EPA/6OO/B-91/016
May 199O
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR BROMOCHLQROMETHANE
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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1
TECHNICAL REPORT DATA
(Please nod Instructions on ike rtvene be fort completing)
. REPORT NO.
'EPA/600/8-91/016
3. RECIPIENT'S ACCESSION NO.
PB91-213702
|4. TITLE AND SUBTITLE
Health and Environmental Effects Document for
Bromochloromethane
6. REPORT DATE
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND 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
16. ABSTRACT
Health and Environmental Effects Documents (HEEDS) are prepared for the Office of
Solid Waste and Emergency Response (OSWER). This document series is intended to
support listings under the Resource Conservation and Recovery Act (RCRA) as well as
o provide health-related limits and goals for emergency and remedial actions under
he Comprehensive Environmental Response, Compensation and Liability Act (CERCLA).
Both published literature and information obtained from Agency Program Office files
are evaluated as they pertain to potential human health, aquatic life and environmen-
tal effects of hazardous waste constituents.
Several quantitative estimates are presented provided sufficient data are
available. For systemic toxicants, these include Reference Doses (RfDs) for chronic
and subchronic exposures for both the inhalation and oral exposures. In the case of
suspected carcinogens, RfDs may not be estimated. Instead, a carcinogenic potency
factor, or q^, is provided. These potency estimates are derived for both oral and
inhalation exposures where possible. In addition, unit risk estimates for air and
drinking water are presented based on inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxicity and carcinogenicity are
derived. The RQ is used to determine the quantity of a hazardous substance for
which notification is required in the event of a release as specified under CERCLA.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COS AT I Field/Croup
STATEMENT
Public
19. SECURITY CLASS (
Unclassified
21. NO. OF PAGES
98
20. SECURITY CLASS (Thispagt)
Unclassified
22. PRICE
EPA Form 2220-1 (It**. 4-77) PMKVIOU* COITION I* OB»OLCTC
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DISCLAIMER
This document has been reviewed 1n accordance with the U.S. Environ-
mental 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.
i
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PREFACE
Health and Environmental Effects Documents (HEEDs) are prepared for the
Office of Solid Haste and Emergency Response (OSWER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for
emergency and remedial actions under the Comprehensive Environmental
Response, Compensation and Liability Act (CERCLA). Both published
literature and Information obtained for Agency Program Office files are
evaluated as they pertain to potential human health, aquatic life and
environmental effects of hazardous waste constituents. The literature
searched for In this document and the dates searched are Included In
"Appendix: Literature Searched." Literature search material Is current up
to 8 months previous to the final draft date listed on the front cover.
Final draft document dates (front cover) reflect the date the document Is
sent to the Program Officer (OSWER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include: Reference doses
(RfDs) for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD, Is an estimate of an
exposure level which would not be expected to cause adverse effects when
exposure occurs during a limited time Interval I.e., for an Interval which
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 focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfOs 1s the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, a carcinogenic potency factor, or
q-j* (U.S. EPA, 1980), Is provided. These potency estimates are derived
for both oral and Inhalation exposures where possible. In addition, unit
risk estimates for air and drinking water are presented based on Inhalation
and oral data, respectively. An RfD may also be derived for the noncarclno-
genlc health effects of compounds that are also carcinogenic.
Reportable quantities (RQs) based on both chronic toxldty and
carclnogenldty are derived. The RQ Is used to determine the quantity of a
hazardous substance for which notification 1s required In the event of a
release as specified under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). These two RQs (chronic toxlclty
and carclnogenldty) represent two of six scores developed (the remaining
four reflect IgnHablHty, reactivity, aquatic toxlclty, and acute mammalian
toxlclty}. Chemical-specific RQs reflect the lowest of these six primary
criteria. The methodology for chronic toxlclty and cancer based RQs are
defined 1n U.S. EPA,, 1984 and 1986a, respectively.
Ill
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EXECUTIVE SUMMARY
Bromochloromethane Is a clear, colorless liquid with a sweet odor
(Stenger, 1978). It Is completely mlsdble with most common organic
solvents (Stenger, 1978} and soluble In water to the extent of 16.7 g/a at
25°C {Tewarl et al., 1982). Current production figures are not available.
Recent manufacturers of bromochloromethane Include Dow Chemical and Ethyl
Corporation (USITC, 1988; SRI, 1989). Bromochloromethane Is used mainly as
a fire-extinguisher fluid In aircraft and portable extinguishers (Stenger,
1978). It Is also used In chemical synthesis (Kuney, 1988).
Bromochloromethane Is expected to degrade relatively slowly In the
atmosphere. Using the method of Atkinson (1987), the half-life with respect
to HO- reaction can be estimated at ~168 days. This suggests that ~2X of
tropospherlc bromochloromethane will diffuse Into the stratosphere and be
destroyed by direct photolysis. Physical removal from the atmosphere by wet
deposition may be possible, but Its relative significance Is not known. A
single blodegradatlon study (Tabak et al., 1981) suggested that blodegrada-
tlon of bromochloromethane 1s an Important environmental fate process.
Volatilization from water and soil surfaces Is a major fate process.
Volatilization half-lives of 4 and 47 hours were estimated for a model river
(1 m deep) and for an environmental pond, respectively (Thomas, 1982; U.S.
EPA, 1986b). Bromochloromethane may leach readily 1n soils, based upon an
estimated K value of 21 (Swann et al., 1983). Aquatic hydrolysis Is not
environmentally significant (Mabey and Mill, 1978).
Bromochloromethane has been detected In drinking water (Suffet et al.,
1980; Lucas, 1984), groundwater (Zoeteman et al., 1981), Lake Ontario and
Niagara River water (1-10 ng/4) (Kaiser et al., 1983) and open seawater
from the Atlantic Ocean (0.02 ng/a) (Class and Ballschmlter, 1988).
1v
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Levels of 0.2-0,4 ppt have been Identified In air over the Atlantic Ocean
(Class and BallschmHer, 1988), while levels of 2.4-2.9 ppt were detected In
the Alaskan Arctic (Rasmussen and Khalll, 1984). Bromochloromethane has
also been Identified In air samples collected near a hazardous waste site 1n
New Jersey (Lareglna et al., 1986). It has been suggested that the presence
of bromochloromethane In marine water and air may be due, In part, to Us
blogenlc formation 1n algae, followed by release to seawater, with subse-
quent volatilization (Class and Ballschmlter, 1988). The classic haloform
reactions responsible for the formation of chloroform and other halomethanes
during chlorlnatlon of drinking water will not produce bromochloromethane
(NAS, 1980).
Summarized toxIcHy data for bromochloromethane consisted of a NOEL of
80 mg/a for fathead minnows, P. promelas. and an LC5Q (duration not'
reported) of >80 rag/a, (U.S. EPA, 1987). Bromochloromethane has been
found In tissues of rainbow trout, S. qalrdnerl. from the Colorado River.
The estimated whole-fish concentration was 8 vg/t (Hlatt, 1983).
Bromochloromethane Is rapidly absorbed by rats In a blphaslc manner
following acute Inhalation exposure (Gargas and Andersen, 1982), but quanti-
tative data are not available regarding the extent of Inhalation exposure or
the rate or extent of oral exposure. There appears to be some distribution
of bromide to the brain of dogs during subchronlc Inhalation exposure
(Svlrbely et al., 1947). Rat tlssueiblood partition coefficients (Gargas et
al., 1986a,b) suggest that bromochloromethane will distribute more readily
to fat than to liver or muscle. Available data Indicate that bromochloro-
methane Is metabolized by two major pathways: an oxldatlve, cytochrome P-450
mediated pathway yielding CO and hallde by putative formyl hallde Inter-
mediates, and a glutathlone (GSH)-dependent cytosollc pathway producing
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COp and hallde (Gargas et al., 1986a). It 1s proposed that a portion of
the oxldatlve pathway also yields a significant amount of C0_ (Gargas et
al.,1986a). Information regarding the rate and extent of bromochloromethane
excretion was not located 1n the literature cHed In Appendix A,
Acute Inhalation LC Qs for mice for 7-hour exposures ranged from
2268-2995 ppm (Svlrbely et al., 1947; Hlghman et al., 1948). Exposure to
5000 ppm (26,460 mg/m3) for 7 hours was not lethal for rats (Torkelson et
al., 1960). Rats survived a single oral dose of 5 g/kg, and all rats died
within 24 hours after a dose of 7 g/kg (Torkelson et al., 1960). An oral
LD5Q of -4300 mg/kg was determined for mice (Svlrbely et al., 1947).
Signs and pathological effects of acute Inhalation and oral exposure to
bromochloromethane are similar; principal effects Include CNS depression and
degeneration of the liver.
Subchronlc Inhalation studies of bromochloromethane have been conducted
with rats, mice, guinea pigs, rabbits and dogs (Torkelson et al., 1960;
MacEwen et al., 1966; Svlrbely et al., 1947; Hlghman et al., 1948). Concen-
trations ranged from 370 ppm (rats) to -1000 ppm (all species); exposures
were usually 5-7 hours/day, 5 days/week ranging from 14 weeks to -6 months.
Generally, minor effects such as decreased body weight, Increased relative
liver and kidney weight and reversible liver and kidney hlstologlcal altera-
tions occurred at concentrations >500 ppm 1n most species. Torkelson et al.
(1960) found that relative liver weight was Increased In rats at concentra-
tions of 370 ppm with hlstologlcal effects occurring at 490 ppm. Exposure
to 1000 ppm caused death and marked liver Injury In mice (Hlghman et al.,
1948). Information regarding the chronic Inhalation toxlclty, subchronlc or
chronic oral toxlclty or teratogenldty of bromochloromethane were not
located. Decreased spermatogenesls and flbrosls occurred In the tubules of
v1
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the testes of guinea pigs and rabbits that were subchronlcally exposed to
-1000 ppm bromochloromethane by Inhalation (Torkelson et al., 1960). The
functional significance of these effects was not evaluated.
Pertinent Information regarding the chronic Inhalation and oral exposure
of human or animals to bromochloromethane were not located In the available
literature cited 1n Appendix A.
The carclnogenUHy of bromochloromethane has not been evaluated.
Bromochloromethane was mutagenlc in Salmonella typhlmurlum and Escher1ch1a
coll bacteria (Simmon, 1976; Simmon et al., 1977; Osterman-Golkar et al.
1983; Strobel and Grummt, 1987) and Induced SCE and chromosome aberrations
1n Chinese hamster cells 1n vitro {Strobel and Grummt, 1987).
An RfD for subchronlc Inhalation exposure of 4 mg/m3 was based on a
NOAEL associated with slightly elevated liver weight but no effect on body>
weight In female rats exposed Intermittently for 195 days {Torkelson et al.,
1960). This study also served as the basis for an RfD of 0.4 mg/m3 for
chronic Inhalation exposure. Oral data were not sufficient for deriving
route-specific RfD values; therefore, the NOAEL from the Inhalation study In
female rats by Torkelson et al. (I960) served as the basis for an RfD of 1
mg/kg/day for subchronlc oral exposure and an RfD of 0.1 mg/kg/day for
chronic oral exposure. An RQ for noncancer chronic toxlclty of 1000 was
based on the occurrence of liver lesions In rats exposed by Inhalation for
114 days.
Bromochloromethane 1s classified In EPA Cancer Group 0 (Not Classifiable
as to Human Carclnogenlclty) because of lack of cardnogenlclty data; this
lack of data precludes calculation of a carcinogenic potency factor or
cancer-based RQ for bromochloromethane.
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TABLE OF CONTENTS
Page
1. INTRODUCTION ]
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1
1.3. PRODUCTION DATA 2
1.4. USE DATA 2
1.5. SUMMARY 2
2. ENVIRONMENTAL FATE AND TRANSPORT 3
2.1. AIR 3
2.2. WATER 3
2.2.1. Hydrolysis 3
2.2.2. Photolysis 4
2.2.3. Mlcroblal Degradation 4
2.2.4. Volatilization 4
2.2.5. Adsorption 5
2.3. SOIL 5
2.3.1. Adsorption/Leaching 5
2.3.2. Mlcroblal Degradation 5
2.3.3. Volatilization 5
2.4. SUMMARY 6
3. EXPOSURE 7
3.1. WATER 7
3.2. FOOD 8
3.3. INHALATION 8
3.4. DERMAL 8
3.5. SUMMARY 9
4. ENVIRONMENTAL TOXICOLOGY 10
4.1. AQUATIC TOXICOLOGY 10
4.1.1. Acute Toxic Effects on Fauna 10
4.1.2. Chronic Effects on Fauna 10
4.1.3. Effects on Flora 10
4.1.4. Effects on Bacteria 10
4.2. TERRESTRIAL TOXICOLOGY 11
4.2.1. Effects on Fauna 11
4.2.2. Effects on Flora 11
vlll
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TABLE OF CONTENTS (cont.)
4.3. FIELD STUDIES 11
4.4. AQUATIC RISK ASSESSMENT 11
4.5. SUMMARY 12
5. PHARMACOKINETCS 13
5.1. ABSORPTION 13
5.2. DISTRIBUTION 14
5.3. METABOLISM 14
5.4. EXCRETION 17
5.5. SUMMARY 18
6. EFFECTS 19
6.1. SYSTEMIC TOXICITY 19
6.1.1. Inhalation Exposure 19
6.1.2. Oral Exposure 22
6.1.3. Other Relevant Information 29
6.2. CARCINOGENICITY 29
6.3. GENOTOXICITY 29
6.4. DEVELOPMENTAL TOXICITY 31
6.5. OTHER REPRODUCTIVE EFFECTS 31
6.6. SUMMARY 32
7. EXISTING GUIDELINES AND STANDARDS 34
7.1. HUMAN 34
7.2. AQUATIC 34
8. RISK ASSESSMENT 35
8.1. CARCINOGENICITY 35
8.1.1. Inhalation 35
8.1.2. Oral 35
8.1.3. Other Routes 35
8.1.4. Height of Evidence 35
8.1.5. Quantitative Risk Estimates 35
8.2. SYSTEMIC TOXICITY 35
8.2.1. Acute Exposure 35
8.2.2. Subchronlc Exposure 36
8.2.3. Chronic Exposure 43
1x
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TABLE OF CONTENTS (cont.)
9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY 45
9.2. BASED ON CARCINOGENICITY 49
10. REFERENCES,
APPENDIX A: LITERATURE SEARCHED
APPENDIX B: SUMMARY TABLE FOR BROMOCHLOROMETHANE
APPENDIX C: DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO
BROMOCHLOROMETHANE
51
61
64
65
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LIST OF TABLES
No. TUIe Page
6-1 Acute Inhalation Lethality of Bromochloromethane 21
6-2 Genotoxlclty Testing of Bromochloromethane 30
9-1 Inhalation Toxldty Summary for Bromochloromethane 46
9-2 Inhalation Composite Scores for Bromochloromethane. ..... 48
9-3 Bromochloromethane: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 50
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LIST OF ABBREVIATIONS
AEL
A/G
CAS
CNS
CO
C02
CS
DUEL
PEL
GSH
HA
NEC
HEO
Km
ow
"-C50
LD50
LDU
LEO
LOAEL
HEO
NOAEL
NOEL
Adverse-effect level
Albumin/globulin
Chemical Abstract Service
Central nervous system
Carbon monoxide
N:
Carbon dioxide
Composite score
Drinking water equivalent level
Frank-effect level
Reduced glutathlone
Health advisory
Human equivalent concentration
Highest effective dose
Concentration In air at which uptake occurs at one-half
the maximum rate
Soil sorptlon coefficient standardized with respect
to organic carbon
Octanol/water partition coefficient
Concentration lethal to 50% of recipients
(and all other subscripted concentration levels)
Dose lethal to 50% of recipients
Log dose units
Lowest effective dose
Lowest-observed-adverse-effect level
Minimum effective dose
No-observed-adverse-effect level
No-observed-effect level
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LIST OF ABBREVIATIONS (cont.)
PEL Permissible exposure limit
ppb Parts per billion
ppm Parts per million
ppt Parts per trillion
RfD Reference dose
RQ Reportable quantity
RVjj Dose-rating value
RVe Effect-rating value
SCE Sister chromatld exchange
SGOT Serum glutamlc oxaloacetlc transamlnase
SGPT Serum glutamlc pyruvlc transamlnase
SIC Sister chromatld exchange, Chinese hamster cells In yjtro
STEL Short-term exposure limit
TLV Threshold limit value
TLV-STEL Threshold limit value-Short-term exposure limit
TWA Time-weighted average
UV Ultraviolet
Vmax Maximum rate of uptake
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
Bromochloromethane Is the common name for the chemical known by the
synonyms chlorobromomethane, methylene chlorobromlde, fluorocarbon 1011 and
Halon 1011 (Chemllne, 1989). The structure, molecular weight, empirical
formula and CAS Registry number for bromochloromethane are as follows:
Br
I
Cl-C-H
I
H
Molecular weight: 129.39
Empirical formula: CH-BrCl
CAS Registry number: 74-97-5
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Bromochloromethane Is a clear, colorless liquid with a sweet odor
(Stenger, 1978). It Is completely mlsdble with most common organic
solvents. Selected physical properties of bromochloromethane are as follows:
Melting point:
Boiling point:
Density (25°C):
Mater solubility
at 25°C:
Vapor pressure
at 25°C:
at 15.72°C:
Log Kow:
A1r odor threshold:
Water odor threshold:
-87.95°C
68.06°C
1.923 g/cm3
16.7 q/i
147.2 mm Hg
93.34 mm Hg
1.41
400 ppm
200 ppm
R1dd1ck et al.. 1986
Rlddlck et al., 1986
Rlddlck et al., 1986
TewaM et al., 1982
Rlddlck et al.. 1986
McDonald et al., 1959
Tewarl et al., 1982
Amoore and Hautala, 1983
Amoore and Hautala, 1983
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Bromochloromethane Is nonflammable and does not have a flash point (Hawley,
1981; Dean, 1985).
1.3. PRODUCTION DATA
Recent production .figures for bromochloromethane are not available. The
public portion of the U.S. EPA TSCA Production File for 1977 lists Dow
Chemical (Midland, HI) as a manufacturer of 1-10 million pounds and Bruckman
Laboratories, Inc. {Memphis, TN) as a manufacturer of 10-100 thousand pounds
(U.S. EPA, 1977).
The 1989 Directory of Chemical Producers (SRI, 1989) lists Ethyl Corpo-
ration (Magnolia, AK) as a current manufacturer of bromochloromethane.
USITC (1988) lists Dow Chemical as a manufacturer during 1987.
Bromochloromethane Is prepared by reacting dlchloromethane with
anhydrous aluminum bromide (treatment with bromine and aluminum) or by'
reaction with hydrogen bromide In the presence of an aluminum hallde
catalyst, followed by water washing and distillation (Stenger, 1978).
1.4. USE DATA
Bromochloromethane Is used mainly as a fire-extinguisher fluid In
aircraft and portable extinguishers (Stenger, 1978). It Is also used In
chemical synthesis (Kuney, 1988).
1.5. SUMMARY
Bromochloromethane Is a clear, colorless liquid with a sweet odor
(Stenger, 1978). It Is completely mlsdble with most common organic
solvents (Stenger, 1978) and soluble In water to the extent of 16.7 g/t at
25°C (Tewarl et al., 1982). Current production figures are not available.
Recent manufacturers of bromochloromethane Include Dow Chemical and Ethyl
Corporation (USITC, 1988; SRI, 1989). Bromochloromethane Is used mainly as
a fire-extinguisher fluid In aircraft and portable extinguishers (Stenger,
1978). It 1s also used 1n chemical synthesis (Kuney, 1988).
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2. ENVIRONMENTAL FATE AND TRANSPORT
2.1. AIR
The relatively high vapor pressure of bromochloromethane (147.2 mm Hg at
25°C) Indicates that 1t probably exists almost entirely In the vapor phase
In the ambient atmosphere (Elsenrelch et al., 1981). Using the method of
Atkinson (1987), the rate constant for the vapor-phase reaction of bromo-
chloromethane with atmospheric H0» can be estimated at 9.55xlO~14
cmVmolecule-sec at 25°C. This rate constant corresponds to a half-life
of -168 days, assuming an average atmospheric 'HO* concentration of 5xl05
molecules/cm3.
Bromochloromethane does not absorb UV light at >290 nm (Cadman and
Simons, 1966). Therefore, direct photolysis will not occur in the tropo-
sphere. However, the relatively long half-life predicted for reaction with
HO* suggests that some bromochloromethane may eventually diffuse Into the
stratosphere, where direct photolysis can destroy the compound. Based on a
half-life of 168 days and a tropospherlc-to-stratospherlc turnover time of
30 years, ~2% of tropospherlc bromochloromethane will diffuse Into the
stratosphere.
Pertinent data regarding the physical removal of bromochloromethane from
the atmosphere were not located In the literature cited In Appendix A.
Bromochloromethane1s water solubility of 16,700 mg/a at 25°C (Tewarl et
al., 1982} suggests that physical removal by wet deposition (rainfall,
dissolution Into clouds, etc.) 1s possible. However, the significance of
physical removal cannot be verified because of lack of experimental data.
2.2. WATER
2.2.1. Hydrolysis. The hydrolysis half-life of bromochloromethane has
been estimated at -44 years at 25°C and pH 7 (Mabey and Mill, 1978).
Therefore, hydrolysis Is not environmentally significant.
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2.2.2. Photolysis. UV spectra, as determined by Cadman and Simons
(1966), predict that direct photolysis of bromochloromethane has no signifi-
cance 1n the environment since no absorption occurs at >290 nm.
2.2.3. Nlcroblal Degradation. Tabak et al. (1981) studied the biodegrad-
abllHy of 114 organic priority pollutants on the U.S. EPA Priority Pollut-
ants List to ascertain mlcroblal degradation and acclimation periods. The
Bunch and Chambers static culture flask blodegradabllHy screening test was
j
performed under a set of controlled experimental conditions that Included
the following parameters: 5 and 10 mg/a concentrations of the test
compound, 5 mg/s. of yeast extract In the synthetic medium, 7-day static
Incubation at 25°C In the dark followed by three weekly subcultures (total-
Ing 28 days of Incubation), and Incorporation of settled domestic wastewater
as the mlcroblal Inoculum. With respect to bromochloromethane, 100% loss of'
compound was observed after the first 7-day Inoculation period and after
each subsequent subculture. The results Indicated significant blodegrada-
tlon with rapid adaptation.
2.2.4. Volatilization. Based upon a water solubility of 16,700 mg/it
and a vapor pressure of 147.2 mm Hg at 25°C (see Section 1.2.), the Henry's
Law constant for bromochloromethane can be estimated to be 0.0015
atm-m3/mol. A Henry's Law constant of this magnitude Indicates that
volatilization from environmental waters may be significant and rapid
(Thomas, 1982). Using a model river estimation method (Thomas, 1982), the
volatilization half-life of bromochloromethane from a river 1 m deep flowing
1 m/sec with a wind velocity of 3 m/sec Is ~4 hours. The estimated
volatilization half-life from a model environmental pond Is -47 hours (U.S.
EPA, 1986b). These estimates Indicate that volatilization Is a significant
environmental fate process for bromochloromethane.
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2.2.5. Adsorption. K estimates presented In Section 2.3.1. predict
that bromochloromethane Is not tightly bound to soil through adsorption.
Therefore, H Is likely that adsorption of bromochloromethane 1n sediments
does not compete with volatilization or blodegradatlon 1n the disappearance
of bromochloromethane from the aquatic environment.
2.3. SOIL
2.3.1. Adsorption/Leaching. Pertinent data regarding the leaching of
bromochloromethane In soil were not located In the available literature
cited 1n Appendix A. A K value of 21 can be estimated using a water
solubility of 16,700 mg/8. and the following regression-derived equatldn
(Lyman, 1982): log K = 3.64-0.55 log (water solubility}. This K
U L wl*
value Indicates very high soil mobility (Swann et a!., 1983).
2.3.2. M1crob1al Degradation. Pertinent data regarding the mlcroblaf
degradation of bromochloromethane In soil were not located In the available
literature cited In Appendix A. The blodegradatlon results of Tabak et al.
(1981) discussed 1n Section 2.2.3. suggest that blodegradatlon of bromo-
chloromethane 1n soil may be significant. Since no other processes are
expected to degrade bromochloromethane In soil to a significant degree,
blodegradatlon Is probably the ultimate degradation process, although the
degradation rate of this process cannot be quantified.
2.3.3. Volatilization. The relatively high vapor pressure of bromo-
chloromethane (147.2 mm Hg at 25°C) suggests significant evaporation from
dry surfaces. In moist soils, evaporation may still be significant near
soil surfaces, although leaching may diminish the relative significance of
volatilization.
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2.4. SUMMARY
Bromochloromethane Is expected to degrade relatively slowly In the
atmosphere. Using the method of Atkinson (1987), the half-life with respect
to HO- reaction can be estimated at -168 days. This suggests that -2% of
tropospherlc bromochloromethane will diffuse Into the stratosphere and be
destroyed by direct photolysis. Physical removal from the atmosphere by wet
deposition may be possible, but Us relative significance Is not known. A
single blodegradatlon study (Tabak et al., 1981) suggested that blodegrada-
tlon of bromochloromethane Is an Important environmental fate process.
Volatilization from water and soil surfaces 1s a major fate process.
Volatilization half-lives of 4 and 47 hours were estimated for a model river
(1 m deep) and for an environmental pond, respectively (Thomas, 1982; U.S.
EPA, 1986b). Bromochloromethane may leach readily In soils, based upon an*
estimated K value of 21 (Swann et al., 1983). Aquatic hydrolysis Is not
environmentally significant {Mabey and Mill, 1978).
031 fed
-6-
01/17/90
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3. EXPOSURE
3.1. HATER
Bromochloromethane was tentatively Identified 1n a drinking water sample
collected In Philadelphia, PA, In August 1976, and In drinking water
concentrates collected from New Orleans, LA, In January 1976 (Suffet et al.,
1980; Lucas, 1984).
Kaiser et al. (1983) collected water samples from 95 stations on Lake
Ontario and 16 stations on the lower Niagara River In 1981 for analysis of
volatile halocarbons. Bromochloromethane was detected In one sample at a
level of 10 ng/9. and In 14 samples at trace levels (detection limit equals
1 ng/l).
Bromochloromethane was qualitatively detected In seawater collected from
the Narragansett Bay, RI, In 1979-1980 (Wakeham et al., 1983). Monitoring'
of the north and south Atlantic Ocean in 1985 yielded a baseline bromo-
chloromethane concentration of 0.02 ng/i (Class and Ballschmlter, 1988).
These Investigators detected the blogenlc presence of bromochloromethane In
specific algae that occur In the Atlantic Ocean, and suggested that the
occurrence of bromochloromethane In marine water and air may result, In
part, from biological emissions from these algae.
Zoeteman et al. (1981) detected a bromochloromethane concentration of 8
ng/l In a contaminated groundwater sample from the Netherlands.
Halomethanes, such as bromodlchloromethane, chlorodlbromomethane and
trlhalomethanes, have been detected 1n drinking waters and other waters
during chlorlnatlon (Allgeler et al., 1980; Arguello et al., 1979; Dore et
al., 1982; Gould et al., 1983). Although bromlnatlon can occur when natural
bromide Is present 1n the water, the classic haloform reactions responsible
for the formation of chloroform and other halomethanes during chlorlnatlon
will not produce bromochloromethane (NAS, 1980).
0316d -7- 02/13/90
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3.2. FOOD
Pertinent data regarding the food monitoring of bromochloromethane were
not located In the available literature cited In Appendix A.
3.3. INHALATION
The average concentrations of bromochloromethane In ambient air
monitored throughout 1983 near Point Barrow, AL (1n the Arctic) were 2.4-2.9
ppt (Rasmussen and KhalU, 1984). The higher concentrations were found 1n
the winter and spring when the Arctic haze was observed. The authors
suggested that the bromochloromethane 1n the Arctic air was primarily due to
transport from anthropogenic sources. Experimental evidence to support this
was not given.
Bromochloromethane was Identified {detection limit of 0.1 ppb) 1n
ambient air samples collected near a hazardous waste site In New Jersey
(Lareglna et al., 1986). The actual concentrations In the samples were not
reported.
Mean bromochloromethane concentrations of 0.2-0.4 ppt were measured In
the air over the open Atlantic Ocean (30°S-40°N) during monitoring 1n 1985
(Class and BallschmUer, 1988). Bromochloromethane was also detected 1n
open seawater and In macro algae collected near various sampling sites. The
presence of bromochloromethane In marine air may be due, In part, to Us
blogenlc formation In algae, followed by release to seawater, with subse-
quent volatilization. Monitoring of baseline concentrations In seawater and
air tend to support this supposition.
3.4. DERMAL
Pertinent data regarding the dermal monitoring of bromochloromethane
were not located 1n the available literature cited 1n Appendix A.
0316d
-8-
01/17/90
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3.5. SUMMARY
Bromochloromethane has been detected In drinking water (Suffet et al.,
1980; Lucas, 1984), groundwater (Zoeteman et al., 1981), Lake Ontario and
Niagara River water (1-10 ng/l) (Kaiser et al., 1983), and open seawater
from the Atlantic Ocean (0.02 ng/8,) (Class and Banschmlter, 1988).
Levels of 0.2-0.4 ppt have been Identified In air over the Atlantic Ocean
(Class and Ballschralter, 1988), while levels of 2.4-2.9 ppt were detected in
the Alaskan Arctic (Rasmussen and Khalll, 1984). Bromochloromethane has
also been Identified 1n air samples collected near a hazardous waste site In
New Jersey (Lareglna et al., 1986). It has been suggested that the presence
of bromochloromethane In marine water and air may be due. In part, to Us
blogenlc formation 1n algae, followed by release to seawater, with subse-
quent volatilization (Class and Ballschmlter, 1988). The classic haloform*
reactions responsible for the formation of chloroform and other halomethanes
during chloMnatlon of drinking water will not produce bromochloromethane
(NAS, 1980).
0316d -9- 02/13/90
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4. ENVIRONMENTAL TOXICOLOGY
4.1. AQUATIC TOXICOLOGY
4.1.1. Acute Toxic Effects on Fauna. U.S. EPA (1987) summarized results
of acute toxldty tests conducted by Dow Chemical Company. No effects were
noted In fathead minnows, Plmephales promelas. exposed to 80 mg/i bromo-
chloromethane. The LCcn (duration not reported) for this species was >80
DU
mg/a. No study details were provided.
4.1.2. Chronic Effects on Fauna.
4.1.2.1. TOXICITY — Pertinent data regarding the effects of chronic
exposure of aquatic fauna to bromochlormethane were not located In the
available literature dted In Appendix A.
4.1.2.2. BIOACCUMULATION/BIOCONCENTRATION — H1att (1983) detected
the presence of bromochloromethane In tissues of rainbow trout. Salmonella
galrdnerl. collected from the Colorado River and reported an estimated
whole-fish concentration of 8 vg/l.
4.1.3. Effects on Flora.
4.1.3.1. TOXICITY — Pertinent data regarding the toxic effects of
exposure of aquatic flora to bromochloromethane were not located In the
available literature cited In Appendix A.
4.1.3.2. BIOCONCENTRATION — Pertinent data regarding the bloconcen-
tratlon potential of bromochloromethane In aquatic flora were not located In
the available literature cited 1n Appendix A.
4.1.4. Effects on Bacteria. Pertinent data regarding the effects of
exposure of aquatic bacteria to bromochloromethane were not located 1n the
available literature cited In Appendix A.
0316d
-10-
02/13/90
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4.2. TERRESTRIAL TOXICOLOGY
4.2.1. Effects on Fauna. Pertinent data regarding the effects of
exposure of terrestrial fauna to bromochloromethane were not located In the
available literature cited 1n Appendix A.
4.2.2. Effects on Flora. Pertinent data regarding the effects of
exposure of terrestrial flora to bromochloromethane were not located In the
available literature cited In Appendix A.
4.3. FIELD STUDIES
Pertinent data regarding the effects of bromochloromethane on flora and
fauna 1n the field were not located In the available literature cited In
Appendix A.
4.4. AQUATIC RISK ASSESSMENT
The lack of pertinent data regarding the effects of exposure of aquatic'
fauna and flora to bromochloromethane precluded the development of a fresh-
water criterion by the method of U.S. EPA/OWRS (1986). Data required for
the development of a freshwater criterion Include the results of acute
assays with a salmonld fish species, a warmwater fish species, a third fish
species or an amphibian, planktonlc and benthlc crustaceans, an Insect, a
«
nonarthropod and nonchordate species and an Insect or species from a phylum
not previously represented. The development of a freshwater criterion will
also require data from chronic toxldty tests with two species of fauna and
one species of algae or vascular plant and at least one bloconcentratlon
study.
The lack of pertinent data regarding the effects of exposure of aquatic
fauna and flora to bromochloromethane prevented the development of a salt-
water criterion by the method of U.S. EPA/OWRS (1986). Data required for
the development of a saltwater criterion Include the results of acute assays
with two chordate species, a nonarthropod and nonchordate species, a mysld
0316d -11- 02/13/90
-------
or panaeld crustacean, two additional nonchordate species and one other
species of marine fauna. The development of a saltwater criterion will also
require data from chronic toxldty tests with two species of fauna and one
species of algae or vascular plant and at least one bloconcentratlon study.
4.5. SUMMARY
Summarized toxldty data for bromochloromethane consisted of a NOEL of
80 mg/a for fathead minnows, £. promelas^ and an LC_0 (duration not
reported) of >80 mg/i (U.S. EPA, 1987). Bromochloromethane has been found
In tissues of rainbow trout, S. galrdneM. from the Colorado River. The
estimated whole-fish concentration was 8 yg/i (Hlatt, 1983).
0316d
01/17/90
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5. PHARMACOKINETICS
5.1. ABSORPTION
Male F344 rats were exposed to nine Initial concentrations of 100-10,000
ppm (529-52,920 mg/m3} bromochloromethane vapor for 175-205 minutes 1n a
closed Inhalation chamber (Gargas and Andersen, 1982). Chamber concentra-
tion disappearance curves Indicated that absorption was blphaslc, consisting
of a rapid equilibrium phase that was completed 1n 70-110 minutes and a slow
phase that was nearly linear after this time. The rapid uptake phase
reportedly represents Initial bloodigas equilibrium. The slow uptake phase,
reportedly representing metabolism and loading Into poorly perfused tissues,
was a composite of a saturable process, which predominated at low concentra-
tions, and a first-order process. Kinetic constants were determined for the
saturable process; these Included a K of 91 ppm {482 mg/m3) and a'
vmaw °f 10*5 mg/kg/hour. Similar data were reported In other studies
IHO X
(Andersen et al., 1980; Gargas and Anderson, 1982). Gargas et al. (I986a,b)
simulated the mixed uptake kinetics of bromochloromethane In rats, using a
physiologically-based pharmacoklnetic model. Information regarding the
extent of respiratory absorption from Inhaled bromochloromethane was not
located 1n the available literature.
Quantitative oral absorption data were not located for bromochloro-
methane. The occurrence of systemic effects In rats and mice following
s
acute oral exposure to bromochloromethane (Section 6.1.3.) provides qualita-
tive evidence of gastrointestinal absorption.
Male F344 rats were exposed to 2500-40,000 ppm (13,230-211,681 mg/m3)
bromochloromethane In air for 4 hours In dermal vapor absorption chambers
without significant Inhalation exposure (McDougal et al., 1985). Blood
concentrations of bromide showed that absorption of bromochloromethane was
0316d -13- 01/17/90
-------
rapid and Increased with Increasing exposure levels; however, the Increase
was not linear. A dermal flux of 0.011-0.164 mg/cmVhour was calculated.
5.2. DISTRIBUTION
Svlrbely et al. (1947) exposed 20 male rats, 3 male rabbits and 2 female
dogs (strains not specified) to -890 ppm (4710 mg/m3) bromochloromethane
for 7 hours/day, 5 days/week for 14 weeks. Both total and organic (vola-
tile) bromide were elevated In the blood and brain of the treated animals,
compared with unexposed controls, following the last 7-hour exposure.
Levels of total bromide In the blood were 6-8 times greater than levels In
the brain. Similarly, levels of organic bromide 1n the blood were 8-12
times greater than levels In the brain.
Rat blood:a1r and rat t1ssue:blood partition coefficients for bromo-
chloromethane have been determined as follows: bloodialr (41.5*0.9),•
fat:blood (325±3), 11ver:blood (29.2±0.5) and muscle:blood (11.U1.8).
Pertinent data regarding the distribution of bromochloromethane follow-
ing oral exposure were not located 1n the available literature cited In
Appendix A.
5.3. METABOLISM
Concentrations of Inorganic bromide Increased In the blood of rats,
guinea pigs, rabbits and dogs as a result of subchronk Inhalation exposure
to bromochloromethane (Svlrbely et al., 1947; Torkelson et al., 1960;
MacEwen et al., 1966) (Section 6.1.1.1.). Carboxyhemoglobln levels
Increased In male Long-Evans rats given a single Intraperltoneal Injection
of 3.0 mrnol "C-bromochloromethane/kg (388.2 mg/kg) 1n corn oil (Kublc et
al., 1974). These data and studies of other dlhalomethanes Indicate that
bromochloromethane 1s metabolized by two major pathways: an oxldatlve,
cytochrome P-450 mediated pathway yielding CO and hallde using putative
0316d
-14-
02/13/90
-------
formyl hallde Intermediates, and a glutathlone-dependent cytosollc pathway
producing C02 and hallde (Gargas et al.t 1986a). Based on physiological
pharmacoklnetlc analysis of plasma bromide and carboxyhemoglobln concentra-
tions In rats pretreated with pyrazole {which Inhibits mlcrosomal oxidation)
and 2,3-epoxypropanol (which depletes glutathlone) and exposed to bromo-
chloromethane by Inhalation, Gargas et al. (1986a) concluded that bromide
was the preferred leaving group In the oxldatlve mechanism, resulting 1n the
formation of formyl chloride rather than formyl bromide. They proposed that
a significant portion (-20-30%) of the putative formyl chloride Intermediate
may react with GSH and other cellular nucleophlles, Instead of spontaneously
decomposing to CO. According to these Investigators, this portion of the
oxldatlve pathway probably yields CO-; a larger proportion of the formyl
chloride Intermediate decomposes to CO when cellular GSH 1s depleted.'
Metabolic pathways of bromochloromethane and other dlhalomethanes are
presented In Figure 5-1.
Gargas et al. (1986a) evaluated the kinetics of bromochloromethane
metabolism, using 4-hour Inhalation studies with male F344 rats. Gas uptake
(disappearance) was determined during exposure to 200-4000 ppm (1058-21,168
mg/m3) In a closed exposure chamber, and plasma bromide levels and
carboxyhemoglobln levels were determined following exposure to constant
concentrations of 51-2006 ppm (270-10,616 mg/m3). The gas uptake data
Indicated that metabolism comprises both first-order and saturable
components; similar data were found In other studies (see Section 5.1.).
The oxldatlve pathway was high affinity and tow capacity, with production of
CO saturable at bromochlormethane concentrations greater than -200 ppm; the
maximum percent carboxyhemoglobln saturation attained was -9%. The maximum
0316d -15- 02/13/90
-------
CYT , P-450 H
CH2X
NADPH
H-O-C-X
OSOL
ci- * •••••
GS-CH2-X
^- NUCL
' (1.
NX-
0
i i
<
GS-C
HO + "
S 2 G-S-C
s.
H
U _ A U — f^M_n 4« I*Sn
2 — 2
NAD* 1
0 *
. // r n .
\
H
V^H*
0
//
GS-C GS-C
\ \
H
i
K
M COOH + GSH
H COOH 4- GSH
CO,
x = halogen atom
CO-
FIGURE 5-1
Proposed Pathways for Dlhalomethane (CH2X2) Metabolism
Source: Gargas et a!., 1986a
0316d
-16-
01/17/90
-------
rate for the metabolism of bromochloromethane to CO was 54 ymol metabo-
11 zed/kg/hour. The GSH pathway was low affinity but high capacity, and a
single first-order process at all exposure concentrations.
Torkelson et al. (1960) determined Inorganic bromide concentrations In
the blood of four female rabbits (strain not specified) exposed to 130 ppm
(688 mg/m3) bromochloromethane by inhalation for 7 hours/day, 5 days/week
for 45 exposures In 66 days. Determinations were performed before and
Immediately after 1, 2, 5, 10, 14, 15 and 45 exposures. Maximum blood
bromide Ion concentrations (-30-35 mg/da) were reached by the end of the
second week.
Levels of Inorganic bromide In the blood were determined In two female
dogs (strain unspecified) after 3-4 and 13-14 weeks of 7 hours/day, 5 days/
week Inhalation exposure to a nominal bromochloromethane concentration of
1000 ppm (measured concentration ~890 ppm [4710 mg/m3]) (Svlrbely et al.,
1947). Blood bromide levels Increased during dally exposure, did not
significantly decline overnight or on days without exposure; however, the
steady Increase throughout the treatment period did not reach maximum by the
end of treatment. Bromide 1on levels In the blood were ~300-360 mg/dj. at
the end of treatment. These findings Indicate a tendency for Inorganic
bromide to accumulate 1n the blood with continued exposure to bromochloro-
methane.
5.4. EXCRETION
Urinary output of Inorganic bromide was determined In two female dogs
(strain unspecified) after 3-4, 10 and 13-14 weeks of 7 hours/day, 5
days/week Inhalation exposure to -890 ppm (4710 mg/m3) bromochloromethane
(Svlrbely et al., 1947). Excretion of bromide markedly declined on
exposure-free days, but tended to Increase overall throughout the treatment
0316d -17- 02/13/90
-------
period. Information regarding the rate and extent of bromochloromethane
excretion was not located In the available literature cited In Appendix A.
5.5. SUMMARY
Bromochloromethane 1s rapidly absorbed by rats In a blphaslc manner
following acute Inhalation exposure (Gargas and Andersen, 1982), but quanti-
tative data are not available regarding the extent of Inhalation exposure or
the rate or extent of oral exposure. There appears to be some distribution
of bromide to the brain of dogs during subchronlc Inhalation exposure
(Svlrbely et a!., 1947). Rat tlssueiblood partition coefficients (Gargas et
al., 1986a,b) suggest that bromochloromethane will distribute more readily
to fat than to liver or muscle. Available data Indicate that bromochloro-
methane Is metabolized by two major pathways: an oxldatlve, cytochrome P-450
mediated pathway yielding CO and hallde (putative formyl hallde Inter-'
mediate} and a glutathlone (GSH)-dependent cytosollc pathway producing CO-
and hallde (Gargas et al., 1986a). It Is proposed that a portion of the
oxldatlve pathway also yields a significant amount of C0_ (Gargas et
al.,1986a). Information regarding the rate and extent of bromochloromethane
excretion was not located 1n the literature cited In Appendix A.
03164
-18-
02/13/90
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6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. ACUTE.
6.1.1.1. INHALATION EXPOSURE — Rutsteln (1963) reported that three
male fire fighters who used chloro- bromomethane as a fIre-extlngulshing
agent had gastrointestinal Irritations (e.g., vomiting, stomach pains} and
manifestations of CNS Involvement (e.g., headache, loss of consciousness).
Acute Inhalation lethality data for bromochloromethane are summarized In
Table 6-1. These data suggest that mice are more susceptible than rats
since 7-hour exposures resulted In LCcns of 2268-2995 ppm (12,000-15,850
all
mg/m3) for mice (Svlrbely et al., 1947; Hlghman et al., 1948), and 7-hour
exposures to 5000 ppm (26,460 mg/m3) were not lethal for rats (Torkelson
et al., 1960). Death was often delayed 1n the mice but generally occurred,
during treatment In the rats exposed to 10,000 ppm. Signs observed 1n the
mice and rats Indicated CNS toxlclty; these Included restlessness, muscular
twitching, uncoordinated movements, labored respiration and narcosis In the
mice (Svlrbely et al., 1947), and drowsiness and unconsciousness In the rats
{Torkelson et al., 1960).
Hlghman et al. (1948) exposed Swiss mice (sex not reported) to 7-17
mg/s, (7000-17,000 mg/m3 or 1323-3212 ppm) bromochloromethane by Inhala-
tion 7 hours/day on 1-5 successive days. H1stolog1cal examination of 79
mice Immediately following exposure showed changes that Included fatty
degeneration of the liver after single exposures of >7 mg/8, and kidneys
after single exposures of >12 mg/i. These effects were most severe within
24 hours of exposure and were minimal or absent after 72 hours. Hlsto-
loglcal examinations were conducted on groups of four to five female rats
(strain not reported) 24 hours following Inhalation exposure to 600-40,000
0316d -19- 05/17/90
-------
ppm (113-7559 mg/m3) bromochloromethane for durations of 7-0.025 hours,
respectively {Torkelson et al., 1960). Unequivocal alterations were
observed only in the liver (small vacuoles 1n parenchyma not typical of
fatty degeneration, often accompanied by Increased liver weight). The
minimum concentration producing hepatic effects after 7-hour exposure was
1500 ppm (7938 mg/m3); exposure to 600 ppm (5175 mg/m3) for 7 hours did
not produce hepatic effects and exposure to 800 ppm (4234 mg/m3) for 7
hours produced equivocal hepatic hlstologlcal alterations.
6.1.1.2. ORAL EXPOSURE — Acute oral toxldty data are available for
rats and mice. Torkelson et al. (1960) fed (apparently by gavage) an
unspecified series of single doses of bromochloromethane In corn oil to
groups of five male rats. Observation for 14 days showed that all rats
survived a dose of 5 g/kg and all rats died within 24 hours after a dose of
7 g/kg. Additional Information regarding this study was not reported.
Groups of 10 mice (strain and sex not reported) were fed (method not
reported) single doses of 500-4400 mg/kg bromochloromethane In olive oil
(Svlrbely et al., 1947). The LD™ (6-day observation) was ~4300 mg/kg.
Signs showing dose-related CNS depression were observed at >500 mg/kg, but
pathological examinations were not conducted and the lowest dose producing
death was not reported. In a related study, unspecified numbers of Swiss
mice (sex not reported) were administered single gavage doses of 0, 500,
3000 or 4500 mg/kg bromochloromethane 1n olive oil (Hlghman et al., 1948).
Hlstologlcal examinations conducted <96 hours after treatment showed no
significant changes at 500 mg/kg.
Effects occurring at >3000 mg/kg Included death, pronounced hepatic
hlstopathology and other pathological changes similar to those resulting
from acute Inhalation exposure. Mice killed 24 hours after the Initial
0316d
-20-
05/17/90
-------
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exposure had severe effects, which Included focal subcapsular necrosis In
the liver (12/50), hydropic degeneration In the liver (5/50) and hemoglobin
casts 1n a few renal tubules (8/32). These effects were generally absent or
slight In mice surviving >48 hours,
Hlghman et al. (1948) also treated a group of -32 Swiss mice (sex not
reported) with single gavage doses of 3000 mg/kg bromochloromethane In olive
oil on 1-10 consecutive days. Several mice were sacrificed after each of
the 10 doses. Hlstologlcal examination of mice that died or were sacrificed
showed fatty degeneration of the liver, kidney and sometimes heart. Other
hepatic effects Included subcapsular necrosis (23/32 mice), hydropic
degeneration (8/32 mice) and an Increased number of mononuclear peMportal
cells (8/32 mice). Effects were most severe 24-48 hours after the Initial
dose and became slight after 80 hours. Opacity of the eyes was observed In
5/19 mice surviving <3 days.
Occluded dermal application of bromochloromethane (5000 mg/kg) to
clipped skin of five rabbits resulted 1n burns and denaturatlon of the skin
with four surviving after 24 hours (Torkelson et al., 1960). Application
without occlusion caused only slight defattlng.
6.1.2. SUBCHRONIC.
6.1.2.1. INHALATION EXPOSURE — Groups of 20 male and 20 female rats
were exposed to nominal concentrations of 0, 500 or 1000 ppm bromochlorome-
thane (490 ppm [2593 mg/m3] or 1010 ppm [5345 mg/m3] actual average
concentrations) 7 hours/day for 79-82 exposures In 114 days (Torkelson et
al., 1960). These concentration correspond to 0, 166.97-173.31 and
344.18-357.25 mg/kg/day assuming a body weight of 0.35 kg, a breathing rate
of 0.223 mVday and a 50% absorption of the Inhaled dose. Because no
effects were observed In male rats at 166.97-173.31 mg/kg/day, a group of 10
0316d
-22-
05/17/90
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female rats were exposed to nominal concentrations of 0 or 400 ppm
bromochloromethane (370 ppm [1958 mg/m3] actual average concentration) 7
hours/ day for 135 exppsures In 195 days {4.85 days/week). This dose
corresponds to 125.96 mg/kg/day assuming a body weight of 0.35 kg, a
breathing rate of 0.223 mVday and a 50% absorption of the Inhaled dose.
The strain of rats was not reported. Body weight gain and survival were
evaluated throughout treatment and pathological examinations were conducted
at termination. The pathological evaluation Included gross examinations,
organ weight determinations (lungs, heart, liver, kidney, spleen and testes)
and hlstologlcal examinations (organs that were weighed, pancreas and
adrenals}.
Hematologlcal examinations of 10 females exposed to 0 or 344.18-357.25
mg/kg/day and blood bromide and blood nitrogen (urea nitrogen and nonproteln,
nitrogen) determinations of three rats/sex from each treatment and control
group were also conducted at termination. Effects attributed to treatment
Included Increased relative liver weights In females at 125.96 mg/kg/day and
both sexes at >166.97-173.31 mg/kg/day, liver hlstopathology In females at
166.97-173.31 mg/kg/day (slight bile duct epithelial proliferation, slight
portal flbrosls, occasional vacuollzatlon) and both sexes at 344.18-357.25
mg/kg/day (effects similar to those at 166.97-173.31 mg/kg/day, cloudy
swelling and vacuollzatlon of hepatocytes) and Increased relative kidney
weights 1n both sexes at 344.18-357.25 mg/kg/day. Blood bromide levels were
elevated In both sexes at all exposure concentrations, but effects typical
of bromlsm (apathy, obesity, Inactivity) were not observed. Terminal
bromide Ion levels were 44-73 mg/da at 125.96 mg/kg/day and as high as 122
mg/di at the higher concentrations.
0316d -23- 05/17/90
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Torkelson et al. (1960) also exposed 10 guinea pigs {strain not
reported) of each sex to 0, 490 or 1010 ppm (2593 or 5345 mg/m3} bromo-
chloromethane 7 hours/day, 5 days/week for 79-82 exposures 1n 114 days.
These doses correspond to 0, 124.79-129.53 and 257.23-267.00 mg/kg/day
assuming a body weight of 0.84 kg, a breathing rate of 0.4 mVday and a
50% absorption of the Inhaled dose. Evaluations of body weight, survival,
pathology, blood bromide and blood nitrogen were conducted as 1n the rat
study. Hematologlcal examinations were conducted on three females from each
group. Treatment-related effects Included decreased body weights In both
sexes at >124.79-129.53 mg/kg/day, Increased relative liver weight In both
sexes at >124.79-129.53 mg/kg/day, Increased relative kidney weight In males
at >124.79-129.53 mg/kg/day, an Increased number of circulating neutrophlls
1n females at >124.79-129.53 mg/kg/day and testlcular effects at 344.18-.
357.25 mg/kg/day (Section 6.5.). Blood bromide levels were elevated 1n both
sexes at both exposure levels.
Torkelson et al. (1960) also exposed 10 female mice (strain not
reported) to 0, 490 or 1010 ppm (2593 or 5345 mg/m3) bromochloromethane 7
hours/day, 5 days/week for 79-82 exposures In 114 days. These dose
correspond to 0, 340.67-353.59 and 702.22-728.88 mg/kg/day assuming a body
weight of 0.03 kg, a breathing rate of 0.039 mVday and a 50% absorption
of the Inhaled dose. Evaluations of body weight, survival and pathology
were conducted as In the rat study. Blood bromide and blood nitrogen
determinations and hematologlcal examinations were not performed.
Significantly decreased body weight and slgnlflcanty Increased relative
liver and kidney weights occurred In both groups of treated mice.
Torkelson et al. (1960) also exposed two rabbits (strain not reported)
of each sex to 0, 490 or 1010 ppm (2593 or 5345 mg/m3) bromochloromethane
0316d
-24-
05/17/90
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7 hours/day, 5 days/week for 79-82 exposures 1n 114 days. These dose
correspond to 0, 137.93-143.16 and 284.32-295.09 mg/kg/day assuming a body
weight of 3.8 kg, a breathing rate of 2 mVday and a 50% absorption of the
Inhaled dose. Evaluations of body weight, survival and pathology were
conducted as 1n the rat study. Blood bromide and blood nitrogen were
determined In all treated and control rabbits except one treated female In
the 137.93-143.16 mg/kg/day group. Hematologlcal examinations were not
performed. The hlstologlcal examinations showed testlcular alterations In
one of the males exposed to 284.32-295.09 mg/kg/day (Section 6.5.}. Blood
bromide levels were elevated 1n both sexes at both exposure levels. Both
sexes appeared to have elevated liver weights, but the small numbers of
rabbits Involved precluded definitive analysis. Results of the blood
nitrogen determinations were not reported.
Torkelson et al. (1960) also exposed one male and one female dog (strain
not reported) to 0 or 370 ppm (1958 mg/m3) bromochloromethane 7 hours/day,
5 days/week for 135 exposures In 195 days. These doses correspond to 0 and
66.93 mg/kg/day assuming a body weight of 12.7 kg, a breathing rate of 4.3
mVday and a 50% absorption of the Inhaled dose. Evaluations of body
weight, survival, blood bromide, blood nitrogen and hematology were
conducted as 1n the rat study. Pathological examinations were not
performed. The only effect reported was elevated blood bromide levels.
Groups of 50 male and 50 female albino rats (descendants of germ-free
Wlstar rats) were exposed to nominal concentrations of 500 or 1000 ppm
bromochloromethane 6 hours/day, 5 days/week for 6 months for a total of 124
exposures (MacEwen et al., 1966). Actual measured concentrations averaged
515 and 1010 ppm (2725 and 5345 mg/m3}, respectively. These doses
correspond to 0, 149.51 and 293.26 mg/kg/day assuming an average body weight
0316d -25- 05/17/90
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of 0.35 kg, a breathing rate of 0.223 mVday and a 50% absorption of the
Inhaled dose. Fifty chamber air-exposed male rats served as controls. Body
weight, serum bromide levels and survival were evaluated throughout the
treatment period. After 2 and 4 months of exposure, groups of 10 rats In
each treatment group and five control rats were subjected to white blood
cell count and clinical chemistry determinations and sacrificed for organ
weight and hlstologlcal examinations. The remainder of the rats were
evaluated at the termination of treatment. The clinical tests consisted of
SGOT, SGPT, total protein, albumin and A/G ratio. It Is not specified
whether organs other than liver, kidney and spleen were weighed and
hlstologkally examined. The only effect attributable to treatment was a
significantly (p<0.01) dose-related decreased body weight gain In male rats
at >149.51 mg/kg/day, the magnitude of which Increased with increasing
duration of exposure. Blood bromide levels were Increased at both concen-
trations throughout the treatment period. The Investigators Indicated that
similar levels of blood bromide In humans may produce mild sedation and
suggested that lethargy and altered eating habits may have been responsible
for the reduction In body weight gain.
MacEwen et al. (1966) also exposed four male and four female beagle dogs
to 0, 515 or 1010 ppm (2725 or 5345 mg/m3) bromochloromethane 6 hours/day,
5 days/week for 6 months for a total of 124 exposures. These doses corre-
spond to 0, 79.45 and 155.84 mg/kg/day assuming an average body weight of
12.7 kg, a breathing rate of 4.3 mVday and a 50% absorption of the
Inhaled dose. Toxlclty was evaluated as 1n the rat study with the addition
of other clinical chemistry tests. Evaluations were performed on groups of
two treated and one control dog after 2 and 4 months and on the remaining
0316d
-26-
05/17/90
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animals at termination of treatment. The only effect attributed to treat-
ment was Increased serum bromide levels at both concentrations throughout
the treatment period.
Twenty male rats (strain not reported) were exposed to 1000 ppm bromo-
chloromethane (nominal concentration) 7 hours/day. 5 days/week for 14 weeks
(Svlrbely et al., 1947). The measured concentration was generally 11% lower
than the calculated value (I.e., 890 ppm or 4710 mg/m3). This dose
corresponds to 299.20 mg/kg/day assuming an average body weight of 0.35 kg,
a breathing rate of 0.223 mVday and a 50% absorption of the Inhaled
dose. A control group appears to have been used, but specific Information
was not reported. Weight gain and survival throughout treatment, histology
after 67 exposures (19 rats) and bromide levels In the blood and brain
Immediately after the last exposure were evaluated. It Is not Indicated
whether tissues other than liver and spleen were hlstologlcally examined.
Effects consisted of a slight Increase of hemoslderln In the spleen and
Increased concentrations of bromide In the blood and brain.
Svlrbely et al. (1947) also exposed three male rabbits and two female
dogs (strains not reported) to 1000 ppm bromochloromethane (measured concen-
tration "890 ppm [4710 mg/m3]) 7 hours/day, 5 days/week for 14 weeks. In
rabbits this dose corresponds to 247.16 mg/kg/day assuming an average body
weight of 3.8 kg, a breathing rate of 2 mVday and a 50% absorption of the
Inhaled dose. In dogs this dose corresponds to 158.99 mg/kg/day assuming an
average body weight of 12.7 kg, a breathing rate of 4.3 mVday and a 50%
absorption of the Inhaled dose. Toxlclty was evaluated as 1n the rat study
with the addition of hematologlcal examinations In both species at "regular"
Intervals, liver function evaluation (bromsulfaleln excretion) and urlnaly-
sls In (Togs at "regular" Intervals and blood Inorganic bromide determina-
tions 1n dogs throughout the treatment period. Effects consisting of a
0316d -27- 05/17/90
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slight Increase of hemoslderln 1n the spleen and kidneys and an Increase In
fat 1n the kidneys occurred In the dogs. Inorganic bromide accumulated In
the blood of the dogs throughout treatment (terminal concentrations were
-300-360 mg/dl).
Hlghman et al. (1948) exposed 100 Strain A mice (sex not reported, age 2
months) and 45 C3H mice (sex not reported, age 3-7 months) to 1000 ppm (5292
mg/m3) bromochloromethane. Use of control groups was not Indicated.
Exposures were administered 5 times/week with occasional long rest periods
of unspecified frequency and duration when necessary, as Indicated by
mortality and abnormal general condition. Calculation of a dose 1n
mg/kg/day Is uncertain given these experimental conditions. Surviving
Strain A mice each received a total of 64 exposures of 3-7 hours In a period
of ~5 months (approximately 143.97-335.93 mg/kg/day corresponding to 3 or 7
hour dosing schedule and assuming an average body weight of 0.03 kg, a
breathing rate of 0.039 mVday and a 50% absorption of the Inhaled dose;
surviving C3H mice each received a total of 49 exposures of 3-7 hours In a
period of 4 months (approximately 150.43-351 mg/kg/day corresponding to 3 or
7 hour dosing schedule and assuming an average body weight of 0.03 kg, a
breathing rate of 0.039 mVday and a 50% absorption of the Inhaled dose).
Most of the mice died at unspecified, Irregular Intervals during treatment,
and some died or were sacrificed at unspecified Intervals following
treatment. A total of 21 mice (one Strain A and 20 C_H) survived until
terminal sacrifice at 13-16 months of age. Hlstologlcal examinations were
conducted on mice that were sacrificed and some (number unspecified) that
died. The mice that died during exposure generally showed slight fatty
changes In the liver and kidneys. Extensive tubular necrosis of the Inner
zone of the renal cortex was observed 1n two strain A mice that died during
0316d
-28-
05/17/90
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the fourth dally exposure. Several other mice that died during exposure
showed coagulation or karyorrhectlc necrosis of a few Isolated liver cells.
Treatment-related effects were not observed 1n the mice that survived until
terminal sacrifice.
6.1.2.2. ORAL EXPOSURE -- Pertinent data regarding subchronlc oral
exposure of humans or animals to bromochloromethane were not located 1n the
available literature cited In Appendix A.
6.1.3. Chronic
6.1.3.1. INHALATION EXPOSURE — Pertinent data regarding the chronic
Inhalation exposure of humans or animals to bromochloromethane were not
located In the available literature cited 1n Appendix A.
6.1.3.2. Oral Exposure — Pertinent data regarding the subchronlc or
chronic oral exposure of humans or animals to bromochloromethane were not
located In the available literature cited 1n Appendix A.
6.2. CARCINOGENICITY
Pertinent data regarding the carclnogenldty of bromochloromethane to
humans or animals following exposure by Inhalation, oral or other routes of
exposure were not located In the available literature cited 1n Appendix A.
6.3. 6ENOTOXICITY
Data from genotoxlclty tests with bromochloromethane are presented In
Table 6-2. Consistently positive results were observed In the reverse
mutation test In Salmonella typhlmuMum {Simmon et a!., 1977; Strobel and
Grummt, 1987; Osterman-Golkar et al., 1983). Metabolic activation was not
required but Increased the response In TA98 and TA100 {Strobel and Grummt,
1987). Positive results were also observed In the reverse mutation and
lambda prophage Induction tests In Escherlchla col 1 (Osterman-Golkar et al.,
1983). Negative results were observed In the mltotlc recombination test 1n
0316d -29- 08/20/90
-------
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Saccharomyces cerevlslae (Simmon, 1976). In the only mammalian test
located, bromochloromethane Induced SCEs and chromosomal aberrations 1n
Chinese hamster FAF cells (Strobel and Grummt, 1987).
6.4. DEVELOPMENTAL TOXICITY
Pertinent data regarding the developmental toxldty of bromochloro-
methane were not located 1n the available literature dted 1n Appendix A.
6.5. OTHER REPRODUCTIVE EFFECTS
Torkelson et al. (1960) exposed groups of 10 male guinea pigs (strain
not reported) to 0, 490 or 1010 ppm bromochloromethane 7 hours/day, 5
days/week for 79-82 exposures 1n 114 days (see Section 6.1.1.1.). These
dose correspond to 0, 124.79-129.53 and 257.23-267.00 mg/kg/day assuming an
average body weight of 0.84 kg, a breathing rate of 0.4 mVday and a 50%
absorption of the Ihnaled dose. H1stolog1cal examination of the testes
showed decreased spermatogenesls In the tubules and flbrosls 1n numerous
tubules with only germinal epithelium remaining 1n the other tubules at
257.23-267.00 mg/kg/day. The average testes-to-body weight ratio was
decreased at 257.23-267.00 mg/kg/day (0.38 vs. 0.46 at 0 and 124.79-129.53
mg/kg/day), but statistical significance was not reported. Reproductive
function was not evaluated.
Torkelson et al. (1960) also exposed groups of two male rabbits (strain
not reported) to 0, 490 or 1010 ppm (2593 or 5345 mg/m3) bromochloro-
methane 7 hours/day, 5 days/week for 79-82 exposures 1n 114 days (see
Section 6.1.1.1.). These doses correspond to 0, 137.93-143.16 and
284.32-295.09 mg/kg/day assuming an average body weight of 3.8 kg, a
breathing rate of 2 mVday and a 50% absorption of the Ihnaled dose.
H1stolog1cal examination showed testlcular tubule changes, characterized by
decreased spermatogenesls with replacement flbrosls 1n one of the rabbits
0316d -31- 08/20/90
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exposed to 284.32-295.09 mg/kg/day. The testlcular histology of the other
rabbit was normal. The average testes-to-body weight ratio for the rats 1n
the 284.32-295.09 mg/kg/day group (0.08) was lower than the ratios for the 0
and 137.93-143.16 mg/kg/day groups (0.16 and 0.17, respectively).
Reproductive function was not evaluated.
6.6. SUMMARY
Inhalation LC s for m)Ce for 7-hour exposures ranged from 2268-2995
ppm (Svlrbely et al., 1947; Hlghman et al., 1948) and exposure to 5000 ppm
(26,460 mg/m3) for 7 hours was not lethal for rats (Torkelson et al.,
1960). Rats survived a single oral dose of 5 g/kg, and all rats died within
24 hours after a dose of 7 g/kg (Torkelson et al., 1960). An oral LDcn of
DU
-4300 mg/kg was determined for mice (Svlrbely et al., 1947). Signs and
*
pathological effects of acute Inhalation and oral exposure to bromochloro-
methane are similar; principal effects Include CNS depression and degenera-
tion of the liver.
Subchronlc Inhalation studies of bromochloromethane have been conducted
with rats, mice, guinea pigs, rabbits and dogs (Torkelson et al., 1960;
MacEwen et al., 1966; Svlrbely et al., 1947; Hlghman et al., 1948). Concen-
trations ranged from 66.93 mg/kg/day (dogs) to 728.88 mg/kg/day (mice);
exposures were usually 5-7 hours/day, 5 days/week ranging from 14 weeks to
-6 months. Generally, minor effects such as decreased body weight,
Increased relative liver and kidney weight and reversible liver and kidney
hlstologlcal alterations occurred at concentrations >500 ppm In most species
evaluated for these endpolnts. Torkelson et al. (1960) found that relative
liver weight was Increased 1n rats at concentrations of 125.96 mg/kg/day.
With hlstologlcal effects occurring at 166.97-173.31 mg/kg/day, exposure to
1000 ppm (143.97-335.93 mg/kg/day) caused death and marked liver Injury 1n
0316d
-32-
08/20/90
-------
mice (Hlghman et al., 1948); however, exposure conditions were not reported
adequately and calculation of this dose to mg/kg/day can not be done
accurately without further Information. Information regarding the chronic
Inhalation toxldty, subchronlc or chronic oral toxldty or teratogenldty
of bromochloromethane were not located. Decreased spermatogenesls and
flbrosls occurred In the tubules of the testes of guinea pigs and rabbits
that were subchronlcally exposed to 344.18-357.25 and 257.23-267.00
mg/kg/day respectively, to bromochloromethane by Inhalation {Torkelson et
al., 1960). The functional significance of these effects was not evaluated.
The carclnogenldty of bromochloromethane has not been evaluated.
Bromochloromethane was mutagenlc In Salmonella typhlmurlum and Escherlchla
CQ_11_ bacteria (Simmon et al., 1977; Osterman-Golkar et al., 1983; Strobe!
and Grummt, 1987) and Induced SCE and chromosome aberrations 1n Chinese
hamster cells In vitro (Strobe! and Grummt, 1987).
0316d -33- 08/20/90
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7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
ACGIH (1989) recommends a TLV-TWA of 200 ppm (1058 mg/m3) and a
TLV-STEL of 250 ppm (1320 mg/m3) for occupational exposure to bromochloro-
methane, but deletion of the STEL 1s proposed. The recommendation for the
TLV-TWA Is based primarily on the subchronlc animal studies evaluated 1n
Section 6.1.1.1. (ACGIH, 1986). OSHA (1989) has promulgated a PEL of 200
ppm (-1050 mg/ma) for occupational exposure to bromochloromethane.
Based on Inhalation toxlclty data, U.S. EPA (1988) has derived 1-day,
10-day, longer-term (child) and longer-term (adult) drinking water HAs of 50
mg/i, 50 mg/fc, 13.1 mg/a and 45.7 mg/9., respectively, for bromo-
chloromethane. U.S. EPA (1988) also calculated a provisional DHEL of 4.6
mg/n for bromochloromethane.
7.2. AQUATIC
Guidelines and standards for the protection of aquatic life from
exposure to bromochloromethane were not located 1n the available literature
cited In Appendix A.
0316d
-34-
08/20/90
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8. RISK ASSESSMENT
8.1. CARCINOGENICITY
8.1.1. Inhalation. Pertinent data regarding the cardnogenldty of
bromochloromethane to humans or animals by Inhalation exposure were not
located 1n the available literature dted In Appendix A. Bromochloromethane
has not been scheduled for cardnogenldty testing by the National
Toxicology Program (NTP, 1989).
8.1.2. Oral. Pertinent data regarding the cardnogenldty of bromo-
chloromethane to humans or animals by oral exposure were not located 1n the
available literature dted In Appendix A.
8.1.3. Other Routes. Pertinent data regarding the cardnogenldty of
bromochloromethane to humans or animals by other routes of exposure were not
located In the available literature dted In Appendix A.
8.1.4. Weight of Evidence. Pertinent cardnogenldty data for humans and
animals were not located In the available literature dted 1n Appendix A;
therefore, bromochloromethane 1s categorized 1n U.S. EPA we1ght-of-evidence
Group 0 (Not Classifiable as to Human Cardnogenldty) using the U.S. EPA
(1986c) classification scheme.
8.1.5. Quantitative Risk Estimates. Derivation of a cardnogendc
potency factor for bromochloromethane Is precluded by the lack of appro-
priate data.
8.2. SYSTEMIC TOXICITY
8.2.1. Acute Exposure.
8.2.1.1. INHALATION — Acute Inhalation lethality data for
bromochloromethane are summarized In Table 6-1. These data suggest that
mice are more susceptible to bromochloromethane exposure by Inhalation than
are rats. Hallmarks of CNS toxldty 1n mice and rats Includes restlessness,
0316d -35- 08/20/90
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muscular twitching, uncoordlnatedmovements, labored respiration, narcosis
(mice), drowsiness (rats) and unconsciousness (rats). Hlghman et al. (1948)
demonstrated fatty degeneration of the liver In Swiss mice after a single
expousre >7 mg/i bromochloromethane and degeneration of the kidneys after
a single exposure to >12 mg/i bromochloromethane. Torkelson et al. (1960)
demonstrated that liver and kidney degeneration 1n rats occured after a
single 7 hour expousure to 1500 ppm, equivocal results at 800 ppm, no
degeneration at 600 ppm bromochloromethane.
8.2.1.2. ORAL -- Torkelson et al. (1960) determines that a 7 g/kg
dose of bromochloromethane was lethal to all rats within 24 hours of dosing
but that all rats survived a dose of 5 g/kg. Svlrbely et al. (1947)
determined a 6-day L05Q to be 4300 mg/kg 1n mice. Signs of CNS depression
were observed at doses > 500 mg/kg. Hlghman et al. (1948) demonstrated
effects In mice at > 3000 mg/kg Including pronouned hepatic hlstopathology
and other acute pathological changes. Mice killed 24 hours after dosing had
severe effects Including focal subcapsular necrosis and hydropic
degeneration of the liver and hemoglobin casts In a few renal tubules.
These effects were generally absent or slight In mice surviving >48 hours.
Occluded dermal application of 5000 mg/kg bromochloromethane to the
clipped skin of five rabbits resulted In burns and denaturatlon of the
skin. Application without occlusion only caused slight defattlng.
8.2.2. Subchronlc Exposure.
8.2.2.1. INHALATION -- Sufficient data are available for derivation
of a subchronlc Inhalation RfD for bromochloromethane. Inhalation RfD
derivation Involves evaluating the quality of the Inhalation exposure-
response data, converting exposure concentrations associated with effects In
0316d
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animals to human equivalent concentrations and dividing these by uncertainty
factors and modifying factors. For gases such as bromochloromethane, which
produce systemic effects and reach steady state within the dally exposure
length, HECs are calculated by adjusting the animal exposure concentrations
to equivalent continuous exposure concentrations and multiplying by the
ratio of the blood/gas partition coefficient 1n the experimental animal to
that In humans.
Evidence for rapid attainment of steady state with bromochloromethane 1s
provided by Gargas and Andersen (1982), who found that the rapid uptake
phase In rats was completed In 70-110 minutes (see Section 5.1.). A
blood/gas partition coefficient for bromochloromethane of 41.5 was reported
for rats (see Section 5.2.), but not for humans. Insufficient data for a,
blood/gas partition coefficient for bromochloromethane was found for humans;
therefore, the ratio of the animal to human blood/gas partition coefficients
Is assumed to be 1. Therefore, HECs (Human equivalent concentrations) for
extraresplratory effects from bromochloromethane are Identical to the
adjusted animal exposure concentration.
Torkelson et al. (1960) exposed 10 female rats (strain not reported) to
370 ppm (1958 mg/m3) bromochloromethane 7 hours/day for 135 exposures 1n
195 days, and groups of 20 rats/sex (strain not reported) to 490 ppm (2593
mg/m3) or 1010 ppm (5345 mg/m3) bromochloromethane 7 hours/day for 79-82
exposures 1n 114 days. These doses correspond to 125.96 mg/kg/day (370
ppm); 166.97-173.31 mg/kg/day (490 ppm); and 344.18-357.25 mg/kg/day (1010
ppm) assuming an average body weight of 0.35 kg, a breathing rate of 0.233
mVday and a 50% absorption of th Inhaled dose. Effects attributed to
treatment Included Increased I1ver-to-body weight ratios at >125.96
mg/kg/day, liver hlstologlcal alterations (e.g., slight flbrosls and
0316d -37- , 08/20/90
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vacuollzatlon) In females at 166.97-173.31 mg/kg/day and both sexes at
344.18-357.25 mg/kg/day and Increased kidney-to-body weight ratio In both
sexes at 344.18-357.25 mg/kg/day. Abnormal hematology. Increased blood
nitrogen levels, decreased body weight gain or symptoms of bromlsm were not
observed at any of the exposure concentrations. As the Increased relative
liver weight was not accompanied by hlstologlcal alterations or other
effects at 125.96 mg/kg/day, this concentration represents a NOAEL and
166.97-173.31 mg/kg/day 1s the lowest LOAEL (Recs. #1 and 2, Appendix C).
Dogs (I/sex) were also exposed to 370 ppm (1958 mg/m3} bromochloromethane
7 hours/day for 135 exposures In 195 days. This exposure corresponds to
66.93 mg/kg/day assuming an average bodw weight of 12.7 kg, a breathing rate
of 4.3 mVday and a 50% absorption of the Inhaled dose. There were no
effects on body weight, blood nitrogen or hematology, but hlstologlcal
examinations and organ weight measurements were not performed. Although
66.93 mg/kg/day Is a NOEL In dogs (Rec. #7, Appendix C), this value Is not
suitable for quantitative risk assess- ment because of the small number of
animals and lack of histology.
Albino rats (50/sex/concentrat1on) and beagle dogs (4/sex/concentratlon)
were exposed to 515 or 1010 ppm {2725 or 5345 mg/ma) bromochloromethane 6
hours/day for 124 exposures 1n 6 months (MacEwen et al., 1966). In rats
these doses corresponds to 149.51 and 293.26 mg/kg/day assuming an average
body weight of 0.35 kg, a breathing rate of 0.223 mVday and a 50%
absorption of the Inhaled dose. In beagle dogs these doses correspond to
79.45 and 155.84 mg/kg/day respectively, assuming an average body weight of
12.7 kg, a breathing rate of 4.3 mVday and a 50% absorption of the
Inhaled dose. Decreased body weight gain In male rats at >149.51 mg/kg/day,
possibly from lethargy associated with elevated blood bromide concentration,
was the only effect attributed to treatment. Hlstologlcal examinations of
0316d
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the liver and other tissues, organ weight measurements and clinical
chemistry evaluations (Including SCOT and SGPT) were unremarkable. In this
study, 149.51 mg/kg/day Is considered a LOAEL associated with reduced growth
rate In rats possibly from bromide-Induced lethargy (Rec. #8, Appendix C).
Twenty male rats (Rec. #10, Appendix C), two female dogs (Rec. #12,
Appendix C) and three male rabbits (Rec. #11, Appendix C) (strains not
reported) were exposed to 890 ppm (4710 mg/m3) bromochloromethane (nominal
concentration) 7 hours/day, 5 days/week for 67 exposures (-14 weeks)
(Svlrbely et al., 1947). In rats this dose corresponds to 299.20 mg/kg/day
assuming an average body weight of 0.35 kg, a breathing rate of 0.223
mVday and a SOX absorption of the Inhaled dose. In dogs this dose
corresponds to 158.99 mg/kg/day assuming an average body weight of 12.7 kg,
a breathing rate of 4.3 mVday and a 50% absorption of the Inhaled dose.
In rabbits this dose corresponds to 247.16 mg/kg/day assuming an average
bodw weight of 3.8 kg, a breathing rate of 2.0 mVday and a 50% absorption
of the Inhaled dose. Slightly Increased hemoslderin occurred In the rats
(spleen) and dogs (spleen and kidneys), and Increased fat occurred In the
kidneys of dogs. Other hlstologlcal alterations such as liver were not
observed and body weight measurements (all species), liver function evalua-
tion (dogs, rabbits) and urlnalysls (dogs, rabbits) were unremarkable. The
247.16 mg/kg/day concentration, therefore, 1s a NOEL 1n rabbits and the
299.20 mg/kg/day Is a LOAEL In rats and 158.99 mg/kg/day Is a LOAEL In dogs.
Guinea pigs (10/sex/concentratlon) (Rec. #3, Appendix C), mice (10/sex/
concentration) (Rec. #4, Appendix C) and rabbits (2/sex/concentratlon) (Rec.
#5. Appendix C) were exposed to 0, 490 or 1010 ppm (2593 or 5345 mg/m3)
bromochlormethane 7 hours/day for 79-82 exposures In 114 days (Torkelson et
al., 1960). In guinea pigs these doses correspond to 0. 124.79-129.53 and
257.23-267.00 mg/kg/day respectively, assuming an average body weight of
0316d -39- 08/20/90
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0.84 kg, a breathing rae of 0.4 mVday and a 50% absorption of the Inhaled
dose. In mice these doses corresponds to 0, 340.67-353.59 and 702.22-728.88
mg/kg/day respectively, assuming an average body weight 0.03 kg, a breathing
rate of 0.039 mVday and a 50% absorption of the Inhaled dose. In rabbits
these dogs corresponds to 0, 137.93-143.16 and 284.32-295.09 mg/kg/day
respectively, assuming an average body weight of 3.8 kg, a breathing rate of
2 mVday and a 50% absorption of the Inhaled dose. The 124.79-129.53
mg/kg/day concentration Is a LOAEL In the guinea pigs and the 340.67-353.59
mg/kg/day concentration Is a LOAEL 1n mice, associated with decreased body
weight, Increased relative liver and kidney weights and neutrophHla (female
guinea pigs). Adverse effects 1n rabbits were limited to testlcular lesions
at the 284.32-295.09 mg/kg/day level
One hundred Strain A mice and 45 C3H mice (sexes not reported) were
exposed for 3-7 hours/day to 1000 ppm (5292 mg/m3) bromochloromethane for
<64 exposures In 5 months (<143.97-335.93 mg/kg/day assuming an average body
weight of 0.03 kg, a breathing rate of 0.039 mVday and a 50% absorption
of the Inhaled dose) and 49 exposures In 4 months (150.43-351.00 mg/kg/day
assuming an average body weight of 0.03 kg, a breathing rate of 0.039
mVday and a 50% absorption of the Inhaled dose), respectively (Hlghman et
al., 1948). The exposures were administered 5 days/week but were
Interrupted by occasional long rest periods (duration and frequency not
reported) when necessary, as Indicated by mortality or abnormal general
condition. Host of the mice (numbers not reported) died during the exposure
period and the mice that died generally had slight fatty changes In the
liver and kidneys. The exposure schedule was not reported In sufficient
detail to permit consideration of this study for quantitative risk
assessment.
0316d
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Acute toxldty data Indicate that the critical effects of exposure to
bromochloromethane appear to be CNS Involvement and hepatotoxldty
(Rutsteln, 1963; Svlrbely et al.t 1947; Torkelson et al., 1960). In the
subchronlc Inhalation studies, reduced rate of body weight gain and elevated
liver weight were the first effects reported at the lower concentrations.
In the absence of histopathologlcal alteration or biochemical evidence of
organ damage or Impaired function, elevated liver weight alone may be
considered a nonadverse effect. Similarly, a slight reduction 1n growth
with no evidence of organic Injury or compromised function may be considered
nonadverse. Several studies, however, have shown that bromide 1on 1s a
consistent metabolite of bromochloromethane In the mammalian species
studied, and that blood levels of bromide Increase In a dose-related manner
In animals exposed by Inhalation (Svlrbely et al., 1947; Torkelson et al.,
1960; MacEwen et al., 1966; Gargas et al., 1986a). MacEwen et al. (1966)
postulated that the reduced body weight gain observed 1n rats exposed to
bromochloromethane may have resulted from lethargy Induced by elevated blood
bromide levels. The conservative approach, therefore, Is to consider
reduced body weight gain a potentially adverse effect of Inhalation exposure
to bromochloromethane.
Reduced body weight gain was reported 1n all species studied (except
rabbits) 1n the subchronlc Inhalation studies reviewed herein. The NOAEL
for this effect 1n rats was the 125.96 mg/kg/daylevel 1n the 195-day study
(Rec. #1, Appendix C) by Torkelson et al. (1960). Using this NOAEL and an
uncertainty factor of 1000 (10 to reflect uncertainties associated with
estimating a human equivalent concentration from animal exposure data, 10 to
reflect uncertlntles associated with extrapolation from a subchronlc study
of chronic toxldty endpolnts, and 10 to protect the most sensitive
0316d -41- 08/20/90
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Individuals) a chronic RfD of 1.26E-02 mg/kg/day Is calculated. Confidence
In the key study Is low because of the relatively small number of animals
and lack of treated males at the lowest (NOAEL) concentration. Confidence
1n the data base and RfO are low because of the lack of developmental and
reproductive data and the lack of adequate evaluation of the effect of
bromochloromethane (elevated blood bromide levels) on CMS function, which
could be the critical effect of exposure.
Two previous risk assessments of bromochloromethane have been performed
by the U.S. EPA. An RfD was not calculated 1n a Health and Environmental
Effects Profile (U.S. EPA, 1985) because the Torkelson et al. (1960) rat
study was considered Inadequate. It did not clearly define a NOAEL for
liver effects and did not test males at the NOAEL concentration. The same
NOAEL, however, was considered sufficient basis for deriving drinking water
longer-term HAs and a provisional DWEL for bromochloromethane (U.S. EPA,
1988).
8.2.2.2. ORAL — Information on the subchronlc oral toxldty of
bromochloromethane was not located. Acute exposure data, however, Indicate
that the critical effects of both Inhalation and oral exposure are CNS signs
and hepatotoxldty. In addition, the critical effects of subchronlc
Inhalation exposure to bromochloromethane are reduced body weight and
hepatotoxldty. The respiratory tract does not appear to be the target
organ for Inhalation exposure to bromochloromethane. The data reviewed In
Section 5.3. suggest that metabolism Involving dehalogenatlon would be
expected with either route of exposure. Therefore, 1n the absence of
subchronlc oral data, 1t 1s appropriate to use Inhalation toxldty data to
derive a subchronlc oral RfD for bromochloromethane.
0316d
-42-
08/20/90
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As discussed In Section 8.2.2.1., a NOAEL of 125.96 mg/kg/day has been
Identified In rats exposed to bromochloromethane for 7 hours/day 135
exposures In 195 days (Torkelson et al., 1960) (Rec. #1, Appendix C). This
dose Is essentially the same as a previously derived estimated absorbed dose
of 130.5 mg/kg/day based on the same NOAEL used to calculate longer-term
drinking water HAs (U.S. EPA, 1988). Applying an uncertainty factor of 100
(10 for Interspedes extrapolation and 10 to protect most sensitive
Individuals), the subchronlc oral RfD for bromo- chloromethane Is 1
mg/kg/day. Confidence 1n the key study Is low (see Section 8.2.1.1.). Low
confidence In the data base and RfD are due to the lack of oral toxlclty
data.
8.2.3. Chronic Exposure.
8.2.3.1. INHALATION — Chronic Inhalation studies of bromo-
chloromethane have not been conducted. It 1s appropriate, therefore, to
derive a chronic .Inhalation RfD for bromochloromethane based on subchronlc
data. Using the subchronlc Inhalation RfD of 1.26E-1 (see Section 8.2.1.1.)
and an additional uncertainty factor of 10 to extrapolate from subchronlc to
chronic exposure, the chronic Inhalation RfD 1s 1.26E-2. Confidence In the
RfD 1s low because of the lack of chronic data, and because confidence 1n
the subchronlc Inhalation RfD Is low.
8.2.3.2. ORAL -- Data on the chronic oral toxlclty of
bromochloromethane were not located. It 1s appropriate to derive a chronic
oral RfD for bromochloromethane based on the subchronlc oral RfD because of
lack of chronic data. Using the subchronlc oral RfD of 1 mg/kg/day {see
Section 8.2.2.1.) and an additional uncertainty factor of 10 to extrapolate
from subchronlc to chronic exposure, the chronic oral RfD 1s 0.1 mg/kg/day.
0316d -43- 08/20/90
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This RfD 1s the same as a previously derived RfD of 0.13 mg/kg/day used to
calculate a provisional DUEL for lifetime exposure (U.S. EPA, 1988).
Confidence 1n the key study 1s low (see Section 8.2.1.1.), and confidence 1n
the data base and RfD are low because of the lack of oral toxldty data.
0316d
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08/20/90
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9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The toxldty of bromoch 1 oromethane Is discussed In Chapter 6, and Inha-
lation data suitable for RQ derivation are summarized In Table 9-1. Chronic
Inhalation data and oral data useful for RQ derivation are not available.
As shown 1n Table 9-1, subchronlc Inhalation exposure to bromochloro-
methane produced decreased body weight gain 1n rats, mice and guinea pigs
(MacEwen et al., 1966; Torkelson et al., 1960), Increased relative organ
weights (liver and/or kidneys) In rats, mice and guinea pigs (Torkelson et
al., 1960), hlstologkal alterations In the liver In rats {Torkelson et al.,
1960) and kidneys In dogs (Svlrbely et al., 1947), Increased hemosldeMn 1n
the spleen of rats (Svlrbely et al., 1947) and testlcular effects In guinea
pigs and rabbits (Torkelson et al., 1960). Death In mice (Hlghman et al.,
1948} was not Included because the exposure protocol was not presented In
sufficient detail from which to estimate a transformed animal dose.
Derivations of CSs for bromochloromethane, based on the lowest equiva-
lent human dose associated with each effect In Table 9-1, are presented 1n
Table 9-2. Changes 1n body and organ weights are assigned an RV of 4.
c
The most appropriate RV for the kidney hlstologlcal alterations Is 5
c
because the effects were slight and reversible. Lesions 1n the liver
Included flbrosls, which may not be reversible; liver lesions were assigned
an RV of 6. Increased hemoslderln warrants an RV of 1 since hematln
e e
formation Is most appropriately viewed as a biochemical effect. The most
appropriate RV for the testlcular alterations Is 6 because It cannot be
determined If the effects were sufficient to Impair fuctlon. Five of the
six CSs correspond to an RQ of 1000. The highest CS (12.22) for liver
lesions In rats (Torkelson et al., 1960) 1s used as the basis for the RQ
0316d -45- 08/20/90
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0316d
-48-
08/20/90
-------
(Table 9-3). This RQ 1s the same as a previously derived RQ (U.S. EPA,
1985), but the previous evaluation did not evaluate the studies by MacEwen
et al. (1966) and Svlrbely et al. (1947).
9.2. BASED ON CARCINOGENICITY
Pertinent data regarding the carclnogenldty of bromochloromethane to
humans or animals by Inhalation, oral or other routes of exposure were not
located 1n the available literature cited 1n Appendix A. Because of the
lack of carclnogenlclty data, bromochloromethane Is categorized 1n U.S. EPA
welght-of-evldence Group D (Not Classifiable as to Human Carclnogenlclty).
Chemicals In EPA Group D are not ranked for cancer hazard or assigned
cancer-based RQs.
0316d -49- 08/20/90
-------
TABLE 9-3
Bromochloromethane
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route:
Species/Sex:
Dose*:
Duration:
Effect:
RVd:
RVe:
CS:
RQ:
Reference:
Inhalation
rat/female
203.65
114 days (79-82 exposures, 7 hours/day)
hlstologlcal lesions 1n Hver
2.04
6
12.22
1000
Torkelson et a!., 1960
'Equivalent human dose
031 fed
-50-
08/20/90
-------
10. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 125-126.
ACGIH {American Conference of Governmental Industrial Hyglenlsts), 1989.
Threshold Limit Values and Biological Exposure Indices for 1989-1990.
Cincinnati, OH. p. 16. 46.
Allgeler, G.D., R.L. Mulllns, Jr., O.A. Wilding, J.S. Zogorskl and S.A.
Hubbs. 1980. TMhalomethane levels at selected water utilities In
Kentucky, USA. Environ. Sc1. Res. 16: 473-490.
Amoore, 3.E. and E. Hautala. 1983. Odor as an aid to chemical safety: Odor
thresholds compared with threshold limit values and volatilities for 214
Industrial chemicals 1n air and water dilution. 3. Appl. Toxlcol. 3:
272-289.
Andersen, H.E., M.L. Gargas, R.A. Jones and L. Jenkins, Jr. 1980. Determi-
nation of the kinetic constants for metabolism of Inhaled toxicants \i± vivo
using gas uptake measurements. Toxlcol. Appl. Pharmacol. 53(1): 100-116.
Arguello, M.D., C.O. Chrlswell, J.S. Fritz et al. 1979. Trlhalomethanes In
water: A report on the occurrence, seasonal variation 1n concentrations, and
precursors of trlhalomethanes. Am. Water Works Assoc. J. 71(9): 504-508.
0316d -51- 08/20/90
-------
Atkinson, R. 1987. A structure-activity relationship for the estimation of
the rate constants for the gas-phase reaction of OH radicals with organic
compounds. Int. J. Chem. K1net. 19: 799-828,
Cadman, P. and J.P. Simons. 1966. Reactions of hot halpmethyl radicals.
Trans. Faraday Soc. 62(3): 631-641.
Chemllne. 1989. Chemical Information Service (CIS). On-Hne computer data
base: July 8, 1989.
Class, T.H. and K. Ballschmlter. 1988. Chemistry of organic traces In
air. VIII. Sources and distribution of bromo- and bromochloromethanes 1n
marine air and surface water of the Atlantic Ocean. J. Atmos. Chem. 6:
35-46.
Crockett, P.M., B. K1l1an, K.S. Crump and R.B. Howe. 1985. Descriptive
Methods for Using Data from Dissimilar Experiments to Locate a No-Adverse-
Toxic-Effects Region 1n the Dose-Duration Plane. Prepared by K.S. Crump and
Company, Inc. under Contract No. 68-01-6807 for Environmental Criteria and
Assessment Office, Cincinnati, OH.
Dean, J.A. 1985. Lange's Handbook of Chemistry, 13th ed. McGraw-Hill Book
Co., New York. p. 7-163.
Dore, M., N. Herlet, J. De Laat and J. Golchon, 1982. Reactivity of
halogens with aqueous mlcropollutants: A mechanism for the formation of
trlhalomethanes. Am. Water Works Assoc. J. 74(2): 103-107.
0316d
-52-
08/20/90
-------
Durkln, P. and W. Meylan. 1989. Users Guide for D2PLOT: A Program for
Dose/Duration Graphs Version 2.00. Prepared by Chemical Hazard Assessment
Division, Syracuse Research Corporation under Contract NO. 68-C8-004 for
Environmental Criteria and Assessment Office, Cincinnati, OH.
Elsenrelch, S.J., B.B. Looney and O.J. Thornton. 1981. Airborne organic
contaminants 1n the Great Lakes ecosystem. Environ. Sc1. Techno!. 15:
30-38.
Gargas, M.I. and M.E. Andersen. 1982. Metabolism of Inhaled bromlnated
hydrocarbons: Validation of gas uptake results by determination of a stable
metabolite. Toxlcol. Appl. Pharmacol. 66(1): 55-68.
Gargas. M.L., H.J. Clewell, II and M.E. Andersen. 1986a. Metabolism of
Inhaled dlhalomethanes in vivo: Differentiation of kinetic constants for two
Independent pathways. Appl. Pharmacol. 82(2): 211-223.
Gargas, H.L., M.E. Andersen, H.J. Clewell and G. Harry. 1986b. A physio-
logically based simulation approach for determining metabolic constants from
gas uptake data. Toxlcol. Appl. Pharmacol. 86: 341-352.
Gould, J.P., R.E. Ramsey, M. Glabbal and F.G. Pohland. 1983. Chapter 36.
Formation of volatile haloorganlc compounds In the chloMnatlon of mundpal
landfill leachates. in: Water ChloMnatlon: Environ. Impact Health Eff. 4:
525-539.
0316d -53- 08/20/90
-------
Hawley, G.6. 1981. The Condensed Chemical Dictionary, 10th ed. Van
Nostrand Relnhold Co., New York. p. 151.
Hlatt, H.H. 1983. Determination of volatile organic compounds 1n fish
samples by vacuum distillation and fused silica capillary gas chromatography-
mass spectrometry. Anal. Chem. 55(3): 506-516.
Hlghman, B., J.L. Svlrbely, W.F. von Oettlngen, W.C. Alford and L.J. Pecora.
1948. Pathologic changes produced by monochloromonobromomethane. Am. Med.
Assoc. Arch. Pathol. 45: 299-305.
Kaiser, K.L.E., M.E. Comba and H. Huneault. 1983. Volatile halocarbon
contaminants In the Niagara River and In Lake Ontario. J. Great Lakes Res.
9: 212-223.
Kublc, V.L., H.W. Anders, R.R. Engel, C.K. Barlow and U.S. Caughey. 1974.
Hetabolism of dlhalomethanes to carbon monoxide. I. |n. vivo studies. Drug
Metab. Dlspos. 2(1): 53-57.
Kuney, J.H. 1988. Chemcyclopedla 1989. Volume 7. American Chemical
Society, Washington, DC. p. 179.
Lareglna, 3.. J.W. BozzelH, R. Markov and S. Glantl. 1986. Volatile
organic compounds at hazardous waste sites and a sanitary landfill In New
Jersey. An up-to-date review of the present situation. Environ. Prog. 5:
18-27.
0316d
-54-
08/20/90
-------
Lucas, S.V. 1984. GC/MS analysis of organlcs 1n drinking water concen-
trates and advanced waste treatment concentrates: Vol. 1. Analysis results
for 17 drinking water, 16 advanced waste treatment and 3 process blank
concentrates. EPA-600/1-84-020A. NTIS PB85-128221. Columbus Labs. Health
Eff. Res. Lab., Columbus, OH. p. 144, 174, 255.
Lyman, H.J. 1982. Adsorption coefficient or soils and sediments. It±:
Handbook of Chemical Property Estimation Methods, W.J. Lyman, W.F. Reehl and
D.H. Rosenblatt, Ed. McGraw-Hill Book Co.. New York. p. 4-9.
Mabey, W. and T. Mill. 1978. Critical review of hydrolysis of organic
compounds 1n water under environmental conditions. J. Phys. Chem. Ref.
Data. 7: 383-415.
MacEwen, 3.D., O.M. McNerney, E.H. Vernot and D.T. Harper. 1966. Chronic
Inhalation toxldty of chlorobromomethane. J. Occup. Med. 8: 251-256.
Mantel, N. and M.A. Schnelderman. 1975. Estimating "safe" levels, a
hazardous undertaking. Cancer Res. 35: 1379-1386.
McDonald, R.A., S.A. Shrader and D.R. Stull. 1959. Vapor pressures and
freezing points of 30 organlcs. J. Chem. {ng. Data. 4: 311-313.
McDougal, J.N., G.W. Jepson, H.J. Clewell and M.E. Andersen. 1985. Dermal
absorption of dlhalomethane vapors. Toxlcol. Appl. Pharmacol. 79: 150-158.
0316d -55- 08/20/90
-------
NAS (National Academy of Science). 1980. Drinking Water and Health. Vol
2. Safe Drinking Hater Committee, National Research Council, National
Academy Press, Washington, OC. p. 151-154.
NTP (National Toxicology Program). 1989. Management Status Report. 7/7/89.
OSHA (Occupational Safety and Health Administration). 1989. 29 CFR Part
1910. A1r Contaminants; Final Rule. p. 2929.
Osterman-Golkar, S., S. Hussaln, S. Walles, B. Anderstam and K. Slgvardsson.
1983. Chemical reactivity and mutagenldty of some dlhalomethanes. Chem.
Blol. Interact. 46(1): 121-130.
Rasmussen, R.A. and M.A.K. Khali!. 1984. Gaseous bromine In the Arctic and
Arctic haze. Geophys. Res. Lett. 11: 433-436.
Rlddlck, J.A., W.B. Bunger and T.K. Sakano. 1986. Organic solvents: Physi-
cal properties and methods of purification. In: Techniques of Chemistry,
4th ed. W1ley-Intersc1ence, New York. 2: 562-563.
Rutsteln, H.R. 1963. Acute chlorobromomethane toxlclty. Arch. Environ.
Health. 7(4): 440-444.
Simmon, V.F. 1976. In Vitro H1crob1olog1cal Hutagenlclty Studies of Dow
Chemical Company Compounds. U.S. EPA/OPTS Public Files, Section 8D.
Document No. 86-870002152. OTS 0515942.
0316d
-56-
08/20/90
-------
Simmon, V.F., K. Kauhanen and R.G. Tardlff. 1977. Mutagenlc activity of
chemicals Identified In drinking water. 2nd Int. Conf. Environmental
Mutagens, Edinburgh, Scotland, July. p. 249-258.
SRI (Stanford Research Institute). 1989. 1989 Directory of Chemical
Producers: United States of America. SRI International, Menlo Park, CA.
p. 491.
Stenger, V.A. 1978. Bromine compounds. lr±: K1rk-0thmer Encyclopedia of
Chemical Technology, Vol. 4, 3rd ed., M. Grayson and D. Eckroth, Ed. 3ohn
Wiley and Sons, Inc., New York. p. 252-253.
Strobe"), K. and T. Grummt. 1987. Aliphatic and aromatic halocarbons as
potential mutagens In drinking water. Part I. Halogenated methanes.
Toxlcol. Environ. Chem. 13(3-4): 205-221.
Suffet, I.H., L. Brenner and P.R. Cairo. 1980. GC/MS Identification of
trace organlcs In Philadelphia drinking waters during a two-year period.
Water Res. 14: 853-867.
Svlrbely, J.L., 8. Hlghman, W.C. Alford and W.F. von Oettlngen. 1947. The
toxlclty and narcotic action of mono-chloro-mono-bromomethane with special
reference to Inorganic and volatile bromide In blood, urine and brain. 3.
Ind. Hyg. Toxlcol. 29: 382-389.
0316d -57- 08/20/90
-------
v_
Swann, R.L., D.A. Laskowskl, P.J. MeCall, K. Vander Kuy and H.J.
Dlshburger. 1983. A rapid method for the estimation of the environmental
parameters octanol/water partition coefficient, soil sorptlon constant,
water to air ratio and water solubility. Res. Rev. 85: 17-28.
Tabak, H.H., S.A. Quave, C.I. Hashnl and E.F. Barth. 1981. Blodegradabll-
t
My studies with organic priority compounds. J. Water Pollut. Control Fed.
53: 1503-1518.
TewaM, Y.B., M.M. Miller, S.P. Waslk and D.E. Martlre. 1982. Aqueous
solubility and octanol/water partition coefficient of organic compounds at
25.0°C. J. Chem. Eng. Data. 27: 451-454.
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Property Estimation Methods, H.J. Lyman, W.F. Reehl and D.H. Rosenblatt, Ed.
McGraw-Hill Book Co., New York. p. 15-1 to 15-32.
Torkelson, T.R., F. Oyen and V.K. Rowe. 1960. The toxldty of bromochloro-
methane (methylene chlorobromlde) as determined on laboratory animals. Am.
Ind. Hyg. Assoc. J. 21: 275-286.
U.S. EPA. 1977. Computer print-out of non-confidential production data
from the TSCA Production File for 1977. Washington, OC.
U.S. EPA. 1980. Guidelines and Methodology Used 1n the Preparation of
Health Effect Assessment Chapters of the Consent Decree Hater Criteria
Documents. Federal Register. 45(231): 79347-79357.
0316d
-58-
08/20/90
-------
U.S. EPA. 1984. Methodology and Guidelines for Ranking Chemicals Based on
Chronic Toxldty Data. Prepared by the Office of Helath and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Solid Waste Emergency Response, Washington, DC.
U.S. EPA. 1985. Health and Environmental Effects Profile for Bromochloro-
methanes. 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.
U.S. EPA. 1986a. Methodology for Evaluating Reportable Quantity Adjust-
ments Pursuant to CERCLA Section 102. Prepared by the Carcinogen Assessment
Group, Office of Health and Environmental Assessment for the Office of
Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1986b. Exams II Computer Model Simulations. Version 2.91.
Athens, GA.
U.S. EPA. 1986c. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA. 1986d. Reference Values for Risk Assessment. Prepared by the
Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington,
DC.
U.S. EPA. 1987. Summary Environmental Data for Bromochloromethane. U.S.
EPA/OPTS Public Files. Flche #0750517073.
0316d -59- 08/20/90
-------
U.S. EPA. 1988. Drinking Water Health Advisory for Bromochloromethane.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking
Water, Washington, DC.
U.S. EPA/OWRS. 1986. Guidelines for Deriving Numerical National Water
Quality Criteria for the Protection of Aquatic Organisms and Their Uses.
Office of Water Regulations and Standards, Criteria and Standards Dlvlson.
NTIS PB85-227049.
USITC (U.S. International Trade Commission). 1988. Synthetic Organic
Chemicals. United States Production and Sales, 1987. USITC Publ. 2118,
*
Washington, DC. p. 15-29.
Hakeham, S.G., J.T. Goodwin and A.C. Davis. 1983. Distributions and fate of
volatile organic compounds 1n Narragansett Bay Rhode Island. Can. J. Fish
Aquat. Sd. 40: 304-321.
Zoeteman, B.C.J., E. Degreef and F.J.J. BMnkman. 1981. Persistency of
organic contaminants 1n groundwater, lessons from soil pollution Incidents
1n the Netherlands. Sc1. Total Environ. 21: 187-202.
0316d
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08/20/90
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APPENDIX A
LITERATURE SEARCHED
This HEED 1s based on data Identified by computerized literature
searches of the following:
CHEMLINE
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXLIT
TOXLIT 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
CAS ONLINE (Chemistry and Aquatic)
HSDB
SCISEARCH
Federal Research 1n Progress
These searches were conducted 1n April, 1989, and the following secondary
sources were reviewed:
ACGIH (American Conference of Governmental Industrial Hyg1en1sts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyg1en1sts).
1987. TLVs: Threshold Limit Values for Chemical Substances 1n the
Work Environment adopted by ACGIH with Intended Changes for
1987-1988. Cincinnati, OH. 114 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and
Sons. NY. 2878 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 28. John WHey and
Sons, NY. p. 2879-3816.
0316d -61- 08/20/90
-------
Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
Grayson, H. and D. Eckroth, Ed. 1978-1984. Klrk-Othmer Encyclo-
pedia of Chemical Technology, 3rd ed. John WHey and Sons, NY. 23
Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, Inc., Littleton, MA. 575 p.
IARC (International Agency for Research on Cancer}. IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. IARC, WHO, Lyons, France.
Jaber, H.M., M.R. Mabey, A.T. I.leu, T.W. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
EPA 600/6-84-010. NTIS PB84-243906. SRI International, Menlo
Park, CA.
NTP (National Toxicology Program). 1987. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1987. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report 1n the Special Review
Program, Registration Standards Program and the Data Call 1n
Programs. Registration Standards and the Data Call 1n Programs.
Office of Pesticide Programs, Washington, DC.
USITC (U.S. International Trade Commission). 1986. Synthetic
Organic Chemicals. U.S. Production and Sales, 1985, USITC Publ.
1892, Washington, DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY.
Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co.,
Inc., Rahway, NJ.
Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
0316d
-62-
08/20/90
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EPA/6OO/8-91/O16
May 199O
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR BROMOCHLOROMETHANE
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
-------
-------
TECHNICAL REPORT DATA
(Fleatt read Instructions on the revtru before completing/
, REPORT NO.
EPA/600/8-91/016
3. RECIPIENT'S ACCESSION NO.
PB91-213702
. TITLE AND SUBTITLE
Health and Environmental Effects Document for
Bromochloromethane
S. REPORT DATE
6. PERFORMING ORGANIZATION CODE
7. AUTHOHISI
B. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
13. TYPE OF REPORT AND PERIOD COVERED
Environmental Criteria and Assessment Office
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. OH 45268
14. SPONSORING AGENCY CODE
EPA/600/22
15. SUPPLEMENTARY NOTES
16. ABSTRACT
Health and Environmental Effects Documents (HEEDS) are prepared for the Office of
Solid Waste and Emergency Response (OSWER). This document series is intended to
support listings under the Resource Conservation and Recovery Act (RCRA) as well as
o provide health-related limits and goals for emergency and remedial actions under
he Comprehensive Environmental Response, Compensation and Liability Act (CERCLA).
Both published literature and information obtained from Agency Program Office files
are evaluated as they pertain to potential human health, aquatic life and environmen-
tal effects of hazardous waste constituents.
Several quantitative estimates are presented provided sufficient data are
available. For systemic toxicants, these include Reference Doses (RfDs) for chronic
and subchronic exposures for both the inhalation and oral exposures. In the case of
suspected carcinogens, RfDs may not be estimated. Instead, a carcinogenic potency
factor, or q^*f is provided. These potency estimates are derived for both oral and
inhalation exposures where possible. In addition, unit risk estimates for air and
drinking water are presented based on inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxicity and carcinogenicity are
derived. The RQ is used to determine the quantity of a hazardous substance for
which notification is required in the event of a release as specified under CERCLA.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Group
DISTRIBUTION STATEMENT
19. SECURITY CLASS (Thit Report)
Unclassi fied
21. NO. OF PAGES
98
20. SECURITY CLASS (This page/
Unclassified
22. PRICE
EPA form 2220-1 .(R«v. 4-77) PREVIOUS COITION i« OBSOLCTE
-------
i
-------
In addition, approximately 30 compendia of aquatic toxlclty data were
reviewed, Including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, W.W. and M.T. Flnley. 1980. Handbook of Acute Toxlclty
of Chemicals to Fish and Aquatic Invertebrates. Summaries of
Toxlclty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, Fish and Wildlife
Serv. Res. Publ. 137, Washington, DC.
McKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Publ. No. 3-A.
Plmental, 0. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
0316d -63- 08/20/90
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0316d
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APPENDIX C
DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO BROHOCHLOROHETHANE
C.I. DISCUSSION
Dose/duration-response graphs for Inhalation and oral exposure to bromo-
chloromethane generated by the method of Crockett et al. (1985) using the
computer software by Durkln and Heylan (1989) developed under contract to
ECAO-C1nc1nnat1 are presented In Figures C-l to C-6. Data used to generate
these graphs are presented In Section C.2. In the generation of these
figures, all responses are classified as adverse (FEL, AEL or LOAEL) or
nonadverse (NOEL or NOAEL) for plotting. The ordlnate expresses Inhalation
exposure 1n either of two ways. In Figures C-l and C-2, the experimental
concentration, expressed as mg/m3, was multiplied by the time parameters
of the exposure protocol (e.g., hours/day and days/week), and Is presented
as expanded experimental concentration [expanded exp cone (mg/m3)]. In
Figures C-3 and C-4, the expanded experimental concentration was multiplied
by the animal Inhalation rate 1n mVday and divided by the animal body
weight In kg to calculate a dally dose In mg/kg/day. The dally dose was
then multiplied by the cube root of the ratio of the animal:human body
weight to adjust for species differences In metabolic rate (Mantel and
Schnelderman, 1975). The result was multiplied by an absorption coefficient
of 0.5 to adjust to an equivalent absorbed dose and then multiplied by 70
kg, the reference human body weight, to express the human equivalent dose as
mg/day for a 70 kg human [human equlv dose (mg/day)]. For oral exposure,
the ordlnate expresses dose as human equivalent dose. The animal dose, 1n
mg/kg/day, 1s multiplied by the cube root of the ratio of the animal:human
body weight to adjust for species differences In basal metabolic rate
0316d -65- 08/20/90
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180000
0
I
ft,
X
C
H
a
ft.
x
hi
108
8.0601
BCMINHRL.D2
(Inhalation Exposure)
0.601 0.61 6.1
EQUIU DURflTlON (fraction lifespan)
ENVELOP METHOD
Key:
F
I
n
N
FEL
LOAEL
NOAEL
NOEL
Solid line - Adverse Effects Boundary
Dashed line - No Adverse Effects Boundary
FIGURE C-l
Dose/Duration - Response Graph for Inhalation Exposure to
Bromochloromethane: Envelope Method (Expanded Experimental Concentration)
0316d
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08/20/90
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B
I
U
0
(j
ft,
X
fi
i
&
X
hi
1800 •:
166
Bronochloronethane
13
14
18
8.6601
BCHINHRL.D2
(Inhalation Exposure)
—«1
i i i i i i it
0.081 e.ei e.i
HUMfiN EQUIU DURATION (fraction lifespan)
CENSORED Dfllfl KEIHOD
Key:
F
L
n
N
FEL
LOAEL
NOAEL
NOEL
Solid line - Adverse Effects Boundary
Dashed line - No Adverse Effects Boundary
FIGURE C-2
Dose/Duration - Response Graph for Inhalation Exposure to
Bromochloromethane: Censored Data Method
(Expanded Experimental Concentration)
031 od
-67-
08/20/90
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A
3
I
0
Q
U
z
I
1086
e
BCMINHHL.D2
(Inhalation Exposure)
e.eei e.ei e.i
HUNflN EQUIU DURflUON (fraction lifespan)
EHUZLOP METHOD
Key:
F
L
n
N
FEL
LOAEL
NOAEL
NOEL
Solid Hne • Adverse Effects Boundary
Dashed line - No Adverse Effects Boundary
FIGURE C-3
Dose/Duration - Response Graph for Inhalation Exposure to
Bromochloromethane: Envelope Method (Human Equivalent Dose)
0316d
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08/20/90
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A
J
1
C
v
0
0
D
M
0.8801
3
(Inhalation Exposure)
BCMINHflL.D2
e.eei e.ei e.i
EQUIU DURflllON (fraction lifespan)
CENSORED DflTR METHOD
Key:
F
L
n
N
PEL
LOAEL
NOAEL
NOEL
Solid Hne « Adverse Effects Boundary
Dashed Hne - No Adverse Effects Boundary
FIGURE C-4
Dose/Duration - Response Graph for Inhalation Exposure to
Bromochloromethane: Censored Data Method (Human Equivalent Dose)
0316d
-69-
08/20/90
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i
t
V
W
0
C
I
1800
-F6-
m
e.eei
I
(Oral Exposure)
B.81
BCMORRL.D2
HUMflN EQUIU DURRTION (fraction lifespan)
ENVELOP METHOD
Key:
F » FEL
N - NOEL
Solid line - Adverse Effects Boundary
Dashed line - No Adverse Effects Boundary
FIGURE C-5
Dose/Duration - Response Graph for Oral Exposure to Bromochloromethane:
Envelope Method
0316d
-70-
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1
hi
0)
0
a
M
£
Z
1808
Bronochlorone thane
1.081
(Oral Exposure)
BCI10RRI.D2
J I
8.61
HUHRN EQUIU DURRTION (fraction lifespan)
CENSORED Dfllfl HETKOD
Key: F » PEL
N » NOEL
Solid line • Adverse Effects Boundary
Dashed Une • No Adverse Effects Boundary
Dose/Duration -
FIGURE C-6
Response Graph for Oral Exposure to Bromochloromethane:
Censored Data Method
0316d
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08/20/90
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(Mantel and Schnelderman, 1975). The result 1s then multiplied by 70 kg,
the reference human body weight, to express the human equivalent dose as
mg/day for a 70 kg human [human equlv dose (mg/day)].
The adverse effects boundary (solid line) Is drawn by Identifying the
lowest adverse effect dose or concentration at the shortest duration of
exposure at which an adverse effect occurred. From this starting point, an
Infinite line Is extended upward, parallel to the dose axis. The starting
point Is then connected to the lowest adverse effect dose or concentration
at the next longer duration of exposure that has an adverse effect dose or
concentration equal to or lower than the previous one. This process 1s
continued to the lowest adverse effect dose or concentration. From this
point, a line parallel to the duration axis Is extended Infinitely to the
right. The adverse effects region lies above the adverse effects boundary.
Using the envelope method, the no adverse effects boundary (dashed line)
Is drawn starting with the point representing the highest no adverse
effects dose or concentration. From this point, a line parallel to the
duration axis 1s extended to the dose or concentration axis. The starting
point 1s then connected to the next equal or lower no adverse effect dose or
concentration at a longer duration of exposure. When this process can no
longer be continued, a line parallel to the dose or concentration axis 1s
dropped to the duration axis. The no adverse effects region lies below the
no adverse effects boundary. At either ends of the graph between the
adverse effects and no adverse effects boundaries are regions of ambiguity.
The area (If any) resulting from Intersections of the adverse effects and no
adverse effects boundaries 1s defined as the region of contradiction.
In the censored data method, all no adverse effect points located 1n the
region of contradiction are dropped from consideration and the no adverse
effects boundary Is redrawn so that 1t does not Intersect the adverse
0316d
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effects boundary, and no region of contradiction 1s generated. This method
results 1n the most conservative definition of the no adverse effects region.
Figures C-l and C-3 present the Inhalation dose/duration-response graphs
generated by the envelope method. The adverse effects boundary Is defined
by the LOAEL for liver hlstologlcal alterations In mice (Rec. #17), LOAELs
for kidney hlstologlcal alterations In dogs (Rec. #12), reduced body weight
and elevated organ weights 1n guinea pigs (Rec. #3), liver hlstologlcal
alterations In rats {Rec. #2) and for reduced body weight 1n rats (Rec. #8).
Using the envelope method (Figures C-l and C-4), the no adverse effects
boundary 1s defined by the acute NOEL for mortality 1n rats (Rec. #14), a
NOAEL for slightly Increased hemosldeMn In the spleen of rats (Rec. #10)
and a NOAEL for Increased liver weight In rats (Rec. #1). Using the
censored data method (Figures C-2 and C-4), the no adverse effects boundary
1s defined by the NOEL for liver hlstologlcal alterations In rats (Rec.
#16), the NOEL 1n rabbits (Figure C-2, Rec. #5) or dogs (Figure C-4, Rec.
#7) and the NOAEL for liver hlstologlcal alterations 1n rats (Rec. #1). The
subchronlc and chronic RfDs for bromochloromethane are based on the NOAEL
for liver hlstologlcal alterations In rats (Rec. #1).
Figures C-5 and C-6 present the oral dose/duration-response graphs. The
adverse effects boundary 1s defined by FELs for mortality 1n rats (Rec. #1)
and mortality 1n mice (Recs. #3, 4 and 6). In Figure C-5 (envelope method),
the no adverse effects boundary Is defined by the NOEL for mortality 1n rats
(Rec. #2) and the NOEL for mortality and hlstopathology 1n mice (Rec. #5).
Using the censored data method (Figure C-6), the no adverse effects boundary
Is defined by a single value, the NOEL for mortality and hlstopathology 1n
mice (Rec. #5). Figures C-5 and C-6 emphasize that additional oral data
(I.e., for longer duration exposures) are needed to Identify a maximal
region of no adverse effects.
0316d -73- 08/20/90
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C.2. DATA USED TO GENERATE OOSE/DURATION-RESPONSE GRAPHS
C.2.1. Inhalation Exposure.
Chemical Name:
CAS Number:
Document Title:
Document Number;
Document Date:
Document Type:
Bromochloromethane
74-97-5
Health and Environmental Effects Document on
Bromochloromethane
Pending
Pending
HEED
RECORD #1 :
Species:
Sex:
Effect:
Route:
Rats
Female
NOAEL
Inhalation
Body Weight: 0.35 kg
Reported Dose: 1958 mg/m3
Converted Dose: 125.96 mg/kg/day
Exposure Period: 195 days
Duration Observation: 195 days
Comment:
Molecular Height: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.8461
Inhal. Exp. days: 135.00
Assumed Inhalation Absorption:
50?4
Citation:
Number Exposed: 10
Number Responses: NR
Type of Effect: HGTIN
Site of Effect: LIVER
Severity Effect: 4
Concentrations studied: 1958, 2593 and 5345 mg/m3 (370, 490
and 1010 ppm or 125.96, -170.14, -350.69 mg/kg/day). Both
sexes treated at higher concentrations. No effects on
histology, hematology, blood nitrogen or body weight.
Torkelson et al., 1960
0316d
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RECORD #2: Species: Rats Body Weight: 0.35 kg
Sex: Both Reported Dose: 2593 mg/m3
Effect: LOAEL Converted Oose: 166.97-173.31 mg/kg/day
Route: Inhalation Exposure Period: 114 days
Duration Observation: 114 days
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.8509-5.0351
Inhal. Exp. days: 79.00-82.00
Assumed Inhalation Absorption: 50%
Number Exposed: 40
Number Responses: NR
Type of Effect: PROLF
SHe of Effect: LIVER
Severity Effect: 5
Comment: 20/sex, 79-82 exposures. See previous record. Effects
Included slight bile duct proliferation, slight portal
flbrosls and occasional vacuollzatlon. Similar effects with
cloudy swelling 1n liver In both sexes at 5345 mg/m3
(344.18-357.25 mg/kg/day}.
Citation: Torkelson et al.f 1960
RECORD #3:
Species:
Sex:
Effect:
Route:
Guinea pigs Body Weight: 0.84 kg
Both Reported Dose: 2593 mg/m3
LOAEL Converted Dose: 124.29-129.53 mg/kg/day
Inhalation Exposure Period: 114 days
Duration Observation: 114 days
Comment:
Citation:
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.8509-5.0351
Inhal. Exp. days: 79.00-82.00
Assumed Inhalation Absorption: 50%
Number Exposed: 20 20 20
Number Responses: NR NR NR
Type of Effect: WGTIN WGTIN WGTDC
SHe of Effect: LIVER KIDNY BODY
Severity Effect: 444
10/sex, 79-82 exposures. Exposure concentrations: 2593 and
5345 mg/m3 {490 and 1010 ppm). Effect on kidney weight only
In males. No effects on histology or blood nitrogen.
Testlcular effects (decreased weight, spermatogenesls) at 5345
mg/m3 {257.23-267.00 mg/kg/day).
Torkelson et al., 1960
0316d
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RECORD #4:
Comment:
Citation:
Species: Mice Body Weight: 0.03 kg
Sex: Female Reported Dose: 5345 mg/m3
Effect: LOAEL Converted Dose: 702.22-728.88 mg/kg/day
Route: Inhalation Exposure Period: 114 days
Duration Observation: 114 days
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.8509-5.0351
Inhal, Exp. days: 79.00-82.00
Assumed Inhalation Absorption: 50%
Number Exposed: 10 10 10
Number Responses: NR NR NR
Type of Effect: WGTDC WGTIN WGTIN
Site of Effect: BODY LIVER KIONY
Severity Effect: 444
79-82 exposures. Exposure concentrations: 2593 and 5345
mg/m3 {490 and 1010 ppm) (340.67-353.59 and 702.22-728.88
mg/kg/day). Same effects at 2593 mg/m3. No effects on
histology. Other endpolnts not examined.
Torkelson et al., 1960
RECORD #5:
Species:
Sex:
Effect:
Route:
Rabbits
Both
NOEL
Inhalation
Body Weight: 3.8 kg
Reported Dose: 2593 mg/m3
Converted Dose: 137.93-143.16 mg/kg/day
Exposure Period: 114 days
Duration Observation: 114 days
Comment:
Citation:
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.8509-5.0351
Inhal. Exp. days: 79.00-82.00
Assumed Absorption Inhalation: SOX
Number Exposed: 4
Number Responses: 0
Type of Effect:
SHe of Effect:
Severity Effect: 3
2/sex, 79-82 exposures. Exposure concentrations: 2593 and
5345 mg/m3 (490 and 1010 ppm) (137.93-143.16 and
284.32-295.09 mg/kg/day, respectively). No effects on
histology, organ weight, body weight or blood nitrogen.
Torkelson et al., 1960
0316d
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RECORD #6: Species: Rabbits Body Weight: 3.8 kg
Sex: Male Reported Dose: 5345 mg/m3
Effect: LOAEL Converted Dose: 284.29-295.09 mg/kg/day
Route: Inhalation Exposure Period: 114 days
Duration Observation: 114 days
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.8509-5.0351
Inhal. Exp. days: 79.00-82.00
Assumed Inhalation Absorption: 50%
Number Exposed: 2
Number Responses: 1
Type of Effect: DEGEN
SHe of Effect: TESTE
Severity Effect: 6
Comment.: See previous record. Decreased spermatogenesls 1n tubules with
flbrosls 1n 1 of 2 males. Decreased relative testes weight.
Citation: Torkelson et al., 1960
RECORD #7:
Species:
Sex:
Effect:
Route:
Dogs
Both
NOEL
Inhalation
Body Weight: 12.7 kg
Reported Dose: 1958 mg/m3
Converted Dose: 66.93 mg/kg/day
Exposure Period: 195 days
Duration Observation: 195 days
Comment:
Citation:
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.8462
Inhal. Exp. days: 135.00
Assumed Inhalation Absorption:
50%
Number Exposed: 2
Number Responses: 0
Type of Effect:
SHe of Effect:
Severity Effect: 4
I/sex. 370 ppm equivalent concentration. No effect on body
weight, blood nitrogen or hematology. Pathological examina-
tions not performed.
Torkelson et al., 1960
0316d
-77-
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RECORD #8;
Comment:
Citation:
Species: Rats Body Weight: 0.32 kg
Sex: Both Reported Dose: 2725 mg/m3
Effect: LOAEL Converted Dose: 149,51 mg/kg/day
Route: Inhalation Exposure Period: 6 months
Duration Observation: 6 months
Molecular Weight: 129.39
Inhalation hours/day: 6.00
Inhalation days/week: 4.8222
Inhal. Exp. days: 124.00
Assumed Inhalation Absorption: 5054
Number Exposed: 100
Number Responses: NR
Type of Effect: WGTDC
SHe of Effect: BODY
Severity Effect: 4
50/sex. Exposure concentrations: 2725 and 5345 mg/m3 {515
and 1010 ppm) (149.51 and 293.26 mg/kg/day, respectively). No
effect on body weight In females. No effect on histology,
organ weights or clinical chemistry at either exposure level.
MacEwen et al., 1966
RECORD #9:
Species:
Sex:
Effect:
Route:
Dogs
Both
NOEL
Inhalation
Body Weight: 12.7 kg
Reported Dose: 5345 mg/m3
Converted Dose: 155.84 mg/kg/day
Exposure Period: 6 months
Duration Observation: 6 months
Comment:
Citation:
Molecular We1ght:129.39
Inhalation hours/day: 6.00
Inhalation days/week: 4.8222
Inhal. Exp. days: 124.00
Assumed Inhalation Absorption:
50%
Number Exposed: 8
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 3
4/sex. Dogs were exposed to 0, 515 or 1010 ppm (2725 or 5345
mg/m3) bromochloromethane (79.45 and 155.84 mg/kg/day,
respectively). No effect on body weight, organ weight,
histology or clinical chemistry.
MacEwen et al., 1966
0316d
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RECORD #10:
Comment:
Species:
Sex:
Effect:
Route:
Rats
Male
NOAEL
Inhalation
Citation:
Body Weight: 0.35 kg
Reported Dose: 4710 mg/m3
Converted Dose: 299.20 mg/kg/day
Exposure Period: 14 weeks
Duration Observation: 14 weeks
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.7857
Inhal. Exp. days: 67.00
Assumed Inhalation Absorption: 50%
Number Exposed: 20
Number Responses: NR
Type of Effect: OTHER
Site of Effect: SPLEN
Severity Effect: 1
890 ppm equivalent concentration. Histology was evaluated
after 67 exposures. Increased hemoslderln 1n spleen. No
other effect on histology or weight gain. Other endpolnts not
evaluated.
Svlrbely et al., 1947
RECORD #11:
Species:
Sex:
Effect:
Route:
Rabbits
Male
NOEL
Inhalation
Body Weight: 3.8 kg
Reported Dose: 4710 mg/m3
Converted Dose: 247.16 mg/kg/day
Exposure Period: 14 weeks
Duration Observation: 14 weeks
Comment:
Citation:
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.7857
Inhal. Exp. days: 67.00
Assumed Inhalation Absorption:
50%
Number Exposed: 3
Number Responses: 0
Type of Effect:
SHe of Effect:
Severity Effect: 3
Exposure concentration Is equivalent to 890 ppm. Histology
evaluated after 67 days. No effect on histology, weight gain,
hematology, liver function or urlnalysls.
Svlrbely et al., 1947
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RECORD #12:
Comment:
Citation:
Species: Dogs Body Weight: 12.7 kg
Sex: Female Reported Dose: 4710 mg/m3
Effect: IOAEL Converted Dose: 158.99 mg/kg/day
Route: Inhalation Exposure Period: 14 weeks
Duration Observation: 14 weeks
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.7857
Inhal. Exp. days: 67.00
Assumed Inhalation Absorption: 50%
Number Exposed: 2
Number Responses: NR
Type of Effect: DEGEN
Site of Effect: KIONY
Severity Effect: 5
890 ppm equivalent concentration. Histology was evaluated
after 67 exposures. Increased fat 1n the kidneys and Increased
hemoslderln In the kidneys and spleen. No effect on weight
gain, hematology, liver function or. urlnalysls.
Svlrbely et al., 1947
RECORD #13:
Species:
Sex:
Effect:
Route:
Rats
Both
PEL
Inhalation
Body Weight: 0.35 kg
Reported Dose: 10000 ppm
Converted Dose: 702.45 mg/kg/day
Exposure Period: 0.29 days
Duration Observation: 14 days
Comment:
Citation:
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 1.00
# Inhal. Exp. days:
Assumed Inhalation Absorption:
50*
Number Exposed: 20
Number Responses: 11
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
Single 7-hour exposure. Concentration not expanded over 24
hours. 6/10 males and 5/10 females died. Deaths generally
occurred during exposure to anesthesia.
Torkelson et al., 1960
0316d
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RECORD #14:
Comment:
Citation:
Species: Rats Body Weight: 0.35 kg
Sex: Both Reported Dose: 5000 ppm
Effect: NOEL Converted Dose: 351.23 mg/kg/day
Route: Inhalation Exposure Period: 0.29 days
Duration Observation: 14 days
Molecular Weight:
Inhalation hours/day: 7.00
Inhalation days/week: 1.00
# Inhal. Exp. days:
Assumed Inhalation Absorption: 50%
Number Exposed: 22
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 10
Single 7-hour exposure. Concentration not expanded over 24
hours. 0/11 males and 0/11 females died.
Torkelson et aK, 1960
RECORD #15:
Species:
Sex:
Effect:
Route:
Rats
F ema 1 e
LOAEL
Inhalation
Body Weight: 0.35 kg
Reported Dose: 1500 ppm
Converted Dose: 105.37 mg/kg/day
Exposure Period: 0.29 days
Duration Observation: 1 day
Molecular Weight:
Inhalation hours/day: 7.00
Inhalation days/week: 1.00
# Inhal. Exp. days:
Assumed Inhalation Absorption:
50%
Number Exposed: 4
Number Responses: NR
Type of Effect: DEGEN
Site of Effect: LIVER
Severity Effect: 5
Comment: Minimum concentration producing unequivocal hepatic effects 24
hours after 7-hour exposure. Concentration not expanded over
24 hours. Effects Included small vacuoles not typical of
fatty degeneration often accompanied by Increased liver weight.
Citation: Torkelson et al., 1960
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RECORD #16: Species: Rats Body Weight: 0.35 kg
Sex: Female Reported Dose: 600 ppm
Effect: NOEL Converted Dose: 42.15 mg/kg/day
Route: Inhalation Exposure Period: 0.29 days
Duration Observation: 1 day
Molecular Weight:
Inhalation hours/day: 7.00
Inhalation days/week: 1.00
# Inhal. Exp. days:
Assumed Inhalation Absorption: 50%
Number Exposed: 4
Number Responses: NR
Type of Effect:
Site of Effect:
Severity Effect: 3
Comment: Maximum concentration that did not produce hepatic hlstologlcal
effects 24 hours after a single 7-hour exposure. Concentration
not expanded over 24 hours.
Citation: Torkelson et al., 1960
RECORD #17:
Species:
Sex:
Effect:
Route:
Mice
NR
LOAEL
Inhalation
Body Weight: 0.03 kg
Reported Dose: 7 mg/s.
Converted Dose: 189.62 mg/kg/day
Exposure Period: 0.29 days
Duration Observation: 1 day
Comment:
Citation:
Molecular Weight:
Inhalation hours/day: 7.00
Inhalation days/week: 1.00
# Inhal. Exp. days:
Assumed Inhalation Absorption:
SOX
Number Exposed: NR
Number Responses: NR
Type of Effect: DEGEN 9
Site of Effect: LIVER
Severity Effect: 5
Single 7-hour exposure. 1323 ppm equivalent concentration.
Concentration not expanded over 24 hours. Fatty degeneration.
Effect observed In mice exposed to concentrations of 7-17
mg/ma for 1-5 days but was minimal/absent after 72 hours.
Hlghman et al., 1948
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RECORD #18:
Comment:
Citation:
Species: Mice Body Weight: 0.03 kg
Sex: NR Reported Dose: 2273 ppm
Effect: FEL Converted Dose: 325.78 mg/kg/day
Route: Inhalation Exposure Period: 0.29 days
Duration Observation: 6 days
Molecular Weight:
Inhalation hours/day: 7.00
Inhalation days/week: 1.00
# Inhal. Exp. days:
Assumed Inhalation Absorption: 50%
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
Concentration not expanded over 24 hours. LC 50 after 72-hour
observation. A similar value was reported by Hlghman et al.
(1948). LCsQS after 8, 24 and 48 hours observation were
2995, 2504 and 2436 ppm, respectively.
Svlrbely et al., 1947
C.2.2. Oral Exposure.
Chemical Name: Bromochloromethane
CAS Number:
Document Title:
Document Number;
Document Date:
Document Type:
74-97-5
Health and Environmental Effects Document on
Bromochloromethane
Pending
Pending
HEED
RECORD #1:
Species:
Sex:
Effect:
Route:
Rats
Male
FEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
DuratlonObservatlon:
0.35 kg
7000 mg/kg/day
7000 mg/kg/day
1 day
1 day
Comment:
Citation:
Number Exposed: 5
Number Responses: 5
Type of Effect: DEATH
S1te~of Effect: BODY
Severity Effect: 10
All rats died within 24 hours of treatment. Dose administered
In corn oil apparently by gavage.
Torkelson et al., 1960
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RECORD #2:
Species:
Sex:
Effect:
Route:
Rats
Hale
NOEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
0.35 kg
5000 mg/kg/day
5000 mg/kg/day
1 day
Duration Observation: 14 days
Number Exposed: 5
Number Responses: 0
Type of Effect:
SHe of Effect:
Severity Effect: 10
Comment:
Citation:
RECORD #3:
No deaths. See previous record.
Torkelson et al. , 1960
Species: Mice Body Weight:
Sex: NR Reported Dose:
Effect: PEL Converted Dose:
Route: Gavage Exposure Period:
Duration Observation:
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
0.03 kg
4300 mg/kg/day
4300 mg/kg/day
1 day
6 days
Comment: Approximate 1059. Doses ranging from 500-4400 mg/kg/day
administered 1n corn oil apparently by gavage to groups of 10
animals.
Citation:
RECORD #4:
Svlrbely
Species:
Sex:
Effect:
Route:
et al., 1947
nice
NR
PEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
0.03 kg
3000 mg/kg/day
3000 mg/kg/day
1 day
Duration Observation: 12 days
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
Comment: Single doses of 500, 3000 and 4500 mg/kg were administered In
corn oil. 12/50 mice that died or were killed at two highest
doses showed subcapsular necrosis In liver. 8/32 showed
hemoglobin casts 1n renal tubules.
Citation: Hlghman et al., 1948
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RECORD |5:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Mice
NR
NOEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
0.03 kg
500 mg/kg/day
500 mg/kg/day
1 day
Duration Observation: 12 days
NR
NR
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
See previous record. No effect on mortality or histology.
Hlghman et al., 1948
RECORD #6:
Comment:
Species;
Sex:
Effect:
Rout:e
Mice
NR
PEL
Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
NR
NR
DEATH
BODY
10
0.03 kg
3000 mg/kg/day
3000 mg/kg/day
5 days
5 days
Citation:
Death In unspecified number of 32 mice that were given single
doses 1n olive oil on 1 to 10 consecutive days. Hlstologlc
examination showed effects Including fatty degeneration of
the liver and kidney and liver subcapsular necrosis.
t
Hlghman et al., 1948
NR = Not reported
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