TECHNICAL REPORT DATA
(fteute rttd Instructions on ttie reverie before compienng)
1. REPORT NO.
EPA/600/8-88/Q37
3. RECIPIENT'S ACCESSION NO
PB88-180245/AS
TITLE AND SUBTITLE
OAT6
Health Effects Assessment for Ethylene Dibromide
•. PERFORMING ORGANIZATION CODE
AUTHOR(S)
. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND AOORESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME ANO AOORESS
Environmental Criteria and Assessment Office
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. OH 45268
13. TYPE OF REPORT ANO PERIOD COVERED
14. SPONSORING AGENCY CODE
EPA/600/22
15- SUPPLEMENTARY NOTES
16. 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 12991 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
carcinogenicity, qi*s have been computed, if appropriate, based on oral and
inhalation data if available.
7.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.IDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Croup
8. DISTRIBUTION STATEMENT
Public
19. SECURITY CLASS (Thu Report/
Unclassified
21. NO. Of PAGES
30. SECURITY CLASS {Thitpagt)
Unclassified .
22. PRICE
Form 2230.1 («•». 4-77) PMKviou* COITION is OMOLKTC
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EPA/600/8-88/037
October, 1987
HEALTH EFFECTS ASSESSMENT
FOR ETHYLENE OIBROMIDE
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 In 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 ethylene
dlbromlde. All estimates of acceptable Intakes and carcinogenic potency
presented In this document should be considered 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 Assess-
ment (OHEA) sources have been extensively utilized:
U.S. EPA. 1984b. Health and Environment Effects Profile for
l,2-01bromoethane. Prepared by the Office of Health and Environ-
mental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Solid Waste and Emergency
Response, Washington, DC.
U.S. EPA. 1985a. Drinking Water Criteria Document for Ethylene
Dlbromlde (EDB). Prepared by the Office of Health and Environ-
mental Assessment, Environmental Criteria and Assessment Office,
U.S. EPA, Cincinnati, OH for the Office of Drinking Water, Wash-
ington, DC.
The Intent In these assessments Is to suggest acceptable exposure levels
for noncarclnogens and risk cancer potency estimates for carcinogens
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited In
scope tending to generate conservative (I.e., protective) estimates.
Nevertheless, the Interim values presented reflect the relative degree of
hazard or risk associated with exposure to the chemical(s) addressed.
Whenever possible, two categories of values have been estimated for
systemic toxicants (toxicants for which cancer Is not the endpolnt of
concern). The first, RfDs (formerly AIS) or subchronlc 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 (I.e., for an
Interval that does not constitute a significant portion of the Hfespan).
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 In ambient air or water where lifetime
exposure Is 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$i) and oral (RfD$o)
exposures.
111
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The RfO (formerly AIC) Is similar In concept and addresses chronic
exposure. It 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 llfespan [see U.S. EPA (1980a) for a discussion of this concept]. The
RfO 1s route-specific and estimates acceptable exposure for either oral
(RfDg). or Inhalation (RfDj) with the Implicit assumption that exposure
by other routes 1s Insignificant.
Composite scores (CSs) for noncardnogens 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 (1984a).
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 (1980a). Since cancer Is a
process that 1s 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 \n 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 Inter-
pretation and use of the quantitative estimates presented.
Ethylene dlbromide 1s a potent carcinogen In animals, causing tumors of
the forestomach of rats and mice orally exposed (NCI, 1978; Van Duuren et
al., 1985) and tumors of the nasal cavity of rats and respiratory tract of
mice exposed by Inhalation (NTP, 1982). U.S. EPA (1984b, 1985a) estimated a
dose of 8x10"' mg/day associated with a cancer risk of 10~5 for oral
exposure to ethylene dlbromlde based on the Incidence of tumors of the fore-
stomach of male rats 1n the NCI (1978) experiment. A potency factor of 85
(mg/kg/dayr1 was estimated from these data. A human q-j* of 1.37
(mg/kg/day)'1 was estimated for Inhalation exposure by applying the multi-
stage model of Howe and Crump (1982) to data regarding the Incidence of
nasal cavity tumors In male rats (NTP, 1982).
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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. Dr. 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 A1r 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 K1m 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 1
4.1.2. Inhalation '
8IOASSAYS
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
. . . 5
. . . 6
. . . 6
7
. . . 8
. . . 8
. . . 8
11
. . . 12
. . . 12
t- . 12
" . . 12
. . . 12
. . . 12
16
. . . 21
. . . 22
. . . 24
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TABLE OF CONTENTS
6.
7.
,PPF
RISK
6.1.
6.2.
6.3.
REFEf
NDIX:
ASSESSMENT .........
SUBCHRONIC REFERENCE DOSE (RfD$) ......
REFERENCE DOSE (RfD)
CARCINOGENIC POTENCY (q-j*)
6.3.1. Oral
6.3.2. Inhalation
FENCES
Summary Table for Ethvlene 01 bromide
Page
....... 25
....... 25
....... 25
....... 25
25
26
32
42
V111
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LIST OF TABLES
No. Title Page
1-1 Selected Chemical and Physical Properties and
Environmental Fate of Ethylene D1 bromide 2
4-1 Summary of Oral Cardnogenldty Bloassay of Ethylene
D1brom1de 14
4-2 Incidence of Tumors of the Forestomach 1n Male and Female
B6C3F1 Mice Exposed to Ethylene D1brom1de (>99% purity)
1n the Drinking Water 17
4-3 Summary of Oral CarclnogenlcHy Bloassay of Ethylene
D1brom1de 18
6-1 Cancer Data Sheet for Derivation of q-|* 28
6-2 Cancer Data Sheet for Derivation of q-j* 29
6-3 Cancer Data Sheet for Derivation of q-j* 30
6-4 Cancer Data Sheet for Derivation of qi* 31
1x
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LIST OF ABBREVIATIONS
CS Composite score
ppb Parts per billion
ppm Parts per million
RfD Reference dose
RfDi Inhalation reference dose
RfDn, Oral reference dose
RfDs Subchronlc reference dose
RfD$i Subchronlc Inhalation reference dose
RfD$Q Subchronlc oral reference dose
TLV Threshold limit value
TWA Time-weighted average
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1. ENVIRONMENTAL CHEMISTRY AND FATE
Selected chemical and physical properties and environmental fate of
ethylene d1bromide are presented In Table 1-1.
In the atmosphere, ethylene dlbromlde should occur mostly In the vapor
phase and will be decomposed by reaction with photochemically generated HO
radical (NLM, 1986). The atmospheric half-life listed In Table 1-1 was
calculated using a reaction rate constant of 0.25xlO-12 cm3/molecule-sec
at 27°C and an ambient HO radical concentration of S.OxlO3 molecules/cm3
(Singh et al., 1981; U.S. EPA, 1986a). In water, the primary removal
process for ethylene dlbromlde Is evaporation (NLM, 1986). The aquatic
half-lives listed have been calculated using a reaeratlon coefficient ratio
of 0.53 and typical oxygen reaeratlon values of 0.04, 0.01 and 0.008
hour-1 for rivers, ponds and lakes, respectively {NLM, 1986; Lyman et al.,
1982). Ethylene dlbromlde should not significantly bloaccumulate or adsorb
to sediments (NLM, 1986). In soil. It Is expected to be partially removed
by volatilization. Low^dsorptlon to soil and monitoring data Indicate that
this compound Is highly mobile In soil and may leach Into groundwater, where
H would tend to persist (NLH, 1986).
0099h -1- 01/22/87
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TABLE 1-1
Selected Chemical and Physical Properties
and Environmental Fate of Ethylene Olbromlde
Property
Value
Reference
CAS number:
Chemical class:
Molecular weight:
Vapor pressure:
Water solubility:
Log octanol/water
partition coefficient:
Bloconcentratlon factor:
Soil adsorpt1o^:oeff1dent:
Half-lives In
Air:
Water:
Soil:
106-93-4
halogenated aliphatic
compound
187.88
11.7 mm Hg (25°C)
4300 mg/l (25°C)
1.76 (.estimated)
<1 (carp, Cyprlnus
carplo)
14-160
40 days (estimated)
32 hours (river)
(estimated)
130 hours (lake)
(estimated)
163 hours (pond)
(estimated)
NA
Jaber et a!.. 1984
Jaber et al.. 1984
Jaber et al., 1984
Kawasaki, 1980
NLM, 1986
Singh et al., 1981;
U.S. EPA, 19863
NLM, 1986;
Lyman et al., 1982
NA = Not available
OQ99h
-2-
01/22/87
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2. ABSORPTION FACTORS IN HUMAN AND EXPERIMENTAL ANIMALS
2.1. ORAL
Plotnlck et al. (1979) administered a single gavage dose of 15 mg/kg
a«C-ethylene dlbromlde 1n corn oil to young adult male Sprague-Dawley rats
and measured the excretion of radioactivity 1n the urine and feces during
the following 48 hours. Fecal excretion accounted for only 1.65% of the
administered dose of radioactivity, suggesting that ethylene dlbromlde was
almost completely absorbed from the gastrointestinal tract.
2.2. INHALATION
Pertinent data regarding the rate or extent of absorption of ethylene
dlbromlde could not be located 1n the available literature.
0099h -3- 10/20/86
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3. TQX1C1TY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. NCI (1978) administered ethylene dlbroralde In corn oil by
gavage to groups of 5 male and 5 female Osborne-Hendel rats and equal
numbers of B6C3F1 mice at 0, 40, 63, 100, 163 or 251 rag/kg, 5 days/week for
6 weeks followed by a 2-week observation period. In rats, mortality
occurred at >100 mg/kg. Mean final body weights were within 10% of those of
controls at <63 mg/kg. The observations In mice are more difficult to
Interpret because of an apparent discrepancy In the data. Although the
dosages administered appear to be those stated above, NCI (1978) reported
that no mortality occurred In males at <159 mg/kg. Deaths occurred In one
251 mg/kg female and one 100 mg/kg female. Effects on body weights were
Inconsistent. At <159 mg/kg, terminal body weights of females were greater
than those of controls. Hales at 63 and 159 mg/kg had terminal body weights
71 and 91% that of controls, respectively.
In another subchronlc study using B6C3F1 mice, Van Duuren et al. (1985)
administered ethylene dlbromlde In drinking water at 2.7, 5.3 or 10.6 mM
(507, 996 or 1992 mg/l) to groups of 5 males and 5 females for 3 months.
Water consumption was measured for mice at the two higher dose levels and
was determined to be 2.6 and 4.0 rni/mouse/day for males and females,
respectively, at 5.3 mM, and 4.0 end 3.8 ml/mouse/day for males and
females, respectively, at 10.6 mM. All mice survived. Terminal body
weights were 24-26 g for females and 28-29 g for males. The authors
reported that body weights of males were slightly depressed and that the
h1stopatho1og1cal appearance of the forestomach at the end of 1 and 3 months
was "unusual"; further Information was not available. Since starting or
average body weights were not provided, estimation of dose on an mg/kg/day
basis 1s not possible.
0099h -4- . 01/22/87
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Aman et al. (1946) treated an unspecified number of rats and guinea pigs
by gavage with 40-50 mg/kg/day of ethylene dlbromlde In oil or In 50%
aqueous alcohol for -4 months and reported no adverse effects Including body
weight changes. The results of the study are Inconclusive, however, because
the study was Incompletely reported (numbers of animals/groups not speci-
fied) and no evaluation of gross or hlstologlcal examination was performed.
3.1.2. Inhalation. Three subchronlc studies (Reznlck et al., 1980;
NHschke et al., 1981; Rowe et al., 1952) evaluated the toxldty of Inhaled
ethylene dlbromlde to rats, mice, guinea pigs, rabbits and monkeys. In the
range-finding study for the chronic cardnogenldty bloassay of ethylene
dlbromlde (NTP, 1982), Reznlck et al. (1980) and NCI (1978) exposed groups
of 4-6 F344 rats and 10 B6C3F1 mice/sex to 0. 3, 15 or 75 ppm (0, 23, 115 or
580 mg/m3) of ethylene dlbromlde for 6 hours/day, 5 days/week for 13
weeks. There was a concentration-related depressed weight gain In male
rats, but weight gain was depressed 1n female rats only at the highest
level. No effect on mortality was observed In the rats; an Increased
mortality rate was observed In low-dose male and high-dose female mice.
Nasal cavity alterations such as cytomegaly; focal hyperplasla, squamous
metaplasia and loss of cilia were observed In the high-dose groups of both
species, but were absent In the control, medium- and low-dose groups. In
addition, swelling and vacuollzatlon of adrenal cortical cells was observed
In the high-dose rats.
The U.S. EPA (1980b) reported the study by NHschke et al. (1981) In
which an unspecified number of male and female rats were exposed to 0, 23,
77 or 3076 mg/m3 for 6 hours/day, 5 days/week for 13 weeks. Decreased
body weight gain, Increased liver and kidney weights, and epithelial hyper-
plasla and squamous metaplasia of the nasal cavity were observed at 3076
0099h -5- 01/22/87
-------
mg/m*. Slight, reversible epithelial hyperplasla was observed In the
nasal cavity of rats exposed to 77 mg/m3. No adverse effects were
observed 1n rats exposed to 23 mg/m3.
Rowe et al. (1952) exposed rats (20/sex/group), guinea pigs {8/sex/
group), rabbits (3 males, 1 female/group) and monkeys (I/sex/group) to 0, 25
or 50 ppm (0, 190 or 380 mg/m3) of ethylene dlbromlde for 7 hours/day, 5
days/week for experimental periods varying from 213-220 days at 25 ppm and
70-91 days at 50 ppm. The toxlcologlcal parameters Investigated were
general appearance and behavior, growth rate, organ and body weights, and
histology of various organs Including Hver, kidney, lung, adrenals and
testes, but not the nasal cavity. No treatment-related adverse effects were
observed In any species at 25 ppm. High mortality from Infections of the
respiratory tract was observed 1n both sexes of exposed guinea pigs and 1n
male rats. At 50 ppm. Increased liver and kidney weights (both sexes).
Increased lung weights (males), decreased testlcular weight and decreased
spleen weight (females) were observed In the rats. High mortality, attrib-
uted to Infections of the respiratory tract, occurred In 10/20 male and 4/20
female rats. Decreased body weight gain, slight central fatty degeneration
of the liver and renal tubular epithelium degeneration were observed In the
guinea pigs. Rabbits and monkeys had slight Increases In liver weights.
The Investigators concluded that rabbits and monkeys and "probably" rats and
guinea pigs tolerated the 25 ppm exposure without adverse effects.
3.2. CHRONIC
3.2.1. Oral. In a cancer bloassay (NCI, 1978), groups of 50 male and 50
female Osborne-Mendel rats and Identical numbers of B6C3F1 mice were treated
by gavage with ethylene dlbromlde In corn oil. The TWA dosages received by
male rats were 27.4 or 29.1 mg/kg/day; by female rats, 26.7 or 28.1
mg/kg/day; and by male and female mice, '0, 43.9 or 76.6 mg/kg/day. Controls
0099h -6- 01/22/87
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consisted of 20 anlmals/sex/spedes. (Further details are provided In
Section 4.2.1.) Dose-related weight depression and early mortality was
observed In the rats and mice, but may have been tumor-related. Treatment-
related, but not dose-related, changes (pellosls hepatls) occurred In the
livers of male but not female rats. Adrenal cortical degeneration was
observed In a small number of treated male and female rats. No adrenal
effects were observed In mice. Although the Incidence of testlcular degen-
eration was not Increased In treated rats, testlcular degeneration occurred
at an earlier age In the ethylene dlbromlde treated rats compared with con-
trols. Testlcular atrophy occurred 1n the mice only at the high dose level.
3.2.2. Inhalation. Two studies (NTP, 1982; Wong et al., 1982) designed
primarily to evaluate the carclnogenldty of ethylene dlbromlde also
reported nonneoplastlc effects of Inhalation exposure to ethylene dlbromlde.
In the NTP (1982) bloassay, groups of 50 F344 rats and 50 B6C3F1 mice were
exposed to 0, 10 or 40 ppm (0, 77 or 310 mg/m3) ethylene dlbromlde
(99.3-99.4% pure) 6 hours/day, 5 days/week for 78-106 weeks. Weight depres-
sion was observed In mice and rats of both sexes. Increased mortality rate
was observed 1n male and female rats exposed to the high dose level. In male
mice exposed to the low dose level, and In female mice exposed to both dose
levels. The Incidence of liver necrosis and renal toxic degeneration was
significantly Increased In male and female rats and In female mice exposed
to the high dose level. The Incidence of testlcular degeneration was
significantly Increased 1n the rats exposed to both dose levels, but was not
altered In mice exposed to ethylene dlbromlde. Female rats had an Increased
Incidence of adrenal cortical degeneration at the high dose level and an
Increased Incidence of retinal atrophy at both dose levels tested. Rats and
mice of both sexes had Inflammatory and hyperplastic lesions In the respira-
tory epithelium.
0099h -7- 01/22/87
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In the Wong et al. (1982) study, groups of 48 Sprague-Oawley rats/sex
were exposed to 0 or 20 ppm (0 or 154 mg/ra3) of ethylene d'ibromlde (99%
purity) for 7 hours/day, 5 days/week for 18 months. Body weight and
survival rate were decreased 1n treated males and females. Testlcular
atrophy was not observed 1n treated rats. Hematologlcal parameters appeared
normal In both males and females after 10-12 months of exposure. The nasal
cavity was not evaluated In the Wong et al. (1982) study.
3.3. TERATOGENIC AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenlc effects of ethyl-
ene dlbromlde after Ingestlon could not be located 1n the available litera-
ture. The antlspermatogenlc effect of Ingesting ethylene dlbromlde, as
evidenced by structurally abnormal sperm displaying low motllHy and density
and a depopulation of the seminiferous tubules, was observed In bulls (Amir
and Volcanl, 1965, 1967); these effects were reversible (Amir and Ben-0av1d,
1973; Amir, 1975; Amir et al., 1977, 1979). Ingestlon of ethylene dlbromlde
by rams has not resulted in adverse spermatogenlc effects (Amir and
Ben-David, 1973). NCI (1978) reported an earlier onset of testlcular
atrophy 1n rats and an Increased Incidence of testlcular atrophy at the high
dose level In mice treated chronically by gavage.
3.3.2. Inhalation. Two Inhalation studies (Short et al., 1976, 1978)
reviewed 1n detail by the U.S. EPA (1984b, 1985a), Indicate that ethylene
dlbromlde 1s teratogenlc 1n rats and mice. A third study evaluated the
behavioral effects of ethylene dlbromlde on pups of exposed rats (Smith and
Goldman, 1983). In the first study, groups of 17-18 pregnant Charles River
CD rats and 9-17 pregnant CD-I mice were exposed to 0 (diet ad libitum), 0
(diet restricted) or 32 ppm (246 mg/m3) of ethylene dlbromlde for 23
hours/day on days 6-15 of gestation (Short et al., 1976). The rats and mice
0099h -8- 10/14/87
-------
were sacrificed on gestaUonal days 20 and 18, respectively. Significantly
decreased food consumption and body weight gain, but no effect on the
mortality rate, was observed 1n the dams of both species. No effect on
fetal weight was observed In rats or mice. Utter size was significantly
decreased In rats, but not mice, exposed to ethylene d1bromide. In addi-
tion, a significantly Increased Incidence of hydrocephaly, wavy ribs and
extra ribs was observed In the pups of rats exposed to ethylene dlbromlde
during gestation. Similar effects were not observed In pups from rats fed
the restricted diets. Although the Incidence of skeletal anomalies and
hydrocephaly was significantly Increased In the fetuses of mice compared
with unrestricted diet fed controls, the biological significance of this
result Is difficult to Interpret because of the Increased Incidence of
skeletal anomalies and hydrocephaly In the diet-restricted mice.
In the second study (Short et al., 1978), groups of 11-17 pregnant
Charles River CD rats and 9-19 pregnant CD-I mice were exposed to 0 (diet ad
libitum). 0 (diet restricted), 20, 38 or 80 ppm (154, 292 or 615 mg/m3) of
ethylene dlbromlde for 23 hours/day on days 6-15 of gestation. The rats and
mice were sacrificed on gestatlonal days 20 and 18, respectively. The
maternal mortality rate was 50 and 100% for the rats and mice, respective-
ly, exposed to 80 ppm, and 41% for the mice exposed to 38 ppm of ethylene
dlbromlde. No live pups or viable fetuses were obtained from the rats
exposed to 80 ppm. Decreased numbers of viable fetuses/litter were observed
In the rats exposed to 80 ppm and In the mice exposed to 80 and 38 ppm. An
Increased Incidence of resorptlons was observed In rats exposed to 80 ppm
and In mice exposed to all levels of ethylene dlbromlde tested. Decreased
fetal body weight was observed In the rats exposed to 38 ppm and In the mice
exposed to 20 and 38 ppm.
0099h -9- 01/22/87
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Groups of 16 pregnant Long-Evans rats were exposed to 0, 0.43, 6.67 or
66.67 ppm (3.3, 51.3 or 512.3 mg/m3) of ethylene dlbromlde 4 hours/day, 3
days/week from day 3-20 of gestation (Smith and Goldman, 1983). Behavioral
testing of the pups (rotorod, open field activity, straight alley activity,
T-maze discrimination and passive avoidance) was performed at Intervals
between 30 and 100 days postpartum. Decreased gestatlonal weight gain of
dams, enhanced rotorod and T-maze discrimination were observed 1n the
middle- and high-dose groups. No behavioral effects were observed at the
lowest dose level evaluated. No effect on Utter size was observed at any
dose level evaluated.
To evaluate the effect of Inhaled ethylene dlbromlde on reproduction,
groups of 18-20 male Charles River CO rats were exposed to 19, 38 or 89 ppm
(146, 292 or 684 mg/m3) of ethylene dlbrcmlde for 7 hours/day, 5 days/week
for 10 weeks (Short et al., 1979). Half of the males were killed after
exposure and their serum testosterone levels and testlcular histology were
examined. The remaining exposed males were mated to females who had been
exposed to 0, 20, 39 or 80 ppm (0, 154, 300 or 615 mg/m3) for 7 hours/day,
7 days/week for 3 weeks. Hales exposed to 89 ppm (684.0 mg/m3) of
ethylene dlbromlde had reduced food consumption, reduced serum testosterone
concentrations and atrophy of the reproductive organs, and failed to Impreg-
nate any females; the females exposed to 80 ppm (615 mg/m3} had abnormal
estrus cycles during exposure. No adver ,e reproductive effects were
observed at lower exposure levels 1n either males or females.
In the carcinogen bloassay In which rat: and mice were exposed to 0.10
or 40 ppm (NTP, 1982) (Chapter 4), the Incidence of testlcular atrophy was
significantly Increased In the F344 rats at both dose levels, but not In the
B6C3F1 mice. Wong et al. (1982) reported that an Increased Incidence of
0099h -10- 10/20/86
-------
testlcular atrophy was not observed 1n the Sprague-Dawley rats exposed to 20
ppm (154 ing/m*) of ethylene d1bromide for 7 hours/day. 5 days/week for 18
months. Both studies used exposure levels of ethylene dlbromlde suffi-
ciently high to be associated with a significantly Increased Incidence of
cancer 1n F344 and Sprague-Dawley and B6C3F1 mice.
3.4. TOXICANT INTERACTIONS
Administration of either of two cytochrome P-450 Inhibitors, d1sulf1ram
and d1ethyld1th1ocarbamate, enhances the carc1nogen1c1ty and hepatic and
testlcular tox1c1ty of ethylene dlbromlde (Wong et al., 1982; Nachtoml,
1980, 1981). Conversely, pretreatment of rats with the mlcrosomal enzyme
Inducer, phenobarbltal, decreased the hepatic toxlclty of ethylene dlbromlde
(Nachtoml, 1980, 1981).
0099h -11- 10/20/86
-------
4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the carcinogenic potential of
ethylene dlbromlde to orally exposed humans could not be located In the
available literature.
4.1.2. Inhalation. No statistically significant effect on the mortality
rate or the Incidence of cancer or respiratory disease was associated with
occupational exposure to ethylene dlbromlde In one published study (Ott et
al., 1980) and two unpublished studies (Ter Haar, 1978). Further details of
the studies are reported In U.S. EPA (1985a). The Interpretation of the
results of these studies, however, Is complicated by small population size,
poorly quantified levels of exposure and concomitant exposure to numerous
other chemicals.
4.2. BIOASSAYS
4.2.1. Oral. Significantly Increased Incidences of a variety of tumors
in rats and mice were reported 1n the MCI (1978) oral bloassay of ethylene
dlbromlde. Technical grade ethylene dlbromlde (purity 96.2-99.6%) was
administered In corn oil by gavage to groups of 50 Osborne-Mendel rats/sex
and 50 B6C3F1 mice/sex. Initially, rats of both sexes were treated with 40
or 80 mg/kg, 5 days/week, and mice of both sexes were treated with 60 or 120
mg/kg, 5 days/week. Groups of 20 rats/sex and 20 mice/sex served as
untreated controls. Identical groups were maintained as vehicle treated
controls. Early mortality In the high-dose rats prompted a 13-week suspen-
sion of treatment after 16 weeks, and a subsequent resumption of treatment
at the same dosage that the low-dose rats were receiving, resulting in TWA
doses of 38 and 41 mg/kg, 5 days/week for low- and high-dose nwles, and 37
and 39 mg/kg, 5 days/week for low- and high-dose females, respectively.
0099h -12- 01/22/87
-------
Male rats were terminated after 49 weeks and female rats were terminated
after 61 weeks.of treatment. No observation period following the treatment
period was provided. Alterations In the dosage level administered to mice
resulted 1n TWA doses of 62 and 107 mg/kg, 5 days/week 1n low- and high-dose
groups, respectively. Treatment of mice continued for 53 weeks; observation
periods without treatment were 24 weeks for high-dose males, 25 weeks for
low-dose males and high-dose females, and 37 weeks for low-dose females. As
summarized In Table 4-1, significantly Increased Incidences of squamous cell
carcinomas of the forestomach (both species, both sexes), hepatocellular
carcinomas and neoplastlc nodules of the liver (female rats), hemanglo-
sarcomas of the circulatory system (male rats) and alveolar/bronchlolar
adenomas (mice, both sexes) were observed. Squamous cell carcinomas of the
forestomach 1n the rats appeared as early as 12-15 weeks after the start of
treatment, and occurred 1n 97-100% of the high-dose males and the low- and
high-dose females that survived beyond 15 weeks of treatment. Forestomach
carcinomas developed In 78-92% of the male mice that survived 26 weeks and
In 76-100% of the female mice that survived 14-18 weeks of treatment.
Van Duuren et al. (1985) noted an Increased Incidence of stomach tumors
1n B6C3F1 mice exposed to ethylene dlbromlde In drinking water for 15-17
months. In th)s experiment, 30 males and 30 females were provided drinking
water containing ethylene dlbromlde (>99% pure) that supplied 116 and 103
mg/kg/day, respectively, until spontaneous death or sacrifice at 15 months
(males) or 17 months (females). Distilled water-treated controls consisted
of 50 mice/sex, apparently sacrificed at 18 months. The concentration of
ethylene dlbromlde In the drinking water depressed water consumption by 25%
In the males and 34% In the females. The Investigators determined that
males consumed ethylene dlbromlde at 116 and females at 103 mg/kg/day.
0099h -13- 10/20/86
-------
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Survival was depressed In treated mice, which was attributed to the develop-
ment of stomach tumors. Necropsy and hlstopathologlcal examination revealed
these tumors to be papniomas and squamous cell carcinomas of the fore-
stomach. Detailed results are presented In Table 4-2. Other statistically
significant Increased Incidences of tumors Included tumors 1n the glandular
stomach and liver of males and the liver of females, but these all repre-
sented extension or metastases of squamous cell carcinomas from the fore-
stomach.
4.2.2. Inhalation. The chronic Inhalation bloassays (NTP, 1982; Wong et
al., 1982; Stlnson et al., 1981) Indicate that ethylene dlbromlde Is asso-
ciated with an Increased Incidence of tumors In rats and mice. Groups of 50
F344 rats/sex and 50 B6C3F1 mice/sex were exposed to 0, 10 or 40 ppm (0, 77
or 307 mg/m3) of ethylene dlbromlde (99.3-99.4% pure) 6 hours/day, 5 days/
week for 78-106 weeks (NTP, 1982). Details are summarized 1r» Table 4-3.
Chronic Inhalation of.ethylene dlbromlde was associated with a significantly
Increased Incidence of nasal tumors 1n both male and female rats at both
dose levels, as well as hemanglosarcomas (splenic) and mesothellomas (tunica
vaginal Is) In male rats exposed to the high dose level, mammary flbro-
adenomas In females exposed to both dose levels, and bronchlolar/alveolar
carcinomas or adenomas and hemanglosarcomas In female rats exposed to the
high dose level. Chronic Inhalation of ethylene dlbromlde was associated
with a significantly Increased Incidence of adenomas or carcinomas In the
respiratory system of male mice exposed to the highest dose level and of
female mice exposed to both dose levels; subcutaneous flbrosarcomas,
hemanglosarcomas and mammary adenocarclnomas 1n female mice exposed to both
dose levels; and nasal carcinomas In female mice exposed to the high dose
level only. For specific Incidences and tumor types, see Table 4-3.
OQ99H -16- 01/22/87
-------
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Although the studies of Wong et al. (1982) and Stlnson et al. (1981) are
limited In their design, they support the association between the Inhalation
of ethylene dlbromlde and the Increased Incidences of tumors In rats and
mice. In the Wong et al. (1982) study designed to evaluate the combined
effect of ethylene dlbromlde Inhalation and dlsulflram Ingestlon, groups of
48 Sprague-Oawley rats of each sex were exposed to 0 or 20 ppm (0 or 154
mg/m3) ethylene dlbromlde (99% purity) for 7 hours/day, 5 days/week for 18
months. A significant Increase In the Incidence of hemanglosarcomas
(splenic) and adrenal tumors (carcinoma, phenochromocytoma and cortical
adenoma) were observed 1n both male and female rats, as well as subcutaneous
tumors In males and mammary tumors (adenoma, fIbroadenoma, carcinoma or
adenocardnoma) In females. The nasal cavities of the rats exposed to
ethylene dlbromlde were not evaluated by Wong et al. (1982). In the Stlnson
et al. (1981) study designed to evaluate the Incidence of tumors in the
nasal cavity only, groups of 49-50 B6C3F1 mice/sex were exposed to 0, 10 or
40 ppm (0, 77 or 307 mg/m3) ethylene dlbromlde for 6 hours/day, 5 days/
week for 90-103 weeks. The mice were kITled within 1 week of the end of
treatment. An Increased Incidence of nasal tumors occurred 1n the female
mice and an Increased Incidence of nasal-epithelial hyperplasla occurred 1n
the male mice at the high dose level only. Neither sex had an elevated
tumor Incidence at the low dose level. The statistical significance of this
observation Is not clear, however, since no probability values were reported.
4.3. OTHER RELEVANT DATA
The mutagenlc activity of ethylene dlbromlde has been reviewed by Fahrlg
(1974), IARC (1977), Rannug (1980) and the U.S. EPA (1984b, 1985a). Posi-
tive results have been reported 1n reverse mutation assays with Salmonella
typhlmuMum strains G46, TA1530, TA1535 and TA100 both with and without
0099h -21- 10/14/87
-------
metabolic activation (Buselmaler et al.. 1976; Brera et al., 1974; Ames and
Yanofsky, 1971; Rannug et al., 1978; Stolzenberg and Mine, 1980; Van
Bladeren et al., 1980; Principe et al., 1981; Shlau et al., 1980). Reduced
rautagenlc activity (Barber et al., 1981} or no mutagenlc activity (Brem et
al., 1974; Principe et al., 1981) 1n S. typhlmurlum strains TA1538 and TA98
also have been observed. Ethylene dlbromlde was mutagenlc to Escher1ch1a
coll with or without metabolic activation {Brem et al., 1974; Hemm1nk1 et
al., 1981), but reverse mutations 1n Bacillus subtlUs occurred only 1n the
presence of rat liver mlcrosomal enzymes (Shlau et al., 1980). The Inci-
dence of recessive lethal mutations In Drosophlla melanogaster was Increased
after exposure to ethylene dlbromlde vapor (Vogel and Chandler, 1974; Kale
and Baum, 1979, 1982). Ethylene dlbromlde was mutagenlc to cultivated
mammalian cells 1n the absence of mlcrosomal activation (Tezuka et al.,
1980; Cllve, 1973; Williams et al., 1982; Tan and Hs1e, 1981; Crespl et al.,
1985), but was not associated with an Increased Incidence of dominant lethal
mutations In either rats or mice (Shlrasu et al., 1984).
4.4. HEIGHT OF EVIDENCE
Based on the results of the NCI (1978) bloassay 1n which a significantly
Increased Incidence 1n squamcus cell carcinoma of the forestomach was
observed trv male and female Osborne-Mendel rats and B6C3F1 mice treated by
gavage 5 days/week for -1 year with ethylene dlbromlde, and a significantly
Increased Incidence 1n nasal epithelial tumors was observed 1n male and
female F344 rats and female B6C3F1 mice Inhaling ethylene dlbromlde for -2
years, ethylene dlbromlde 1s -nost appropriately classified In GAG Group 82
and IARC Group 2B (U.S. EPA, 1985b). CAG Group B2 chemicals are probable
human carcinogens and Include chemicals for which the evidence for carclno-
genlclty Is adequate In animals but Inadequate In humans (U.S. EPA, 1986).
0099h -22- 01/22/87
-------
IARC Group 2B Includes chemicals for which there 1s sufficient evidence of
carclnogenldty 1n animals but Inadequate cardnogenlcHy data 1n humans
(IARC, 1982).
0099H -23- 10/20/86
-------
5. REGULATORY STANDARDS AND CRITERIA
The ACGIH (1985, 1986) has classified ethylene dlbromlde as an A2
chemical. Indicating Us potential to cause tumors In humans based on Its
cardnogenlclty 1n rats and mice after oral (NCI, 1978) and Inhalation (NTP,
1982) exposure. No TLV has been assigned to ethylene dlbromlde, but the
skin notation used with ethylene dlbromlde Indicates the potential contribu-
tion dermal absorption may have on the body burden of Individuals exposed to
ethylene dlbromlde. OSHA (1985) no longer promulgates a standard for
ethylene dlbromlde exposure.
The U.S, EPA has suspended the use of pesticide products containing
ethylene dlbromlde as a soil fumlgant (U.S. EPA, 1983). U.S. EPA (1984b,
1985a) reports tolerances for ethylene dlbromlde In food products of 900 ppb
for raw grain for human consumption, 150 ppb for flour and 30 ppb for
ready-to-eat products.
0099h -24- 10/14/87
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6. RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE DOSE (RfD$)
The results of the NCI (1978) and NTP (1982) bloassays In which ethylene
dlbromlde was associated with significantly Increased Incidences of tumors
1n rats and mice preclude the derivation of RfDc values for ethylene
O
dlbromlde.
6.2. REFERENCE DOSE (RfD)
The results of the NCI (1978) and NTP (1982) bloassays In which rats and
mice had significantly Increased Incidences of tumors preclude derivation of
RfD values.
6.3. CARCINOGENIC POTENCY (q.,*)
6.3.1. Oral. Carc1nogen1c1ty bloassays In laboratory animals can provide
a basis for estimating the carcinogenic risk of ethylene dlbromlde to
humans. Several studies have demonstrated the carclnojgenlclty of ethylene
dlbromlde 1n rodents exposed by Inhalation {NTP, 1982; Wong, 1982; Stlnson
et a!., 1981), oral Intubation (NCI, 1978) and dermal application. Because
unequivocal evidence of cardnogenldty In man from ethylene dlbromlde
exposure Is not available, animal studies must be relied upon for assessment
of the risks for humans.
The U.S. EPA (1984b, 1985a) used the data from the NCI (1978) study In
the derivation of doses of ethylene dlbromlde associated with excess cancer
risk. A high Incidence of forestomach carcinoma was observed In all
exposure-specles-sex groups In a relatively short period of time.
0099h -25- 10/14/87
-------
To use these data, a mathematical model that Incorporated variable
partial lifetime exposure was developed (U.S. EPA, 19845). In this model
(Thorslund, 1982), a human risk at age t that Is due to an exposure of d
mg/kg/day from age s to f was estimated from the equation:
P(t,d) = l-e-&.958xlO-14 x d x [(t-s)7-6-(t-f)7-6] (&_•,)
However, a numerical mistake was found 1n the derivation of the
parameter 6.958xlO~14 In the Thorslund paper. In deriving the dose
correction factor on page 19, the statement was made that 0.59x7/5=0.708,
whereas the correct result Is actually 0.826. With this correction, the
parameter 6.958xlO~14 becomes 8.228xlO"14.
That equation, however, was based upon an equivalency assumption between
species on an mg/kg basis. Assuming mg/surface area exposure equivalency, a
70 kg human and a 500 g rat, the exponent 1n the above equation Is multl-
1/1
plied by (70/0.5) = 5.192, which gives the'result:
P(t,d) = 1-6-4.215x10-13 x d x [(t-s)7-6-(t-f)7-&;j (6_2)
For continuous lifetime exposure, s=o and t and f are 76.2 years so that
the dose-dependence of the lifetime risk becomes:
P(d)=l-e'«»d
where d 1s the mg/kg/day dose. This 1s equivalent to a q,* value of 85
(mg/kg/day)~l or 0.085 (vg/kg/day)~a. The water concentration
corresponding to a 10~4, 10~s and 10~* lifetime risk Is, assuming a
drinking water Intake of 2 I/day, 4xlO~2, 4x10~3 and 4xlO"4 mg/a,
respectively. If the exposure duration 1s less than a lifetime, the risk
depends on both the duration and the age of exposure as given In the
previous equation.
6.3.2. Inhalation. The NTP (1982) experiment 1n which a high Incidence
of tumors 1n the nasal cavity were observed In rats and a high Incidence of
0099h -26- 10/14/87
-------
tumors of the respiratory tract were observed In mice Is appropriately
chosen as the basis for estimation of carcinogenic potency due to Inhalation
exposure. In keeping with the methodology endorsed by U.S. EPA (1980a) for
estimating carcinogenic potencies to humans from animal exposure data, the
multistage model was applied to the data presented 1n Tables 6-1, 6-2, 6-3
and 6-4. The highest human q * Is 1.37 (mg/kg/day)"1 based on the
Incidence of tumors of the nasal cavity 1n male rats (NTP, 1982). This
value Is chosen to represent the carcinogenic potency of ethylene dlbromlde
to humans exposed by Inhalation.
0099h -27- 10/14/87
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TABLE 6-1
Cancer Data Sheet for Derivation of q-|*
Compound: Ethylene d1bromide
Reference: NTP, 1982
Species, Strain, Sex: rat, F344, male
Body weight: 0.300 kg
(estimated from graphic data provided by Investigators)3
Length of exposure (le) = 88 weeks high dose, 103 weeks low dose
Length of experiment (Le) = 88 weeks high dose, 103 weeks low dose
Llfespan of animal (L) = 104 weeks
.Tumor site and type: total tumors of the nasal cavity
Route, vehicle: Inhalation
Incidence
Experimental Doses Transformed Dose No. Responding/No. Tested
or Exposures (mg/kg/day) or Examined
0 0 0/50
10 ppm (77 mg/m3)b 9.0c»d 39/50
40 ppm (307 mg/m3)b 22.3c'e 41/50
Human q.,* * 1.37 (mg/kg/day)~lf'9
aAlthough the Investigators reported that body weights of high-dose rats
were below those of controls throughout the study, statistical analysis was
not performed and visual Inspection of graphic data did not suggest that
differences were biologically significant.
Exposure 6 iiours/day, 5 days/week
cTransformed dose calculated by expanding to continuous exposure and assum-
ing Inhalation volume of 0.105 (W/0.113)2/3 (U.S. EPA, 1985c) where M =
estimated body weight of 0.300 kg.
Includes a factor of (103/104)3 to convert for less-than-Hfetlme
duration of experiment.
elncludes a factor of (88/104)3 to convert for less-than-Hfetlme
duration of experiment.
High dsse data dropped to accommodate chl-square goodness of fit.
Qlncludss a factor of (70/0.300)1/3 to account for differences In body
weight between rats and humans.
0099h -28- 10/14/87
-------
TABLE 6-2
Cancer Data Sheet for Derivation of q-|*
Compound: Ethylene dlbromide
Reference: NTP, 1982
Species, Strain, Sex: rat, F344, female
Body weight: 0.225 kg
(estimated from graphic data provided by Investigators)3
Length of exposure (1e) = 91 weeks high dose, 103 weeks low dose
Length of experiment (Le) * 91 weeks high dose, 104 weeks low dose
Llfespan of animal (L) = 104 weeks
Tumor site and type: total tumors of the nasal cavity
Route, vehicle: Inhalation
Incidence
Experimental Doses Transformed Dose * Mo. Responding/No. Tested
or Exposures (mg/kg/day) or Examined
0
10 ppm
40 ppm
(77 mg/m3)0
(307 mg/m3)b
0
10. lc
27.ic.d
1/50
34/50
43/50
Human q-)* = 0.73 (mg/kg/day)~ie
aAHhough the Investigators reported that body weights of high-dose rats
were below those of controls throughout the study, statistical analysis was
not performed and visual Inspection of graphic data did not suggest that
differences were biologically significant.
Exposure 6 hours/day, 5 days/week
transformed dose calculated by expanding to continuous exposure and assum-
ing an Inhalation volume of 0.105 (W/0.113)2/3 (U.S. EPA, 1985c) where
W = estimated body weight of 0.225 kg.
^Includes a factor of (91/104)3 to correct for less-than-Hfetlme
duration of experiment.
elnclude~s a factor of (70/0.225)1/3 to account for differences 1n body
weight between rats and humans.
0099h -29- 10/14/87
-------
TABLE 6-3
Cancer Data Sheet for Derivation of q-|*
Compound: Ethylene dlbromide
Reference: NTP, 1982
Species, Strain, Sex: mouse, B6C3F1, male
Body weight: 0.035 kg control and low group; 0.027 kg high group (estimated
from graphic data provided by Investigators)
Length of exposure (le) = 78 weeks
Length of experiment (Le) = 78 weeks
Llfespan of animal (L) = 104 weeks
Tumor site and type: total respiratory tract tumors
Route, vehicle: Inhalation
Incidence
Experimental Doses Transformed Dose No. Responding/No. Tested
or Exposures (mg/kg/day) or Examined
0 0 0/41
10 ppm (77 mg/m3)3 0.6b»c 3/48
40 ppm (307 mg/m3)* 2.3c«d 25/46
Human q-j* = 0.21 (mg/kg/day)'1
Exposure 6 hours/day, 5 days/week
^Transformed dose calculated by expanding to continuous exposure and assum-
ing an Inhalation volume of 0.0345(W/0.025)2/3 where W = estimated body
weight of 0.035 kg. .
clncludes a factor of (78/104)3 and (0.035/70)1/3 to correct for
Iess-than-ltfet1me length of experiment and convert from an animal to human
dose 1n derivation of human q-j*.
^Transformed dose calculated by expanding to continuous exposure and assum-
ing an Inhalation volume of 0.0345{W/0.025)2/3 where W = estimated body
weight of 0.027 kg.
0099h -30- TO/14/87
-------
TABLE 6-4
Cancer Data Sheet for Derivation of q-|*
Compound: Ethylene
-------
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0099h -41- 10/14/87
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