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Dichloromethane
CASRN 75-09-2
Contents
0070
Dichloromethane; CASRN 75-09-2
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Dichloromethane
File On-Line 01/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 03/01/1988
Inhalation RfC Assessment (I.B.) no data 09/01/1991
Carcinogenicity Assessment (II.) on-line 02/01/1995
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Dichloromethane
CASRN -- 75-09-2
Primary Synonym -- Methylene Chloride
Last Revised -- 03/01/1988
The oral Reference Dose (RfD) is based on the assumption that thresholds exist
for certain toxic effects such as cellular necrosis. It is expressed in units
of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily exposure to the human population
(including sensitive subgroups) that is likely to be without an appreciable
risk of deleterious effects during a lifetime. Please refer to the Background
Document for an elaboration of these concepts. RfDs can also be derived for
the noncarcinogenic health effects of substances that are also carcinogens.
Therefore, it is essential to refer to other sources of information concerning
the carcinogenicity of this substance. If the U.S. EPA has evaluated this
substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
Liver toxicity NOAEL: 5.85 and 6.47 100 1 6E-2
mg/kg/day for males mg/kg/day
2-Year Rat Drinking and females,
Water Bioassay respectively
National Coffee LOAEL: 52.58 and
Association, 1982 58.32 mg/kg/day for
males and females,
respectively
*Conversion Factors: Doses reflect actual values and not nominal ones.
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
National Coffee Association. 1982. 24-Month chronic toxicity and
oncogenicity study of methylene chloride in rats. Final Report. Prepared by
Hazleton Laboratories America, Inc., Vienna, VA. (Unpublished)
The chosen study appears to have been very well conducted, with 85 rats/ sex
at each of four nominal dose groups (i.e., 5, 50, 125 and 250 mg/kg/day) for 2
years. A high-dose recovery group of 25 rats/sex, as well as two control
groups of 85 and 50 rats/sex, was also tested. Many effects were monitored.
Treatment related histological alterations of the liver were evident at
nominal doses of 50 mg/kg/day or higher. The low nominal dose of 5 mg/kg/day
was a NOAEL.
The supporting data base is limited. A NOAEL of 87 mg/cu.m was reported in
one inhalation study (Haun et al., 1972). [The equivalent oral dose is about
28 mg/kg bw/day (i.e., 87 mg/cu.m x 0.5 x 0.223 cu.m/day/0.35 kg; these
exposure values are for rats).]
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- (10a x 10h) The 100-fold factor accounts for both the expected intra-
and interspecies variability to the toxicity of this chemical in lieu of
specific data.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
None.
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- High
Data Base -- Medium
RfD -- Medium
The study is given a high confidence rating because a large number of animals
of both sexes were tested in four dose groups, with a large number of
controls. Many effects were monitored and a dose-related increase in severity
was observed. The data base is rated medium to low because only a few studies
support the NOAEL. Medium confidence in the RfD follows.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- U.S. EPA, 1985
Other EPA Documentation -- None
Agency Work Group Review -- 06/24/1985, 07/08/1985, 11/06/1985
Verification Date -- 11/06/1985
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Dichloromethane
CASRN -- 75-09-2
Primary Synonym -- Methylene Chloride
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Dichloromethane
CASRN -- 75-09-2
Primary Synonym -- Methylene Chloride
Last Revised -- 02/01/1995
Section II provides information on three aspects of the carcinogenic
assessment for the substance in question; the weight-of-evidence judgment of
the likelihood that the substance is a human carcinogen, and quantitative
estimates of risk from oral exposure and from inhalation exposure. The
quantitative risk estimates are presented in three ways. The slope factor is
the result of application of a low-dose extrapolation procedure and is
presented as the risk per (mg/kg)/day. The unit risk is the quantitative
estimate in terms of either risk per ug/L drinking water or risk per ug/cu.m
air breathed. The third form in which risk is presented is a drinking water
or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1
in 1,000,000. The rationale and methods used to develop the carcinogenicity
information in IRIS are described in The Risk Assessment Guidelines of 1986
(EPA/600/8-87/045) and in the IRIS Background Document. IRIS summaries
developed since the publication of EPA's more recent Proposed Guidelines for
Carcinogen Risk Assessment also utilize those Guidelines where indicated
(Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to
Section I of this IRIS file for information on long-term toxic effects other
than carcinogenicity.
__II.A. EVIDENCE FOR CLASSIFICATION AS TO HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CLASSIFICATION
Classification --B2; probable human carcinogen
Basis -- Based on inadequate human data and sufficient evidence of
carcinogenicity in animals; increased incidence of hepatocellular neoplasms
and alveolar/bronchiolar neoplasms in male and female mice, and increased
incidence of benign mammary tumors in both sexes of rats, salivary gland
sarcomas in male rats and leukemia in female rats. This classification is
supported by some positive genotoxicity data, although results in mammalian
systems are generally negative.
___II.A.2. HUMAN CARCINOGENICITY DATA
Inadequate. Neither of two studies of chemical factory workers exposed to
dichloromethane showed an excess of cancers (Ott et al., 1983; Friedlander et
al., 1978; Hearne and Friedlander, 1981). The Ott et al. (1983) study was
designed to examine cardiovascular effects, and consequently the study period
was too short to allow for latency of site-specific cancers. In the
Friedlander et al. (1978) study, exposures were low, but the data provided
some suggestion of an increased incidence of pancreatic tumors. This study
was recently updated to include a larger cohort, followed through 1984, and an
investigation of possible confounding factors (Hearne et al., 1986, 1987). A
nonsignificant excess in pancreatic cancer deaths was observed, which was
interpreted by EPA (1987a) as neither clear evidence of carcinogenicity in
humans, nor evidence of noncarcinogenicity. An update of the Ott et al.
(1983) study, based on longer follow-up, indicated possible elevation of liver
and biliary tract cancers (TSCA section 8(e) submission no. 8eHQ-0198-0772
FLWP et seq., 1989).
___II.A.3. ANIMAL CARCINOGENICITY DATA
Sufficient. Dichloromethane administered in the drinking water induced a
significant increase in combined hepatocellular carcinoma and neoplastic
nodules in female F344 rats and a nonsignificant increase in combined
hepatocellular carcinoma and neoplastic nodules in male B6C3F1 mice (NCA,
1982, 1983). Two inhalation studies with dichloromethane have shown an
increased incidence of benign mammary tumors in both sexes of Sprague-Dawley
(Burek et al., 1984) and F344 (NTP, 1986) rats. Male Sprague-Dawley rats had
increased salivary gland sarcoma (Burek et al., 1984) and female F344 rats had
increased leukemia incidence (NTP, 1986). Both sexes of B6C3F1 mice developed
liver and lung tumors after dichloromethane treatment (NTP, 1986).
In a 2-year study by the National Coffee Association (1982, 1983), groups
of 85 F344 rats/sex/dose received 5, 50, 125, or 250 (mg/kg)/day of
dichloromethane in the drinking water. Control groups consisted of 135
rats/sex. In female rats the incidence of combined hepatocellular carcinoma
and neoplastic nodules was statistically significantly increased in the 50 and
250 mg/kg dose groups when compared with matched controls (0/134, 1/85, 4/83,
1/85, and 6/85 in the five dose groups 0, 5, 50, 125, and 250 (mg/kg)/day,
respectively). The incidence of hepatocellular carcinoma alone was not
significantly increased (0/134, 0/85, 2/83, 0/85, 2/85). The combined
incidence of hepatocellular carinoma and neoplastic nodules in controls and
the 4 dose groups (472 rats: 4 with carcinoma and 8 with neoplastic nodules)
was similar to that for historical controls (419 rats; 5 with carcinoma, 19
with neoplastic nodules). Male rats showed no increase in liver tumors.
In the same National Coffee Association study (1982, 1983), B6C3F1 mice
received 0, 60, 125, 185, or 250 (mg/kg)/day of dichloromethane in drinking
water. Treatment groups consisted of 50 female mice and 200, 100, 100, and
125 male mice (low to high dose). One hundred females and 125 males served as
controls. Male mice had an increased incidence of combined neoplastic nodules
and hepatocellular carcinoma (24/125, 51/200, 30/100, 31/99, 35/125). The
increase was not dose-related, but the pairwise comparisons for the two mid-
dose groups were reported to be statistically significant (U.S. EPA, 1985a).
The hepatocellular carcinoma incidence alone for male mice (which was about 55
to 65% of the total) was not significantly elevated. Female mice did not have
increased liver tumor incidence. The EPA (1985b) regarded this study as
suggestive but not conclusive evidence for carcinogenicity of dichloromethane.
A gavage bioassay of dichloromethane conducted by NTP (1982) has not been
published because of high mortality, much of which was attributed to gavage
accidents.
Inhalation exposure of 107 to 109 Syrian hamsters/sex/dose to 0, 500,
1500, or 3500 ppm of dichloromethane for 6 hours/day, 5 days/week for 2 years
did not induce neoplasia (Burek et al., 1984). Sprague-Dawley rats (129/sex/
dose) were exposed under the same conditions. Female rats administered the
highest dose experienced significantly reduced survival from 18-24 months.
Female rats showed a dose-related increase in the average number of benign
mammary tumors per rat (1.7, 2.3, 2.6, 3.0), although the numbers of rats with
tumors were not significantly increased. A similar response was observed in
male rats, but to a lesser degree. In the male rats there was a statistically
significant positive trend in the incidence of sarcomas of the salivary gland
(1/93, 0/94, 5/91, 11/88); the incidence was significantly elevated at the
high dose. There is a question as to whether these doses reached the MTD,
particularly in the hamsters and the male rats. In another study (Dow
Chemical Co., 1982), 90 Sprague-Dawley rats/sex were exposed by inhalation to
0, 50, 200, or 500 ppm dichloromethane for 20 months (male) or 24 months
(female). No salivary tumors were observed, but there was an exposure-related
increase in the total number of benign mammary tumors in female rats, although
the increase was not statistically significant in any individual exposure
group.
Groups of 50 each male and female F344/N rats and B6C3F1 mice were exposed
to dichloromethane by inhalation, 6 hours/day, 5 days/week for 2 years (NTP,
1986). Exposure concentrations were 0, 1000, 2000, or 4000 ppm for rats and
0, 2000, or 4000 ppm for mice. Survival of male rats was low; however, this
apparently was not treatment-related. Survival was decreased in a treatment-
related fashion for male and female mice and female rats. Mammary adenomas
and fibroadenomas were significantly increased in male and female rats after
survival adjustment, as were mononuclear cell leukemias in female rats. Among
treated mice of both sexes there were significantly increased incidences of
hepatocellular adenomas and carcinomas, and of alveolarbronchiolar adenomas
and carcinomas, by life table tests. Adenomas and carcinomas were
significantly increased alone as well as in combination. In addition, there
were significant dose-related increases in the number of lung tumors per
animal multiplicity in both sexes of mice.
Two inhalation assays using dogs, rabbits, guinea pigs, and rats showed no
tumors, but were not conducted for the lifetime of the animals (Heppel et al.,
1944; MacEwen et al., 1972). Theiss et al., (1977) injected Strain A male
mice intraperitoneally with 0, 160, 400, or 800 mg/kg of dichloromethane 16 to
17 times, over 5 to 6 weeks. Survival of the animals was poor. The animals
remaining 24 weeks after the first treatment were killed and examined for lung
tumors; pulmonary adenomas were found.
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
Dichloromethane was mutagenic for Salmonella typhimurium with or without
the addition of hepatic enzymes (Green, 1983) and produced mitotic
recombination in yeast (Callen et al., 1980). Results in cultured mammalian
cells have generally been negative, but dichloromethane has been shown to
transform rat embryo cells and to enhance viral transformation of Syrian
hamster embryo cells (Price et al., 1978; Hatch et al., 1983). Although
chlorinated solvents have often been suspected of acting through a
nongenotoxic mechanism of cell proliferation, Lefevre and Ashby (1989) found
methylene chloride to be unable to induce hepatocellular division in mice.
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
___II.B.1. SUMMARY OF RISK ESTIMATES
Oral Slope Factor -- 7.5E-3 per (mg/kg)/day
Drinking Water Unit Risk -- 2.1E-7 per (ug/L)
Extrapolation Method -- Linearized multistage procedure, extra risk
Drinking Water Concentrations at Specified Risk Levels:
Risk Level Concentration
-------------------- -------------
E-4 (1 in 10,000) 5E+2 ug/L
E-5 (1 in 100,000) 5E+1 ug/L
E-6 (1 in 1,000,000) 5E+0 ug/L
___II.B.2. DOSE-RESPONSE DATA (CARCINOGENICITY, ORAL EXPOSURE)
Tumor Type -- hepatocellular adenomas or carcinomas (NTP) and hepatocellular
cancer and neoplastic nodules (NCA)
Test Animals -- mouse/B6C3F1 (female, NTP; male, NCA)
Route -- inhalation (NTP); drinking water (NCA)
Reference -- NTP, 1986; National Coffee Association (NCA), 1983
Dose
---------------------------------
Human
Administered Equivalent Tumor
(ppm) mg/kg/day (mg/kg)/day Incidence Reference
----- ----------- ----------- --------- ---------
0 0 0 3/50 NTP, 1986
2000 1582 122 16/48
4000 3162 244 40/48
0 0 24/125 NCA, 1983
60 4.5 51/200
125 9.4 30/100
185 14.0 31/99
250 18.9 35/125
___II.B.3. ADDITIONAL COMMENTS (CARCINOGENICITY, ORAL EXPOSURE)
The slope factor is an arithmetic mean of slope factors derived from
NTP(1986) and the National Coffee Association (1983) data, 2.6E-3 per
(mg/kg)/day and 1.2E-2 per (mg/kg)/day, respectively. The use of liver tumor
data from the NTP inhalation bioassay was considered valid since
dichloromethane is rapidly absorbed following either inhalation or ingestion.
Dose conversions used the mean body weight for female mice at the
midpoint of the bioassay, and an estimated inhalation rate of 0.0407
cu.m/day. To obtain estimates of unit risk for humans, an inhalation rate of
20 cu.m/day was assumed. Dichloromethane was considered to be well-absorbed
as a vapor at low doses. No pharmacokinetic or metabolism data have been
used to modify the oral unit risk estimate, because such analyses have not
yet been carried out.
The unit risk should not be used if the water concentration exceeds 5E+4
ug/L, since above this concentration the unit risk may not be appropriate.
___II.B.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, ORAL EXPOSURE)
Adequate numbers of animals were used in both assays. Risk estimates
were based on the more sensitive sex in each study. The two risk estimates
were within a factor of 5.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
___II.C.1. SUMMARY OF RISK ESTIMATES
Inhalation Unit Risk -- 4.7E-7 per (ug/cu.m)
Extrapolation Method -- Linearized multistage procedure, extra risk
Air Concentrations at Specified Risk Levels:
Risk Level Concentration
-------------------- -------------
E-4 (1 in 10,000) 2E+2 ug/cu.m
E-5 (1 in 100,000) 2E+1 ug/cu.m
E-6 (1 in 1,000,000) 2E+0 ug/cu.m
___II.C.2. DOSE-RESPONSE DATA FOR CARCINOGENICITY, INHALATION EXPOSURE
Tumor Type -- combined adenomas and carcinomas
Test Animals -- mouse/B6C3F1, female
Route -- inhalation
Reference -- NTP, 1986
Dose
--------------------------------------------
Transformed Human
Administered Animal Equivalent Tumor
Tumor Type (ppm) (mg/kg)/day (mg/kg)/day Incidence
---------- ------------ ----------- ----------- ---------
Liver 0 0 0 3/45
2000 1582 356 16/46
4000 3162 712 40/46
Lung 0 0 0 3/45
2000 1582 356 30/46
4000 3162 712 41/46
___II.C.3. ADDITIONAL COMMENTS (CARCINOGENICITY, INHALATION EXPOSURE)
The unit risk of 4.7E-7 per (ug/cu.m), which incorporates information on
pharmacokinetics and metabolism of dichloromethane, is approximately
nine-fold lower than the previous applied dose estimate (U.S. EPA, 1987a,b).
Internal dose estimates were based on the metabolism of dichloromethane by
the glutathione-s-transferase pathway, as estimated by the model developed by
Andersen et al. (1987). The internal dose was corrected for interspecies
differences in sensitivity by using the surface area correction factor.
Calculation of a slope factor from the unit risk is inappropriate when
pharmacokinetic models are used. (When dose-response relationships are
figured on the basis of internal or metabolized dose, a slope factor in terms
of per (mg/kg)/day represents a back calculation using different absorption
assumptions than the pharmacokinetic models. This introduces possible
contradictions.)
The unit risk should not be used if the air concentration exceeds 2E+4
ug/cu.m, since above this concentration the unit risk may differ from that
stated. Since the unit risk is based on a pharmacokinetic model, the risk
may change with alterations in exposure patterns. Thus, the unit risk
presented here may not be applicable to acute, high exposures.
___II.C.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, INHALATION EXPOSURE)
Adequate numbers of animals were observed and tumor incidences were
significantly increased in a dose-dependent fashion. Analysis excluding
animals that died before observation of the first tumors produced similar
risk estimates, as did time-to-tumor analysis. The use of animal and human
metabolism and pharmacokinetic data reduces some of the uncertainty typically
associated with dose-risk extrapolation. A great deal of uncertainty still
exists, however, in the estimates of internal dose generated by the model of
Andersen et al. (1987). Important uncertainties remain regarding the
pharmacokinetics, pharmacodynamics, and mechanisms of carcinogenicity for
dichloromethane.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1985a,b, 1987a,b
The Addendum to the Health Assessment Document, the Update to the Health
Assessment Document and Addendum, and the Technical Analysis of New Methods
and Data for dichloromethane have received Agency and external review,
including a review by the Science Advisory Board (SAB). Although the last two
documents are not yet finalized and the SAB comments are not yet incorporated,
these do not alter this document's analyses or conclusions.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 11/12/1986, 12/04/1986, 04/06/1989
Verification Date -- 04/06/1989
___II.D.3. U.S. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_VI. BIBLIOGRAPHY
Substance Name -- Dichloromethane
CASRN -- 75-09-2
Primary Synonym -- Methylene Chloride
Last Revised -- 08/01/1991
__VI.A. ORAL RfD REFERENCES
Haun, C.C., E.H. Vernot, K.I. Darmer Jr. and S.S. Diamond. 1972. Continous
animal exposure to low levels of dichloromethane. AMRL-TR-72-13. In:
Proceedings of the 3rd Annual Conference on Environmental Toxicology, Wright-
Patterson Air Force Base, Ohio, Aerospace Medical Research Laboratory.
p. 199-208.
National Coffee Association. 1982. 24-Month chronic toxicity and oncogenicity
study of methylene chloride in rats. Final Report. Prepared by Hazleton
Laboratories America, Inc., Vienna, VA. (Unpublished)
U.S. EPA. 1985. Drinking Water Criteria Document for Methylene Chloride.
Office of Drinking Water, Washington, DC.
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Andersen, M.E., H.J. Clewell, III, M.L. Gargas, F.A. Smith and R.H. Reitz.
1987. Physiologically based pharmacokinetics and the risk assessment process
for methylene chloride. Toxicol. Appl. Pharmacol. 87: 185-205.
Burek, J.D., K.D. Nitschke, T.J. Bell, et al. 1984. Methylene chloride: A
two year inhalation toxicity and oncogenicity study in rats and hamsters.
Fund. Appl. Toxicol. 4: 30-47.
Callen, D.F., C.R. Wolf and R.M. Philpot. 1980. Cytochrome P-450 mediated
genetic activity and cytotoxicity of seven halogenated aliphatic hydrocarbons
in Saccharomyces cerevisiae. Mutat. Res. 77: 55-63.
Dow Chemical Company. 1982. Methylene chloride: A two-year inhalation and
oncogenicity study in rats. Toxicology Research Laboratory, Health and
Environmental Sciences, Dow Chemical Company, Midland, MI.
Friedlander, B.R., F.T. Hearne and S. Hall. 1978. Epidemiologic
investigation of employees chronically exposed to methylene chloride. J.
Occup. Med. 20(10): 657-666.
Green, T. 1983. The metabolic activation of dichloromethane and
chlorofluoromethane in a bacterial mutation assay using Salmonella
typhimurium. Mutat. Res. 118(4): 277-288.
Hatch, G.G., P.D. Mamay, M.L. Ayer, B.C. Casto and S. Nesnow. 1983. Chemical
enhancement of viral transformation in Syrian hamster embryo cells by gaseous
and volatile chlorinated methanes and ethanes. Cancer Res. 43: 1945-1950.
Hearne, F.T. and B.R. Friedlander. 1981. Follow-up of methylene chloride
study. J. Occup. Med. 23: 660.
Hearne, F.T., F. Grose, J.W. Pifer and B.R. Friedlander. 1986. Methylene
chloride mortality study update. Eastman Kodak Company, Rochester, NY.
June 16.
Hearne, F.T., F Grose, J.W. Pifer, B.R. Friedlander and R.L. Raleigh. 1987.
Methylene Chloride mortality study: dose-response characterization and animal
model comparison. J. Occup. Med. 29 (3): 217-228.
Heppel, L.A., P.A. Neal, T.L. Perrin, M.L. Orr and V.T. Porterfield. 1944.
Toxicology of dichloromethane (methylene chloride). I. Studies on effects of
daily inhalation. J. Ind. Hyg. Toxicol. 26(1): 8-21.
Lefevre, P.A. and J. Ashby. 1989. Evaluation of dichloromethane as an
inducer of DNA synthesis in B6C3F1 mouse liver. Carcinogenesis. 10(6):
1067-1072.
MacEwen, J.D., E.H. Vernot and C.C. Haun. 1972. Continuous animal exposure
to dichloromethane. AMRL-TR-72-28, Systems Corporation Report No. W-71005.
Wright Patterson Air Force Base, Ohio, Aerospace Medical Research. AD746295.
NCA (National Coffee Association). 1982. Twenty-four-month chronic toxicity
and oncogenicity study of methylene chloride in rats. Final Report. Prepared
by Hazleton Laboratories, America, Inc., Vienna, VA. Unpublished.
NCA (National Coffee Association). 1983. Twenty-four month oncogenicity
study of methylene chloride in mice. Final Report. Prepared by Hazleton
Laboratories, America, Inc., Vienna, VA.
NTP (National Toxicology Program). 1982. Draft technical report on the
carcinogenesis bioassay of dichloromethane (methylene chloride) (CAS No. 75-
09-2) in F344/N rats and B6C3F1 mice (gavage study). Research Triangle Park,
NC and Bethesda, MD. Unpublished. NTP-82-061.
NTP (National Toxicology Program). 1986. Toxicology and carcinogenesis
studies of dichloromethane (methylene chloride) (CAS No. 75-09-2) in F344/N
rats and B6C3F1 mice (inhalaltion studies). NTP-TRS-306.
Ott, M.G., L.K. Skory, B.B. Holder, J.M. Bronson and P.R. Williams. 1983.
Health evaluation of employees occupationally exposed to methylene chloride:
Mortality. Scand. J. Work Environ. Health. 9(Suppl. 1): 8-16.
Price, P.J., C.M. Hassett and J.I. Mansfield. 1978. Transforming
activities of trichloroethylene and proposed industrial alternatives. In
Vitro. 14(3): 290-293.
Thiess, J.C., G.D. Stoner, M.B. Shimkin and E.K. Weisburger. 1977. Test
for carcinogenicity of organic contaminants of United States drinking waters
by pulmonary tumor response in strain A mice. Cancer Res. 37: 2717-2720.
Toxic Substances Control Act. 1989. Section 8(e) submission no. 8eHQ-0198-
0772 FLWP et seq.
U.S. EPA. 1985a. Health Assessment Document for Dichloromethane (Methylene
Chloride). Final Report. Office of Health and Environmental Assessment,
Washington, D.C. EPA/600/8-82/004F.
U.S. EPA. 1985b. Addendum to the Health Assessment Document for
Dichloromethane (methylene chloride). Updated carcinogenicity assessment.
Prepared by the Carcinogen Assessment Group, OHEA, Washington, DC. EPA/600/8-
82/004FF.
U.S. EPA. 1987a. Update to the Health Assessment Document and Addendum for
Dichloromethane (Methylene Chloride): Pharmacokinetics, Mechanism of Action
and Epidemiology. Review Draft. Office of Health and Environmental
Assessment, Washington, DC. EPA/600/8-87/030A.
U.S. EPA. 1987b. Technical Analysis of New Methods and Data Regarding
Dichloromethane Hazard Assessments. Review Draft. Office of Health and
Environmental Assessment, Washington, DC. EPA/600/8- 87/029A.
_VII. REVISION HISTORY
Substance Name -- Dichloromethane
CASRN -- 75-09-2
Primary Synonym -- Methylene Chloride
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
04/20/1987 II.C.1. Unit Risk corrected from 4.1E-4 to 4.1E-6
05/21/1987 II.A.2. Missing text replaced in 3rd paragraph
03/01/1988 I.A.1. Dose conversion clarified
03/01/1988 I.A.2. Text revised
03/01/1988 II.B.3. Text revised
03/01/1988 II.B.4. Confidence statement revised
03/01/1988 II.C.3. Text revised
03/01/1988 II.C.4. Confidence statement revised
03/01/1988 II.D.3. Primary contact changed
03/01/1988 III.A. Health Advisory added
01/01/1989 II. Carcinogen summary noted as pending change
10/01/1989 II.B.3. Inhalation rate corrected in paragraph 1
10/01/1989 II.C.2. Dose corrections in mg/kg/day
10/01/1989 II.C.3. Inhalation rate corrected in paragraph 1
10/01/1989 II.D.3. Contacts phone number changed
08/01/1990 IV.F.1. EPA contact changed
09/01/1990 II. Carcinogen assessment revised following re-evaluation
09/01/1990 II.C.1. Inhalation unit risk changed
09/01/1990 VI. Bibliography on-line
01/01/1991 II.C.1. Paragraph moved to II.C.3.
01/01/1991 II.C.1. Inhalation slope factor removed (global change)
08/01/1991 VI.C. Citations clarified
09/01/1991 I.B. Inhalation RfC now under review
01/01/1992 IV. Regulatory actions updated
02/01/1995 II.D.3. Primary contact changed
VIII. SYNONYMS
Substance Name -- Dichloromethane
CASRN -- 75-09-2
Primary Synonym -- Methylene Chloride
Last Revised -- 01/31/1987
75-09-2
Aerothene MM
Chlorure de methylene
DCM
Dichlormethan, uvasol
Dichloromethane
1,1-Dichloromethane.
Freon 30
Methane dichloride
Methane, dichloro-
Methylene bichloride
Methylene Chloride
Methylene dichloride
Metylenu chlorek
Narkotil
NCI-C50102
R 30
Solaesthin
Solmethine
WLN: G1G
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0070.HTM
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