The
following is from (page 50-51):
PRIORITIZED
CANDIDATE CHEMICALS UNDER CONSIDERATION FOR CARCINOGENICITY
EVALUATION: BATCH #1.
Office of Environmental Health Hazard Assessment, California
Environmental Protection Agency May 1997.http://www.oehha.ca.gov/prop65/pdf/batch1.pdf
CARCINOGENICITY
DATA SUMMARY: CHLOROFLUOROMETHANE
Chlorofluoromethane
(Halocarbon 31; CAS number 593-70-4) occurs as an impurity
in commercial grades of dichlorofluoromethane (Halocarbon
21). This compound was identified for review because of
positive bioassay data. Chlorofluoromethane was reviewed
by IARC in 1986. IARC concluded that the evidence of carcinogenicity
was inadequate in humans and limited in animals (group
3 carcinogen). No more recent information on the evidence
for carcinogenicity of the agent identified by the literature
searches conducted. However, a new structure-activity
analysis is now available. These results, in addition
to the study reviewed by IARC, are briefly described below.
Carcinogenicity
Data available:
Epidemiological studies
No data on long-term effects of human exposure to chlorofluoromethane
were available to IARC (1986) or identified in subsequent
literature searches by OEHHA.
Animal bioassays
1. Rat long-term gavage study: Longstaff et al., 1984.
Squamous cell carcinoma and fibrosarcoma
of the stomach were reported in 92% of exposed males and
94% of exposed females: Background incidence of
these lesions in both sexes was 1%. The study authors
were unable to determine whether the sites of origin of
the tumors were in the forestomach only or in both forestomach
and glandular stomach.
Other
relevant data
Chlorofluoromethane was found to
be a highly active mutagen in the Salmonella reverse mutation
assay, and to induce transformation of BHK21 cells in
vitro (Longstaff et al., 1984). A computerized
analysis of structure-activity relationships based on
a set of rules generated by US EPA experts (Oncologic,
version 1.0) finds that chlorofluoromethane
is of high-to-moderate concern. (This is the highest level
of concern noted for chemicals which are not included
in the database of carcinogenicity bioassay results from
which the program rules are derived.)
Preliminary
evaluation of carcinogenicity and exposure data:
There is a MEDIUM level of carcinogenicity concern over
chlorofluoromethane since evidence of carcinogenicity
has been observed in both sexes of the rat in the one
available study. In this single dose-level study, carcinogenic
effects were observed at the site of application. Although
the study was smaller and more limited in design than
the standard bioassay, the extremely
high level of incidence relative to controls of a relatively
uncommon tumor is noteworthy. No tests in other
species have been reported. The concern is reinforced
by the observations of mutagenicity and cell transforming
ability in short-term tests, and by the results of a computerized
analysis of structure-activity relationships based on
rules generated by US EPA experts (Oncologic, version
1.0), which predicts that chlorofluoromethane is of high-to-moderate
concern (i.e., the highest level of concern possible on
chemicals which have not been included in the programÕs
database).
There
is a LOW level of concern over the extent of exposure
since chlorofluoromethane is not manufactured in bulk
or naturally abundant, although it occurs as an impurity
in a commodity chemical (IARC, 1986). NIOSH (1983) estimated
that 2,703 workers were potentially exposed to chlorofluoromethane,
but levels were probably low since this compound is only
present as an impurity. IARC (1986) characterized the
exposure potential as limited.
References
International
Agency for Research on Cancer (IARC,1986). IARC Monographs
on the evaluation of carcinogenic risks to humans, Volume
41. IARC, Lyon. pp. 229-235, Chlorofluoromethane.
Longstaff
E, Robinson M, Bradbrook C, Styles JA, Purchase IFH (1984).
Genotoxicity and carcinogenicity of fluorocarbons: Assessment
by short-term in vitro tests and chronic exposure in rats.
Toxicol Appl Pharmacol 72:15-31.
National
Institute for Occupational Safety and Health (NIOSH, 1983).
National Occupational Exposure Survey for 1983, cited
in the NIOSH database RTECS (Registry of Toxicological
Effects of Chemical Substances).
