INFORMATION REGARDING CHLOROFORM AND SOLVENT
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~DngQZP:1
CHLOROFORM
CASRN: 67-66-3
Major Uses :
As a solvent for
fats, oils, rubber, alkaloids, waxes, gutta-percha, resins; as cleansing agent;
in fire extinguishers to lower the freezing temp of carbon tetrachloride; in the
rubber industry.
Major Uses :
EXTRACTION & PURIFICATION SOLVENT
- EG, FOR PENICILLIN
Major Uses :
As a solvent for
coating compositions of urea or melamine resins and for preparations of
lubricant additives and plasticizers; surface-active agents; lubricant
additives, rubber chemicals, flotation agents, antifoam agent; flavoring agent;
reaction medium for hydrogen pyroxide production; defoamer.
Consumption Patterns :
Hydrochlorofluorocarbon 22 (HCFC-22), 98%
(refrigerants 70%; fluoropolymers 30%); miscellaneous, including laboratory
reagents and extraction solvents for pharmaceuticals,
2%.
Hazardous Reactivities & Incompatibilities :
Chloroform and
acetone interact vigorously & exothermally in presence of solid potassium
hydroxide or calcium hydroxide to form
1,1,1-trichloro-2-hydroxy-2-methylpropane. A laboratory incident involving the
bursting of a solvent residues bottle was attributed to
this reaction.
Preventive Measures :
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/
Cleanup Methods :
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 :
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/
Disposal Methods :
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/
Metabolism/Metabolites :
Studies were made with male Wistar rats on the
effects of 50% food restriction on the metabolism of ... chloroform.
... The activities of liver drug-metabolizing enzymes for this solvent
was enhanced almost equally without exception by one-day food restriction,
although the restriction produced no significant increase in the microsomal
protein and cytochrome p450 contents. Thus, food restriction enhances metabolism
of chloroform in the liver.
Therapeutic Uses :
MEDICATION (VET): USED/ EXTERNALLY, AS
LINIMENT-TYPE COUNTERIRRITANT FOR RELIEF OF DEEP SEATED PAIN, TO EXPEL SCREWWORM
LARVAE FROM WOUNDS, AS SKIN CLEANSER (FAT SOLVENT),
& AS SKIN COOLANT & LOCAL ANESTHETIC DUE TO ITS EVAPORATION. ...
INTERNALLY, IT IS GIVEN IN VARIOUS MIXT WELL DIL TO AVOID GASTRIC IRRITATION ...
. /FORMER USE/
Artificial Pollution Sources :
Emissions from its production and indirect
production (in the manufacture of ethylene dichloride); chlorination of drinking
water, municipal sewage, cooling water in electric power generating plants;
produced during the atmospheric photodegradation of trichloroethylenes; auto
exhaust; from its use as an extractant or solvent,
chemical intermediate, dry cleaning agent, fumigant ingredient, in fluorocarbon
22 production, synthetic rubber production (1-2).
Food Survey Values :
A pilot study was conducted in 1980 to measure
chloroform in five "Market Basket" food
samples collected from grocery stores in New Jersey, North Carolina, and
Washington, D.C.(1). Chloroform concns in cola soft
drinks avgd 49 ug/l while in non-cola soft drinks 11 ug/l(1). A typical chloroform
level in soft drinks is about 23 ug/l(1). One of the five dairy composites also
contained chloroform: milk and cheese avgd 4 ng/g and
one butter samples contained 12 ng/g(1). Ice cream and mayonnaise also contained
chloroform at 12 and 23 ng/g, respectively(1). Another
FDA study of VOCs in margarines detected chloroform in
5 of 18 samples collected at stores and in 13 of 19 finished products collected
at manufacturing plants(1). The levels were much higher at the manufacturing
plants than in the stores, with two samples between 100 and 150 ng/g and ten
others between 15 and 50 ng/g. It was later determined that VOCs migrated from
the packaging glues into the margarine(1). In a study of 18 table-ready food
items, ten contained chloroform with the highest levels
occuring in butter 670 ng/g, Cheddar cheese 80 ng/g, granola 57 ng/g, and peanut
butter 29 ng/g(1). Mean values of 14 samples of butter was 364 ng/g; 8 samples
of cheese 182 ng/g; 11 samples of cereal 60 ng/g; 7 samples of peanut butter
51.3 ng/g; and 12 samples of highly processed foods 122 ng/g(1). The sources of chloroform
in food are not clearly understood however migration of chloroform
from packaging solvents, glues, and inks has been
documented(1).
Probable Routes of Human Exposure :
Shell Chem Co, Rocky Mountain Arsenal - mean
TWA were 2.6, 0.4 and 0.2 ppm for production operaters, drummers/bottle fillers
and maintenance/utility personnel (pesticide plant)(1). Polish pharmaceutical
plant 2 - 205 ppm(1); police forensic lab - 8 hr TWA - 15.8 ppm (range 2.6-46.4
ppm)(1); film manufacturing plant using a solvent
containing 22% chloroform 1968-72 - 7-170 ppm (mean 47
ppm, 79 samples)(1).
Analytic Laboratory Methods :
EPA Method EMSLC 551. Determination of
Chlorination Disinfection Byproducts and Chlorinated Solvents
in Drinking Water by Liquid-Liquid Extraction and Gas Chromatography with
Electron-Capture Detection.
TSCA Test Submissions :
Chloroform (CAS #
67-66-3) was evaluated for clastogenicity in Chinese Hamsters (5/sex/treatment
group) exposed by oral gavage to doses of 0 (solvent
control), 40, 120, and 400 mg/kg bw with subsequent harvest, preparation and
analysis of metaphase bone marrow cells (100 cells/animal) at 6 (high dose), 24
(all doses), and 48 (high dose) hours post-treatment. Hamsters of 400 mg/kg
doses exhibited signs of toxicity including hypoactivity, closed eyes, and
arrested food consumption. Slight enhancement of chromosomal aberrations was
statistically significant (Mann-Whitney-U-test) 6 and 24 hours after doses of
400 mg/kg, although the rate was still within the range of historical negative
controls. Further, outside the range of historical controls, no dose-response
relationship was demonstrated. The study authors noted an inference of chloroform
mutagenicity, however, based on the nature of marked damage (multiple
aberrations, chromosomal disintegration, and exchanges) associated with oral chloroform
at doses of 120 and 400 mg/kg (6-, 24-, and 48-hour assessments). In repeat
study, exposing groups of hamsters to doses of 0 (solvent
control), 120, and 400 mg/kg bw, 24-hour cytogenetic assay again revealed a
slight but statistically significant increase in chromosome aberrations in
association with 400 mg/kg doses, failing again to demonstrate a dose-response
relationship for rates of damage (chromosome breaks) beyond the range of
historical controls. Distinctly heavy damage (multiple aberrations and
exchanges) characterized the chloroform-induced
aberrations at 400 mg/kg in 6/6000 metaphase bone marrow cells.
TSCA Test Submissions :
The rate of chloroform
(CAS # 67-66-3, CHCl3) metabolism was evaluated in 6-hour in vitro bioassay with
microsomal fractions of liver and kidney from B6C3F1 mice, F344 rats, Syrian
Golden hamsters, and humans. Microsomal protein preparations of each species
were incubated for 30 minutes with labeled 14CHCl3 in dimethyl formamide, a
NADPH regenerating system and a potassium phosphate buffer (pH 7.4). Boiled
enzyme preparations containing equivalent amounts of protein served as controls.
The reaction terminated at 30 minutes, CO2 generated by the enzymatic reaction
was measured and the solution's unreacted substrate (14CHCl3) and water-soluble
reaction products separated by solvent extraction
(unlabeled CHCl3). Liquid scintillation assay in combined species analysis
(mice, rats, hamsters, and humans) documented a rate of 14CHCl3
biotransformation to water-soluble metabolite proportional to time for 10-30 min
and proportional to protein concentration up to 1-2 mg protein per incubation.
This reaction was wholly inhibited by boiling the enzyme prior to incubation.
Reaction rates or MFO (mixed function oxidase) activities (nmoles
oxidized/min/mg protein at 0.049-0.058 mM CHCl3) in liver microsomes of mouse,
rat, and hamster ranged from 0.0199 (rat) to 0.133 (hamster) nmoles/min/mg
protein. Human liver microsomes demonstrated a broad activity range from 0.003 -
0.017 nmoles/min/mg protein (mean +/- s.d. = 0.00816 +/- 0.00448), the slowest
rates among tested mammals. Descending rates of CHCl3 metabolism in the kidney
were found in mice (0.0102 nmoles/min/mg protein), hamsters (0.00562 nmoles/min/mg
protein), and rats (0.000928 nmoles/min/mg protein). Human kidney samples were
limited and failed to demonstrate microsomal rates of CHCl3 metabolism above the
minimal detection limit (0.0003 nmoles/min/mg protein at 0.06 mM CHCl3).
Species-specific metabolic indices were subsequently derived by computer
optimization of kinetics study data associated with 1-20 mM 14CHCl3 for
development of a physiologically-based pharmacokinetic (PB-PK) model of chloroform
toxicity.
GLCC RELATED TOXIC SUBSTANCES
FOUND IN THE CAMP POND AND CAMP WATER WELL 2003 AND 2004