|
1-Chloro-1,1-difluoroethane
CASRN 75-68-3
Contents
0661
1-Chloro-1,1-difluoroethane; CASRN 75-68-3
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 1-Chloro-1,1-difluoroethane
File On-Line 07/01/1995
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) on-line 07/01/1995
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- 1-Chloro-1,1-difluoroethane
CASRN -- 75-68-3
Primary Synonym -- HCFC-142b
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- 1-Chloro-1,1-difluoroethane
CASRN -- 75-68-3
Primary Synonym -- HCFC-142b
Last Revised -- 07/01/1995
The inhalation Reference Concentration (RfC) is analogous to the oral RfD and
is likewise based on the assumption that thresholds exist for certain toxic
effects such as cellular necrosis. The inhalation RfC considers toxic effects
for both the respiratory system (portal-of-entry) and for effects peripheral
to the respiratory system (extrarespiratory effects). It is expressed in
units of mg/cu.m. In general, the RfC is an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily inhalation exposure of the
human population (including sensitive subgroups) that is likely to be without
an appreciable risk of deleterious effects during a lifetime. Inhalation RfCs
were derived according to the Interim Methods for Development of Inhalation
Reference Doses (EPA/600/8-88/066F August 1989) and subsequently, according to
Methods for Derivation of Inhalation Reference Concentrations and Application
of Inhalation Dosimetry (EPA/600/8-90/066F October 1994). RfCs can also be
derived for the noncarcinogenic health effects of substances that are
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.B.1. INHALATION RfC SUMMARY
Critical Effect Exposures* UF MF RfC
-------------------- ----------------------- ----- --- ---------
No adverse effects NOAEL: 82,620 mg/cu.m 300 1 5E+1
(20,000 ppm) mg/cu.m
2-Year Rat Inhalation NOAEL(ADJ): 14,710 mg/cu.m
Study NOAEL(HEC): 14,710 mg/cu.m
Seckar et al., 1986 LOAEL: None
LOAEL(ADJ): None
LOAEL(HEC): None
*Conversion Factors and Assumptions: MW = 101. Assuming 25 C and 760 mmHg,
NOAEL (mg/cu.m) = NOAEL (ppm) x MW/24.45 = 82,620. NOAEL(ADJ) = 82,620 x 6
hours/24 hours x 5 days/7 days = 14,710 mg/cu.m. The NOAEL(HEC) was
calculated for a gas:extrarespiratory effect assuming periodicity was
attained. Because the b:a lambda values are unknown for the experimental
animals species (a) and humans (h), a default value of 1.0 is used for this
ratio. NOAEL(HEC) = 14,710 x (b:a lambda(a)/b:a lambda(h)) = 14,710 mg/cu.m.
___I.B.2. PRINCIPAL AND SUPPORTING STUDIES (INHALATION RfC)
Seckar, J.A., H.J. Trochimowicz, G.K. Hogan. 1986. Toxicological evaluation
of hydrochlorofluorocarbon 142b. Fund. Chem. Toxicol. 24(3): 237-240.
Groups of 110 Sprague-Dawley rats/sex were whole-body exposed for 6
hours/day, 5 days/week for 104 weeks to 0, 1000, 10,000, or 20,000 ppm 1-
chloro-1,1-difluoroethane (HCFC-142b) (99.85-99.99% pure), which corresponds
to 0, 4130, 41,310, or 82,620 mg/cu.m, respectively. The corresponding
duration-adjusted concentrations were 0, 738, 7380, or 14,710 mg/cu.m,
respectively. The animals were observed for clinical signs of toxicity. Body
weight was measured weekly during the first 14 weeks and biweekly through week
80. Hematological, clinical chemistry, and urinalysis evaluations were
conducted on 10 animals/sex/group at 12, 18, and 24 months. Organ weights
were recorded for all animals sacrificed after 1 year of exposure. Gross and
microscopic tissue examination of over 45 tissues, including sectioning of
brain and lungs, was performed on the animals in the control and high-exposure
groups only. It is not clear to what extent the nasal tract tissues were
examined. The HCFC-142b vapor was generated by evaporating the liquid test
material in a stream of metered air. The test atmosphere concentration was
assayed 6 times/day by gas-liquid chromatography. Mean daily chamber
concentrations were found to be within 10% of the nominal concentrations.
There were no exposure-related effects on mortality, clinical signs, food
consumption, body weight, behavior, ocular characteristics, hematology,
clinical pathology, urinalysis, organ weights, or gross or microscopic
pathology. Nonneoplastic effects were similar for both treated and control
animals and were limited to typical age-related degenerative changes.
Bronchopneumonia was evident in some treated and control animals. The study
NOAEL is 20,000 ppm [NOAEL(HEC) = 14,710 mg/cu.m]; a LOAEL was not achieved.
___I.B.3. UNCERTAINTY AND MODIFYING FACTORS (INHALATION RfC)
UF -- An uncertainty factor of 10 is used to protect unusually sensitive
individuals. A full factor of 10 is also applied for data base deficiencies,
due to lack of reproductive studies and the absence of chronic information on
a second species. A partial uncertainty factor of 3 is used for interspecies
extrapolation. The total uncertainty is 300.
MF -- None
___I.B.4. ADDITIONAL STUDIES / COMMENTS (INHALATION RfC)
A 90-day toxicity study was performed on groups of 27 male and female ChR-
CD rats and 4 male beagle dogs/group that were whole body-exposed to 0, 1000,
or 10,000 HCFC-142b (99.7% pure) for 6 hours/day, 5 days/week (Kelly, 1976).
These concentrations corresponded to 0, 4130, or 41,310 mg/cu.m., respectively
(duration-adjusted values = 0, 738, or 7380 mg/cu.m, respectively). The
experimental protocol was similar to that described above for the chronic
study, except that hematology, urinalysis, and clinical chemistry
determinations were conducted at approximately monthly intervals in 10
rats/sex/group and in all dogs. Approximately 35-40 tissues were examined
microscopically (it is not clear whether the nasal cavity was examined).
There were no deaths, clinical signs of toxicity, or treatment-related effects
on body weight, hematology, urinalysis, clinical chemistry, or gross or
microscopic pathology. The lack of a significant increase in urinary fluoride
indicates that HCFC-142b was not metabolized to any significant degree. This
study demonstrates a NOAEL of 10,000 ppm [NOAEL(HEC) = 7380 mg/cu.m] under
these exposure conditions; a LOAEL was not achieved.
A 13-week cytogenetics study in male rats was conducted concurrently with
the 2-year study (Bio/dynamics, 1983; Seckar et al., 1986). In this study, 10
rats/group were exposed as in the principal study. No treatment-related
effects on mortality, body-weight gain, or gross pathology were noted.
The lack of toxicity of HCFC-142b also was demonstrated in a 2-week study
conducted by Moore (1976). In this study, ChR-CD rats (10 males/group) exposed
to 0 or 20,000 ppm HCFC-142b for 6 hours/day, 5 days/week exhibited no
exposure-related effects on survival, body weight gain, hematology, clinical
chemistry, urinalysis, or gross or microscopic pathology. Salivation was noted
in the animals during exposure to HCFC-142b. This concentration corresponds to
82,620 mg/cu.m and becomes 14,710 mg/cu.m when duration adjusted.
In rats, short-term (single or repeated) exposures to relatively high
concentrations of HCFC-142b result in reversible CNS depression. The 4-hour
lethal concentration in the rat is about 126,000 ppm (Wier, 1962). High
exposures cause signs of pronounced CNS depression such as labored breathing
and unconsciousness. At all, except very high doses, CNS depression is fully
reversible, with no clinical sequelae being noted after repeated exposures and
continued observation.
Lester and Greenberg (1950) conducted whole-body exposures in 10 rats (sex
and strain unspecified) to 100,000 ppm (413,100 mg/cu.m) for 16 hours/day.
All animals died within nine exposures: 6 in 7 days, 2 in 8 days, and 2 in 9
days. All animals were examined grossly, and sections of lung and liver were
examined for histopathology. Lungs of all animals showed signs of severe
irritation, having extensive consolidation and advanced lobar pneumonia. In a
subsequent experiment, five rats were exposed to 10,000 ppm (41,310 mg/cu.m),
16 hours daily for a period of 2 months, with no apparent effects. The lungs
of 2/5 of these animals revealed evidence of inflammation, but sufficient
information is not given to conclude that this effect was treatment related.
These studies have a number of significant experimental (apparently no control
animals were used) and reporting deficiencies that preclude their use in
quantitative risk assessment.
Culik and Kelly (1976) exposed 25 pregnant ChR-CD rats/group to 0, 1000,
or 10,000 ppm HCFC-142b (0, 4130, or 41,300 mg/cu.m, respectively) for 6
hours/day; 13 females were exposed on gestation days 4-13, and 12 females were
exposed on gestation days 6-15. The rationale given for these two treatment
regimes was that the former corresponded to the time before implantation and
the latter to the period of organogenesis; however, the two groups were
combined for evaluation of all parameters. Dams were examined for the numbers
of corpora lutea, implantation sites, the number and location of live and dead
fetuses and late and early resorptions, and the weight and crown-rump length
of all live fetuses. All fetuses were examined for external anomalies, and
approximately half of the fetuses from each litter were examined for skeletal
abnormalities. Except for increased preimplantation losses noted in both
exposure groups, no adverse effects were noted. This effect was not
concentration-related and difficult to interpret because, as already
mentioned, the dams exposed to HCFC-142b after implantation were not listed
separately in the study. No maternal toxicity was described in the study.
Because of the procedural and reporting inadequacies in this study, no effect
levels were assigned.
Damske et al. (1978) exposed 20 pregnant CRL:COBS CD (SD) BR rats to 0,
3259, or 9420 ppm HCFC-142b (0, 13,460, or 38,905 mg/cu.m, respectively) for 6
hours/day on gestation days 6-15. Dams were sacrificed on day 20, and the
fetuses were weighed, sexed, and examined for external malformations. One-
third of the fetuses from each litter were examined for internal
malformations, and the remainder were examined for skeletal abnormalities.
There were no clearly exposure-related maternal effects that resulted from
exposure to HCFC-142b, nor were there exposure-related embryotoxicity,
variation in sex ratio, effects on fetal growth, or incidence of visceral
defects. Some skeletal variations described by the study authors were
classified as "commonly encountered" or "unusual skeletal variations", but no
further information is given. Reduced ossification was described for several
areas, including the interparietal and supraoccipital bones of the skull and
the hyoid bone, although no concentration-related trends in incidence were
apparent. Although these results are suggestive of developmental toxicity, no
clear effect levels could be assigned from this study.
Cardiac sensitization was tested in a stress challenge test with 12
healthy male dogs. After a 5-minute inhalation of 50,000 ppm (206,500
mg/cu.m) stress (noise) elicited marked responses (a life-threatening cardiac
arrhythmia) in five (41.7%) of the dogs.
The metabolism of HCFC-142b was studied in male Sprague-Dawley and Fischer
344 rats (Dodd et al., 1993). Groups of eight animals were exposed (nose-only)
to room air or to 10,000 ppm HCFC-142b for 2 hours. Immediately after the
termination of exposure, four exposed animals and one control animal were
sacrificed, and samples of liver, kidney, heart, lung, muscle, skin, fat,
testes, and blood were processed for analysis. The remaining animals were
placed in metabolism cages for 24 hours, and urine and feces were collected.
The parent compound was found in the tissues assayed immediately after
exposure but not in tissue samples assayed 24 hours after exposure, indicating
complete elimination of the compound within 24 hours. A carboxylic acid
metabolite of HCFC-142b, chlorodifluoroacetic acid, was measured in the urine.
The presence of this metabolite indicates that HCFC-142b is oxidatively
metabolized.
The ozone depleting and global warming potential of this compound relative
to other chlorofluorocarbon substitutes is discussed by Jarabek et al. (1994).
___I.B.5. CONFIDENCE IN THE INHALATION RfC
Study -- Medium
Data Base -- Medium
RfC -- Medium
The principal study was well conducted but failed to identify a LOAEL.
The lack of toxicological response of this compound at the upper concentration
used in the principal study demonstrates this compound is without adverse
effects, although only for the endpoints examined and only in a single
species. The data base is given a medium to low level of confidence because a
chronic inhalation study exists in only one species, and there are no
reproductive toxicity studies. The developmental toxicity following
inhalation exposure has been studied but is not considered totally adequate.
A medium to low confidence in the RfC follows.
___I.B.6. EPA DOCUMENTATION AND REVIEW OF THE INHALATION RfC
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
This assessment was peer reviewed by external scientists. This review was
completed on 05/18/1995. Their comments have been carefully evaluated and
considered in the revision and finalization of this IRIS summary. A record of
these comments is included in the IRIS documentation files.
Other EPA Documentation -- None
Agency Work Group Review -- 09/24/1992
Verification Date -- 09/24/1992
___I.B.7. EPA CONTACTS (INHALATION RfC)
Please contact the IRIS Hotline for all questions concerning this
assessment or IRIS, in general, at (301) 345-2870 (phone), (301) 345-2876 (FAX)
or Hotline.IRIS@epamail.epa.gov (internet address).
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- 1-Chloro-1,1-difluoroethane
CASRN -- 75-68-3
Primary Synonym -- HCFC-142b
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. BIBLIOGRAPHY
Substance Name -- 1-Chloro-1,1-difluoroethane
CASRN -- 75-68-3
Primary Synonym -- HCFC-142b
Last Revised -- 07/01/1995
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfC REFERENCES
Bio/dynamics. 1983. A study in the rat of the cytogenetic effect of
inhalation of fluorocarbon 142b, with attachment and cover letter dated March
27, 1992. EPA/OTS Doc. No. 86-920000865. NTIS/OTS 0535423.
Culik, R. and D.P. Kelly. 1976. Embryotoxic and teratogenic studies in rats
with inhaled chlorodifluoroethane (FC 142b). E.I. Du Pont de Nemours and Co.,
Haskell Laboratory for Toxicology and Industrial Medicine. EPA/OTS Doc. No.
86-890000866. NTIS/OTS 0520981.
Damske, D.R., F.J. Mecler and R.P. Beliles. 1978. Teratology study in rats.
Isotron 142b. Monochlorodifluoroethane. Litton Bionetics, Kensington, MD.
LBI Project No. 20890.
Dodd, D.E., W.T. Brashear and A. Vinegar. 1993. Metabolism and
pharmacokinetics of selected Halon replacement candidates. Toxicol. Lett.
68: 37-47.
Jarabek, A.M., J.W. Fisher, R. Rubenstein, et al. 1994. Mechanistic insights
aid the search for CFC substitutes: Risk assessment of HCFC-123 as an
example. Risk Analysis. 14(3): 231-250.
Kelly, D.P. 1976. Ninety-day inhalation exposure of rats and dogs to vapors
of 1-chloro-1,1-difluoroethane (FC-142b). E.I. Du Pont de Nemours and Co.,
Haskell Laboratory for Toxicology and Industrial Medicine. Haskell Laboratory
Report No. 469-76.
Lester, D. and L.A. Greenberg. 1950. Acute and chronic toxicity of some
halogenated derivatives of methane and ethane. Arch. Ind. Hyg. Occup. Med.
2: 335-344.
Moore, B.L. 1976. Subacute (two-week) inhalation toxicity.
Chlorodifluoroethane. E.I. Du Pont de Nemours and Co., Haskell Laboratory for
Toxicology and Industrial Medicine. EPA/OTS Doc. No. 86-890000864. NTIS/OTS
0520979.
Seckar, J.A., H.J. Trochimowicz and G.K. Hogan. 1986. Toxicological
evaluation of hydrochlorofluorocarbon 142b. Fund. Chem. Toxicol. 24(3):
237-240. (Several volumes of the original study were consulted and are part
of the literature file for this compound.)
Wier, J. 1962. Inhalation toxicity test-acute. 1-Chloro-1,1-difluoroethane
(K-142b) distillation residue. E.I. Du Pont de Nemours and Co., Haskell
Laboratory for Toxicology and Industrial Medicine. Haskell Laboratory Report
No. 30-62.
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- 1-Chloro-1,1-difluoroethane
CASRN -- 75-68-3
Primary Synonym -- HCFC-142b
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
10/01/1992 I.B. Inhalation RfC now under review
07/01/1995 I.B. Inhalation RfC summary on-line
07/01/1995 VI.B. Inhalation RfC references on-line
04/01/1997 III.,IV., Drinking Water Health Advisories, EPA Regulatory Actions, and
V. Supplementary Data were removed from IRIS on or before April
1997. IRIS users were directed to the appropriate EPA Program
Offices for this information.
VIII. SYNONYMS
Substance Name -- 1-Chloro-1,1-difluoroethane
CASRN -- 75-68-3
Primary Synonym -- HCFC-142b
Last Revised -- 10/01/1992
75-68-3
Ethane, 1-chloro-1,1-difluoro-
FREON 142B
Hydrochlorofluorocarbon 142b
1-chloro-1,1-difluoroethane
alpha-CHLOROETHYLIDENE FLUORIDE
CFC 142b
CFC 1426
Chlorodifluoroethane
Chlorofluorocarbon 142b
FC 142b
FC142b
Freon 142
Freon 142b
Genetron 101
Genetron 142b
Gentron 142B
HSDB 2881
Propellant 142b
R 142b
1,1-DIFLUORO-1-CHLOROETHANE
HCFC-142b
.
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/subst/0661.htm
|