...
http://www.dow.com/dog/safe/ehs2.htm
MedNets
: A medical search engine and health portal
... What immediate health effects may result from ethylene
oxide exposure?
Most exposures to ethylene oxide occur from breathing the gas. ...
http://www.mednets.com/index.cfm/fuseaction/articles_ethylene_oxide_poisoning_and_exposure_toxicolog
y-Ethylene/active_search/1/get_search_results.htm
More Results From: www.mednets.com
Human
Health Risk Documents: Literature Summaries
... Programs, US Environmental Protection Agency, VA; Dennis M. Opresko,
August 1999,
Literature Summary Report, Ethylene Oxide (CHEG-000563), Health
Effects ...
http://riskassessment.ornl.gov/finddocs.cfm?DocType=LITERATURE
Great Lakes Chemical Corporation and the Pathfinders Camp