TECHNICAL REPORT DATA
ffleate read Instructions on tht rtveru before completing)
1. REPORT NO.
EPA/600/8-88/023
2.
3. RECIPIENTS ACCESSION NO.
PB88-179486/AS
4. TITLE AND SUBTITLE
5. REPORT DATE
Health Effects Assessment for bis(2-Chloroethyl)ether
«. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
8. PERFORMING ORGANIZATION REPORT NO
9. PERFORMING ORGANIZATION NAME ANO ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME ANO ADDRESS
Environmental Criteria and Assessment Office
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. OH 45268
13. TYPE OF REPORT AND PERIOD COVERED
14. SPONSORING AGENCY CODE
EPA/600/22
15. SUPPLEMENTARY NOTES
6. ABSTRACT
This report summarizes and evaluates information relevant to a preliminary interim
assessment of adverse health effects associated with specific chemicals or compounds.
The Office of Emergency and Remedial Response (Superfund) uses these documents in
preparing cost-benefit analyses under Executive Order 32991 for decision-making under
CERCLA. All estimates of acceptable intakes and carcinogenic potency presented in
this document should be considered as preliminary and reflect limited resources
allocated to this project. The intent in these assessments is to suggest acceptable
exposure levels whenever sufficient data are available. The interim values presented
reflect the relative degree of hazard associated with exposure or risk to the
chemical(s) addressed. Whenever possible, two categories of values have been
estimated for systemic toxicants (toxicants for which cancer is not the endpoint of
concern). The first, RfD$ or subchronic reference dose, is an estimate of an exposure
level that would not be expected to cause adverse effects when exposure occurs during
a limited time interval. The RfD is an estimate of an exposure level that would not
be expected to cause adverse effects when exposure occurs for a significant portion
of the lifespan. For compounds for which there is sufficient evidence of
carcinogenic!ty, qi*s have been computed, if appropriate, based on oral and
inhalation data if available.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
6.IDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Croup
8. DISTRIBUTION STATEMENT
Public
19. SECURITY CLASS (This Report I
Unclassified
21. NO. of PAGES
20. SECURITY CLASS (This page I
Unclassified
22. PRICE
EPA fmnt 2220-1 (R»». 4-77) PREVIOUS KOITION is OMOLCTC
/SO
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EPA/600/8-88/023
Hay, 1987
HEALTH EFFECTS ASSESSMENT
FOR BIS(2-CHLOROETHYL)ETHER
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
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DISCLAIMER
This document has been reviewed 1n accordance with the U.S.
Environmental Protection Agency's peer and administrative review policies
and approved for publication. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with b1s(2-
chloroethyl)ether. All estimates of acceptable Intake and carcinogenic
potency presented 1n this document should be considered as preliminary and
reflect limited resources allocated to this project. Pertinent toxlcologlc
and environmental data were located through on-Hne literature searches of
the TOXLINE and the CHEMFATE/OATALOG data bases. The basic literature
searched supporting this document 1s current up to May, 1986. Secondary
sources of information have also been relied upon In the preparation of this
report and represent large-scale health assessment efforts that entail
extensive peer and Agency review. The following Office of Health and
Environmental Assessment (OHEA) sources have been extensively utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria Document for
Chloroalkyl Ethers. Prepared by the Office of Health and Environ-
mental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Water Regulations and Standards,
Washington, DC. EPA 440/5-80-030. NTIS PB 81-117418.
U.S. EPA. 1980b. Hazard Profile for B1s(2-chloroethyl )ether.
Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Solid Waste and Emergency Response, Washington, DC.
The Intent 1n these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited 1n
scope tending to generate conservative (I.e., protective) estimates.
Nevertheless, the Interim values presented reflect the relative degree of
hazard associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for
systemic toxicants (toxicants for which cancer 1s not the endpolnt of
concern). The first, RfD$ (formerly AIS) or subchronlc reference dose, 1s
an estimate of an exposure level that would not be expected to cause adverse
effects when exposure occurs during a limited time Interval (I.e., for an
Interval that does not constitute a significant portion of the llfespan).
This type of exposure estimate has not been extensively used, or rigorously
defined, as previous risk assessment efforts have been primarily directed
towards exposures from toxicants 1n ambient air or water where lifetime
exposure 1s assumed. Animal data used for RFD$ estimates generally
Include exposures with durations of 30-90 days. Subchronlc human data are
rarely available. Reported exposures are usually from chronic occupational
exposure situations or from reports of acute accidental exposure. These
values are developed for both Inhalation (RfD$j) and oral (RfD$Q)
exposures.
111
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The RfO (formerly AIC) 1s similar 1n concept and addresses chronic
exposure. It 1s an estimate of an exposure level that would not be expected
to cause adverse effects when exposure occurs for a significant portion of
the llfespan [see U.S. EPA (1980c) for a discussion of this concept]. The
RfD 1s route-specific and estimates acceptable exposure for either oral
(RfOg) or Inhalation (RfOj) with the Implicit assumption that exposure
by other routes 1s Insignificant.
Composite scores (CSs) for noncarclnogens have also been calculated
where data permitted. These values are used for Identifying reportable
quantities and the methodology for their development 1s explained 1n U.S.
EPA (1983).
For compounds for which there Is sufficient evidence of carclnogenlclty
RfD$ and RfD values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980c). Since cancer 1s a
process that Is not characterized by a threshold, any exposure contributes
an Increment of risk. For carcinogens, q-|*s have been computed, If appro-
priate, based on oral and Inhalation data 1f available.
1v
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ABSTRACT
In order to place the risk assessment evaluation In proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate
Interpretation and use of the quantitative estimates presented.
B1s(2-chloroethyl)ether was carcinogenic 1n orally exposed mice,
associated with an Increased Incidence of hepatomas. The EPA weight of
evidence classification for cardnogenlclty 1s Group 82 because of strong
response 1n mice and supporting mutagenlcHy findings. The U.S. EPA (1980a)
derived a q-|* of 1.1 (mg/kg/day)"1 from the study 1n mice. This q-|*
1s adopted for the purposes of this document. Because the chemical Is a
carcinogen In animals, H 1s Inappropriate to derive RfD$ and RfO values.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Or. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and John Helms (Office of
Toxic Substances) was the Project Officer. The final documents 1n this
series were prepared for the Office of Emergency and Remedial Response,
Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of Air Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by the following:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by the
following:
Bette Zwayer, Jacky Bohanon and Kim Davidson
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1.
2.2.
ORAL
INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.
3.2.
3.3.
3.4.
SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
CHRONIC
3.2.1. Oral
3.2.2. Inhalation
TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3.1. Oral
3.3.2. Inhalation
TOXICANT INTERACTIONS
CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
HEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
Page
. . . 1
. , . 3
. . . 3
. . . 3
. . . 4
. . . 4
. . . 4
4
4
. . . 4
4
4
. . . 4
. . . 4
. . . 5
6
. . . 6
. . . 6
6
6
. . . 6
. . . 6
. . . 8
. . . 8
. . . 10
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 11
6.1. SUBCHRONIC REFERENCE DOSE (RfOs) 11
6.1.1. Oral (RfDso) 11
6.1.2. Inhalation (RfD$i) 11
6.2. REFERENCE DOSE (RfD) 11
6.2.1. Oral (RfD0) 11
6.2.2. Inhalation (RfDi) 11
6.3. CARCINOGENIC POTENCY (q-|*) 11
6.3.1. Oral 11
6.3.2. Inhalation 11
7. REFERENCES 13
APPENDIX: Oral Summary Table for B1s(2-chloroethyl )ether 1n
Male C57B1/6xC3H/Anf Mice 17
V111
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LIST OF ABBREVIATIONS
CS Composite score
ppm Parts per million
STEL Short-term exposed level
RfD Reference dose
RfDj Inhalation reference dose
RfDg Oral reference dose
RfDgj Subchronlc Inhalation reference dose
RfD$o Subchronlc oral reference dose
TLV Threshold limit value
TWA Time-weighted average
1x
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
b1s(2-chloroethyl)ether are presented In Table 1-1. Synonyms for b1s-
(2-chloroethyl )ether are: sym-dkhloroethyl ether; 1,1' -oxyb1s(2-ch!oro-
ethane); B,Q'-d1chloroethyl ether; OCEE and Chlorex.
In the atmosphere, b1s(2-chloroethylJether Is expected to exist
primarily 1n the vapor phase. The atmospheric half-life listed 1n Table 1-1
1s the half-life for the reaction of gaseous b1s(2-chloroethyl)ether with
photochemlcally generated hydroxyl radicals. Based on a rate constant of
1.79X10-11 cmVmolecule-sec at 25°C and an ambient hydroxyl radical
concentration of 8.0x10* molecules/cm3, a half-life of 13.44 hours has
been calculated (U.S. EPA, 1986a). Considering Us relatively high water
solubility (1.74x10* mg/s. at 20°C), b1s(2-chloroethyl) ether also 1s
Hkely to be removed by wet deposition from the atmosphere.
The half-life of b1s(2-chloroethyl)ether In aqueous and soil systems
could not be located 1n the available literature. In aqueous systems,
volatilization and hydrolysis may be Important removal mechanisms, although
the former process 1s expected to be much faster than the latter (Callahan
et al., 1979). Based on the bloconcentratlon factor and soil adsorption
coefficient, bloaccumulatlon 1n aquatic organisms and adsorption to sus-
pended solids and sediments should not be significant. In soils with low
sorptlon constant, b1s(2-chloroethylJether should be mobile and groundwater
contamination may occur below solid waste landfills (Wilson et al., 1981;
DeWalle and Chlan, 1981). Based on Us vapor pressure (0.75 mm Hg at 20°C),
b1s(2-chloroethyl)ether should volatilize relatively rapidly from dry soil
surfaces.
0086h -1- 01/22/87
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TABLE 1-1 .
Selected Physical and Chemical Properties and Half-Lives for
B1s(2-Chloroethyl)Ether
Property
Value
Reference
CAS number:
Chemical class:
Molecular weight:
Chemical Structure:
Freezing point:
Boiling point:
Vapor pressure:
Water solubility:
Log octanol/water
partition coefficient:
B1oconcentrat1on factor
Soil adsorption:
coefficient
111-44-4
aliphatic haloether
143.01
Cl H H Cl
II II
H-C-C-0-C-C-H
II II
H H H H
-50°C
178.5°C
0.75 mm Hg (20°C)
1.74xl04 mg/8. (20°C)
1.02x10* mg/l (temp-
erature unspecified)
1.29
11, blueglll sunflsh
(Lepomls macrochlrus)
80, fine sand
ACGIH, 1986
ACGIH, 1986
Weber et al.
1981
Velth et al., 1980
Callahan et al., 1979
Hansch and Leo, 1985
Velth et al., 1980
Wilson et al., 1981
Half-lives:
Air
Water
Soil
-13 hours
NA
NA
U.S. EPA, 1986a
NA = Not available
0086h
-2-
01/22/87
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
B1s(2-ch1oroethy1)ether appears to be nearly completely absorbed from
the gastrointestinal tract of rats. Llngg et al. (1982) administered a 40
mg/kg dose of l4C-b1s(2-chloroethyl )ether 1n corn oil by gavage to adult
male Sprague-Dawley rats and measured the radioactivity 1n expired air
excreta, carcass and cage wash at 48 hours posttreatment. Only 2.4X of the
administered dose of radioactivity was located 1n the feces. Total recovery
accounted for 80.9/4 of the administered dose. These data suggest that
gastrointestinal absorption was nearly complete.
2.2. INHALATION
Limited data concerning the Inhalation absorption of b1s(2-chloroethyl)
ether were available. Schrenk et al. (1933) reported that exposure to bis
(2-chloroethyl)ether In guinea pigs was assolcated with brain, liver and
kidney congestion as well as lung congestion. These results suggest some
absorption by the respiratory tract.
0086h -3- 09/05/86
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Pertinent data regarding the oral subchronlc toxlclty of
b1s(2-chloroethyl)ether could not be located 1n the available literature.
3.1.2. Inhalation. Pertinent data regarding the Inhalation subchronlc
toxldty of b1s(2-chloroethyl )ether could not be located 1n the available
literature.
3.2. CHRONIC
3.2.1. Oral. Welsburger et al. (1981) gave groups of 26 male and 26
female Charles River CD rats 25 or 50 mg/kg b1s(2-chlorethyl)ether by
gavage, twice weekly for 18 months, followed by a 6-month observation
period. Negative and vehicle controls were also maintained. High-dose
females had a higher mortality rate than negative or pooled vehicle controls
and survival was unaffected 1n males. Mean body weights were lower In
treated females and high-dose males than In the corresponding controls.
3.2.2. Inhalation. Pertinent data regarding the chronic Inhalation
toxldty of b1s(2-chlorethyl )ether could not be located 1n the available
literature.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenlc and reproductive
effects after oral administration of b1s(2-chlorethy i Jether could not be
located 1n the available literature.
3.3.2. Inhalation. Pertinent data regarding the teratogenlc and repro-
ductive effects after Inhalation exposure to b1s(2-chlorethyl)ether could
not be located 1n the available IHeratue.
0086h -4- 09/05/86
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3.4. TOXICANT INTERACTIONS
Pertinent data regarding the toxicant Interactions of b1s(2-chloro-
ethyl)ether with other chemicals could not be located In the available
literature.
0086h -5- 09/05/86
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4. CARCINOGENICITY
4.1. :HUMAN DATA
4.1.1. Oral. Pertinent data regarding the carclnogenlcHy to humans of
b1s(2-ch1oroethyl)ether from oral exposure could not be located 1n the
available literature.
4.1.2. Inhalation. Pertinent data regarding the carclnogenlcHy to
humans of b1s(2-chloroethyl)ether from Inhalation could not be located In
the available literature.
4.2. BIOASSAYS
4.2.1. Oral. Innes et al. (1969) gave groups of 18 male and 18 female
mice of two different cross strains 100 mg/kg of b1s(2-chloroethyl)ether by
stomach tube from age 7-28 days and thereafter In the diet at 300 ppm until
week 80. The Incidence of hepatomas 1n males of both strains and females of
one strain were statistically higher than controls. Details are presented
1n Table 4-1.
Helsburger et al. (1981) obtained negative results In an oral carclno-
genlcHy assay 1n which Charles Liver CD rats of both sexes were given 25
and 50 mg/kg/day of b1s(2-chloroethyl )ether twice weekly for 18 months,
followed by a 6-month observation period. Although the authors suggested
that the doses for males were not sufficient to elicit a carcinogenic
response, they nonetheless concluded that b1s(2-chloroethylJether was not
carcinogenic In rats.
4.2.2. Inhalation. Pertinent data regarding the carclnogenlcHy to
animals of b1s(2-chloroethyl)ether from Inhalation could not be located In
the available literature.
0086h -6- 09/05/86
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TABLE 4-1
Incidence of Hepatomas In Two Strains of Mice Given Oral Doses
of B1s(2-chloroethyl)ether for -18 months3
Strain Sex
Controls0
C57Bl/6xC3H/Anf M
Controls0
C57Bl/6xC3H/Anf F
Controls0
C57B1/6xAKR M
Doseb
(mg/kg/day)
0
39
0
39
0
39
Tumor Incidence
(p value)
8/79
14/16 (p<0.01)
0/87
4/18 (p<0.01)
5/90
9/17 (p<0.01)
aSource: Innes et al., 1969
bDose as calculated by U.S. EPA (1980a) based on dietary consumption of
300 ppm and assuming a mouse consumes 13% of Us body weight as food/day.
°Pooled control data were used because statistical tests revealed Uttle
heterogeneity among groups.
0086h -7- 09/05/86
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4.3. OTHER RELEVANT INFORMATION
B1s(2-chloroethy1)ether was negative 1n qualitative tests. Van Duuren
et al. (1972) observed no Initiating activity 1n the 2-stage mouse skin
assay using phorbol myrlstate acetate as a promoter. Weekly subcutaneous
Injections of 1 mg b1s(2-ch1oroethyl)ether showed a borderline Increase
(p>0.05) 1n the Incidence of Injection site sarcomas In exposed female
ICR/Ha Swiss mice (Van Duuren et al., 1972). No tumors were detected at
sites distant from the Injection site. Male mice Injected 1ntraper1toneally
with b1s(2-chloroethyl)ether did not exhibit a pulmonary tumor response
significantly different from that of controls (Thless et al., 1973).
B1s(2-chloroethyl )ether was positive In mlcroblal mutagenlcHy tests and
negative In mammalian test systems. Using different tester strains of
Escherlchla coll. Salmonella typhlmuMum and Bacillus subtlUs. Shlrasu et
al. (1975) found b1s(2-chloroethyl)ether to be a direct-acting mutagen.
Positive results were obtained In S. typhlmuMum strain TA100 with b1s(2-
chloroethyl)ether vapors (Simmon et al., 1977). Jorgenson et al. (1977)
obtained negative results In mice using the heritable translocatlon test.
4.4. WEIGHT OF EVIDENCE
The degree of evidence on carclnogenlclty of b1s(2-chloroethyl)ether 1n
humans 1s considered Inadequate because of the lack of human case reports or
epidemiologies studies. The degree of evidence 1n animals 1s considered
sufficient; although b1s(2-chloroethylJether was not carcinogenic In rats by
the oral route (Welsburger et al., 1981), 1t elicited hepatomas 1n mice
after oral exposure (Innes et al., 1969). Two limitations of the Innes et
al. (1969) study are noted. First, an Increased tumor Incidence was
observed In a tumor type (hepatoma) that often occurs spontaneously 1n
0086h -8- 05/26/87
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mice. Second, hepatomas In mice are difficult to classify. In the rat
study It Is difficult to evaluate carcinogenic potential of
b1s(2-chloroethylJether because the exposure was less than a lifetime.
These limitations and negative results obtained In qualitative tests
(Van Duuren et al., 1972; Thless et al., 1973) suggested that the quality of
evidence for b1s(2-chloroethyl)ether was more appropriately viewed as
limited; however, assigning this chemical to Group 82, probable human
carcinogen, Is appropriate because the Incidences observed 1n the Innes et
al. (1969) study were very high (53-88%) and were statistically
significantly greater than controls. The supporting details of this study
together with the positive mutagenlcHy findings do not warrant a
downgrading of the mouse liver tumor response. Therefore,
b1s(2-chloroethyl)ether 1s assigned to EPA Group B2: probable human
carcinogen (U.S. EPA, 1986b).
0086H -9- 05/26/87
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5. REGULATORY STANDARDS AND CRITERIA
U.S. EPA (1980a) derived the criteria of 0.003, 0.030 and 0.30 vq/i
at risk levels of 10~7, 10~6 and 10~5, respectively, based on the
Incidence of hepatomas 1n strain (C57Bl/6xC3H/Anf)F. male mice orally
exposed for 80 weeks. In deriving these criteria, a bloconcentratlon factor
of 6.9 was applied and dally consumption of 2 l water and 6.5 g of fish
was assumed. NAS (1980) estimated that at a concentration of 1 yg/l,
the risk of cancer for both sexes was 8.1xlO~7. The upper 95% confidence
estimate was 1.2xlO~«.
ACGIH (1986) recommended a TLV-TWA of 5 ppm (-30 mg/m3) and a TLV-STEL
of 10 ppm (-60 mg/m3) and noted that skin exposure may contribute to
overall exposure. OSHA (1985) adopted a celling of 15 ppm (90 mg/m3) and
also noted that b1s(2-chloroethyl)ether may be absorbed through the skin.
0086h -10- 03/10/87
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6. RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE DOSE (RfDc)
O
6.1.1. Oral (RfDSQ). It 1s Inappropriate to derive an RfDSQ because
b1s(2-chloroethyl )ether 1s a carcinogen.
6.1.2. Inhalation (RfDSI). It 1s Inappropriate to derive an ..
because b1s(2-chloroethyl )ether Is a carcinogen.
6.2. REFERENCE DOSE (RfD)
6.2.1. Oral (RfDQ). It 1s Inappropriate to derive an RfD_ because
b1s(2-ch1oroethyl )ether 1s a carcinogen.
6.2.2. Inhalation (RfD,). It Is Inappropriate to derive an RfD.
because b1s(2-chloroethyl jether 1s a carcinogen.
6.3. CARCINOGENIC POTENCY (q.,*)
6.3.1. Oral. U.S. EPA (1980a) used the linearized multistage model to
derive a q * of 1.1 (mg/kg/day)'1. The q * was based on a hepatoma
Incidence of 14/16 (p<0.01) 1n male mice (strain C57Bl/6xC3H/Anf ) given 39
mg/kg/day b1s(2-chloroethyl )ether for 80 weeks, compared with an Incidence
of 8/79 In controls. The data used 1n the derivation of this q * are
presented In Table 6-1. Although some of the assumptions and calculations
applied In this derivation vary slightly from current methodology (U.S. EPA,
1980c), the q * of 1.1 (mg/kg/day)'1 Is adopted as the q * for orally
exposed humans for the purposes of this document.
6.3.2. Inhalation. Data were Insufficient for deriving an Inhalation q *
0086h -11- 05/07/87
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TABLE 6-1
Cancer Data Sheet for Derivation of a q-|*
Compound: b1s(2-chloroethyl)ether
Reference: Innes et al., 1969
Specles/straln/sex: C5781/6xC3H/Anf male mice
Route/vehicle: oral: gavage followed by diet
Length of exposure (le) = 560 days
Length of experiment (Le) = 560 days
Llfespan of animal (L) = 560 days
Body weight = 0.03 kg (assumed)
Tumor site and type: hepatomas
Exposure
(ppm)
0
300
Transformed Dose
(mg/kg/day)
0
39
Incidence
No. Responding/No.
8/79
14/16
Tested
Unadjusted q-i* = 8.6xlO"2 (mg/kg/day)"1
Human q-j* = 1.1 (mg/kg/day)'1
0086h -12- 03/10/87
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7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 186.
Callahan, M.A., M.W. Sllmak, N.W. Gabel, et al. 1979. Water-Related Envi-
ronmental Fate of 129 Priority Pollutants, Vol. II. U.S. EPA, Washington,
DC. EPA 440/4-79-0298.
Dewalle, F.B. and E.S.K. Chlan. 1981. Detection of trace organlcs In well
water near a solid waste landfill. J. Am. Water Works Assoc. 73: 206-211.
Hansch, C. and Leo, A.J. 1985. Medchem Project Issue No. 26. Pomona
College, Claremont, CA.
Innes, J.R.M., B.M. inland, M.G. Valevlo, et al. 1969. Bloassay of pesti-
cides and Industrial chemicals for tumor1gen1dty 1n mice: A preliminary
note. J. Natl. Cancer Inst. 42: 1101.
Jorgenson, T.A., C.J. Rushbrook, G.W. Newell and R.G. Tardlff. 1977. Study
of the mutagenlc potential of b1s-(2-chloroethyl) and b1s-(2-chlor1sopropyl)
ethers In mice by the heritable translocatlon test. Toxlcol. Appl.
Pharmacol. 41: 196-197.
0086h -13- 01/22/87
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L1ngg, R.D., W.H. Kaylor, S.M. Pyle, M.M. Domino, C.C. Smith and G.F. Wolfe.
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