ECAO-CIN-G101
FINAL DRAFT
environmental Protection ECAO-C IN-G1 01
May, 1990
Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR BROMOCHLOROMETHANE
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268 &•& M&MMf&A'fateto* 'Agency
Region 5, Library
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DISCLAIMER
This report Is an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
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PREFACE
Health and Environmental Effects Documents (HEEOs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
1s 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 1s 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
(RfOs) for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD, 1s 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), 1s 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 RfO may also be derived for the noncarclno-
genlc health effects of compounds that are also carcinogenic.
Reportable quantities (RQs) based on both chronic toxlclty and
carclnogenlclty are derived. The RQ Is used to determine the quantity of a
hazardous substance for which notification Is required 1n the event of a
release as specified under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). These two RQs (chronic toxldty
and carclnogenlclty) represent two of six scores developed (the remaining
four reflect IgnltabllHy, 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.
111
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EXECUTIVE SUMMARY
Bromochloromethane 1s a clear, colorless liquid with a sweet odor
(Stenger, 1978). It 1s completely mlsclble with most common organic
solvents (Stenger, 1978) and soluble In water to the extent of 16.7 g/i 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 1n aircraft and portable extinguishers (Stenger,
1978). It Is also used In chemical synthesis (Kuney, 1988).
Bromochloromethane Is expected to degrade relatively slowly 1n 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 Us 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 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 1n soils, based upon an
estimated K value of 21 (Swann et al., 1983). Aquatic hydrolysis 1s not
environmentally significant (Mabey and Mill, 1978).
Bromochloromethane has been detected 1n 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/l) (Class and BallschmHer, 1988).
1v
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Levels of 0.2-0.4 ppt have been Identified 1n 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 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 In algae, followed by release to seawater, with subse-
quent volatilization (Class and BallschmHer, 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 toxldty data for bromochloromethane consisted of a NOEL of
80 mg/i for fathead minnows, P. promelas. and an LC5Q (duration not
reported) of >80 mg/l (U.S. EPA, 1987). Bromochloromethane has been
found 1n tissues of rainbow trout, S. galrdnerl. from the Colorado River.
The estimated whole-fish concentration was 8 v9/l (H1att, 1983).
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 al., 1947). Rat t1ssue:blood partition coefficients (Gargas et
al., 1986a,b) suggest that bromochloromethane will distribute more readily
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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 1n Appendix A.
Acute Inhalation LC5Qs 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
L05Q 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 1n mice (Hlghman et al.,
1948). Information regarding the chronic Inhalation toxlclty, subchronlc or
chronic oral toxldty or teratogenldty of bromochloromethane were not
located. Decreased spermatogenesls and flbrosls occurred 1n 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 1n the available
literature cited 1n Appendix A.
The carclnogenlcKy of bromochloromethane has not been evaluated.
Bromochloromethane was mutagenlc In Salmonella typhlmurlum and EscheMchla
coll bacteria (Simmon, 1976; 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).
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 1n 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/m* for
chronic Inhalation exposure. Oral data were not sufficient for deriving
route-specific RfD values; therefore, the NOAEL from the Inhalation study 1n
female rats by Torkelson et al. (1960) served as the basis for an RfO of 1
mg/kg/day for subchronlc oral exposure and an RfO of 0.1 mg/kg/day for
chronic oral exposure. An RQ for noncancer chronic toxldty of 1000 was
based on the occurrence of liver lesions In rats exposed by Inhalation for
114 days.
Bromochloromethane 1s classified 1n EPA Cancer Group D (Not Classifiable
^
as to Human CardnogenlcHy) because of lack of carclnogenlclty data; this
lack of data precludes calculation of a carcinogenic potency factor or
cancer-based RQ for bromochloromethane.
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pathological effects of acute Inhalation and oral exposure to bromochloro-
methane are similar; principal effects Include CNS depression and degenera-
tion of the liver.
The cardnogenlcUy of bromochloromethane has not been evaluated.
Bromochloromethane was mutagenlc In Salmonella typhlmurlum and Escherlchla
coll bacteria (Simmon, 1976; 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 (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/ma 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. (1960) 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 D (Not Classifiable
as to Human CardnogenlcUy} because of lack of cardnogenlcUy 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
1.1. 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 TOXICOL06Y 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
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TABLE OF CONTENTS (cont.)
Page
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. Weight 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.
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. Weight of Evidence 35
8.1.5. Quantitative Risk Estimates 35
8.2. SYSTEMIC TOXICITY "* 35
8.2.1. Acute Exposure 35
8.2.2. Oral Exposure 36
8.2.3. Subchronlc Chronic Exposure 43
1x
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TABLE OF CONTENTS (cont.)
Page
9. REPORTABLE QUANTITIES 45
9.1. BASED ON SYSTEMIC TOXICITY 45
9.2. BASED ON CARCINOGENICITY 49
10. REFERENCES 51
APPENDIX A: LITERATURE SEARCHED 61
APPENDIX B: SUMMARY TABLE FOR BROMOCHLOROMETHANE 64
APPENDIX C: DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO
BROMOCHLOROMETHANE 65
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LIST OF TABLES
No. Title 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
x1
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LIST OF ABBREVIATIONS
AEL Adverse-effect level
A/G Albumin/globulin
CAS Chemical Abstract Service
CNS Central nervous system
CO Carbon monoxide
C02 Carbon dioxide
CS Composite score
DWEL Drinking water equivalent level
PEL Frank-effect level
GSH Reduced glutathlone
HA Health advisory
HEC Human equivalent concentration
HEO Highest effective dose
Km Concentration 1n air at which uptake occurs at one-half
the maximum rate
Koc Soil sorptlon coefficient standardized with respect
to organic carbon
Kow Octanol/water partition coefficient
LC5Q Concentration lethal to 50% of recipients
(and all other subscripted concentration levels)
1050 Dose lethal to 50% of recipients
LDU Log dose units
LED Lowest effective dose
i
LOAEL Lowest-observed-adverse-effect level
MED Minimum effective dose
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
xll
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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
RV(j Dose-rating value
RVe Effect-rating value
SCE Sister chromatic! exchange
SGOT Serum glutamlc oxaloacetlc transamlnase
SGPT Serum glutamlc pyruvlc transamlnase
SIC Sister chromatic! exchange, Chinese hamster cells l£ vitro
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 1s 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 1s 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):
Water 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/cm*
16.7 g/l
147.2 mm Hg
93.34 mm Hg
1.41
400 ppm
200 ppm
Rlddlck et al., 1986
Rlddlck et al., 1986
Rlddlck et al., 1986
Tewarl et al., 1982
Rlddlck et al., 1986
McDonald et al., 1959
Tewarl et al., 1982
Amoore and Hautala, 1983
Amoore and Hautala, 1983
0316d
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01/17/90
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Bromochloromethane 1s 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, MI) 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 wUh 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 1s used mainly as a fire-extinguisher fluid 1n
aircraft and portable extinguishers (Stenger, 1978). It Is also used In
chemical synthesis (Kuney, 1988).
1.5. SUHHARY
Bromochloromethane 1s a clear, colorless liquid wHh a sweet odor
(Stenger, 1978). It Is completely mlsdble wHh most common organic
solvents (Stenger, 1978) and soluble 1n water to the extent of 16.7 g/l at
25°C (TewaM et al., 1982). Current production figures are not available.
Recent manufacturers of bromochloromethane Include Dow Chemical and Ethyl
Corporation (USITC, 1988; SRI, 1989). Bromochloromethane 1s used mainly as
a fire-extinguisher fluid In aircraft and portable extinguishers (Stenger,
1978). It 1s also used In 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
1n the ambient atmosphere (Elsenrelch et a!., 1981). Using the method of
Atkinson (1987), the rate constant for the vapor-phase reaction of bromo-
chloromethane with atmospheric HO- 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 H0« concentration of 5xl05
molecules/cm3.
Bromochloromethane does not absorb UV light at >290 nm (Cadman and
Simons, 1966). Therefore, direct photolysis will not occur 1n 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 tropospheMc-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.
Bromochloromethane's water solubility of 16,700 rog/i at 25°C (TewaM et
a!., 1982) suggests that physical removal by wet deposition (rainfall.
dissolution Into clouds, etc.) Is 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 1s 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. Mlcroblal Degradation. Tabak et al. (1981) studied the blodegrad-
abinty of 114 organic priority pollutants on the U.S. EPA Priority Pollut-
ants List to ascertain m1crob1al degradation and acclimation periods. The
Bunch and Chambers static culture flask blodegradablllty screening test was
performed under a set of controlled experimental conditions that Included
the following parameters: 5 and 10 mg/i concentrations of the test
compound, 5 mg/i 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/i
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-mVmol. 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 1s -4 hours. The estimated
volatilization half-life from a model environmental pond 1s -47 hours (U.S.
EPA, 1986b). These estimates Indicate that volatilization Is a significant
environmental fate process for bromochloromethane.
0316d -4- 02/13/90
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2.2.5. Adsorption. KOC estimates presented 1n Section 2.3.1. predict
that bromochloromethane 1s not tightly bound to soil through adsorption.
Therefore, It Is likely that adsorption of bromochloromethane 1n sediments
does not compete with volatilization or blodegradatlon In the disappearance
of bromochloromethane from the aquatic environment.
2.3. SOIL
2.3.1. Adsorption/Leaching. Pertinent data regarding the leaching of
bromochloromethane 1n soil were not located In the available literature
dted 1n Appendix A. A K value of 21 can be estimated using a water
solubility of 16,700 mg/l and the following regression-derived equation
(Lyman, 1982): log KQC = 3.64-0.55 log (water solubility). This K
value Indicates very high soil mobility (Swann et a!., 1983).
2.3.2. H1crob1al Degradation. Pertinent data regarding the mlcroblal
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 In Section 2.2.3. suggest that blodegradatlon of bromo-
chloromethane 1n soil may be significant. Since no other processes are
expected to degrade bromochloromethane 1n soil to a significant degree,
blodegradatlon 1s 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 1s expected to degrade relatively slowly 1n 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 1s not known. A
single blodegradatlon study (Tabak et a!., 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 a!., 1983). Aquatic hydrolysis 1s not
environmentally significant (Mabey and Mill, 1978).
0316d -6- 01/17/90
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3. EXPOSURE
3.1. WATER
Bromochloromethane was tentatively Identified 1n a drinking water sample
collected In Philadelphia, PA, 1n 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 1n 1981 for analysis of
volatile halocarbons. Bromochloromethane was detected In one sample at a
level of 10 ng/i and In 14 samples at trace levels (detection limit equals
1 ng/l).
Bromochloromethane was qualitatively detected 1n seawater collected from
the Narragansett Bay, RI, 1n 1979-1980 (Wakeham et al., 1983). Monitoring
of the north and south Atlantic Ocean 1n 1985 yielded a baseline bromo-
chloromethane concentration of 0.02 ng/l (Class and Ballschmlter, 1988).
These Investigators detected the blogenlc presence of bromochloromethane In
specific algae that occur 1n the Atlantic Ocean, and suggested that the
occurrence of bromochloromethane 1n marine water and air may result, 1n
part, from biological emissions from these algae.
Zoeteman et al. (1981) detected a bromochloromethane concentration of 8
ug/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; Oore et
al., 1982; Gould et al., 1983). Although bromlnatlon can occur when natural
bromide 1s present In 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
-------
3.2. FOOD
Pertinent data regarding the food monitoring of bromochloromethane were
not located 1n the available literature cited 1n Appendix A.
3.3. INHALATION
The average concentrations of bromochloromethane In ambient air
monitored throughout 1983 near Point Barrow, AL (In the Arctic) were 2.4-2.9
ppt (Rasmussen and Khalll, 1984). The higher concentrations were found In
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) In
ambient air samples collected near a hazardous waste site 1n New Jersey
(Lareglna et al., 1986). The actual concentrations 1n 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 In 1985
(Class and BallschmHer, 1988). Bromochloromethane was also detected in
open seawater and 1n 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
-------
3.5. SUMMARY
Bromochloromethane has been detected 1n drinking water (Suffet et al.,
1980; Lucas, 1984), groundwater (Zoeteman et al., 1981), Lake Ontario and
Niagara River water (1-10 ng/i) (Kaiser et al., 1983), and open seawater
from the Atlantic Ocean (0.02 ng/4) (Class and BalIschmlter, 1988).
Levels of 0.2-0.4 ppt have been Identified 1n 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 KhalU, 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).
0316d -9- 02/13/90
-------
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 \n fathead minnows, Plmephales promelas. exposed to 80 mg/i bromo-
chloromethane. The 1C.- (duration not reported) for this species was >80
mg/i. 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 cited In Appendix A.
4.1.2.2. BIOACCUMULATION/BIOCONCENTRATION — Hlatt (1983) detected
the presence of bromochloromethane In tissues of rainbow trout, Salmonella
qalrdnerl. collected from the Colorado River and reported an estimated
whole-fish concentration of 8 yg/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 1n aquatic flora were not located In
the available literature cited In 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 dted in Appendix A.
0316d -10- 02/13/90
-------
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 1n the
available literature cited In 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 1n 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 dted 1n
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 salmon Id 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.
v
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/i for fathead minnows, P. promelas. and an LC5Q (duration not
reported) of >80 mg/l (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/l (Hlatt, 1983).
0316d -12- 01/17/90
-------
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 tn 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 blood-.gas 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
V of 10.5 mg/kg/hour. Similar data were reported In other studies
(Andersen et al., 1980; Gargas and Anderson, 1982). Gargas et al. (1986a,b)
simulated the mixed uptake kinetics of bromochloromethane In rats, using a
physiologically-based pharmacoklnetlc model. Information regarding the
extent of respiratory absorption from Inhaled bromochloromethane was not
located In the available literature.
Quantitative oral absorption data were not located for bromochloro-
methane. The occurrence of systemic effects 1n rats and mice following
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/m*}
bromochloromethane In air for 4 hours 1n dermal vapor absorption chambers
without significant Inhalation exposure (McOougal 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/cma/hour 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 1n the blood and brain of the treated animals,
compared with unexposed controls, following the last 7-hour exposure.
Levels of total bromide 1n the blood were 6-8 times greater than levels In
the brain. Similarly, levels of organic bromide In the blood were 8-12
times greater than levels 1n the brain.
Rat blood:a1r and rat t1ssue:blood partition coefficients for bromo-
chloromethane have been determined as follows: blood:a1r (41.5^0.9),
fat:blood (325±3), 11ver:blood (29.2+0.5) and muscle:blood (11.1+1.8).
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 subchronlc Inhalation exposure
to bromochloromethane (Svlrbely et al., 1947; Torkelson et al., 1960;
MacEwen et al., 1966) (Section 6.1.1.1.). Carboxyhemoglobln levels
Increased 1n male Long-Evans rats given a single IntraperHoneal Injection
of 3.0 mmol l*C-bromochloromethane/kg (388.2 mg/kg) 1n corn oil (Kublc et
al., 1974). These data and studies of other dlhalomethanes Indicate that
bromochloromethane Is 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 CO^ and hallde (Gargas et al., 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 1n the oxldatlve mechanism, resulting In the
formation of formyl chloride rather than formyl bromide. They proposed that
a significant portion (-20-30X) 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 C0~; 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 1n 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/m'). 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 low capacity, with production of
CO saturable at bromochlormethane concentrations greater than ~200 ppm; the
maximum percent carboxyhemoglobln saturation attained was ~9X. The maximum
0316d -15- 02/13/90
-------
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1
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1 1 H
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0316d
FIGURE 5-1
Proposed Pathways for D1 halomethane (CH2X2) Metabolism
Source: Gargas et al., 1986a
-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/dl) were reached by the end of the
second week.
Levels of Inorganic bromide In the blood were determined 1n 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 Ion levels In the blood were -300-360 mg/dl 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 1n 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/m*) 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 1n 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 al., 1947). Rat t1ssue:blood 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 1s 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 C0~
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 In the literature cited 1n Appendix A.
0316d -18- 02/13/90
-------
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-extinguishing
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 1n
Table 6-1. These data suggest that mice are more susceptible than rats
since 7-hour exposures resulted 1n LC^s of 2268-2995 ppm (12,000-15,850
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 In the mice but generally occurred
during treatment 1n 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 1n 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/i (7000-17,000 mg/m* 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/i 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. H1sto-
logUal 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/m») for 7 hours did
not produce hepatic effects and exposure to 800 ppm (4234 mg/m3) for 7
hours produced equivocal hepatic histologlcal 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 1n olive oil
(Svlrbely et al., 1947). The LD5Q (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 rag/kg bromochloromethane In olive oil (Hlghman et al., 1948).
Histologlcal 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 1n 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 1n olive
on 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 perlportal
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 In burns and denaturatlon of the skin
with four surviving after 24 hours (Torkelson et al., 1960). Application
without occlusion caused only slight defatUng.
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/m«] or 1010 ppm [5345 mg/m»] 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 m'/day 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 exposures 1n 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 1n 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 1on levels were 44-73 rog/di 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/m») bromo-
chloromethane 7 hours/day, 5 days/week for 79-82 exposures In 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 in 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 1n 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 In 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.
•x
Significantly decreased body weight and slgnlfUanty Increased relative
liver and kidney weights occurred 1n 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/m») bromochloromethane
0316d -24- 05/17/90
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7 hours/day, 5 days/week for 79-82 exposures In 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/m*) 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 In 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
bromochloronethane 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/m1), 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 histologlcal 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 1s not specified
whether organs other than Hver, kidney and spleen were weighed and
hlstologlcally examined. The only effect attributable to treatment was a
significantly (p<0.01) dose-related decreased body weight gain 1n 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 1n humans may produce mild sedation and
suggested that lethargy and altered eating habits may have been responsible
for the reduction In body weight gain.
HacEwen et al. (1966) also exposed four male and four female beagle dogs
to 0, 515 or 1010 ppm (2725 or 5345 mg/m'} 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 m»/day and a 50% absorption of the
9
Inhaled dose. Toxldty was evaluated as In trie rat study wUh 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
-------
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 a!., 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/m*]) 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 m'/day and a 50%
absorption of the Inhaled dose. Toxldty was evaluated as In the rat study
with the addition of hematologlcal examinations 1n both species at "regular"
Intervals, liver function evaluation (bromsulfaleln excretion) and urlnaly-
s1s In dogs 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 In the kidneys occurred In the dogs. Inorganic bromide accumulated 1n
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 1s 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 m'/day 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 CjH) survived until
terminal sacrifice at 13-16 months of age. HlstologUal 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 1n 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
-------
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 In 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 1n 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 1n 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 In Appendix A,
6.2. CARCINOGENICITY
Pertinent data regarding the carclnogenlclty 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. GENOTOXICITY
Data from genotoxlclty tests with bromochloromethane are presented 1n
Table 6-2. Consistently positive results were observed 1n the reverse
mutation test in Salmonella typhlmurlum (Simmon et al., 1977; Strobel and
Grummt, 1907; Osterman-Golkar et al., 1983). Metabolic activation was not
required but Increased the response 1n TA98 and TA100 (Strobel and Gruramt,
1987). Positive results were also observed In the reverse mutation and
lambda prophage Induction tests 1n Escher1ch1a coll (Osterman-Golkar et al.,
1983). Negative results were observed In the mltotlc recombination test In
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 (Strobe! and Grummt, 1987).
6.4. DEVELOPMENTAL TOXICITY
Pertinent data regarding the developmental toxldty of bromochloro-
methane were not located 1n the available literature cited 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. (I960) also exposed groups of two male rabbits (strain
not reported) to 0, 490 or 1010 ppm (2593 or 5345 mg/m") bromochloro-
methane 7 hours/day, 5 days/week for 79-82 exposures In 114 days (see
Section 6.1.1.1.). These doses correspond to 0, 137.93-143.16 and
284.32-295.09 ng/kg/day assuming an average body weight of 3.8 kg, a
breathing rate of 2 m'/day 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
-------
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 In
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 LCrQs for mice 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 L0-n of
-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 1n most species
T
evaluated for these endpolnts. Torkelson et al. (1960) found that relative
liver weight was Increased In 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 In
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 toxlclty 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 subchronkally 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 cardnogenldty of bromochloromethane has not been evaluated.
Bromochloromethane was mutagenlc 1n Salmonella typh1mur1um and EscheMchla
coll bacteria (Simmon et al., 1977; Osterman-Golkar et al., 1983; Strobel
and Grummt, 1987) and Induced SCE and chromosome aberrations 1n Chinese
hamster cells jjn vitro (Strobel 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/m») 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/m3) 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/a, 50 mg/l, 13.1 mg/l and 45.7 mg/l, respectively, for bromo-
chloromethane. U.S. EPA (1988) also calculated a provisional DWEL of 4.6
mg/l 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
dted 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 cited 1n 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 cited 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 1n the available literature dted In Appendix A.
8.1.4. Height of Evidence. Pertinent cardnogenldty data for humans and
animals were not located 1n the available literature dted In Appendix A;
therefore, bromochloromethane 1s categorized 1n U.S. EPA we1ght-of-evidence
Group D (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. SYSTEHIC TOXICITY
8.2.1. Acute Exposure.
8.2.1.1. INHALATION — Acute Inhalation lethality data for
bromochloromethane are summarized 1n 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/t 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 LD,.. to be 4300 mg/kg 1n mice. Signs of CNS depression
were observed at doses > 500 mg/kg. Hlghman et al. (1948) demonstrated
effects 1n 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 1n a few renal tubules.
These effects were generally absent or slight 1n mice surviving >48 hours.
Occluded dermal application of 5000 mg/kg bromochloromethane to the
clipped skin of five rabbits resulted 1n burns and denaturatlon of the
skin. Application without occlusion only caused slight defattlng.
8.2.2. Subchronlc Exposure.
8.2.2.1. IMHALATIOH — Sufficient data *re available for derivation
of a subchronic 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 -36- 08/20/90
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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 1n humans.
Evidence for rapid attainment of steady state with bromochloromethane 1s
provided by Gargas and Andersen (1982), who found that the rapid uptake
phase 1n rats was completed 1n 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
1s 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/m*) bromochloromethane 7 hours/day for 135 exposures 1n
195 days, and groups of 20 rats/sex (strain not reported) to 490 ppm (2593
mg/m') or 1010 ppm (5345 mg/m") 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/m") bromochloromethane
7 hours/day for 135 exposures 1n 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 50X 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 1s a NOEL 1n dogs (Rec. #7, Appendix C), this value 1s 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/concentrat1on)
were exposed to 515 or 1010 ppm (2725 or 5345 mg/m") bromochloromethane 6
hours/day for 124 exposures 1n 6 months (MacEwen et a!., 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 «g/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 -38- 08/20/90
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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 1s considered a LOAEL associated with reduced growth
rate 1n 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
m'/day 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 m»/day 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 m'/day and a 50* absorption
of the Inhaled dose. Slightly Increased hemoslderln occurred 1n the rats
(spleen) and dogs (spleen and kidneys), and Increased fat occurred 1n 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 In rabbits and the
299.20 mg/kg/day Is a LOAEL 1n rats and 158.99 mg/kg/day 1s a LOAEL 1n dogs.
Guinea pigs (I0/sex/concentrat1on) (Rec. f3, Appendix C), mice (10/sex/
concentration) (Rec. #4, Appendix C) and rabbits (2/sex/concentrat1on) (Rec.
#5, Appendix C) were exposed to 0, 490 or 1010 ppm (2593 or 5345 mg/m*)
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
-------
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 1s a LOAEL In the guinea pigs and the 340.67-353.59
mg/kg/day concentration 1s 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/m*) bromochloromethane for
<64 exposures 1n 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 1n 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 1n the
liver and kidneys. The exposure schedule was not reported In sufficient
detail to permit consideration of this study for quantitative risk
assessment.
0316d -40- 08/20/90
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Acute toxldty data Indicate that the critical effects of exposure to
bromochloromethane appear to be CNS Involvement and hepatotoxIcHy
(Rutsteln, 1963; Svlrbely et al., 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 Is a
consistent metabolite of bromochloromethane 1n the mammalian species
studied, and that blood levels of bromide Increase 1n a dose-related manner
1n 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 In rats exposed to
bromochloromethane may have resulted from lethargy Induced by elevated blood
bromide levels. The conservative approach, therefore, 1s 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 In the 195-day study
(Rec. #1, Appendix C) by Torkelson et al. (I960). 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
-------
Individuals) a chronic RfD of 1.26E-02 mg/kg/day Is calculated. Confidence
In the key study 1s 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 RfD 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 toxlclty of
bromochloromethane was not located. Acute exposure data, however, Indicate
that the critical effects of both Inhalation and oral exposure are CNS signs
and hepatotoxlclty. In addition, the critical effects of subchronlc
Inhalation exposure to bromochloromethane are reduced body weight and
hepatotoxlclty. The respiratory tract does not appear to be the target
organ for Inhalation exposure to bromochloromethane. The data reviewed 1n
Section 5.3. suggest that metabolism Involving dehalogenatlon would be
\
expected with either route of exposure. Therefore. 1n the absence of
subchronlc oral data, U 1s appropriate to use Inhalation toxlclty data to
derive a subchronlc oral RfO for bromochloromethane.
0316d -42- 08/20/90
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As discussed 1n Section 8.2.2.1., a NOAEL of 125.96 mg/kg/day has been
Identified 1n rats exposed to bromochloromethane for 7 hours/day 135
exposures 1n 195 days (Torkelson et a!., 1960) (Rec. #1, Appendix C). This
dose 1s 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 1n the data base and RfD are due to the lack of oral toxldty
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 1n the
RfD Is low because of the lack of chronic data, and because confidence 1n
the subchronlc Inhalation RfD 1s low.
8.2.3.2. ORAL — Data on the chronic oral toxldty of
bromochloromethane were not located. It Is appropriate to derive a chronic
oral RfD for bromochloromethane based on the subchronlc oral RfD because of
i
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
-------
This RfO 1s the same as a previously derived RfD of 0.13 mg/kg/day used to
calculate a provisional DWEL for lifetime exposure (U.S. EPA, 1988).
Confidence 1n the key study Is 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
.44. 08/20/90
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9. REPORTABLE QUANTITIES
9.1. BASED 0* SYSTEMIC TOXICITY
The toxldty of bromochloromethane Is discussed 1n Chapter 6, and Inha-
lation data suitable for RQ derivation are summarized 1n 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), hlstologlcal alterations 1n the liver 1n rats (Torkelson et al.,
1960) and kidneys In dogs (Svlrbely et al., 1947), Increased hemoslderln 1n
the spleen of rats (Svlrbely et al., 1947) and testlcular effects 1n guinea
pigs and rabbits (Torkelson et al., 1960). Death 1n mice (Hlghman et al.,
1948) was not Included because the exposure protocol was not presented 1n
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 1n Table 9-1, are presented 1n
Table 9-2. Changes 1n body and organ weights are assigned an RV of 4.
The most appropriate RV for the kidney hlstologlcal alterations 1s 5
because the effects were slight and reversible. Lesions In 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 1s most appropriately viewed as a Biochemical effect. The most
appropriate RV for the testlcular alterations 1s 6 because 1t cannot be
determined 1f 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 1n rats {Torkelson et al., 1960) 1s used as the basis for the RQ
0316d -45- 08/20/90
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(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 HacEwen
et al. (1966) and Svlrbely et al. (1947).
9.2. BASED ON CARCINOGENICITY
Pertinent data regarding the cardnogenldty 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 cardnogenldty data, bromochloromethane 1s categorized 1n U.S. EPA
we1ght-of-ev1dence Group D (Not Classifiable as to Human Cardnogenldty).
Chemicals In EPA Group 0 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: Inhalation
Species/Sex: rat/female
Dose*: 203.65
Duration: 114 days (79-82 exposures, 7 hours/day)
Effect: h1sto!og1cal lesions In liver
RVd: 2.04
RVe: 6
CS: 12.22
RQ: 1000
Reference: Torkelson et a!., 1960
*Equ1valent human dose
0316d -50- 08/20/90
-------
10. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1986.
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Allgeler, G.O., R.L. Mulllns, Jr., D.A. Wilding, J.S. Zogorskl and S.A.
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4
Arguello, M.O., C.O. Chriswe11, J.S. Fritz et al. 1979. Tr1halomethanes 1n
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0316d -51- 08/20/90
-------
Atkinson, R. 1987. A structure-activity relationship for the estimation of
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Cadman, P. and J.P. Simons. 1966. Reactions of hot halomethyl radicals.
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Class, T.H. and K. BallschmHer. 1988. Chemistry of organic traces 1n
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.W., 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 In 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
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Dore, M., N. Merlet, 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
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Ourkln, P. and H. Meylan. 1989. Users Guide for D2PLOT: A Program for
Dose/Duration Graphs Version 2.00. Prepared by Chemical Hazard Assessment
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E1senre1ch, S.J., B.B. Looney and D.J. Thornton. 1981. Airborne organic
contaminants 1n the Great Lakes ecosystem. Environ. Sd. Technol. 15:
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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
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Gargas, M.L., M.E. Andersen, H.J. Clewell and G. Harry. 1986b. A physio-
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Gould, J.P., R.E. Ramsey, M. G1abba1 and F.G. Pohland. 1983. Chapter 36.
Formation of volatile haloorganlc compounds 1n the chlorlnatlon of munclpal
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525-539.
0316d -53- 08/20/90
-------
Hawley, G.G. 1981. The Condensed Chemical Dictionary, 10th ed. Van
Nostrand Relnhold Co., New York. p. 151.
H1att, M.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, M.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 1n the Niagara River and 1n Lake Ontario. J. Great Lakes Res.
9: 212-223.
Kublc, V.L., H.U. Anders, R.R. Engel, C.H. Barlow and M.S. Caughey. 1974.
Metabolism of dlhalomethanes to carbon monoxide. I. In. 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. J., J.W. BozzelH, R. Markov and. S. Glantl. 1986. Volatile
organic compounds at hazardous waste sites and a sanitary landfill 1n 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
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Eff. Res. Lab., Columbus, OH. p. 144, 174, 255.
Lyman, W.J. 1982. Adsorption coefficient or soils and sediments, in:
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.
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McDonald, R.A., S.A. Shrader and O.R. Stull. 1959. Vapor pressures and
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McOougal, J.N., 6.U. Jepson, H.3. Clewell and M.E. Andersen. 1985. Dermal
absorption of d1halomethane vapors. Toxlcol. Appl. Pharmacol. 79: 150-158.
0316d -55- 08/20/90
-------
NAS (National Academy of Science). 1980. Drinking Hater and Health. Vol
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1910. A1r Contaminants; Final Rule. p. 2929.
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1983. Chemical reactivity and mutagenldty of some dlhalomethanes. Chem.
B1ol. Interact. 46(1): 121-130.
Rasmussen, R.A. and M.A.K. KhalH. 1984. Gaseous bromine 1n the Arctic and
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Rutsteln, H.R. 1963. Acute chlorobromomethane toxldty. Arch. Environ.
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Chemical Company Compounds. U.S. EPA/OPTS Public Files, Section 80.
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0316d -56- 08/20/90
-------
Simmon, V.F., K. Kauhanen and R.G. Tardlff. 1977. Mutagenlc activity of
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SRI (Stanford Research Institute). 1989. 1989 Directory of Chemical
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potential mutagens 1n 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 1n Philadelphia drinking waters during a two-year period.
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toxldty and narcotic action of mono-chloro-roono-bromomethane with special
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0316d -57- 08/20/90
-------
Swann, R.L., D.A. Laskowskl, P.J. McCall, K. Vander Kuy and H.J.
Dlshburger. 1983. A rapid method for the estimation of the environmental
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Uy studies with organic priority compounds. J. Water Pollut. Control Fed.
53: 1503-1518.
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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, W.J. Lyman, W.F. Reehl and O.H. Rosenblatt, Ed.
McGraw-Hill Book Co., New York. p. 15-1 to 15-32.
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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, DC.
U.S. EPA. 1980. Guidelines and Methodology Used 1n the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water 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 ToxIcHy 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.
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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. 1986
-------
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 D1v1son.
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.
Wakeham, 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. Brlnkman. 1981. Persistency of
organic contaminants 1n groundwater, lessons from soil pollution Incidents
In the Netherlands. Scl. Total Environ. 21: 187-202.
0316d -60- 08/20/90
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APPENDIX A
LITERATURE SEARCHED
This HEED Is 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)
HSD8
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 In 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. 2B. John Wiley 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, M. and D. Eckroth, Ed. 1978-1984. K1rk-0thmer Encyclo-
pedia of Chemical Technology, 3rd ed. John WHey and Sons, NY. 23
Volumes.
Hamilton, A. and H.I. 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., W.R. Mabey, A.T. L1eu, 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. 1964. 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 In the Special Review
Program, Registration Standards Program and the Data Call In
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, NO.
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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In addition, approximately 30 compendia of aquatic toxldty 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 Toxldty
of Chemicals to F1sh and Aquatic Invertebrates. Summaries of
Toxldty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Oept. Interior, F1sh 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, D. 1971. Ecological Effects of Pesticides on Non-Target
Spedes. 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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APPENDIX C
DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO BROMOCHLOROHETHANE
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 Meylan (1989) developed under contract to
ECAO-C1nc1nnat1 are presented In Figures C-l to C-6. Data used to generate
these graphs are presented 1n 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 1s presented
as expanded experimental concentration [expanded exp cone (mg/m")]. 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 1n kg to calculate a dally dose 1n mg/kg/day. The dally dose was
then multiplied by the cube root of the ratio of the animalrhuman body
weight to adjust for species differences 1n 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 1n basal metabolic rate
0316d -65- 08/20/90
-------
teeeee
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n
9
v
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fi
fi.
X
hi
e.eeei
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(Inhalation Exposure)
e.wi e.ei e.i
HUHRN EOUIU DURflTIQN (fraction Hftspan)
DWELO? HEIHOD
Key:
F
L
n
N
FEL
LOAEL
NOAEL
NOEL
Solid lint • Advtrse Effects Boundary %
Dashed lint • No Advtrst Efftcts Boundary
FIGURE C-1
Dose/Duration - Response Graph for Inhalation Exposure to
Bromochloronethane: Envelope Method (Expanded Experimental Concentration)
0316d
-66-
08/20/90
-------
180008 -
A
n
t
I
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u
c
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Q
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t
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1888 t
8.0081
BCHINHRL D2
(Inhalation Exposure)
0061 0.01 0.1
HUhflH EOUIU OURflTION (fraction 1 if wan)
CENSORED DRIB METHOD
Key:
F
L
n
N
PEL
LOAEL
NOAEL
NOEL
Solid line . Adverse Effects Boundary
Dashed line • Mo Adverse Effects Boundary
FIGURE C-2
Dose/Duration - Response Graph for Inhalation Exposure to
Bromochloromethane: Censored Data Method
(Expanded Experimental Concentration)
0316d
-67-
08/20/90
-------
1000000
1688
6.0601
19
(Inhalation Exposure)
BCrtlNHRL D2
0.061 1.61 6.1
HUHRN EQUIU OURRTIQN (fraction 1 if wan)
IMUOOPHEIHOO
Key:
F
L
n
N
FEL
LOAEL
NOAEL
NOEL
Solid line - Adverse Effects Boundary
Dashed line - Ho Adverse Effects Boundary
FIGURE C-3
Dose/Duration - Response Graph for Inhalation Exposure to
Bromochloronethane: Envelope Itethod (Human Equivalent Dose)
0316d
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leeeeee r
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£
V
9!
0
fi
o
c
leee
e.eeei
e.eei e.ei 0.1
HUMflN EQUUI DUBflTlON (fraction lifttpan)
(Inhalation Exposure) CENSORED DflTfl METHOD
BOIINHflL D2;
Key:
F
L
n
N
FEL
LOAEL
NOAEL
NOEL
Solid line • Adverse Effects Boundary
Dashed line • No Adverse Effects Boundary
FIGURE C-4
Dose/Duration - Response Graph for Inhalation Exposure to
Bromochloromethane: Censored Data Method (Human Equivalent Dose)
0316d
-69-
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9
v
5
M
leeeee
18888 •-
1668
Bronoch1orone thane
6.881
3
(Oral Exposure)
BCMORflL 02
15
-K-
HUHflH EQUIU DUWTIOH (friction lifwpan)
DWELOP NEIHOO
j I
8.81
Key: F . FEL
N . NOEL
Solid lint - Advtrst Effects Boundary
Dashed line . No Adverse Effects Boundary
FIGURE C-5
Dose/Duration - Response Graph for Oral Exposure to Bronochloromethane:
Envelope Method
03164
-70-
08/20/90
-------
188880
A
1
\
I
V
tn
0
Q
0
u
Bronochloronethane
1688
BCI10RRL D2
(Oral Exposure)
•HIS
46-
J L
e.ei
HUttflN EQUIU DUBflTION (fraction liftspan)
CENSORED MIR METHOD
Key: F » PEL
N . NOEL
Solid line • Adverse Effects Boundary *
Dashed line • 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) 1s 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 1s 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)
1s 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 (1f any) resulting from Intersections of the adverse effects and no
adverse effects boundaries Is 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 1s redrawn so that H does not Intersect the adverse
0316d -72- 08/20/90
-------
effects boundary, and no region of contradiction Is 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 1s defined
by the LOAEL for liver hlstologlcal alterations 1n mice (Rec. #17), LOAELs
for kidney hlstologlcal alterations 1n dogs (Rec. #12), reduced body weight
and elevated organ weights 1n guinea pigs (Rec. #3), liver hlstologlcal
alterations 1n 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 hemoslderln In the spleen of rats (Rec. #10)
and a NOAEL for Increased liver weight 1n rats (Rec. #1). Using the
censored data method (Figures C-2 and C-4), the no adverse effects boundary
Is defined by the NOEL for liver hlstologlcal alterations 1n 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 In rats (Rec. #1). The
subchronlc and chronic RfDs for bromochloromethane are based on the NOAEL
for liver hlstologlcal alterations 1n rats (Rec. #1).
Figures C-5 and C-6 present the oral dose/duration-response graphs. The
adverse effects boundary 1s defined by FfLs 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 1s defined by the NOEL for mortality In rats
(Rec. #2) and the NOEL for mortality and hlsiopathology 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 in
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 DOSE/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
Bromochloromethane
Pending
Pending
HEED
Effects Document on
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 Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.8461
Inhal. Exp. days: 135.00
Assumed Inhalation Absorption:
50%
Citation:
Number Exposed: 10
Number Responses: NR
Type of Effect: WGTIN
Site of Effect: LIVER
Severity Effect: 4
Concentrations studied: 1958, 2593 and 5345 mg/ma (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 12: Species: Rats Body Weight: 0.35 kg
Sex: Both Reported Dose: 2593 mg/m3
Effect: LOAEL Converted Dose: 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 In liver In both sexes at 5345 mg/m3
(344.18-357.25 mg/kg/day).
Citation: Torkelson et al., 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 WGTOC
SHe of Effect: LIVER KIDNY BODY
Severity Effect: 4 4,4
10/sex, 79-82 exposures. Exposure concentrations: 2593 and
5345 mg/m* (490 and 1010 ppm). Effect on kidney weight only
1n males. No effects on histology or blood nitrogen.
Testlcular effects (decreased weight, spermatogenesls) at 5345
mg/m» (257.23-267.00 mg/kg/day).
Torkelson et al., 1960
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RECORD #4: 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: SOX
Number Exposed: 10 10 10
Number Responses: NR NR NR
Type of Effect: WGTOC WGTIN WGTIN
SHe of Effect: BODY LIVER KIONY
Severity Effect: 444
Comment: 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.
Citation: Torkelson et a!., 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: 50%
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 rag/m» (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 a!., 1960
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RECORD #6: Species: Rabbits Body Weight: 3.8 kg
Sex: Male Reported Dose: 5345 mg/m»
Effect: LOAEL Converted Dose: 284.29-295.09 mg/kg/day
Route: Inhalation Exposure Period: 114 days
Duration Observation: 114 days
Molecular Height: 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/m»
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:
50X
Number Exposed: 2
Number Responses: 0
Type of Effect:
Site 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
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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: 50X
Number Exposed: 100
Number Responses: NR
Type of Effect: WGTDC
Site 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 1n 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:
Molecular We1ght:l29.39
Inhalation hours/day: 6.00
Inhalation days/week: 4.8222
Inhal. Exp. days: 124.00
Assumed Inhalation Absorption:
50%
Citation:
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/ra») 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
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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: 50X
Number Exposed: 20
Number Responses: NR
Type of Effect: OTHER
SHe 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/m1
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 1s 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 Height: 12.7 kg
Sex: Female Reported Dose: 4710 mg/m3
Effect: LOAEL 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
SHe of Effect: KIDNY
Severity Effect: 5
890 ppm equivalent concentration. Histology was evaluated
after 67 exposures. Increased fat 1n the kidneys and Increased
hemosldeMn 1n 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 Height: 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 Height: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 1.00
f 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:
SHe 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 al., 1960
RECORD #15:
Species:
Sex:
Effect:
Route:
Rats
Female
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
Comment:
Citation:
Molecular Weight:
Inhalation hours/day: 7.00
Inhalation days/week: 1.00
# Inhal. Exp. days:
Assumed Inhalation Absorption:
SOX
Number Exposed: 4
Number Responses: NR
Type of Effect: DE6EN
SUe of Effect: LIVER
Severity Effect: 5
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.
Torkelson et al., 1960
0316d
-81-
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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: 50X
Number Exposed: 4
Number Responses: NR
Type of Effect:
SHe 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 a!., 1960
RECORD #17:
Comment:
Species:
Sex:
Effect:
Route:
Mice
NR
LOAEL
Inhalation
Citation;
Body Weight: 0.03 kg
Reported Dose: 7 mg/i
Converted Dose: 189.62 mg/kg/day
Exposure Period: 0.29 days
Duration Observation: 1 day
Molecular Weight:
Inhalation hours/day: 7.00
Inhalation days/week: 1.00
f Inhal. Exp. days:
Assumed Inhalation Absorption: 50%
Number Exposed: NR
Number Responses: NR
Type of Effect: DEGEN
SHe of Effect: LIVER
Severity Effect: 5
Single 7-hour exposure. 1323 ppm equivalent concentration.
Concentration not expanded over/ 24 hours. Fatty degeneration.
Effect observed 1n mice exposed to concentrations of 7-17
mg/m* for 1-5 days but was minimal/absent after 72 hours.
Hlghman et al., 1948
0316d
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RECORD |18:
Comment:
Citation:
Species: Mice Body Weight: 0.03 kg
Sex: NR Reported Dose: 2273 ppm
Effect: PEL 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
f 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). LCsos 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
Hale
PEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Dura tlonObser vat Ion:
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
Site of Effect: BODY
Severity Effect: 10
All rats died within 24 hours of treatment. Dose administered
1n corn oil apparently by gavage.
Torkelson et al., 1960
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RECORD #2:
Comment:
Citation:
Comment:
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:
Site 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
Approximate LDso- Doses ranging from 500-4400 mg/kg/day
administered In corn oil apparently by gavage to groups of 10
animals.
Svlrbely et al.. 1947
RECORD |4: Species: Mice
Sex: NR
Effect: PEL
Route: Gavage
Number Exposed:
Number Responses:
Type of Effect:
SHe 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
1 day
12 days
Citation:
Single doses of 500, 3000 and 4500 mg/kg were administered 1n
corn oil. 12/50 mice that died or were killed at two highest
doses showed subcapsular necrosis 1n liver. 8/32 showed
hemoglobin casts 1n renal tubules.
Hlghman et al., 1948
0316d
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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 16:
Species:
Sex:
Effect:
Rout:e
Mice
NR
PEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
0.03 kg
3000 mg/kg/day
3000 mg/kg/day
5 days
5 days
Comment:
Citation:
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
Death In unspecified number of 32 mice that were given single
doses 1n olive oil on 1 to 10 consecutive days. H1stolog1c
examination showed effects Including fatty degeneration of
the liver and kidney and liver subcapsular necrosis.
Hlghman et al., 1948
NR = Not reported
0316d
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A
J
D
C
18080 "
1880
Bronoch1orone thane
r i i r
8.881
3
(Oral Exposure)
BCMORRL D2
•N5
-K-
i i i
e.8i
HUKRN EQUIV DURRTION (fraction 1 if wan)
CENSORED DATR KETHOD
Key: F . FEL
N . NOEL
Solid Hne - Adverse Effects Boundary *
Dashed Hne « No Adverse Effects Boundary
Dose/Duration -
FIGURE C-6
Response Graph for Oral Exposure to Bromochloromethane:
Censored Data Method
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(Mantel and Schnelderman, 1975). The result Is 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) 1s 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 1s extended upward, parallel to the dose axis. The starting
point 1s 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 1s 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 (1f any) resulting from Intersections of the adverse effects and no
adverse effects boundaries Is 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 1s redrawn so that It does not Intersect the adverse
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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 1s defined
by the LOAEL for liver hlstologlcal alterations In mice (Rec. #17), LOAELs
for kidney hlstologlcal alterations 1n dogs (Rec. #12), reduced body weight
and elevated organ weights 1n guinea pigs (Rec. #3), liver hlstologlcal
alterations 1n rats (Rec. #2) and for reduced body weight In 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
Is defined by the NOEL for liver hlstologlcal alterations 1n 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 In rats (Rec. #1). The
subchronlc and chronic RfOs for bromochloromethane are based on the NOAEL
for liver hlstologlcal alterations 1n rats (Rec. #1).
Figures C-5 and C-6 present the oral dose/duration-response graphs. The
adverse effects boundary Is defined by FRs 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 1s defined by the NOEL for mortality 1n rats
(Rec. #2) and the NOEL for mortality and hlsiopathology 1n mice (Rec. #5).
Using the censored data method (Figure C-6), the no adverse effects boundary
1s defined by a single value, the NOEL for mortality and hlstopathology In
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.
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C.2. DATA USED TO GENERATE DOSE/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
Bromochloromethane
Pending
Pending
HEED
Effects Document on
RECORD #1:
Species:
Sex:
Effect:
Route:
Rats
Female
NOAEL
Inhalation
Body Weight: 0.35 kg
Reported Dose: 1958 mg/m9
Converted Dose: 125.96 mg/kg/day
Exposure Period: 195 days
Duration Observation: 195 days
Comment:
Molecular Weight: 129.39
Inhalation hours/day: 7.00
Inhalation days/week: 4.8461
Inhal. Exp. days: 135.00
Assumed Inhalation Absorption:
50%
Citation:
Number Exposed: 10
Number Responses: NR
Type of Effect: WGTIN
Site of Effect: LIVER
Severity Effect: 4
Concentrations studied: 1958, 2593 and 5345 mg/m' (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 a!., 1960
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RECORD #2: Species: Rats Body Weight: 0.35 kg
Sex: Both Reported Dose: 2593 mg/m3
Effect: LOAEL Converted Dose: 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 vacuoHzatlon. Similar effects with
cloudy swelling In liver 1n both sexes at 5345 mg/m3
(344.18-357.25 mg/kg/day).
Citation: Torkelson et al., 1960
RECORD #3:
Species:
Sex:
Effect:
Route:
Guinea pigs Body Weight: 0.64 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: W6TIN WGTIN WGTDC
Site of Effect: LIVER KIDNY BODY
Severity Effect: 4 4,4
10/sex, 79-82 exposures. Exposure concentrations: 2593 and
5345 mg/m' (490 and 1010 ppm). Effect on kidney weight only
1n males. No effects on histology or blood nitrogen.
Testlcular effects (decreased weight, spermatogenesls) at 5345
mg/m» (257.23-267.00 mg/kg/day).
Torkelson et al., 1960
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RECORD #4: 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
SHe of Effect: BODY LIVER KIDNY
Severity Effect: 444
Comment: 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/m8. No effects on
histology. Other endpolnts not examined.
Citation: 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: 50%
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
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RECORD #6: Species: Rabbits Body Weight: 3.8 kg
Sex: Male Reported Dose: 5345 mg/m"
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: 50X
Number Exposed: 2
Number Responses: 1
Type of Effect: DEGEN
Site of Effect: TESTE
Severity Effect: 6
Comment: See previous record. Decreased spermatogenesls In tubules with
flbrosls 1n 1 of 2 males. Decreased relative testes weight.
Citation: Torkelson et a!., 1960
RECORD #7:
Species:
Sex:
Effect:
Route:
Dogs
Both
NOEL
Inhalation
Body Weight: 12.7 kg
Reported Dose: 1958 mg/ma
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
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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: 50%
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 1n 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/ma
Converted Dose: 155.84 mg/kg/day
Exposure Period: 6 months
Duration Observation: 6 months
Comment:
Citation;
Molecular We1ght:l29.39
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:
SHe of Effect:
Severity Effect: 3
4/sex. Dogs were exposed to 0, 515 or 1010 ppm (2725 or 5345
mg/m*) 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
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RECORD #10:
Comment:
Species:
Sex:
Effect:
Route:
Rats
Hale
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 uMnalysls.
Svlrbely et al., 1947
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RECORD #12:
Comment:
Citation:
Species: Dogs Body Height: 12.7 kg
Sex: Female Reported Dose: 4710 mg/m3
Effect: LOAEL 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: SOX
Number Exposed: 2
Number Responses: NR
Type of Effect: DEGEN
Site of Effect: KIDNY
Severity Effect: 5
890 ppm equivalent concentration. Histology was evaluated
after 67 exposures. Increased fat 1n the kidneys and Increased
hemoslderln 1n 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
FEL
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:
Number Exposed: 20
Number Responses: 11
Type of Effect: DEATH
SHe of Effect: BODY
Severity Effect: 10
Single 7-hour exposure. Concentration not
hours. 6/10 males and 5/10 females died.
occurred during exposure to anesthesia.
Torkelson et al.. 1960
50%
expanded over 24
Deaths generally
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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: 50X
Number Exposed: 22
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 10
Single 7-hour exposure. Concentration not expanded over
hours. 0/11 males and 0/11 females died.
Torkelson et al., 1960
24
RECORD #15:
Species:
Sex:
Effect:
Route:
Rats
Female
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
Comment:
Citation:
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
SHe of Effect: LIVER
Severity Effect: 5
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.
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:
SHe 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/l
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:
50%
Number Exposed: NR
Number Responses: NR
Type of Effect: DEGEN
SHe of Effect: LIVER
Severity Effect: 5
Single 7-hour exposure. 1323 ppm equivalent concentration.
Concentration not expanded over,' 24 hours. Fatty degeneration.
Effect observed 1n mice exposed to concentrations of 7-17
mg/m* 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: PEL 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 59 after 72-hour
observation. A similar value was reported by Hlghman et al.
(1948). LC50S 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:
74-97-5
Health and Environmental Effects Document on
Bromochloromethane
Pending
Pending
Document Type: HEED
RECORD #1:
Species:
Sex:
Effect:
Route:
Rats
Male
PEL
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
Site of Effect: BODY
Severity Effect: 10
All rats died within 24 hours of treatment. Dose administered
1n corn oil apparently by gavage.
Torkelson et al., 1960
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RECORD #2:
Comment:
Species:
Sex:
Effect:
Route:
Rats
Hale
NOEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation: 14 days
0.35 kg
5000 mg/kg/day
5000 mg/kg/day
1 day
Number Exposed: 5
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 10
Comment: No deaths. See previous record.
Citation: Torkelson et al., 1960
RECORD #3: Species: Mice
Sex: NR
Effect: PEL
Route: Gavage
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
NR
NR
DEATH
BODY
10
0.03 kg
4300 mg/kg/day
4300 mg/kg/day
1 day
6 days
Approximate LDsQ. Doses ranging from 500-4400 mg/kg/day
administered In corn oil apparently by gavage to groups of 10
animals.
Citation:
RECORD *4:
SvUbely
Species:
Sex:
Effect:
Route:
et al.. 1947
Mice
NR
PEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
0.03 kg
3000 mg/kg/day
3000 mg/kg/day
1 day
12 days
Comment:
Citation:
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
Single doses of 500. 3000 and 4500 mg/kg were administered 1n
corn oil. 12/50 mice that died or were killed at two highest
doses showed subcapsular necrosis 1n liver. 8/32 showed
hemoglobin casts 1n renal tubules.
Hlghman et al., 1948
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RECORD #5:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Mice
NR
NOEL
Gavage
Body Height:
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. H1stolog1c
examination showed effects Including fatty degeneration of
the liver and kidney and liver subcapsular necrosis.
Hlghman et al., 1948
NR = Not reported
tfJ. &tvJfomncnt^t Protection Agency
Region 5, library (PL-12J)
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