EPA/6OO/B-91/016
                                         May 199O
  HEALTH AND ENVIRONMENTAL  EFFECTS DOCUMENT
            FOR BROMOCHLQROMETHANE
 ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND  ENVIRONMENTAL ASSESSMENT
      OFFICE OF RESEARCH AND DEVELOPMENT
     U.S.  ENVIRONMENTAL PROTECTION AGENCY
             CINCINNATI, OH 45268

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i

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                                                                                                   1
                                   TECHNICAL REPORT DATA
                            (Please nod Instructions on ike rtvene be fort completing)
  . REPORT NO.
 'EPA/600/8-91/016
             3. RECIPIENT'S ACCESSION NO.
              PB91-213702
|4. TITLE AND SUBTITLE

  Health and Environmental Effects Document for
  Bromochloromethane
             6. REPORT DATE
             6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
                                                           8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
                                                            10. PROGRAM ELEMENT NO.
                                                            11. CONTRACT/GRANT NO.
 12. SPONSORING AGENCY NAME AND ADDRESS
  Environmental Criteria and Assessment Office
  Office  of Research and Development
  U.S.  Environmental Protection  Agency
  Cincinnati.  OH  45268	
             13. TYPE OF REPORT AND PERIOD COVERED
             14. SPONSORING AGENCY CODE

                EPA/600/22
 15. SUPPLEMENTARY NOTES
 16. ABSTRACT
      Health  and Environmental Effects Documents (HEEDS) are prepared for the Office of
 Solid Waste  and Emergency Response  (OSWER).   This document series  is intended to
 support listings under the Resource Conservation and Recovery Act  (RCRA) as well as
  o provide health-related limits and goals  for emergency and remedial actions under
  he Comprehensive Environmental Response, Compensation and Liability Act (CERCLA).
 Both published  literature and information obtained from Agency Program Office files
 are evaluated as they pertain to potential  human health, aquatic life and environmen-
 tal effects  of  hazardous waste constituents.
      Several quantitative estimates are  presented provided sufficient data are
 available.   For systemic toxicants, these include Reference Doses  (RfDs) for chronic
 and subchronic  exposures for both the inhalation and oral exposures.   In the case of
 suspected carcinogens, RfDs may not be estimated.  Instead, a carcinogenic potency
 factor, or q^,  is provided.  These potency estimates are derived  for both oral and
 inhalation exposures where possible.  In addition, unit risk estimates for air and
 drinking water  are presented based on inhalation and oral data, respectively.
 Reportable quantities (RQs) based on both chronic toxicity and carcinogenicity are
 derived.  The RQ is used to determine the quantity of a hazardous  substance for
 which notification is required in the event  of a release as specified under CERCLA.
17.
                                KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
                                               b.lDENTIFIERS/OPEN ENDED TERMS
                           c. COS AT I Field/Croup
             STATEMENT
  Public
19. SECURITY CLASS (
  Unclassified
21. NO. OF PAGES
   98
                                               20. SECURITY CLASS (Thispagt)
                                                 Unclassified
                                                                          22. PRICE
 EPA Form 2220-1 (It**. 4-77)   PMKVIOU* COITION I* OB»OLCTC

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                                  DISCLAIMER

    This document  has  been  reviewed  1n  accordance with  the U.S.  Environ-
mental  Protection  Agency's   peer   and administrative  review  policies  and
approved for  publication.   Mention of  trade  names  or commercial  products
does not constitute endorsement or recommendation for use.
i
                                       11

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                                    PREFACE

    Health and  Environmental  Effects  Documents (HEEDs) are  prepared  for  the
Office of  Solid  Haste  and Emergency Response  (OSWER).  This  document  series
Is Intended to support  listings  under  the Resource  Conservation  and Recovery
Act  (RCRA)  as   well  as  to  provide  health-related  limits  and  goals  for
emergency  and   remedial   actions  under   the  Comprehensive  Environmental
Response,  Compensation  and   Liability   Act   (CERCLA).     Both   published
literature and   Information  obtained  for   Agency  Program  Office  files  are
evaluated  as  they  pertain  to  potential   human  health,  aquatic  life  and
environmental   effects   of  hazardous   waste  constituents.    The  literature
searched  for   In  this  document  and  the   dates  searched  are  Included  In
"Appendix: Literature  Searched."  Literature  search material Is  current  up
to 8  months   previous  to the  final draft  date listed on  the  front  cover.
Final draft  document  dates  (front  cover)   reflect  the date  the document  Is
sent to the Program Officer  (OSWER).

    Several quantitative  estimates  are presented  provided  sufficient  data
are  available.    For   systemic   toxicants,   these   Include:  Reference  doses
(RfDs) for chronic and  subchronlc exposures  for both the  Inhalation and oral
exposures.  The  subchronlc  or  partial  lifetime  RfD, Is an estimate  of  an
exposure  level  which would  not  be  expected  to  cause adverse  effects  when
exposure  occurs  during  a limited time  Interval  I.e., for an  Interval  which
does  not  constitute a  significant portion  of the  Hfespan.   This type  of
exposure  estimate  has  not been  extensively used,  or rigorously  defined  as-
previous  risk assessment  efforts  have  focused  primarily on  lifetime exposure
scenarios.  Animal  data  used  for  subchronlc estimates  generally  reflect
exposure  durations  of   30-90  days.   The general  methodology  for  estimating
subchronlc RfOs   1s the  same as  traditionally employed for  chronic  estimates,
except that subchronlc  data  are utilized when available.

    In the case  of  suspected  carcinogens,  a carcinogenic potency  factor,  or
q-j*  (U.S. EPA,   1980),  Is  provided.    These potency  estimates  are  derived
for both  oral and  Inhalation  exposures where  possible.   In  addition,  unit
risk estimates for  air  and  drinking water   are  presented  based on  Inhalation
and oral  data, respectively.  An  RfD may also  be  derived  for the noncarclno-
genlc health  effects of compounds that  are  also carcinogenic.

    Reportable   quantities   (RQs)  based   on   both   chronic   toxldty  and
carclnogenldty  are derived.  The RQ  Is used  to determine  the quantity of a
hazardous  substance  for  which  notification  1s  required  In  the event of  a
release   as   specified   under   the  Comprehensive   Environmental   Response,
Compensation   and Liability  Act  (CERCLA).    These  two RQs  (chronic  toxlclty
and carclnogenldty)  represent  two  of  six  scores   developed  (the remaining
four reflect  IgnHablHty, reactivity,  aquatic toxlclty,  and acute mammalian
toxlclty}.  Chemical-specific  RQs  reflect  the lowest  of  these six  primary
criteria.  The  methodology  for  chronic toxlclty  and cancer  based RQs  are
defined 1n U.S.  EPA,, 1984 and 1986a, respectively.
                                      Ill

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                              EXECUTIVE SUMMARY
    Bromochloromethane  Is   a   clear,  colorless  liquid  with  a  sweet  odor
(Stenger,  1978).   It  Is   completely  mlsdble  with  most  common  organic
solvents (Stenger,  1978} and  soluble In water  to  the extent of 16.7  g/a  at
25°C {Tewarl  et  al.,  1982).  Current production  figures are not  available.
Recent   manufacturers  of bromochloromethane  Include  Dow  Chemical  and  Ethyl
Corporation (USITC, 1988;  SRI,  1989).  Bromochloromethane  Is used  mainly  as
a  fire-extinguisher  fluid  In  aircraft  and portable  extinguishers  (Stenger,
1978).   It Is  also used In  chemical synthesis  (Kuney,  1988).
    Bromochloromethane  Is   expected   to degrade  relatively  slowly  In  the
atmosphere.  Using the method of Atkinson  (1987), the half-life  with  respect
to  HO-  reaction  can be estimated  at  ~168 days.  This suggests that  ~2X  of
tropospherlc  bromochloromethane  will  diffuse  Into  the  stratosphere  and  be
destroyed by direct photolysis.  Physical  removal from the  atmosphere by wet
deposition may be  possible,  but Its  relative  significance Is not  known.   A
single   blodegradatlon  study  (Tabak et al., 1981) suggested that blodegrada-
tlon of  bromochloromethane  1s  an   Important  environmental  fate  process.
Volatilization  from  water and  soil   surfaces  Is  a  major  fate  process.
Volatilization half-lives  of 4 and 47 hours were  estimated  for  a model river
(1 m deep)  and  for an  environmental  pond, respectively (Thomas,  1982;  U.S.
EPA, 1986b).  Bromochloromethane may leach readily  1n soils, based  upon  an
estimated K   value  of 21   (Swann  et  al.,  1983).  Aquatic  hydrolysis  Is not
environmentally significant (Mabey  and Mill,  1978).
    Bromochloromethane  has  been  detected  In  drinking water  (Suffet  et  al.,
1980; Lucas,  1984),  groundwater (Zoeteman et al.,  1981),  Lake Ontario and
Niagara  River water  (1-10 ng/4)  (Kaiser  et  al.,  1983)  and open  seawater
from  the  Atlantic  Ocean   (0.02  ng/a)  (Class  and  Ballschmlter,  1988).

                                      1v

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Levels of  0.2-0,4 ppt  have  been Identified In  air  over  the Atlantic  Ocean
(Class and BallschmHer, 1988), while levels of  2.4-2.9 ppt  were  detected  In
the  Alaskan  Arctic  (Rasmussen  and  Khalll, 1984).   Bromochloromethane has
also been Identified In air  samples collected  near a  hazardous  waste  site  1n
New Jersey (Lareglna et al., 1986).  It  has  been suggested  that the presence
of bromochloromethane  In  marine water and  air may be due,  In  part,  to  Us
blogenlc formation  1n  algae,  followed  by release to seawater, with  subse-
quent volatilization  (Class  and Ballschmlter,  1988).  The  classic haloform
reactions responsible for the  formation  of  chloroform and other halomethanes
during chlorlnatlon  of drinking  water   will  not produce bromochloromethane
(NAS, 1980).
    Summarized  toxIcHy  data for bromochloromethane  consisted  of a NOEL  of
80  mg/a  for  fathead   minnows,  P.  promelas.   and  an  LC5Q  (duration  not'
reported)  of  >80  rag/a,  (U.S.   EPA,  1987).     Bromochloromethane  has  been
found In  tissues of rainbow trout,  S.  qalrdnerl.  from the Colorado  River.
The estimated whole-fish concentration  was 8 vg/t (Hlatt,  1983).
    Bromochloromethane  Is  rapidly  absorbed  by  rats  In a  blphaslc  manner
following acute  Inhalation exposure (Gargas  and  Andersen, 1982),  but  quanti-
tative data are  not available  regarding  the  extent of Inhalation  exposure  or
the rate or  extent  of  oral   exposure.   There appears  to  be  some distribution
of  bromide  to  the  brain  of  dogs  during  subchronlc  Inhalation  exposure
(Svlrbely et al., 1947).  Rat  tlssueiblood  partition  coefficients (Gargas  et
al.,  1986a,b)  suggest   that  bromochloromethane will   distribute more  readily
to fat  than  to  liver  or  muscle.  Available data  Indicate  that bromochloro-
methane Is metabolized  by two  major pathways:  an oxldatlve,  cytochrome P-450
mediated pathway yielding CO  and hallde by  putative  formyl   hallde  Inter-
mediates,  and  a  glutathlone   (GSH)-dependent  cytosollc  pathway  producing

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COp and  hallde (Gargas et  al.,  1986a).   It  1s proposed  that  a portion  of
the oxldatlve  pathway also  yields a  significant  amount  of  C0_ (Gargas  et
al.,1986a).  Information regarding the  rate and  extent  of  bromochloromethane
excretion was not located  1n the  literature cHed In  Appendix  A,
    Acute  Inhalation  LC  Qs  for  mice  for   7-hour   exposures   ranged   from
2268-2995  ppm  (Svlrbely et  al.,  1947;  Hlghman et  al.,  1948).  Exposure  to
5000 ppm  (26,460 mg/m3) for 7 hours  was  not  lethal  for rats (Torkelson  et
al., 1960).  Rats  survived  a single oral  dose  of  5  g/kg,  and all  rats  died
within 24  hours  after a dose  of 7 g/kg  (Torkelson  et  al.,  1960).  An  oral
LD5Q  of  -4300  mg/kg was  determined  for mice  (Svlrbely  et  al.,  1947).
Signs  and  pathological effects  of  acute Inhalation  and   oral  exposure  to
bromochloromethane are similar;  principal  effects  Include  CNS depression and
degeneration of the liver.
    Subchronlc  Inhalation studies  of  bromochloromethane have been  conducted
with  rats, mice,  guinea  pigs,  rabbits and  dogs  (Torkelson et al.,  1960;
MacEwen et al.,  1966;  Svlrbely et  al.,  1947;  Hlghman et al.,  1948).  Concen-
trations ranged  from 370 ppm  (rats)   to  -1000  ppm  (all species);  exposures
were usually 5-7  hours/day,  5  days/week ranging from 14 weeks to -6  months.
Generally,  minor  effects  such as  decreased  body weight,  Increased relative
liver and  kidney weight and  reversible  liver  and kidney hlstologlcal  altera-
tions occurred at concentrations >500  ppm  1n  most  species.  Torkelson et al.
(1960) found that  relative  liver weight was  Increased  In  rats at  concentra-
tions  of  370 ppm with  hlstologlcal  effects  occurring  at  490 ppm.   Exposure
to  1000  ppm caused death and  marked liver Injury  In mice (Hlghman et  al.,
1948).  Information regarding  the  chronic  Inhalation toxlclty, subchronlc or
chronic  oral  toxlclty or   teratogenldty of   bromochloromethane  were  not
located.   Decreased  spermatogenesls  and flbrosls occurred  In the tubules of
                                      v1

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the  testes  of guinea  pigs  and  rabbits  that were  subchronlcally  exposed  to
-1000  ppm bromochloromethane  by Inhalation  (Torkelson  et  al.,  1960).   The
functional significance of these effects was not evaluated.
    Pertinent Information regarding  the  chronic  Inhalation  and  oral  exposure
of human  or  animals  to bromochloromethane were not  located  In  the available
literature cited 1n Appendix A.
    The   carclnogenUHy  of   bromochloromethane   has   not   been  evaluated.
Bromochloromethane was  mutagenlc  in  Salmonella  typhlmurlum and  Escher1ch1a
coll  bacteria (Simmon,  1976;  Simmon  et  al., 1977;  Osterman-Golkar et  al.
1983;  Strobel and  Grummt, 1987) and  Induced SCE  and  chromosome aberrations
1n Chinese hamster cells 1n vitro {Strobel and Grummt,  1987).
    An  RfD  for   subchronlc  Inhalation  exposure  of  4  mg/m3 was  based  on  a
NOAEL  associated with  slightly  elevated  liver  weight  but no effect  on  body>
weight  In female rats  exposed  Intermittently for  195 days {Torkelson et  al.,
1960).   This  study  also  served as  the basis  for an RfD  of  0.4 mg/m3  for
chronic  Inhalation  exposure.   Oral   data  were not  sufficient   for  deriving
route-specific RfD values; therefore,  the  NOAEL  from the Inhalation  study In
female  rats  by  Torkelson  et  al. (I960)  served as  the  basis for an  RfD  of  1
mg/kg/day  for  subchronlc  oral  exposure  and  an  RfD  of 0.1  mg/kg/day  for
chronic  oral  exposure.   An  RQ  for  noncancer chronic  toxlclty of  1000  was
based  on  the occurrence of  liver  lesions In rats  exposed  by  Inhalation  for
114 days.
    Bromochloromethane  1s classified  In  EPA  Cancer Group 0  (Not Classifiable
as to  Human  Carclnogenlclty) because  of  lack of  cardnogenlclty  data;  this
lack  of  data precludes  calculation  of  a  carcinogenic potency  factor  or
cancer-based RQ  for bromochloromethane.

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                             TABLE OF CONTENTS
                                                                       Page
1.  INTRODUCTION	     ]

    1.1.   STRUCTURE AND CAS NUMBER	     1
    1.2.   PHYSICAL AND CHEMICAL PROPERTIES 	     1
    1.3.   PRODUCTION DATA	     2
    1.4.   USE DATA	     2
    1.5.   SUMMARY	     2

2.  ENVIRONMENTAL FATE AND TRANSPORT	     3

    2.1.   AIR	     3
    2.2.   WATER	     3

           2.2.1.   Hydrolysis	     3
           2.2.2.   Photolysis	     4
           2.2.3.   Mlcroblal Degradation 	     4
           2.2.4.   Volatilization	     4
           2.2.5.   Adsorption	     5

    2.3.   SOIL	     5

           2.3.1.   Adsorption/Leaching 	     5
           2.3.2.   Mlcroblal Degradation 	     5
           2.3.3.   Volatilization	     5

    2.4.   SUMMARY	     6

3.  EXPOSURE	     7

    3.1.   WATER	     7
    3.2.   FOOD	     8
    3.3.   INHALATION	     8
    3.4.   DERMAL	     8
    3.5.   SUMMARY	     9

4.  ENVIRONMENTAL TOXICOLOGY	    10

    4.1.   AQUATIC TOXICOLOGY 	    10

           4.1.1.   Acute Toxic Effects on Fauna	    10
           4.1.2.   Chronic Effects on Fauna	    10
           4.1.3.   Effects on Flora	    10
           4.1.4.   Effects on Bacteria 	    10

    4.2.   TERRESTRIAL TOXICOLOGY 	    11

           4.2.1.   Effects on Fauna	    11
           4.2.2.   Effects on Flora	    11
                                    vlll

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                          TABLE  OF  CONTENTS  (cont.)
    4.3.   FIELD STUDIES	   11
    4.4.   AQUATIC RISK ASSESSMENT	   11
    4.5.   SUMMARY	   12

5.  PHARMACOKINETCS	   13

    5.1.   ABSORPTION	   13
    5.2.   DISTRIBUTION	   14
    5.3.   METABOLISM	   14
    5.4.   EXCRETION	   17
    5.5.   SUMMARY	   18

6.  EFFECTS	   19

    6.1.   SYSTEMIC TOXICITY	   19

           6.1.1.   Inhalation Exposure 	   19
           6.1.2.   Oral Exposure	   22
           6.1.3.   Other  Relevant Information	   29

    6.2.   CARCINOGENICITY	   29
    6.3.   GENOTOXICITY	   29
    6.4.   DEVELOPMENTAL TOXICITY 	   31
    6.5.   OTHER REPRODUCTIVE EFFECTS 	   31
    6.6.   SUMMARY	   32

7.  EXISTING GUIDELINES AND STANDARDS 	   34

    7.1.   HUMAN	   34
    7.2.   AQUATIC	   34

8.  RISK ASSESSMENT	   35

    8.1.   CARCINOGENICITY	   35

           8.1.1.   Inhalation	   35
           8.1.2.   Oral	   35
           8.1.3.   Other  Routes	   35
           8.1.4.   Height of Evidence	   35
           8.1.5.   Quantitative Risk Estimates 	   35

    8.2.   SYSTEMIC TOXICITY	   35

           8.2.1.   Acute  Exposure	   35
           8.2.2.   Subchronlc Exposure 	   36
           8.2.3.   Chronic Exposure	   43
                                     1x

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                           TABLE  OF  CONTENTS  (cont.)
 9.  REPORTABLE QUANTITIES
     9.1.   BASED ON SYSTEMIC TOXICITY 	   45
     9.2.   BASED ON CARCINOGENICITY	   49
10.  REFERENCES,
APPENDIX A: LITERATURE SEARCHED	
APPENDIX B: SUMMARY TABLE FOR BROMOCHLOROMETHANE 	
APPENDIX C: DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO
            BROMOCHLOROMETHANE 	
51

61
64

65

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                               LIST OF  TABLES
No.                               TUIe                                Page
6-1     Acute Inhalation Lethality of Bromochloromethane	   21
6-2     Genotoxlclty Testing of Bromochloromethane	   30
9-1     Inhalation Toxldty Summary for Bromochloromethane	   46
9-2     Inhalation Composite Scores for Bromochloromethane.  .....   48
9-3     Bromochloromethane: Minimum Effective Dose (MED)  and
        Reportable Quantity (RQ)	   50
                                     x1

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                             LIST OF  ABBREVIATIONS
AEL
A/G
CAS
CNS
CO
C02
CS
DUEL
PEL
GSH
HA
NEC
HEO
Km
 ow
"-C50

LD50
LDU
LEO
LOAEL
HEO
NOAEL
NOEL
Adverse-effect level
Albumin/globulin
Chemical Abstract Service
Central nervous system
Carbon monoxide
    N:
Carbon dioxide
Composite score
Drinking water equivalent level
Frank-effect level
Reduced glutathlone
Health advisory
Human equivalent concentration
Highest effective dose
Concentration In air at which uptake occurs at one-half
the maximum rate
Soil sorptlon coefficient standardized with respect
to organic carbon
Octanol/water partition coefficient
Concentration lethal to 50% of recipients
(and all other subscripted concentration levels)
Dose lethal  to 50% of recipients
Log dose units
Lowest effective dose
Lowest-observed-adverse-effect level
Minimum effective dose
No-observed-adverse-effect level
No-observed-effect level

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                         LIST OF  ABBREVIATIONS (cont.)

PEL                Permissible exposure limit
ppb                Parts per billion
ppm                Parts per million
ppt                Parts per trillion
RfD                Reference dose
RQ                 Reportable quantity
RVjj                Dose-rating value
RVe                Effect-rating value
SCE                Sister chromatld exchange
SGOT               Serum glutamlc oxaloacetlc transamlnase
SGPT               Serum glutamlc pyruvlc transamlnase
SIC                Sister chromatld exchange, Chinese hamster cells In yjtro
STEL               Short-term exposure limit
TLV                Threshold limit value
TLV-STEL           Threshold limit value-Short-term exposure limit
TWA                Time-weighted average
UV                 Ultraviolet
Vmax               Maximum rate of uptake

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                               1.   INTRODUCTION
1.1.   STRUCTURE AND CAS NUMBER
    Bromochloromethane  Is  the  common  name  for  the  chemical  known  by  the
synonyms chlorobromomethane,  methylene  chlorobromlde,  fluorocarbon 1011  and
Halon  1011   (Chemllne,  1989).  The  structure, molecular  weight,  empirical
formula and CAS Registry number for bromochloromethane  are  as  follows:
                                       Br
                                       I
                                    Cl-C-H
                                       I
                                       H
Molecular weight:  129.39
Empirical formula:  CH-BrCl
CAS Registry number:  74-97-5
1.2.   PHYSICAL AND CHEMICAL PROPERTIES
    Bromochloromethane  Is  a  clear,   colorless  liquid  with  a  sweet  odor
(Stenger,  1978).   It  Is  completely  mlsdble  with  most   common   organic
solvents.  Selected physical properties of bromochloromethane are as  follows:
     Melting point:
     Boiling point:
     Density (25°C):
     Mater solubility
       at 25°C:
     Vapor pressure
       at 25°C:
       at 15.72°C:
     Log Kow:
     A1r odor threshold:
     Water odor threshold:
-87.95°C
68.06°C
1.923 g/cm3

16.7 q/i

147.2 mm Hg
93.34 mm Hg
1.41
400 ppm
200 ppm
R1dd1ck et al.. 1986
Rlddlck et al., 1986
Rlddlck et al., 1986
TewaM et al., 1982

Rlddlck et al.. 1986
McDonald et al., 1959
Tewarl et al., 1982
Amoore and Hautala, 1983
Amoore and Hautala, 1983
0316d
     -1-
                     01/17/90

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Bromochloromethane  Is  nonflammable  and  does not have a  flash  point  (Hawley,
1981; Dean, 1985).
1.3.   PRODUCTION DATA
    Recent production .figures  for  bromochloromethane  are not  available.   The
public  portion of  the  U.S.  EPA  TSCA  Production  File  for  1977 lists  Dow
Chemical  (Midland,  HI) as  a  manufacturer  of 1-10 million pounds and  Bruckman
Laboratories,  Inc.  {Memphis, TN) as  a manufacturer  of 10-100  thousand pounds
(U.S. EPA, 1977).
    The 1989  Directory of  Chemical  Producers (SRI, 1989)  lists  Ethyl Corpo-
ration  (Magnolia,  AK)  as  a   current  manufacturer  of  bromochloromethane.
USITC (1988) lists  Dow Chemical as  a manufacturer during 1987.
    Bromochloromethane   Is  prepared   by   reacting   dlchloromethane   with
anhydrous  aluminum  bromide  (treatment  with  bromine  and aluminum)  or  by'
reaction  with  hydrogen  bromide  In the   presence   of  an  aluminum  hallde
catalyst, followed by water washing and distillation (Stenger,  1978).
1.4.   USE DATA
    Bromochloromethane  Is  used  mainly  as  a  fire-extinguisher  fluid  In
aircraft  and  portable  extinguishers  (Stenger,   1978).   It Is  also   used  In
chemical synthesis  (Kuney, 1988).
1.5.   SUMMARY
    Bromochloromethane  Is  a  clear,  colorless   liquid  with  a  sweet  odor
(Stenger,  1978).   It  Is  completely  mlsdble  with  most  common   organic
solvents  (Stenger,  1978)  and soluble In  water  to the extent of  16.7  g/t  at
25°C  (Tewarl  et  al.,  1982).  Current  production figures  are  not available.
Recent  manufacturers  of bromochloromethane Include  Dow Chemical and  Ethyl
Corporation (USITC,  1988;  SRI,  1989).  Bromochloromethane  Is  used mainly  as
a  fire-extinguisher  fluid  In aircraft  and  portable  extinguishers  (Stenger,
1978).  It 1s also used 1n chemical synthesis (Kuney,  1988).
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                     2.  ENVIRONMENTAL FATE AND TRANSPORT
2.1.   AIR
    The relatively high vapor pressure of  bromochloromethane  (147.2 mm  Hg  at
25°C)  Indicates  that  1t probably exists  almost  entirely In  the  vapor  phase
In  the  ambient atmosphere  (Elsenrelch  et al.,  1981).   Using the method  of
Atkinson  (1987),  the  rate  constant  for  the  vapor-phase reaction of bromo-
chloromethane  with   atmospheric  H0»   can  be   estimated  at   9.55xlO~14
cmVmolecule-sec  at  25°C.   This rate  constant  corresponds  to  a  half-life
of  -168  days, assuming  an  average  atmospheric  'HO*  concentration of  5xl05
molecules/cm3.
    Bromochloromethane  does not  absorb  UV   light  at  >290  nm  (Cadman and
Simons, 1966).   Therefore,  direct photolysis  will not  occur in  the tropo-
sphere.  However,  the  relatively long half-life predicted  for reaction with
HO*  suggests  that some  bromochloromethane may  eventually  diffuse Into the
stratosphere, where direct  photolysis  can  destroy  the compound.    Based  on  a
half-life of  168 days  and  a tropospherlc-to-stratospherlc  turnover  time  of
30  years,   ~2%  of  tropospherlc  bromochloromethane  will   diffuse  Into the
stratosphere.
    Pertinent data regarding the physical  removal  of  bromochloromethane from
the  atmosphere  were  not  located In  the  literature  cited  In  Appendix  A.
Bromochloromethane1s  water   solubility  of  16,700  mg/a  at   25°C   (Tewarl  et
al.,  1982}   suggests   that  physical   removal   by  wet  deposition  (rainfall,
dissolution  Into clouds, etc.)  1s  possible.   However,  the  significance  of
physical removal cannot be verified  because of lack of experimental data.
2.2.   WATER
2.2.1.   Hydrolysis.    The  hydrolysis  half-life  of  bromochloromethane has
been  estimated  at  -44  years  at  25°C  and  pH  7  (Mabey  and  Mill, 1978).
Therefore, hydrolysis  Is not environmentally significant.
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2.2.2.   Photolysis.   UV  spectra,  as  determined  by   Cadman   and  Simons
(1966), predict  that direct  photolysis  of  bromochloromethane  has  no signifi-
cance 1n the environment since no absorption occurs at  >290 nm.
2.2.3.   Nlcroblal Degradation.  Tabak  et  al.  (1981) studied  the  biodegrad-
abllHy of  114  organic  priority pollutants on the  U.S.  EPA Priority Pollut-
ants  List  to ascertain  mlcroblal  degradation  and  acclimation periods.   The
Bunch and  Chambers  static culture flask blodegradabllHy  screening test was
                                                                        j
performed  under  a  set  of controlled  experimental conditions that Included
the  following  parameters:   5  and  10  mg/a  concentrations  of  the  test
compound,  5 mg/s.  of yeast  extract  In the synthetic  medium, 7-day  static
Incubation  at 25°C  In  the dark followed by  three  weekly subcultures (total-
Ing 28 days  of  Incubation),  and  Incorporation  of  settled domestic  wastewater
as the mlcroblal  Inoculum.   With respect  to  bromochloromethane,  100% loss of'
compound was observed  after the  first 7-day Inoculation  period  and  after
each  subsequent  subculture.   The  results  Indicated significant  blodegrada-
tlon with rapid adaptation.
2.2.4.   Volatilization.   Based upon   a  water  solubility  of  16,700  mg/it
and a vapor pressure of 147.2 mm  Hg at 25°C  (see  Section 1.2.),  the Henry's
Law   constant   for   bromochloromethane  can   be   estimated   to   be  0.0015
atm-m3/mol.   A  Henry's  Law  constant  of  this   magnitude  Indicates  that
volatilization  from  environmental  waters  may   be  significant  and  rapid
(Thomas, 1982).   Using  a model  river  estimation  method  (Thomas,  1982),  the
volatilization half-life of  bromochloromethane from a  river 1 m  deep flowing
1   m/sec with  a  wind  velocity  of  3  m/sec  Is  ~4  hours.   The  estimated
volatilization half-life  from a  model   environmental pond  Is  -47  hours (U.S.
EPA,  1986b).  These estimates  Indicate that volatilization Is a significant
environmental fate process for bromochloromethane.
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2.2.5.   Adsorption.   K    estimates  presented  In  Section  2.3.1.   predict
that  bromochloromethane Is  not  tightly  bound  to  soil  through  adsorption.
Therefore,  H  Is likely that  adsorption  of bromochloromethane  1n  sediments
does  not  compete with volatilization or blodegradatlon  1n  the disappearance
of bromochloromethane from the aquatic environment.
2.3.   SOIL
2.3.1.   Adsorption/Leaching.   Pertinent   data  regarding  the  leaching  of
bromochloromethane  In  soil  were  not  located   In  the available  literature
cited  1n  Appendix  A.   A  K    value  of  21  can  be estimated  using  a  water
solubility  of   16,700  mg/8.  and  the following  regression-derived  equatldn
(Lyman,  1982):  log  K     =   3.64-0.55  log  (water  solubility}.   This  K
                      U L                                                   wl*
value Indicates very high soil mobility  (Swann  et a!.,  1983).
2.3.2.   M1crob1al  Degradation.   Pertinent  data   regarding   the  mlcroblaf
degradation of  bromochloromethane  In  soil  were  not located In the  available
literature cited  In  Appendix A.  The blodegradatlon results of  Tabak et al.
(1981)  discussed 1n  Section  2.2.3.  suggest   that  blodegradatlon of  bromo-
chloromethane  1n soil  may  be  significant.   Since  no  other  processes  are
expected  to degrade  bromochloromethane  In soil  to  a  significant  degree,
blodegradatlon  Is  probably  the ultimate  degradation  process, although  the
degradation rate of this process cannot  be quantified.
2.3.3.   Volatilization.   The  relatively  high  vapor  pressure  of  bromo-
chloromethane  (147.2  mm Hg  at 25°C)  suggests  significant evaporation  from
dry  surfaces.   In  moist  soils,  evaporation  may still  be significant  near
soil  surfaces,  although leaching  may diminish  the relative  significance of
volatilization.
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2.4.   SUMMARY
    Bromochloromethane  Is  expected   to   degrade  relatively  slowly  In  the
atmosphere.  Using the method of Atkinson  (1987), the  half-life with  respect
to  HO-  reaction  can be  estimated  at -168 days.  This suggests that -2%  of
tropospherlc  bromochloromethane  will diffuse  Into  the  stratosphere  and  be
destroyed by direct photolysis.  Physical  removal from the  atmosphere  by wet
deposition may be  possible, but Us  relative  significance Is  not  known.   A
single  blodegradatlon  study (Tabak et al., 1981) suggested  that blodegrada-
tlon  of  bromochloromethane  Is  an   Important  environmental  fate  process.
Volatilization  from  water  and  soil  surfaces  1s  a  major  fate  process.
Volatilization half-lives of 4 and 47 hours were  estimated  for  a model  river
(1 m deep)  and  for an  environmental  pond, respectively  (Thomas,  1982;  U.S.
EPA, 1986b).   Bromochloromethane  may leach readily  In soils,  based  upon  an*
estimated  K    value  of  21  (Swann  et al., 1983).  Aquatic  hydrolysis  Is not
environmentally significant {Mabey and Mill,  1978).
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                                 3.   EXPOSURE
3.1.   HATER
    Bromochloromethane was tentatively  Identified  1n a  drinking  water  sample
collected  In  Philadelphia,   PA,  In  August  1976,  and  In  drinking  water
concentrates collected from New Orleans, LA,  In  January 1976  (Suffet  et al.,
1980; Lucas, 1984).
    Kaiser  et  al.  (1983)  collected  water  samples  from 95 stations on  Lake
Ontario and  16 stations  on the  lower  Niagara River In 1981  for  analysis  of
volatile  halocarbons.   Bromochloromethane  was  detected In one  sample  at  a
level of  10 ng/9. and  In  14  samples  at trace levels (detection  limit  equals
1 ng/l).
    Bromochloromethane was qualitatively detected  In seawater collected from
the Narragansett Bay,  RI, In  1979-1980 (Wakeham et al.,  1983).   Monitoring'
of  the  north  and  south   Atlantic  Ocean in  1985  yielded  a  baseline  bromo-
chloromethane  concentration   of  0.02  ng/i   (Class  and Ballschmlter,  1988).
These  Investigators  detected  the blogenlc presence of  bromochloromethane  In
specific  algae that  occur In  the Atlantic Ocean, and  suggested that  the
occurrence  of  bromochloromethane  In  marine water and air  may  result,  In
part, from biological emissions from these algae.
    Zoeteman et  al.  (1981) detected a  bromochloromethane  concentration  of 8
ng/l In a contaminated groundwater sample from the Netherlands.
    Halomethanes,  such  as  bromodlchloromethane,  chlorodlbromomethane  and
trlhalomethanes,  have been  detected  1n drinking waters  and  other  waters
during  chlorlnatlon  (Allgeler et al.,  1980; Arguello   et  al.,  1979;  Dore  et
al., 1982;  Gould et  al.,  1983).   Although  bromlnatlon  can  occur when natural
bromide  Is  present  1n the water, the  classic haloform reactions responsible
for  the formation of  chloroform and  other  halomethanes during chlorlnatlon
will not produce bromochloromethane (NAS, 1980).

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3.2.   FOOD
    Pertinent data  regarding  the food monitoring of  bromochloromethane were
not located In the available literature cited In Appendix A.
3.3.   INHALATION
    The   average   concentrations  of   bromochloromethane  In  ambient   air
monitored throughout 1983 near Point Barrow, AL  (1n  the  Arctic) were 2.4-2.9
ppt (Rasmussen  and  KhalU,  1984).  The  higher  concentrations were  found  1n
the  winter  and  spring  when  the Arctic  haze  was   observed.   The  authors
suggested that  the bromochloromethane  1n the Arctic  air  was  primarily due to
transport from  anthropogenic  sources.   Experimental  evidence  to support  this
was not given.
    Bromochloromethane  was   Identified  {detection   limit  of  0.1   ppb)   1n
ambient  air   samples  collected  near  a hazardous waste   site  In  New  Jersey
(Lareglna et  al., 1986).  The actual  concentrations  In  the  samples  were  not
reported.
    Mean  bromochloromethane  concentrations  of  0.2-0.4 ppt were measured  In
the air  over  the open Atlantic  Ocean  (30°S-40°N) during  monitoring  1n  1985
(Class  and BallschmUer,  1988).  Bromochloromethane was  also  detected  1n
open seawater and In macro algae collected  near various  sampling  sites.   The
presence  of  bromochloromethane  In marine  air  may  be due,  In  part,  to  Us
blogenlc  formation  In algae,  followed by   release  to seawater, with  subse-
quent volatilization.  Monitoring of baseline concentrations  In seawater  and
air tend to support  this supposition.
3.4.   DERMAL
    Pertinent  data   regarding  the  dermal   monitoring of  bromochloromethane
were not located 1n  the available literature cited 1n Appendix A.
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3.5.   SUMMARY
    Bromochloromethane has  been detected  In  drinking water (Suffet  et  al.,
1980;  Lucas,  1984),  groundwater  (Zoeteman  et al.,  1981),  Lake Ontario  and
Niagara  River  water   (1-10  ng/l)  (Kaiser  et al.,  1983),  and  open  seawater
from   the  Atlantic  Ocean   (0.02   ng/8,)   (Class   and  Banschmlter,   1988).
Levels of  0.2-0.4 ppt have  been Identified  In  air over the  Atlantic  Ocean
(Class and Ballschralter,  1988), while  levels  of  2.4-2.9  ppt were detected in
the  Alaskan  Arctic  (Rasmussen  and Khalll,  1984).  Bromochloromethane  has
also been  Identified 1n air  samples  collected near  a hazardous waste site In
New Jersey (Lareglna et al.,  1986).   It  has  been  suggested  that the presence
of  bromochloromethane  In  marine water and  air  may  be  due. In  part,  to  Us
blogenlc formation  1n algae,  followed by release  to seawater, with subse-
quent  volatilization  (Class  and  Ballschmlter,  1988).  The  classic  haloform*
reactions  responsible for the  formation  of  chloroform and  other halomethanes
during chloMnatlon  of drinking  water  will  not produce  bromochloromethane
(NAS, 1980).
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                         4.  ENVIRONMENTAL TOXICOLOGY
4.1.   AQUATIC TOXICOLOGY
4.1.1.   Acute Toxic  Effects  on Fauna.   U.S.  EPA (1987)  summarized  results
of acute  toxldty  tests  conducted  by Dow Chemical Company.   No  effects  were
noted  In  fathead  minnows,  Plmephales promelas.  exposed  to  80  mg/i  bromo-
chloromethane.  The  LCcn  (duration  not  reported) for  this  species was  >80
                       DU
mg/a.  No study details were provided.
4.1.2.   Chronic Effects on Fauna.
    4.1.2.1.   TOXICITY — Pertinent  data  regarding   the  effects of  chronic
exposure  of  aquatic  fauna  to  bromochlormethane  were  not   located  In  the
available literature dted In Appendix A.
    4.1.2.2.   BIOACCUMULATION/BIOCONCENTRATION — H1att   (1983)    detected
the  presence  of  bromochloromethane  In  tissues of rainbow trout.  Salmonella
galrdnerl.  collected  from  the  Colorado  River  and  reported  an  estimated
whole-fish concentration of 8 vg/l.
4.1.3.   Effects on Flora.
    4.1.3.1.   TOXICITY — Pertinent  data  regarding  the  toxic  effects  of
exposure  of aquatic  flora  to  bromochloromethane were not  located  In  the
available literature cited In Appendix A.
    4.1.3.2.   BIOCONCENTRATION —  Pertinent  data regarding  the  bloconcen-
tratlon potential of  bromochloromethane  In  aquatic flora  were not  located In
the available literature cited 1n Appendix A.
4.1.4.   Effects  on  Bacteria.   Pertinent  data  regarding  the   effects  of
exposure  of  aquatic  bacteria to bromochloromethane  were not located  1n the
available literature cited In Appendix A.
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4.2.   TERRESTRIAL TOXICOLOGY
4.2.1.   Effects  on   Fauna.    Pertinent  data  regarding   the   effects   of
exposure of  terrestrial  fauna to bromochloromethane were  not  located  In  the
available literature cited 1n Appendix A.
4.2.2.   Effects  on   Flora.    Pertinent  data  regarding   the   effects   of
exposure of  terrestrial  flora to bromochloromethane were  not  located  In  the
available literature cited In Appendix A.
4.3.   FIELD STUDIES
    Pertinent  data  regarding  the effects of  bromochloromethane  on  flora  and
fauna  1n  the  field  were not  located In the available literature  cited  In
Appendix A.
4.4.   AQUATIC RISK ASSESSMENT
    The lack of  pertinent  data regarding the  effects  of  exposure of aquatic'
fauna and  flora  to  bromochloromethane precluded the development  of  a  fresh-
water criterion  by  the  method of  U.S.  EPA/OWRS (1986).   Data  required  for
the  development   of  a  freshwater  criterion   Include  the  results  of  acute
assays with  a  salmonld fish  species, a  warmwater  fish species,  a third fish
species or  an  amphibian,  planktonlc and benthlc  crustaceans, an  Insect,  a
                                                                           «
nonarthropod and  nonchordate  species and an  Insect or  species from a  phylum
not previously  represented.   The development  of a  freshwater  criterion will
also require data from chronic toxldty tests with  two species  of  fauna  and
one  species  of  algae  or  vascular  plant and at least  one bloconcentratlon
study.
    The lack of  pertinent  data regarding the  effects  of  exposure of aquatic
fauna and  flora  to  bromochloromethane prevented  the  development of a  salt-
water criterion  by  the  method of  U.S.  EPA/OWRS (1986).   Data  required  for
the development of a saltwater  criterion Include the  results of  acute  assays
with two chordate species, a  nonarthropod  and nonchordate  species, a  mysld

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or  panaeld  crustacean,  two  additional  nonchordate  species and  one  other
species of marine fauna.  The development of a  saltwater  criterion will  also
require data  from  chronic  toxldty tests with  two species of fauna and  one
species of algae or  vascular plant and at least  one bloconcentratlon  study.
4.5.   SUMMARY
    Summarized  toxldty  data for bromochloromethane  consisted  of  a NOEL of
80  mg/a  for   fathead  minnows,   £.   promelas^  and  an  LC_0  (duration  not
reported)  of  >80  mg/i (U.S.  EPA,  1987).   Bromochloromethane has been  found
In  tissues  of  rainbow  trout, S.  galrdneM.  from  the  Colorado River.   The
estimated  whole-fish concentration was 8 yg/i  (Hlatt,  1983).
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                             5.  PHARMACOKINETICS
5.1.   ABSORPTION
    Male F344 rats were  exposed  to nine Initial  concentrations of 100-10,000
ppm  (529-52,920 mg/m3}  bromochloromethane  vapor  for  175-205 minutes  1n  a
closed  Inhalation  chamber  (Gargas  and  Andersen,  1982).   Chamber concentra-
tion disappearance curves  Indicated that  absorption  was blphaslc, consisting
of a rapid  equilibrium phase  that  was  completed  1n 70-110 minutes and a slow
phase  that  was nearly  linear  after   this  time.   The  rapid uptake  phase
reportedly  represents  Initial  bloodigas equilibrium.   The slow uptake phase,
reportedly  representing  metabolism and  loading  Into  poorly perfused tissues,
was a composite  of a  saturable process, which  predominated at low concentra-
tions, and  a first-order  process.   Kinetic constants  were determined for the
saturable  process;  these  Included  a  K   of   91  ppm  {482  mg/m3)  and  a'
vmaw  °f  10*5   mg/kg/hour.   Similar  data were   reported  In  other  studies
 IHO X
(Andersen et al., 1980;  Gargas and Anderson, 1982).   Gargas et al. (I986a,b)
simulated  the mixed  uptake kinetics of bromochloromethane In rats,  using  a
physiologically-based  pharmacoklnetic  model.    Information   regarding  the
extent  of   respiratory  absorption  from  Inhaled  bromochloromethane was  not
located 1n the available literature.
    Quantitative  oral absorption   data  were  not located for  bromochloro-
methane.   The   occurrence  of   systemic  effects  In rats  and  mice  following
                  s
acute oral  exposure  to bromochloromethane (Section 6.1.3.) provides qualita-
tive evidence of gastrointestinal absorption.
    Male F344  rats  were exposed  to  2500-40,000 ppm  (13,230-211,681  mg/m3)
bromochloromethane In  air  for 4 hours  In dermal  vapor  absorption  chambers
without  significant   Inhalation  exposure  (McDougal  et  al.,  1985).   Blood
concentrations  of  bromide  showed  that  absorption of  bromochloromethane was
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rapid and  Increased with  Increasing  exposure  levels; however,  the  Increase
was not linear.  A dermal flux of 0.011-0.164 mg/cmVhour  was calculated.
5.2.   DISTRIBUTION
    Svlrbely et al. (1947) exposed 20 male  rats,  3  male  rabbits  and  2 female
dogs  (strains  not  specified) to  -890  ppm (4710 mg/m3)  bromochloromethane
for  7  hours/day,  5 days/week for  14 weeks.   Both  total  and  organic  (vola-
tile) bromide  were  elevated   In  the  blood and brain  of the  treated  animals,
compared  with  unexposed  controls,   following  the  last  7-hour  exposure.
Levels of  total  bromide In  the  blood were  6-8 times greater  than  levels  In
the  brain.   Similarly,  levels   of  organic   bromide  1n  the  blood were  8-12
times greater than levels In  the brain.
    Rat  blood:a1r and  rat  t1ssue:blood  partition  coefficients  for  bromo-
chloromethane  have  been  determined   as  follows:   bloodialr   (41.5*0.9),•
fat:blood (325±3), 11ver:blood (29.2±0.5)  and muscle:blood (11.U1.8).
    Pertinent data  regarding the distribution of  bromochloromethane follow-
ing  oral  exposure  were not  located 1n  the  available  literature  cited  In
Appendix A.
5.3.   METABOLISM
    Concentrations  of   Inorganic  bromide  Increased  In  the  blood  of  rats,
guinea pigs, rabbits and dogs as a result  of  subchronk  Inhalation  exposure
to  bromochloromethane   (Svlrbely  et  al.,   1947;  Torkelson  et  al.,  1960;
MacEwen  et   al.,  1966)   (Section   6.1.1.1.).     Carboxyhemoglobln  levels
Increased  In  male Long-Evans rats  given  a  single  Intraperltoneal  Injection
of  3.0  mrnol  "C-bromochloromethane/kg  (388.2  mg/kg) 1n  corn oil (Kublc  et
al.,  1974).   These data  and studies of  other dlhalomethanes  Indicate  that
bromochloromethane  1s   metabolized  by   two major   pathways:  an  oxldatlve,
cytochrome  P-450  mediated  pathway  yielding  CO  and hallde  using  putative
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formyl  hallde Intermediates,  and  a glutathlone-dependent  cytosollc  pathway
producing  C02 and  hallde  (Gargas  et  al.t  1986a).   Based  on  physiological
pharmacoklnetlc  analysis  of  plasma bromide  and  carboxyhemoglobln concentra-
tions  In  rats  pretreated with  pyrazole {which Inhibits mlcrosomal oxidation)
and  2,3-epoxypropanol  (which  depletes  glutathlone)  and  exposed  to  bromo-
chloromethane  by Inhalation,  Gargas  et  al.  (1986a)  concluded  that  bromide
was the preferred leaving  group  In  the oxldatlve mechanism, resulting 1n the
formation of  formyl chloride rather  than  formyl  bromide.   They  proposed that
a significant  portion  (-20-30%)  of  the putative  formyl chloride Intermediate
may react with GSH  and  other cellular  nucleophlles,  Instead of  spontaneously
decomposing  to CO.   According  to  these  Investigators,  this portion of  the
oxldatlve  pathway  probably  yields  CO-;  a  larger proportion  of  the  formyl
chloride  Intermediate  decomposes   to   CO when   cellular   GSH  1s  depleted.'
Metabolic  pathways   of  bromochloromethane   and  other  dlhalomethanes  are
presented In Figure 5-1.
    Gargas  et  al.   (1986a)  evaluated  the   kinetics  of  bromochloromethane
metabolism, using 4-hour Inhalation  studies  with male  F344 rats.   Gas uptake
(disappearance)  was determined during exposure  to 200-4000 ppm (1058-21,168
mg/m3)  In  a  closed   exposure  chamber,  and   plasma  bromide  levels  and
carboxyhemoglobln  levels   were  determined   following   exposure  to  constant
concentrations  of   51-2006 ppm  (270-10,616  mg/m3).    The  gas  uptake  data
Indicated   that   metabolism   comprises  both   first-order  and   saturable
components;  similar  data  were found  In  other  studies  (see Section  5.1.).
The oxldatlve  pathway was  high affinity  and  tow  capacity,  with  production of
CO saturable  at  bromochlormethane  concentrations greater  than  -200 ppm;  the
maximum percent  carboxyhemoglobln  saturation attained  was  -9%.   The maximum
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                     CYT , P-450        H
               CH2X
                       NADPH
H-O-C-X
OSOL
ci- * •••••
GS-CH2-X
^- NUCL
' (1.
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H
i
K
              M COOH  +  GSH
                H  COOH  4-  GSH
                CO,
   x = halogen atom
                   CO-
                                FIGURE 5-1
           Proposed  Pathways for Dlhalomethane (CH2X2) Metabolism
                       Source:   Gargas et a!., 1986a
0316d
-16-
01/17/90

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rate  for   the  metabolism  of  bromochloromethane  to  CO was  54  ymol  metabo-
11 zed/kg/hour.  The  GSH pathway  was  low affinity  but high capacity,  and  a
single first-order process at all exposure concentrations.
    Torkelson  et  al. (1960)  determined  Inorganic bromide  concentrations  In
the blood  of  four female  rabbits  (strain not specified) exposed  to  130 ppm
(688  mg/m3)  bromochloromethane  by  inhalation for  7 hours/day,  5 days/week
for  45 exposures  In  66  days.   Determinations  were  performed  before  and
Immediately after  1,  2,  5,  10,  14,  15  and 45  exposures.   Maximum  blood
bromide  Ion  concentrations  (-30-35  mg/da) were  reached by  the  end of  the
second week.
    Levels of  Inorganic  bromide In the  blood were  determined  In  two female
dogs  (strain  unspecified)  after  3-4  and 13-14 weeks  of  7 hours/day,  5  days/
week  Inhalation  exposure  to  a  nominal  bromochloromethane  concentration  of
1000  ppm  (measured concentration  ~890  ppm [4710  mg/m3]) (Svlrbely  et al.,
1947).   Blood  bromide   levels   Increased   during  dally  exposure,  did  not
significantly  decline  overnight  or  on  days  without exposure;  however,  the
steady Increase throughout the  treatment  period did  not  reach  maximum by the
end of  treatment.   Bromide  1on levels  In  the  blood were ~300-360 mg/dj.  at
the end  of  treatment.   These  findings  Indicate  a  tendency   for  Inorganic
bromide to accumulate  1n  the blood with continued  exposure  to bromochloro-
methane.
5.4.   EXCRETION
    Urinary output  of  Inorganic  bromide was  determined  In two  female dogs
(strain  unspecified)  after   3-4,  10  and  13-14  weeks   of  7  hours/day,  5
days/week  Inhalation  exposure  to  -890  ppm (4710 mg/m3)  bromochloromethane
(Svlrbely  et  al.,  1947).   Excretion   of  bromide  markedly  declined  on
exposure-free days,  but  tended  to Increase overall  throughout  the treatment


0316d                               -17-                             02/13/90

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period.   Information  regarding  the  rate  and  extent of  bromochloromethane
excretion was not located In the available literature cited In Appendix A.
5.5.   SUMMARY
    Bromochloromethane  1s   rapidly  absorbed  by  rats  In  a blphaslc  manner
following acute  Inhalation  exposure  (Gargas  and Andersen,  1982),  but quanti-
tative data are  not  available  regarding the  extent  of Inhalation  exposure  or
the rate  or  extent  of oral exposure.  There  appears  to  be some distribution
of  bromide  to   the  brain  of  dogs  during   subchronlc  Inhalation  exposure
(Svlrbely et a!., 1947).   Rat  tlssueiblood  partition  coefficients  (Gargas  et
al.,  1986a,b)  suggest that  bromochloromethane  will  distribute more readily
to  fat  than  to  liver  or  muscle.   Available  data  Indicate that bromochloro-
methane Is metabolized by  two  major  pathways: an oxldatlve, cytochrome P-450
mediated  pathway yielding CO and  hallde  (putative formyl  hallde  Inter-'
mediate}  and  a   glutathlone  (GSH)-dependent  cytosollc pathway  producing  CO-
and hallde  (Gargas   et al.,  1986a).   It  Is  proposed  that a portion  of  the
oxldatlve  pathway  also   yields   a   significant amount  of  C0_  (Gargas   et
al.,1986a).  Information regarding  the rate  and extent of  bromochloromethane
excretion was not located 1n the literature cited In Appendix A.
03164
-18-
02/13/90

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                                  6.   EFFECTS
6.1.   SYSTEMIC TOXICITY
6.1.1.   ACUTE.
    6.1.1.1.   INHALATION  EXPOSURE  — Rutsteln   (1963)  reported  that  three
male  fire   fighters  who used  chloro- bromomethane  as a  fIre-extlngulshing
agent  had  gastrointestinal  Irritations  (e.g.,  vomiting,  stomach  pains}  and
manifestations of  CNS  Involvement  (e.g.,  headache,  loss of  consciousness).
Acute  Inhalation  lethality  data for  bromochloromethane are summarized  In
Table  6-1.   These  data suggest  that mice  are more  susceptible  than  rats
since  7-hour  exposures  resulted In  LCcns of  2268-2995  ppm (12,000-15,850
                                        all
mg/m3)  for  mice  (Svlrbely et  al.,  1947;  Hlghman  et al.,  1948),  and  7-hour
exposures  to  5000  ppm (26,460  mg/m3)  were not  lethal  for  rats  (Torkelson
et al.,  1960).   Death was often  delayed 1n the mice  but generally occurred,
during  treatment  In the rats  exposed  to 10,000 ppm.  Signs  observed  1n  the
mice and rats  Indicated CNS  toxlclty; these  Included  restlessness, muscular
twitching,   uncoordinated movements,  labored respiration and  narcosis  In  the
mice (Svlrbely et  al.,  1947),  and drowsiness  and  unconsciousness  In the rats
{Torkelson  et al., 1960).
    Hlghman  et  al.  (1948)  exposed  Swiss  mice  (sex  not  reported) to  7-17
mg/s,  (7000-17,000  mg/m3  or  1323-3212  ppm)  bromochloromethane  by  Inhala-
tion  7 hours/day  on  1-5 successive  days.  H1stolog1cal  examination of  79
mice  Immediately  following   exposure  showed   changes  that  Included  fatty
degeneration  of  the  liver  after  single  exposures  of >7  mg/8, and  kidneys
after  single  exposures of  >12 mg/i.   These effects were most  severe  within
24  hours  of  exposure and were  minimal  or  absent  after  72 hours.   Hlsto-
loglcal examinations  were  conducted  on  groups  of  four  to five  female  rats
(strain not reported)  24 hours  following Inhalation  exposure  to  600-40,000


0316d                               -19-                             05/17/90

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ppm  (113-7559  mg/m3)  bromochloromethane  for  durations  of  7-0.025  hours,
respectively  {Torkelson   et   al.,   1960).   Unequivocal   alterations   were
observed  only  in  the liver  (small vacuoles  1n parenchyma  not typical  of
fatty  degeneration,  often accompanied  by   Increased  liver  weight).   The
minimum  concentration  producing hepatic  effects after  7-hour   exposure  was
1500  ppm (7938 mg/m3);  exposure to  600  ppm  (5175 mg/m3)  for  7 hours  did
not  produce  hepatic  effects  and  exposure  to  800  ppm (4234  mg/m3)  for  7
hours produced equivocal  hepatic hlstologlcal alterations.
    6.1.1.2.   ORAL EXPOSURE  —  Acute  oral toxldty data  are available  for
rats  and mice.  Torkelson  et  al. (1960)  fed  (apparently by gavage)  an
unspecified  series  of  single doses  of bromochloromethane  In  corn  oil  to
groups  of  five male  rats.   Observation  for 14  days   showed  that  all  rats
survived a  dose of  5  g/kg and all   rats died within  24  hours  after a dose of
7  g/kg.  Additional   Information   regarding  this  study  was  not  reported.
Groups  of  10  mice (strain  and  sex  not reported)  were   fed  (method  not
reported) single  doses  of 500-4400  mg/kg  bromochloromethane  In olive  oil
(Svlrbely et al.,  1947).  The  LD™  (6-day observation)  was   ~4300  mg/kg.
Signs showing dose-related CNS  depression were  observed  at >500 mg/kg,  but
pathological  examinations  were  not conducted  and the  lowest dose  producing
death was  not  reported.   In  a  related  study,  unspecified numbers of  Swiss
mice  (sex  not  reported)  were  administered  single  gavage  doses of 0,  500,
3000  or  4500 mg/kg bromochloromethane  1n  olive oil (Hlghman et al.,  1948).
Hlstologlcal  examinations  conducted   <96  hours  after treatment  showed  no
significant changes at 500 mg/kg.
    Effects  occurring at >3000 mg/kg  Included  death,  pronounced  hepatic
hlstopathology  and  other  pathological  changes  similar  to  those  resulting
from  acute   Inhalation  exposure.   Mice  killed  24  hours  after the  Initial
0316d
-20-
05/17/90

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exposure  had  severe effects,  which Included  focal  subcapsular necrosis  In
the liver  (12/50),  hydropic  degeneration  In the liver  (5/50) and  hemoglobin
casts 1n a few renal tubules  (8/32).   These  effects  were generally absent  or
slight In mice surviving >48 hours,
    Hlghman et al.  (1948) also  treated a group of  -32 Swiss mice  (sex not
reported) with single gavage doses  of  3000  mg/kg bromochloromethane In  olive
oil on  1-10  consecutive  days.   Several  mice  were  sacrificed after each  of
the 10 doses.  Hlstologlcal examination of mice that  died or  were  sacrificed
showed fatty  degeneration of the  liver,  kidney  and sometimes  heart.   Other
hepatic   effects   Included   subcapsular   necrosis    (23/32  mice),   hydropic
degeneration  (8/32  mice)  and an  Increased  number  of  mononuclear  peMportal
cells (8/32 mice).   Effects were  most  severe  24-48 hours after the Initial
dose and  became  slight  after  80 hours.  Opacity of  the eyes  was observed  In
5/19 mice surviving <3 days.
    Occluded  dermal  application   of  bromochloromethane  (5000   mg/kg)   to
clipped skin of  five  rabbits  resulted  1n burns and  denaturatlon of the skin
with  four  surviving after  24  hours (Torkelson et  al.,  1960).  Application
without occlusion caused only slight defattlng.
6.1.2.   SUBCHRONIC.
    6.1.2.1.    INHALATION EXPOSURE  — Groups of  20  male  and  20 female rats
were exposed  to  nominal  concentrations of 0,  500 or  1000 ppm bromochlorome-
thane  (490  ppm  [2593  mg/m3]   or  1010  ppm  [5345  mg/m3]  actual  average
concentrations)  7  hours/day for  79-82 exposures  In  114 days  (Torkelson  et
al.,  1960).   These  concentration  correspond   to   0,   166.97-173.31  and
344.18-357.25 mg/kg/day assuming  a body  weight of 0.35 kg, a breathing rate
of  0.223  mVday and  a  50%  absorption  of the  Inhaled  dose.  Because  no
effects were observed  In  male rats at  166.97-173.31  mg/kg/day,  a  group of  10
0316d
-22-
05/17/90

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female  rats  were  exposed  to  nominal  concentrations   of  0  or   400   ppm
bromochloromethane  (370  ppm  [1958 mg/m3]  actual  average  concentration)  7
hours/  day  for   135  exppsures  In 195  days  {4.85 days/week).   This  dose
corresponds  to  125.96 mg/kg/day  assuming  a  body weight of  0.35  kg,  a
breathing  rate  of 0.223 mVday and a  50% absorption of  the  Inhaled  dose.
The  strain of rats  was  not  reported.   Body weight gain  and  survival  were
evaluated  throughout  treatment  and pathological  examinations  were  conducted
at  termination.   The  pathological evaluation  Included  gross  examinations,
organ weight determinations (lungs, heart,  liver,  kidney, spleen  and testes)
and  hlstologlcal  examinations  (organs  that  were weighed,   pancreas   and
adrenals}.
    Hematologlcal examinations  of  10 females  exposed  to 0 or  344.18-357.25
mg/kg/day and blood bromide and blood nitrogen  (urea nitrogen  and nonproteln,
nitrogen)  determinations of  three rats/sex  from each  treatment  and control
group were also  conducted at  termination.   Effects attributed  to  treatment
Included Increased relative liver  weights  In  females at  125.96 mg/kg/day and
both  sexes  at >166.97-173.31   mg/kg/day,  liver  hlstopathology  In  females  at
166.97-173.31  mg/kg/day  (slight bile  duct epithelial  proliferation,  slight
portal  flbrosls,  occasional  vacuollzatlon)  and  both sexes at 344.18-357.25
mg/kg/day  (effects   similar   to  those   at   166.97-173.31  mg/kg/day,  cloudy
swelling  and  vacuollzatlon  of hepatocytes)  and  Increased relative  kidney
weights 1n both  sexes  at 344.18-357.25  mg/kg/day.   Blood bromide levels  were
elevated  In  both sexes at all  exposure concentrations,  but  effects typical
of  bromlsm  (apathy,  obesity,  Inactivity)  were  not  observed.   Terminal
bromide  Ion  levels  were 44-73  mg/da at 125.96 mg/kg/day and  as  high  as 122
mg/di at the higher  concentrations.
0316d                               -23-                             05/17/90

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    Torkelson  et  al.   (1960)   also  exposed  10   guinea   pigs   {strain  not
reported) of  each sex  to 0,  490  or 1010  ppm (2593 or  5345 mg/m3}  bromo-
chloromethane  7  hours/day,  5  days/week  for  79-82  exposures 1n  114 days.
These  doses  correspond   to  0,  124.79-129.53  and  257.23-267.00 mg/kg/day
assuming a  body weight  of 0.84 kg,  a breathing  rate  of 0.4 mVday and  a
50% absorption  of  the  Inhaled dose.   Evaluations  of body weight, survival,
pathology,   blood  bromide and  blood nitrogen  were conducted as  1n   the rat
study.  Hematologlcal examinations were conducted  on  three females from  each
group.   Treatment-related  effects   Included  decreased body  weights   In  both
sexes at >124.79-129.53  mg/kg/day, Increased  relative  liver weight   In  both
sexes at >124.79-129.53 mg/kg/day,  Increased relative kidney  weight  In males
at >124.79-129.53  mg/kg/day,  an  Increased number  of  circulating  neutrophlls
1n  females  at  >124.79-129.53  mg/kg/day  and  testlcular  effects  at   344.18-.
357.25 mg/kg/day (Section 6.5.).  Blood bromide levels were  elevated  1n  both
sexes at both exposure levels.
    Torkelson  et  al.   (1960)   also  exposed  10   female   mice   (strain  not
reported) to  0,  490 or  1010 ppm  (2593 or  5345 mg/m3) bromochloromethane  7
hours/day,   5  days/week   for  79-82  exposures  In  114   days.    These  dose
correspond   to  0,  340.67-353.59 and  702.22-728.88  mg/kg/day  assuming a  body
weight  of  0.03 kg, a  breathing rate  of  0.039 mVday  and a 50%  absorption
of  the  Inhaled dose.   Evaluations of  body weight,  survival and pathology
were  conducted as  In  the  rat  study.   Blood  bromide  and  blood  nitrogen
determinations   and   hematologlcal   examinations   were   not    performed.
Significantly  decreased   body  weight  and   slgnlflcanty  Increased  relative
liver and kidney weights  occurred In both  groups of treated mice.
    Torkelson  et  al.  (1960) also  exposed  two  rabbits (strain not reported)
of  each sex to 0, 490  or 1010 ppm (2593 or  5345  mg/m3)  bromochloromethane
0316d
-24-
05/17/90

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7  hours/day,  5  days/week  for  79-82  exposures  1n  114 days.   These  dose
correspond  to  0, 137.93-143.16  and  284.32-295.09 mg/kg/day assuming  a  body
weight of  3.8  kg, a breathing rate of  2  mVday and a 50%  absorption  of  the
Inhaled  dose.    Evaluations   of  body  weight,  survival  and  pathology  were
conducted  as  1n the  rat  study.   Blood  bromide  and  blood  nitrogen  were
determined  In  all treated and control  rabbits  except one  treated  female  In
the  137.93-143.16  mg/kg/day   group.    Hematologlcal   examinations  were  not
performed.   The hlstologlcal   examinations  showed testlcular alterations  In
one of  the males exposed to  284.32-295.09  mg/kg/day  (Section 6.5.}.   Blood
bromide  levels  were elevated  1n both  sexes  at both  exposure levels.   Both
sexes  appeared  to  have   elevated  liver weights,  but the  small  numbers  of
rabbits  Involved  precluded  definitive  analysis.    Results  of   the  blood
nitrogen determinations were not  reported.
    Torkelson et al. (1960) also exposed one  male and one  female  dog (strain
not reported)  to 0  or 370  ppm (1958 mg/m3)  bromochloromethane 7  hours/day,
5 days/week  for  135  exposures In 195 days.   These  doses correspond  to 0 and
66.93 mg/kg/day  assuming  a  body weight of  12.7 kg, a breathing rate  of  4.3
mVday  and  a   50%  absorption of  the  Inhaled  dose.   Evaluations  of  body
weight,  survival,   blood  bromide,   blood   nitrogen  and   hematology  were
conducted  as   1n  the  rat   study.     Pathological   examinations   were   not
performed.  The only effect  reported  was elevated blood bromide levels.
    Groups  of  50 male and  50 female  albino  rats  (descendants of  germ-free
Wlstar  rats)  were  exposed  to  nominal  concentrations  of  500 or  1000  ppm
bromochloromethane 6 hours/day,  5  days/week  for 6 months for a total  of 124
exposures  (MacEwen  et  al.,  1966).   Actual  measured  concentrations  averaged
515  and   1010   ppm  (2725  and  5345   mg/m3},   respectively.   These  doses
correspond to 0,  149.51 and 293.26 mg/kg/day  assuming an average  body weight


0316d                               -25-                             05/17/90

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of 0.35  kg,  a  breathing  rate of  0.223  mVday and  a  50% absorption of  the
Inhaled dose.  Fifty chamber air-exposed male  rats  served  as  controls.   Body
weight,  serum bromide  levels  and survival  were  evaluated  throughout  the
treatment period.   After  2 and  4  months  of exposure,  groups  of 10 rats  In
each  treatment  group and  five  control  rats were  subjected  to white  blood
cell  count  and clinical  chemistry determinations  and  sacrificed for  organ
weight  and   hlstologlcal   examinations.   The  remainder  of  the  rats   were
evaluated at  the  termination  of  treatment.   The clinical  tests  consisted  of
SGOT,  SGPT,   total  protein,  albumin  and  A/G ratio.   It  Is  not  specified
whether  organs  other  than  liver,  kidney  and  spleen  were  weighed  and
hlstologkally  examined.   The only  effect  attributable  to  treatment  was  a
significantly  (p<0.01)  dose-related  decreased  body weight gain  In male  rats
at  >149.51   mg/kg/day,  the  magnitude  of   which   Increased  with  increasing
duration of  exposure.   Blood bromide levels  were  Increased at  both concen-
trations throughout  the treatment  period.   The  Investigators  Indicated  that
similar  levels  of  blood   bromide  In humans  may produce  mild  sedation  and
suggested that  lethargy and  altered eating  habits may  have been responsible
for the reduction In body  weight gain.
    MacEwen  et al.  (1966)  also exposed four  male  and four  female beagle dogs
to 0,  515  or 1010  ppm  (2725 or 5345 mg/m3) bromochloromethane  6  hours/day,
5 days/week  for  6 months  for  a  total of 124  exposures.   These  doses corre-
spond  to  0,  79.45  and  155.84 mg/kg/day assuming  an average  body weight  of
12.7  kg,  a   breathing  rate  of 4.3 mVday   and  a  50%  absorption  of  the
Inhaled dose.  Toxlclty was  evaluated as 1n the rat study with  the  addition
of other clinical  chemistry  tests.  Evaluations  were performed  on groups  of
two  treated  and  one control  dog after  2 and  4  months and on  the  remaining
0316d
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animals at  termination  of treatment.  The  only  effect attributed to  treat-
ment  was  Increased  serum bromide levels  at  both concentrations  throughout
the treatment period.
    Twenty male  rats  (strain not reported) were  exposed to 1000  ppm  bromo-
chloromethane (nominal  concentration)  7  hours/day.  5 days/week for 14 weeks
(Svlrbely et al., 1947).  The measured concentration was  generally 11% lower
than  the  calculated value  (I.e.,  890  ppm   or  4710  mg/m3).   This  dose
corresponds to 299.20 mg/kg/day  assuming  an average body weight  of 0.35  kg,
a  breathing  rate  of  0.223  mVday   and  a  50%  absorption  of  the   Inhaled
dose.  A  control  group  appears  to have  been  used, but  specific  Information
was not  reported.  Weight gain and  survival throughout  treatment, histology
after  67  exposures  (19  rats)  and   bromide  levels  In  the  blood and brain
Immediately after  the  last  exposure were  evaluated.   It  Is  not Indicated
whether  tissues  other  than  liver and  spleen  were hlstologlcally examined.
Effects  consisted  of a  slight  Increase of  hemoslderln In  the   spleen  and
Increased concentrations of bromide  In the blood  and brain.
    Svlrbely et  al.  (1947)  also exposed three male  rabbits and  two  female
dogs  (strains not reported)  to 1000  ppm  bromochloromethane  (measured concen-
tration "890  ppm [4710 mg/m3])  7 hours/day,  5 days/week for  14  weeks.   In
rabbits this  dose  corresponds  to 247.16  mg/kg/day  assuming an average body
weight of  3.8 kg,  a  breathing rate  of 2  mVday  and a 50% absorption  of  the
Inhaled dose.  In dogs  this  dose corresponds to 158.99  mg/kg/day  assuming an
average body  weight  of 12.7 kg, a  breathing  rate of  4.3  mVday and a  50%
absorption of the  Inhaled dose.   Toxlclty was  evaluated  as  1n  the rat study
with  the addition of hematologlcal examinations In  both  species at "regular"
Intervals, liver  function evaluation (bromsulfaleln excretion) and  urlnaly-
sls  In  (Togs  at  "regular" Intervals  and  blood  Inorganic bromide  determina-
tions  1n  dogs  throughout the  treatment  period.   Effects   consisting of a

0316d                               -27-                             05/17/90

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slight Increase of  hemoslderln  1n  the spleen and kidneys and  an  Increase  In
fat  1n  the  kidneys occurred  In  the  dogs.  Inorganic bromide  accumulated  In
the  blood  of  the  dogs  throughout  treatment  (terminal  concentrations  were
-300-360 mg/dl).
    Hlghman et al.  (1948) exposed  100  Strain A  mice  (sex not reported,  age 2
months) and 45 C3H  mice  (sex  not reported,  age  3-7  months)  to 1000 ppm  (5292
mg/m3)  bromochloromethane.   Use  of  control   groups   was   not   Indicated.
Exposures were  administered 5 times/week  with  occasional long rest  periods
of  unspecified  frequency  and   duration  when  necessary,  as  Indicated  by
mortality  and  abnormal  general  condition.    Calculation   of   a  dose  1n
mg/kg/day  Is  uncertain  given   these  experimental   conditions.    Surviving
Strain A mice each  received a total  of 64 exposures  of  3-7  hours  In a period
of ~5  months  (approximately 143.97-335.93 mg/kg/day corresponding  to 3  or  7
hour  dosing  schedule  and  assuming  an average body weight  of  0.03 kg,  a
breathing  rate  of  0.039  mVday  and  a 50% absorption of the Inhaled  dose;
surviving C3H mice each received a  total  of  49 exposures of  3-7  hours  In  a
period of 4 months  (approximately  150.43-351 mg/kg/day corresponding  to  3  or
7  hour  dosing schedule  and assuming  an  average body weight  of   0.03  kg,  a
breathing  rate  of  0.039  mVday  and a 50%  absorption of the  Inhaled dose).
Most of  the  mice  died at unspecified, Irregular  Intervals  during treatment,
and  some  died   or  were   sacrificed  at  unspecified   Intervals  following
treatment.   A  total  of  21 mice  (one Strain  A  and  20  C_H)  survived  until
terminal  sacrifice at 13-16  months  of age.  Hlstologlcal  examinations  were
conducted  on  mice  that  were  sacrificed   and  some (number  unspecified)  that
died.   The mice  that  died during  exposure  generally  showed slight  fatty
changes  In  the  liver and  kidneys.   Extensive  tubular necrosis of the  Inner
zone of  the  renal cortex was observed 1n  two strain  A mice that  died during
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the  fourth dally  exposure.   Several  other  mice  that  died  during  exposure
showed coagulation  or  karyorrhectlc  necrosis of a  few  Isolated  liver  cells.
Treatment-related effects were  not  observed  1n the mice  that survived until
terminal sacrifice.
    6.1.2.2.   ORAL  EXPOSURE -- Pertinent  data  regarding  subchronlc  oral
exposure of humans  or  animals to bromochloromethane were  not located  1n the
available  literature cited In Appendix A.
6.1.3.   Chronic
    6.1.3.1.   INHALATION  EXPOSURE  —  Pertinent  data  regarding  the  chronic
Inhalation  exposure of  humans  or   animals  to  bromochloromethane were  not
located In the available literature cited 1n  Appendix A.
    6.1.3.2.   Oral  Exposure  —  Pertinent  data  regarding  the subchronlc  or
chronic oral  exposure  of  humans or animals  to bromochloromethane were  not
located In the available literature cited 1n  Appendix A.
6.2.   CARCINOGENICITY
    Pertinent  data   regarding  the carclnogenldty  of  bromochloromethane  to
humans or  animals  following  exposure by Inhalation, oral  or  other routes  of
exposure were not located In the available literature cited 1n Appendix A.
6.3.   6ENOTOXICITY
    Data  from genotoxlclty  tests  with  bromochloromethane are  presented  In
Table  6-2.   Consistently  positive  results   were  observed  In  the  reverse
mutation  test  In Salmonella  typhlmuMum {Simmon  et  a!.,  1977;  Strobel  and
Grummt, 1987;  Osterman-Golkar et al.,  1983).   Metabolic  activation was  not
required but  Increased the response  In  TA98 and  TA100  {Strobel and  Grummt,
1987).  Positive results  were  also  observed  In   the  reverse mutation  and
lambda prophage  Induction tests  In  Escherlchla  col 1 (Osterman-Golkar  et al.,
1983).  Negative results were observed In the mltotlc  recombination  test  1n


0316d                               -29-                             08/20/90

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0316d
-30-
08/20/90

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Saccharomyces  cerevlslae   (Simmon,   1976).    In   the   only   mammalian   test
located,  bromochloromethane  Induced  SCEs  and  chromosomal  aberrations  1n
Chinese hamster FAF cells (Strobel and Grummt,  1987).
6.4.   DEVELOPMENTAL TOXICITY
    Pertinent  data  regarding  the   developmental  toxldty  of  bromochloro-
methane were not located 1n the available literature  dted 1n Appendix A.
6.5.   OTHER REPRODUCTIVE EFFECTS
    Torkelson  et  al.  (1960)  exposed groups of  10 male guinea  pigs  (strain
not  reported)  to   0,  490  or  1010  ppm  bromochloromethane   7  hours/day,  5
days/week  for  79-82  exposures  1n 114  days (see  Section 6.1.1.1.).   These
dose correspond  to 0, 124.79-129.53  and 257.23-267.00  mg/kg/day  assuming  an
average  body  weight  of  0.84 kg, a  breathing  rate of  0.4  mVday and  a  50%
absorption  of  the  Ihnaled  dose.   H1stolog1cal  examination  of the  testes
showed  decreased  spermatogenesls  In  the  tubules  and  flbrosls  1n  numerous
tubules  with   only  germinal  epithelium  remaining  1n  the other tubules  at
257.23-267.00  mg/kg/day.    The   average   testes-to-body  weight  ratio  was
decreased at  257.23-267.00  mg/kg/day  (0.38 vs.  0.46  at 0 and  124.79-129.53
mg/kg/day),  but statistical  significance  was  not  reported.   Reproductive
function was not evaluated.
    Torkelson  et al.  (1960) also exposed groups of two male rabbits  (strain
not  reported)  to  0,  490  or  1010  ppm  (2593 or   5345 mg/m3)  bromochloro-
methane  7  hours/day,  5  days/week  for  79-82 exposures   1n 114 days  (see
Section   6.1.1.1.).    These  doses   correspond   to  0,  137.93-143.16  and
284.32-295.09  mg/kg/day  assuming an average  body  weight  of  3.8  kg,  a
breathing  rate  of  2 mVday  and a  50%  absorption  of  the Ihnaled  dose.
H1stolog1cal examination  showed  testlcular tubule changes,  characterized  by
decreased  spermatogenesls  with  replacement  flbrosls  1n  one of  the  rabbits


0316d                               -31-                             08/20/90

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exposed  to  284.32-295.09 mg/kg/day.   The  testlcular  histology of  the  other
rabbit was  normal.   The  average testes-to-body weight ratio  for  the rats 1n
the 284.32-295.09 mg/kg/day group  (0.08) was  lower  than  the ratios  for  the 0
and   137.93-143.16   mg/kg/day   groups   (0.16   and   0.17,   respectively).
Reproductive function was not evaluated.
6.6.   SUMMARY
    Inhalation  LC   s for  m)Ce   for  7-hour exposures  ranged  from  2268-2995
ppm  (Svlrbely  et  al., 1947;  Hlghman  et al.,  1948) and exposure  to  5000  ppm
(26,460  mg/m3) for   7  hours was  not  lethal  for  rats  (Torkelson  et  al.,
1960).  Rats survived a  single  oral  dose  of 5 g/kg, and all rats  died within
24  hours  after a  dose of 7 g/kg (Torkelson et al., 1960).   An oral  LDcn of
                                                                        DU
-4300  mg/kg was  determined  for  mice  (Svlrbely  et al.,  1947).   Signs  and
                                                                             *
pathological effects  of  acute  Inhalation  and oral exposure  to  bromochloro-
methane are  similar;  principal  effects Include CNS depression and  degenera-
tion of the liver.
    Subchronlc  Inhalation  studies  of bromochloromethane have been  conducted
with  rats,  mice,  guinea pigs,  rabbits and  dogs  (Torkelson et  al.,  1960;
MacEwen et al., 1966; Svlrbely  et  al.,  1947;  Hlghman  et al., 1948).   Concen-
trations  ranged from 66.93  mg/kg/day  (dogs)  to  728.88  mg/kg/day  (mice);
exposures were usually  5-7 hours/day,  5  days/week ranging  from  14  weeks to
-6  months.    Generally,  minor  effects   such as  decreased  body   weight,
Increased relative  liver and kidney  weight and reversible  liver and  kidney
hlstologlcal alterations occurred  at  concentrations >500 ppm In most species
evaluated for  these  endpolnts.   Torkelson et al.  (1960) found that  relative
liver  weight  was  Increased  1n  rats  at  concentrations  of  125.96 mg/kg/day.
With hlstologlcal  effects  occurring at 166.97-173.31 mg/kg/day,  exposure to
1000 ppm  (143.97-335.93  mg/kg/day) caused  death  and  marked  liver  Injury 1n
0316d
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mice (Hlghman et  al.,  1948);  however, exposure conditions were  not  reported
adequately  and  calculation  of   this  dose  to mg/kg/day can  not  be  done
accurately without  further Information.   Information  regarding  the  chronic
Inhalation toxldty,  subchronlc  or  chronic  oral  toxldty or  teratogenldty
of  bromochloromethane  were  not  located.   Decreased  spermatogenesls  and
flbrosls  occurred  In the  tubules  of the  testes  of guinea pigs  and  rabbits
that  were   subchronlcally   exposed   to  344.18-357.25   and   257.23-267.00
mg/kg/day  respectively,  to  bromochloromethane by  Inhalation  {Torkelson  et
al., 1960).  The functional significance of these  effects was  not evaluated.
    The   carclnogenldty   of   bromochloromethane  has   not been  evaluated.
Bromochloromethane was  mutagenlc  In  Salmonella  typhlmurlum and  Escherlchla
CQ_11_ bacteria  (Simmon et  al.,  1977; Osterman-Golkar  et al.,  1983;  Strobe!
and  Grummt,  1987)  and   Induced  SCE  and chromosome aberrations  1n  Chinese
hamster cells In vitro (Strobe! and Grummt, 1987).
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                     7.   EXISTING  GUIDELINES AND  STANDARDS
7.1.   HUMAN
    ACGIH  (1989)  recommends  a  TLV-TWA  of  200  ppm   (1058  mg/m3)  and  a
TLV-STEL of  250  ppm (1320 mg/m3)  for occupational exposure  to  bromochloro-
methane, but  deletion  of the  STEL  1s proposed.    The  recommendation  for the
TLV-TWA  Is  based  primarily  on the  subchronlc  animal  studies  evaluated  1n
Section  6.1.1.1.  (ACGIH, 1986).   OSHA (1989) has  promulgated a PEL  of 200
ppm (-1050 mg/ma) for occupational exposure to bromochloromethane.
    Based on  Inhalation toxlclty  data,  U.S.  EPA  (1988) has  derived  1-day,
10-day,  longer-term  (child)  and longer-term (adult) drinking  water  HAs of 50
mg/i,   50   mg/fc,   13.1   mg/a   and   45.7  mg/9.,    respectively,   for   bromo-
chloromethane.  U.S.  EPA (1988)  also calculated  a  provisional  DHEL  of 4.6
mg/n for bromochloromethane.
7.2.   AQUATIC
    Guidelines  and  standards  for  the  protection  of  aquatic  life  from
exposure to   bromochloromethane were  not  located 1n  the available literature
cited In Appendix A.
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                             8.  RISK ASSESSMENT
8.1.   CARCINOGENICITY
8.1.1.   Inhalation.   Pertinent  data   regarding   the   cardnogenldty  of
bromochloromethane  to humans  or animals  by  Inhalation  exposure  were not
located 1n the available literature dted  In Appendix A.  Bromochloromethane
has   not   been   scheduled   for  cardnogenldty  testing   by  the  National
Toxicology Program (NTP,  1989).
8.1.2.   Oral.   Pertinent   data  regarding  the cardnogenldty  of  bromo-
chloromethane to humans or  animals  by  oral exposure were not located 1n the
available literature dted  In Appendix  A.
8.1.3.   Other  Routes.   Pertinent  data  regarding  the  cardnogenldty  of
bromochloromethane to humans or animals by other routes of exposure were not
located In the available  literature  dted  In  Appendix A.
8.1.4.   Weight of Evidence.   Pertinent cardnogenldty data  for  humans and
animals were  not  located  In  the available  literature dted  1n  Appendix A;
therefore, bromochloromethane  1s  categorized  1n U.S. EPA we1ght-of-evidence
Group  0  (Not Classifiable  as  to Human Cardnogenldty) using  the  U.S. EPA
(1986c) classification scheme.
8.1.5.   Quantitative  Risk   Estimates.    Derivation  of   a  cardnogendc
potency factor  for  bromochloromethane  Is  precluded by  the  lack  of  appro-
priate data.
8.2.   SYSTEMIC TOXICITY
8.2.1.   Acute Exposure.
    8.2.1.1.    INHALATION — Acute     Inhalation    lethality    data     for
bromochloromethane are  summarized  In  Table  6-1.   These data  suggest   that
mice  are  more susceptible  to bromochloromethane exposure  by  Inhalation  than
are rats.   Hallmarks of CNS  toxldty 1n mice and rats  Includes restlessness,


0316d                               -35-                             08/20/90

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muscular  twitching,  uncoordlnatedmovements,   labored  respiration,  narcosis
(mice), drowsiness  (rats) and  unconsciousness  (rats).   Hlghman et al.  (1948)
demonstrated  fatty  degeneration of  the liver  In  Swiss mice  after  a  single
expousre  >7  mg/i bromochloromethane  and  degeneration  of the  kidneys  after
a  single  exposure to >12 mg/i bromochloromethane.   Torkelson  et  al.  (1960)
demonstrated  that  liver  and  kidney  degeneration  1n  rats  occured after  a
single  7   hour  expousure  to  1500  ppm,  equivocal   results  at  800 ppm,  no
degeneration at 600 ppm bromochloromethane.
    8.2.1.2.   ORAL -- Torkelson  et  al.   (1960)  determines   that  a  7   g/kg
dose of bromochloromethane  was lethal to  all  rats  within 24 hours of  dosing
but  that   all  rats  survived  a dose  of  5  g/kg.   Svlrbely  et  al.  (1947)
determined a  6-day  L05Q to  be 4300 mg/kg 1n mice.  Signs of  CNS depression
were  observed at  doses >  500  mg/kg.   Hlghman  et al.  (1948)  demonstrated
effects In  mice  at  >  3000  mg/kg Including pronouned  hepatic  hlstopathology
and other acute pathological changes.   Mice killed  24  hours  after dosing had
severe   effects    Including   focal   subcapsular    necrosis   and   hydropic
degeneration  of   the  liver  and hemoglobin  casts  In  a  few  renal  tubules.
These effects were generally absent or slight In mice surviving >48 hours.
    Occluded  dermal  application of  5000  mg/kg bromochloromethane to  the
clipped  skin of  five  rabbits  resulted   In  burns  and  denaturatlon of  the
skin.  Application without occlusion only caused slight defattlng.
8.2.2.   Subchronlc  Exposure.
    8.2.2.1.   INHALATION -- Sufficient  data   are  available   for  derivation
of  a  subchronlc   Inhalation  RfD   for  bromochloromethane.    Inhalation  RfD
derivation  Involves  evaluating  the   quality   of   the  Inhalation  exposure-
response data, converting exposure  concentrations associated with effects In
0316d
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animals to  human  equivalent  concentrations  and  dividing these by uncertainty
factors and  modifying factors.   For gases  such  as  bromochloromethane,  which
produce systemic  effects and  reach steady  state  within the  dally  exposure
length, HECs  are  calculated  by adjusting the animal  exposure concentrations
to  equivalent  continuous  exposure concentrations  and  multiplying  by  the
ratio  of  the blood/gas  partition  coefficient  1n the experimental animal  to
that In humans.
    Evidence  for  rapid attainment  of  steady state  with  bromochloromethane  1s
provided  by  Gargas  and  Andersen   (1982),  who  found that  the  rapid  uptake
phase  In   rats was   completed  In  70-110  minutes   (see Section  5.1.).   A
blood/gas  partition  coefficient  for bromochloromethane  of  41.5  was  reported
for  rats  (see Section 5.2.),  but  not  for  humans.   Insufficient data  for  a,
blood/gas  partition  coefficient for bromochloromethane  was  found for  humans;
therefore, the ratio  of  the  animal  to  human blood/gas  partition  coefficients
Is assumed  to be  1.   Therefore,  HECs  (Human equivalent  concentrations)  for
extraresplratory  effects  from   bromochloromethane   are  Identical   to  the
adjusted animal exposure  concentration.
    Torkelson et  al.  (1960)  exposed 10 female  rats  (strain not  reported)  to
370  ppm  (1958 mg/m3) bromochloromethane 7 hours/day  for  135  exposures  1n
195 days, and groups of 20  rats/sex  (strain not reported)  to 490 ppm (2593
mg/m3) or  1010 ppm   (5345 mg/m3)  bromochloromethane 7 hours/day for  79-82
exposures   1n 114  days.   These  doses  correspond  to  125.96 mg/kg/day  (370
ppm);  166.97-173.31  mg/kg/day (490  ppm);  and  344.18-357.25  mg/kg/day  (1010
ppm) assuming an  average body weight  of  0.35 kg,  a breathing rate  of  0.233
mVday and   a 50%  absorption of   th  Inhaled  dose.   Effects attributed  to
treatment    Included   Increased   I1ver-to-body   weight   ratios   at   >125.96
mg/kg/day,   liver  hlstologlcal   alterations   (e.g.,   slight   flbrosls  and


0316d                               -37-                    ,         08/20/90

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vacuollzatlon)  In  females  at  166.97-173.31  mg/kg/day  and  both  sexes  at
344.18-357.25  mg/kg/day  and  Increased  kidney-to-body weight  ratio In  both
sexes  at  344.18-357.25   mg/kg/day.   Abnormal  hematology.  Increased  blood
nitrogen levels,  decreased  body  weight  gain or symptoms  of bromlsm were not
observed at  any of the  exposure  concentrations.   As the  Increased  relative
liver  weight  was  not  accompanied   by  hlstologlcal  alterations  or  other
effects  at  125.96 mg/kg/day,  this  concentration  represents  a  NOAEL  and
166.97-173.31  mg/kg/day  1s  the  lowest  LOAEL  (Recs.  #1  and 2, Appendix C).
Dogs  (I/sex)  were also  exposed  to 370  ppm (1958 mg/m3}  bromochloromethane
7  hours/day  for  135  exposures  In  195  days.   This  exposure corresponds  to
66.93 mg/kg/day assuming an average bodw weight of 12.7  kg,  a  breathing rate
of  4.3 mVday  and a  50%  absorption  of  the  Inhaled dose.   There were  no
effects  on  body   weight,  blood  nitrogen   or   hematology,  but  hlstologlcal
examinations  and   organ  weight  measurements  were  not  performed.   Although
66.93 mg/kg/day Is  a  NOEL In dogs (Rec. #7, Appendix C),  this  value  Is not
suitable for  quantitative  risk assess- ment  because of  the small  number  of
animals and lack of histology.
    Albino rats (50/sex/concentrat1on) and beagle dogs  (4/sex/concentratlon)
were  exposed  to 515  or  1010 ppm  {2725  or 5345 mg/ma)  bromochloromethane 6
hours/day  for  124  exposures  1n  6 months  (MacEwen  et  al.,  1966).   In  rats
these doses  corresponds  to  149.51 and  293.26  mg/kg/day assuming an  average
body  weight  of  0.35 kg,  a  breathing  rate  of  0.223 mVday  and  a  50%
absorption of  the  Inhaled  dose.   In  beagle  dogs these doses  correspond  to
79.45 and  155.84  mg/kg/day  respectively,  assuming an average body  weight  of
12.7  kg,   a  breathing  rate  of   4.3  mVday  and  a  50% absorption  of  the
Inhaled dose.  Decreased body weight  gain  In  male rats  at >149.51 mg/kg/day,
possibly from  lethargy associated  with  elevated blood bromide  concentration,
was  the  only effect  attributed  to treatment.  Hlstologlcal examinations  of
0316d
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the  liver  and  other   tissues,   organ   weight   measurements   and   clinical
chemistry evaluations  (Including  SCOT and SGPT) were unremarkable.   In  this
study,  149.51 mg/kg/day  Is considered a  LOAEL  associated with  reduced growth
rate In rats possibly from bromide-Induced lethargy (Rec. #8,  Appendix C).
    Twenty  male  rats  (Rec.  #10,  Appendix C),  two female  dogs  (Rec.  #12,
Appendix  C) and  three  male rabbits  (Rec.  #11,  Appendix  C)  (strains  not
reported) were  exposed  to 890  ppm (4710 mg/m3)  bromochloromethane  (nominal
concentration)   7  hours/day,  5  days/week  for  67  exposures   (-14  weeks)
(Svlrbely et al.,  1947).  In rats this  dose corresponds to  299.20 mg/kg/day
assuming  an average  body weight of  0.35  kg,   a  breathing  rate  of  0.223
mVday  and  a   SOX  absorption  of  the  Inhaled  dose.   In  dogs  this  dose
corresponds to 158.99  mg/kg/day  assuming an  average body weight  of  12.7 kg,
a breathing rate of  4.3 mVday  and  a  50% absorption  of  the  Inhaled  dose.
In  rabbits  this dose  corresponds to  247.16  mg/kg/day  assuming  an  average
bodw weight  of  3.8 kg,  a breathing rate of  2.0 mVday and a  50% absorption
of  the  Inhaled  dose.   Slightly  Increased hemoslderin  occurred In  the  rats
(spleen)  and  dogs  (spleen and  kidneys), and  Increased fat  occurred  In the
kidneys  of  dogs.   Other hlstologlcal  alterations such  as   liver  were  not
observed  and body  weight measurements (all species), liver  function evalua-
tion (dogs,  rabbits)  and urlnalysls  (dogs, rabbits) were  unremarkable.   The
247.16  mg/kg/day  concentration,  therefore,  1s  a  NOEL  1n  rabbits  and  the
299.20 mg/kg/day Is a LOAEL In rats and 158.99  mg/kg/day Is a LOAEL  In dogs.
    Guinea  pigs  (10/sex/concentratlon)  (Rec.  #3, Appendix C),  mice  (10/sex/
concentration)  (Rec. #4,  Appendix C)  and rabbits (2/sex/concentratlon)  (Rec.
#5.  Appendix  C) were  exposed to  0,  490  or  1010  ppm  (2593  or  5345  mg/m3)
bromochlormethane 7  hours/day for 79-82  exposures  In 114  days  (Torkelson  et
al., 1960).  In  guinea  pigs   these doses correspond to 0. 124.79-129.53 and
257.23-267.00 mg/kg/day  respectively,  assuming  an average   body weight  of

0316d                               -39-                              08/20/90

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0.84 kg,  a  breathing rae of 0.4 mVday  and  a  50% absorption of the  Inhaled
dose.  In mice these doses corresponds to 0, 340.67-353.59 and  702.22-728.88
mg/kg/day respectively, assuming an average body weight 0.03 kg, a breathing
rate of  0.039  mVday and a  50%  absorption  of  the Inhaled dose.  In  rabbits
these  dogs   corresponds   to  0,  137.93-143.16  and  284.32-295.09  mg/kg/day
respectively, assuming an average body weight of  3.8 kg,  a breathing  rate of
2  mVday and  a  50%  absorption of  the  Inhaled dose.   The  124.79-129.53
mg/kg/day concentration  Is a  LOAEL  In the guinea pigs and the  340.67-353.59
mg/kg/day concentration  Is  a LOAEL 1n mice, associated  with decreased body
weight,  Increased relative liver and  kidney weights and neutrophHla  (female
guinea pigs).  Adverse effects 1n rabbits were limited to  testlcular  lesions
at the 284.32-295.09 mg/kg/day level
    One  hundred  Strain  A  mice  and  45  C3H  mice (sexes  not  reported) were
exposed  for  3-7  hours/day to  1000 ppm  (5292  mg/m3)  bromochloromethane for
<64 exposures In 5 months  (<143.97-335.93 mg/kg/day assuming an average body
weight of 0.03 kg,  a  breathing rate of  0.039 mVday and a 50% absorption
of the  Inhaled  dose) and 49  exposures  In 4 months (150.43-351.00 mg/kg/day
assuming  an average  body weight  of  0.03  kg,  a  breathing rate  of 0.039
mVday and  a 50% absorption of  the  Inhaled dose), respectively (Hlghman et
al.,    1948).    The   exposures   were  administered   5   days/week   but  were
Interrupted   by  occasional  long  rest periods  (duration   and  frequency  not
reported) when  necessary,  as  Indicated  by  mortality or  abnormal   general
condition.  Host of the  mice (numbers not reported) died  during the exposure
period and  the mice  that died  generally had  slight  fatty  changes  In  the
liver  and  kidneys.   The exposure schedule  was  not reported  In sufficient
detail   to   permit   consideration   of  this  study  for   quantitative  risk
assessment.
0316d
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    Acute  toxldty  data Indicate  that  the critical  effects  of exposure  to
bromochloromethane   appear   to   be  CNS   Involvement  and   hepatotoxldty
(Rutsteln,  1963;  Svlrbely  et  al.t  1947;  Torkelson et  al.,  1960).   In  the
subchronlc  Inhalation studies, reduced rate of  body  weight  gain  and  elevated
liver weight  were the  first  effects reported  at  the  lower  concentrations.
In  the  absence of  histopathologlcal alteration or  biochemical evidence  of
organ  damage  or  Impaired  function,  elevated  liver   weight  alone  may  be
considered  a  nonadverse  effect.    Similarly,  a slight  reduction  1n  growth
with no evidence of  organic Injury  or compromised  function  may be  considered
nonadverse.   Several  studies,  however,  have  shown  that  bromide  1on  1s  a
consistent  metabolite   of   bromochloromethane  In  the  mammalian   species
studied, and  that blood levels of bromide Increase  In  a dose-related manner
In animals  exposed  by  Inhalation  (Svlrbely  et al., 1947;  Torkelson  et  al.,
1960; MacEwen  et  al.,  1966;  Gargas et al.,  1986a).   MacEwen et  al.  (1966)
postulated  that  the  reduced  body  weight  gain observed  1n rats  exposed  to
bromochloromethane may  have resulted from  lethargy  Induced  by elevated  blood
bromide  levels.    The  conservative  approach,  therefore,   Is  to  consider
reduced body weight  gain a  potentially adverse effect  of Inhalation  exposure
to bromochloromethane.
    Reduced  body  weight gain  was  reported  1n all  species  studied  (except
rabbits)  1n the  subchronlc  Inhalation  studies  reviewed herein.  The  NOAEL
for  this  effect  1n  rats was  the  125.96  mg/kg/daylevel  1n  the  195-day  study
(Rec. #1,  Appendix  C)  by Torkelson  et al. (1960).   Using  this  NOAEL and  an
uncertainty  factor   of  1000  (10   to  reflect  uncertainties associated  with
estimating a human equivalent  concentration from animal  exposure data,  10  to
reflect uncertlntles  associated  with extrapolation  from a subchronlc  study
of  chronic  toxldty  endpolnts,   and  10  to  protect  the  most   sensitive


0316d                               -41-                              08/20/90

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Individuals) a  chronic  RfD of 1.26E-02 mg/kg/day  Is  calculated.   Confidence
In  the  key study Is  low  because of  the  relatively  small number  of  animals
and  lack  of treated males at  the lowest  (NOAEL)  concentration.   Confidence
1n  the  data base and RfO  are low because  of  the lack of  developmental  and
reproductive  data  and  the  lack of  adequate  evaluation  of  the  effect  of
bromochloromethane  (elevated  blood bromide  levels)   on  CMS function,  which
could be the critical effect of exposure.
    Two previous  risk  assessments of bromochloromethane  have  been performed
by  the  U.S. EPA.   An RfD  was not calculated  1n a Health  and  Environmental
Effects Profile (U.S.  EPA,  1985) because  the  Torkelson  et  al.  (1960)  rat
study  was   considered  Inadequate.  It  did not  clearly  define  a  NOAEL  for
liver effects  and did not  test  males at the NOAEL concentration.  The same
NOAEL,  however,  was considered sufficient basis for  deriving  drinking  water
longer-term  HAs and  a  provisional  DWEL  for  bromochloromethane  (U.S.  EPA,
1988).
    8.2.2.2.   ORAL — Information  on   the   subchronlc  oral    toxldty   of
bromochloromethane  was  not located.   Acute exposure  data,  however,  Indicate
that the critical effects  of  both Inhalation and oral exposure are CNS  signs
and  hepatotoxldty.    In  addition,   the   critical   effects   of  subchronlc
Inhalation  exposure  to  bromochloromethane  are  reduced  body  weight  and
hepatotoxldty.   The  respiratory  tract does  not appear  to  be  the  target
organ  for  Inhalation exposure to bromochloromethane.  The data reviewed  In
Section  5.3.  suggest  that   metabolism  Involving  dehalogenatlon  would  be
expected  with  either   route  of  exposure.  Therefore,   1n  the  absence  of
subchronlc  oral  data,  1t   1s  appropriate  to use Inhalation toxldty  data  to
derive a subchronlc oral RfD for  bromochloromethane.
0316d
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08/20/90

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    As discussed  In  Section 8.2.2.1., a  NOAEL of 125.96 mg/kg/day  has  been
Identified  In  rats  exposed  to  bromochloromethane  for  7  hours/day   135
exposures In  195  days  (Torkelson et al., 1960)  (Rec.  #1, Appendix  C).   This
dose Is essentially the  same as  a  previously derived estimated absorbed  dose
of  130.5  mg/kg/day based  on  the  same NOAEL  used  to  calculate  longer-term
drinking water HAs  (U.S.  EPA,  1988).  Applying an uncertainty factor  of 100
(10  for  Interspedes   extrapolation  and   10  to  protect   most  sensitive
Individuals),  the  subchronlc   oral   RfD   for  bromo-  chloromethane   Is   1
mg/kg/day.  Confidence 1n  the  key  study Is  low  (see Section 8.2.1.1.).   Low
confidence  In  the data  base  and  RfD  are  due to  the lack   of  oral  toxlclty
data.
8.2.3.   Chronic Exposure.
    8.2.3.1.   INHALATION — Chronic    Inhalation    studies    of     bromo-
chloromethane  have  not  been   conducted.   It  1s  appropriate,  therefore,  to
derive a  chronic  .Inhalation RfD for bromochloromethane based  on subchronlc
data.  Using the  subchronlc Inhalation RfD  of  1.26E-1  (see  Section  8.2.1.1.)
and an additional uncertainty  factor  of  10  to  extrapolate from subchronlc  to
chronic exposure, the  chronic  Inhalation RfD  1s  1.26E-2.  Confidence  In the
RfD  1s  low  because of  the lack of  chronic  data, and  because  confidence  1n
the subchronlc Inhalation RfD  Is low.
    8.2.3.2.   ORAL -- Data    on    the    chronic    oral     toxlclty    of
bromochloromethane were  not  located.   It 1s appropriate  to  derive  a chronic
oral RfD  for  bromochloromethane  based on the  subchronlc  oral  RfD because  of
lack  of  chronic  data.   Using  the  subchronlc  oral  RfD  of   1  mg/kg/day  {see
Section 8.2.2.1.) and  an additional uncertainty factor of 10 to extrapolate
from subchronlc to chronic  exposure,  the chronic  oral  RfD 1s 0.1 mg/kg/day.
0316d                               -43-                             08/20/90

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This  RfD  1s  the same as a  previously  derived  RfD of 0.13 mg/kg/day used  to
calculate  a  provisional  DUEL  for  lifetime   exposure  (U.S.   EPA,   1988).
Confidence 1n the key study  1s  low  (see  Section  8.2.1.1.),  and  confidence  1n
the data base and RfD are low because of  the lack of oral  toxldty  data.
0316d
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                           9.   REPORTABLE  QUANTITIES
9.1.   BASED ON SYSTEMIC TOXICITY
    The  toxldty  of  bromoch 1 oromethane Is discussed In Chapter 6,  and  Inha-
lation data suitable  for RQ derivation are  summarized  In  Table 9-1.  Chronic
Inhalation data and oral data useful for RQ derivation  are not available.
    As  shown  1n  Table 9-1,  subchronlc  Inhalation  exposure  to  bromochloro-
methane  produced  decreased body  weight  gain  1n  rats,  mice and  guinea  pigs
(MacEwen  et  al.,  1966;  Torkelson  et  al.,   1960),  Increased  relative  organ
weights  (liver  and/or kidneys) In  rats,  mice and guinea pigs  (Torkelson  et
al., 1960), hlstologkal alterations In the  liver  In rats  {Torkelson  et  al.,
1960) and  kidneys  In  dogs   (Svlrbely et al.,  1947),  Increased  hemosldeMn  1n
the spleen of  rats (Svlrbely et al.,  1947)  and  testlcular  effects  In guinea
pigs and  rabbits  (Torkelson et al.,  1960).   Death In  mice  (Hlghman  et  al.,
1948} was  not   Included  because the exposure  protocol  was  not presented  In
sufficient detail from which to estimate a transformed  animal dose.
    Derivations of  CSs for  bromochloromethane,  based  on  the  lowest  equiva-
lent human dose associated with  each  effect In Table  9-1,  are presented  1n
Table 9-2.   Changes  1n  body  and  organ  weights  are assigned  an RV  of  4.
                                                                     c
The  most  appropriate RV   for  the  kidney   hlstologlcal  alterations  Is   5
                         c
because  the  effects   were  slight  and  reversible.   Lesions  1n  the  liver
Included flbrosls, which may  not  be reversible; liver  lesions  were assigned
an  RV   of  6.   Increased  hemoslderln   warrants  an  RV   of  1  since  hematln
     e                                                e
formation  Is most appropriately  viewed  as   a  biochemical  effect.  The  most
appropriate RV   for  the  testlcular alterations  Is  6 because It  cannot  be
determined If  the effects  were sufficient   to  Impair  fuctlon.  Five of the
six CSs  correspond  to an  RQ  of  1000.   The  highest  CS  (12.22)  for  liver
lesions   In  rats (Torkelson  et al., 1960)  1s used as the  basis  for the  RQ
0316d                               -45-                             08/20/90

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-48-
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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  MacEwen
et al.  (1966) and Svlrbely et al.  (1947).
9.2.   BASED ON CARCINOGENICITY
    Pertinent  data  regarding  the carclnogenldty  of bromochloromethane  to
humans  or  animals  by Inhalation,  oral  or other routes of  exposure were not
located  1n  the  available  literature cited  1n Appendix  A.  Because of  the
lack  of  carclnogenlclty data,  bromochloromethane Is categorized  1n U.S.  EPA
welght-of-evldence Group  D  (Not  Classifiable  as to  Human Carclnogenlclty).
Chemicals  In  EPA  Group  D  are  not  ranked  for  cancer  hazard  or assigned
cancer-based RQs.
0316d                               -49-                             08/20/90

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                                  TABLE 9-3
                              Bromochloromethane
           Minimum  Effective Dose  (MED) and Reportable Quantity (RQ)
Route:
Species/Sex:
Dose*:
Duration:
Effect:
RVd:
RVe:
CS:
RQ:
Reference:
Inhalation
rat/female
203.65
114 days (79-82 exposures,  7 hours/day)
hlstologlcal lesions 1n Hver
2.04
6
12.22
1000
Torkelson et a!., 1960
'Equivalent human dose
031 fed
            -50-
08/20/90

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                                10.   REFERENCES

ACGIH  (American  Conference  of Governmental  Industrial  Hyg1en1sts).   1986.
Documentation of the Threshold  Limit  Values  and  Biological  Exposure  Indices,
5th ed.  Cincinnati, OH.  p. 125-126.

ACGIH  {American  Conference  of Governmental  Industrial  Hyglenlsts),   1989.
Threshold  Limit  Values  and  Biological  Exposure  Indices  for  1989-1990.
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Allgeler,  G.D.,  R.L.  Mulllns,  Jr.,  O.A.  Wilding,  J.S. Zogorskl  and  S.A.
Hubbs.   1980.   TMhalomethane  levels  at  selected   water   utilities   In
Kentucky, USA.  Environ. Sc1. Res.  16: 473-490.

Amoore, 3.E. and E.  Hautala.   1983.   Odor  as an  aid to chemical safety: Odor
thresholds  compared with  threshold  limit  values  and  volatilities  for  214
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272-289.

Andersen, H.E.,  M.L. Gargas, R.A.  Jones  and  L.  Jenkins,  Jr.  1980.   Determi-
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Arguello, M.D.,  C.O. Chrlswell, J.S.  Fritz et al.   1979.  Trlhalomethanes  In
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0316d                               -51-                             08/20/90

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Atkinson, R.   1987.  A  structure-activity  relationship  for  the estimation of
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Class,  T.H.  and  K. Ballschmlter.   1988.    Chemistry  of  organic  traces  In
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Crockett, P.M.,  B. K1l1an,  K.S.  Crump  and  R.B.  Howe.  1985.   Descriptive
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Dore,  M., N.  Herlet,  J.   De  Laat  and  J.  Golchon,   1982.    Reactivity  of
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0316d
-52-
08/20/90

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Durkln,  P.  and  W.  Meylan.   1989.   Users Guide  for D2PLOT:  A Program  for
Dose/Duration  Graphs  Version 2.00.   Prepared  by Chemical  Hazard  Assessment
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Elsenrelch,  S.J.,  B.B.  Looney  and  O.J.  Thornton.   1981.  Airborne  organic
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Gargas.  M.L.,  H.J.  Clewell,  II and M.E. Andersen.   1986a.   Metabolism  of
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Gargas, H.L.,  M.E.  Andersen, H.J.  Clewell and G. Harry.   1986b.   A  physio-
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Gould, J.P.,  R.E.  Ramsey, M. Glabbal  and F.G.  Pohland.   1983.  Chapter  36.
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525-539.
0316d                               -53-                             08/20/90

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Hawley,  G.6.   1981.    The  Condensed   Chemical  Dictionary,  10th  ed.   Van
Nostrand Relnhold Co., New York.  p. 151.

Hlatt,  H.H.    1983.   Determination  of  volatile  organic  compounds  1n  fish
samples by vacuum distillation and fused silica capillary gas chromatography-
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Kaiser,  K.L.E.,   M.E.  Comba  and  H.  Huneault.   1983.   Volatile  halocarbon
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Kublc,  V.L., H.W.  Anders,  R.R.  Engel,  C.K.  Barlow and  U.S.  Caughey.   1974.
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Kuney,  J.H.    1988.    Chemcyclopedla   1989.    Volume  7.   American  Chemical
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Lareglna,  3..  J.W.  BozzelH,  R.  Markov  and  S.  Glantl.   1986.   Volatile
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0316d
-54-
08/20/90

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Lucas,  S.V.   1984.   GC/MS  analysis  of  organlcs  1n  drinking water  concen-
trates  and  advanced  waste treatment concentrates: Vol.  1.   Analysis  results
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Eff. Res. Lab., Columbus, OH.  p. 144, 174, 255.

Lyman,  H.J.    1982.   Adsorption  coefficient   or  soils  and   sediments.   It±:
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Mabey,  W.  and  T.  Mill.   1978.  Critical  review of  hydrolysis of  organic
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0316d                               -55-                             08/20/90

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NAS  (National  Academy of Science).   1980.   Drinking Water and  Health.   Vol
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Osterman-Golkar, S.,  S. Hussaln,  S. Walles,  B.  Anderstam and  K.  Slgvardsson.
1983.  Chemical  reactivity and mutagenldty of  some  dlhalomethanes.   Chem.
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Rasmussen, R.A. and M.A.K.  Khali!.  1984.   Gaseous  bromine In the Arctic and
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Rlddlck,  J.A., W.B. Bunger  and  T.K. Sakano.   1986.   Organic solvents:  Physi-
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Simmon,  V.F.   1976.   In  Vitro H1crob1olog1cal  Hutagenlclty  Studies of  Dow
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0316d
-56-
08/20/90

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Simmon, V.F.,  K.  Kauhanen  and  R.G. Tardlff.   1977.   Mutagenlc  activity  of
chemicals  Identified  In  drinking  water.   2nd  Int.  Conf.  Environmental
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Stenger,  V.A.   1978.   Bromine  compounds.   lr±:  K1rk-0thmer  Encyclopedia  of
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Suffet,  I.H.,  L.   Brenner  and  P.R.  Cairo.   1980.   GC/MS  Identification  of
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                                                                       v_
Swann,  R.L.,   D.A.   Laskowskl,   P.J.  MeCall,   K.   Vander  Kuy  and   H.J.
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Tabak, H.H., S.A.  Quave,  C.I.  Hashnl  and E.F. Barth.  1981.   Blodegradabll-
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TewaM, Y.B.,  M.M.  Miller, S.P.  Waslk  and  D.E.  Martlre.   1982.   Aqueous
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-58-
08/20/90

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U.S. EPA.   1984.   Methodology and Guidelines for  Ranking  Chemicals  Based  on
Chronic Toxldty  Data.   Prepared by  the  Office of Helath  and  Environmental
Assessment, Environmental  Criteria and  Assessment  Office,  Cincinnati,  OH for
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Athens, GA.

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Register.  51(185): 33992-34003.

U.S. EPA.   1986d.   Reference  Values  for  Risk  Assessment.   Prepared  by the
Office  of  Health and  Environmental   Assessment,  Environmental  Criteria  and
Assessment Office, Cincinnati, OH for the  Office of Solid Waste,  Washington,
DC.

U.S. EPA.   1987.   Summary  Environmental  Data  for  Bromochloromethane.   U.S.
EPA/OPTS Public Files.  Flche #0750517073.

0316d                               -59-                             08/20/90

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U.S.  EPA.    1988.   Drinking  Water  Health  Advisory for  Bromochloromethane.
Prepared by  the Office  of  Health  and  Environmental  Assessment,  Environmental
Criteria and Assessment Office,  Cincinnati,  OH  for  the Office  of  Drinking
Water, Washington, DC.

U.S.  EPA/OWRS.    1986.   Guidelines  for  Deriving  Numerical  National  Water
Quality  Criteria  for  the  Protection  of  Aquatic Organisms  and  Their  Uses.
Office of  Water  Regulations  and  Standards, Criteria and  Standards  Dlvlson.
NTIS PB85-227049.

USITC  (U.S.  International   Trade   Commission).    1988.  Synthetic   Organic
Chemicals.    United  States  Production  and  Sales,  1987.   USITC  Publ.  2118,
                                                                            *
Washington, DC.   p.  15-29.

Hakeham, S.G., J.T. Goodwin and A.C. Davis.   1983.  Distributions  and fate of
volatile organic  compounds  1n Narragansett Bay  Rhode  Island.  Can.  J.  Fish
Aquat. Sd.  40:  304-321.

Zoeteman,  B.C.J.,  E.  Degreef and  F.J.J.  BMnkman.   1981.   Persistency  of
organic  contaminants  1n groundwater,  lessons  from  soil  pollution  Incidents
1n the Netherlands.   Sc1. Total Environ.   21:  187-202.
0316d
-60-
08/20/90

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                                  APPENDIX A

                              LITERATURE  SEARCHED
    This  HEED  1s  based  on  data  Identified  by  computerized  literature

searches of the following:


              CHEMLINE
              TSCATS
              CASR online (U.S. EPA Chemical Activities Status Report)
              TOXLINE
              TOXLIT
              TOXLIT 65
              RTECS
              OHM TADS
              STORET
              SRC Environmental Fate Data Bases
              SANSS
              AQUIRE
              TSCAPP
              NTIS
              Federal Register
              CAS ONLINE (Chemistry and Aquatic)
              HSDB
              SCISEARCH
              Federal Research 1n Progress


These  searches  were conducted  1n  April, 1989,  and the  following  secondary

sources were reviewed:
    ACGIH  (American  Conference of  Governmental  Industrial  Hyg1en1sts).
    1986.   Documentation  of the  Threshold  Limit Values  and  Biological
    Exposure Indices, 5th ed.  Cincinnati, OH.

    ACGIH  (American  Conference of  Governmental  Industrial  Hyg1en1sts).
    1987.   TLVs:  Threshold  Limit Values  for  Chemical  Substances  1n  the
    Work  Environment  adopted   by   ACGIH  with   Intended  Changes   for
    1987-1988.  Cincinnati,  OH.  114 p.

    Clayton,  G.D. and  F.E.  Clayton,  Ed.    1981.   Patty's  Industrial
    Hygiene  and  Toxicology,  3rd rev.  ed.,  Vol.  2A.   John  Wiley  and
    Sons. NY.  2878 p.

    Clayton,  G.D. and  F.E.  Clayton,  Ed.    1981.   Patty's  Industrial
    Hygiene  and  Toxicology,  3rd rev.  ed.,  Vol.  28.   John  WHey  and
    Sons, NY.  p. 2879-3816.
0316d                               -61-                             08/20/90

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    Clayton,  G.D.   and  F.E.  Clayton,  Ed.    1982.   Patty's  Industrial
    Hygiene  and  Toxicology,  3rd rev.  ed.,  Vol.  2C.   John Wiley  and
    Sons, NY.  p. 3817-5112.

    Grayson, H.  and D. Eckroth,  Ed.   1978-1984.   Klrk-Othmer  Encyclo-
    pedia of Chemical Technology, 3rd  ed.   John  WHey  and Sons,  NY.   23
    Volumes.

    Hamilton, A. and H.L.  Hardy.  1974.   Industrial  Toxicology,  3rd  ed.
    Publishing Sciences Group, Inc., Littleton, MA.   575 p.

    IARC  (International  Agency  for  Research on Cancer}.  IARC  Mono-
    graphs  on  the   Evaluation  of  Carcinogenic  Risk   of Chemicals  to
    Humans.  IARC,  WHO, Lyons, France.

    Jaber,  H.M.,  M.R.  Mabey,  A.T.   I.leu,  T.W.  Chou  and  H.L.  Johnson.
    1984.    Data  acquisition   for   environmental   transport  and   fate
    screening for compounds  of Interest  to  the Office of  Solid  Waste.
    EPA  600/6-84-010.    NTIS  PB84-243906.    SRI  International,   Menlo
    Park, CA.

    NTP  (National Toxicology  Program).  1987.   Toxicology Research  and
    Testing  Program.   Chemicals   on   Standard  Protocol.   Management
    Status.

    Ouellette,  R.P. and   J.A.  King.   1977.   Chemical  Week  Pesticide
    Register.  McGraw-Hill  Book Co., NY.

    Sax, I.N.  1984.   Dangerous  Properties  of Industrial  Materials,  6th
    ed.  Van Nostrand Relnhold Co.,  NY.

    SRI  (Stanford   Research  Institute).  1987.   Directory  of  Chemical
    Producers.  Menlo Park, CA.

    U.S.  EPA.   1986.  Report  on Status  Report  1n  the  Special  Review
    Program,  Registration   Standards  Program  and   the  Data   Call   1n
    Programs.  Registration  Standards  and  the  Data  Call  1n  Programs.
    Office of Pesticide Programs, Washington, DC.

    USITC  (U.S.   International  Trade  Commission).   1986.   Synthetic
    Organic  Chemicals.   U.S.   Production  and  Sales,  1985,  USITC  Publ.
    1892, Washington, DC.

    Verschueren,  K.   1983.  Handbook  of  Environmental Data on  Organic
    Chemicals, 2nd  ed.   Van Nostrand Relnhold Co., NY.

    Wlndholz, M., Ed.  1983.   The Merck Index,  10th ed.   Merck and Co.,
    Inc., Rahway, NJ.

    Worthing, C.R.  and S.B.  Walker,  Ed.   1983.  The  Pesticide  Manual.
    British Crop Protection Council.  695  p.
0316d
-62-
08/20/90

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                                         EPA/6OO/8-91/O16
                                         May  199O
  HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
            FOR BROMOCHLOROMETHANE
 ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH  AND ENVIRONMENTAL ASSESSMENT
      OFFICE OF RESEARCH AND DEVELOPMENT
     U.S.  ENVIRONMENTAL PROTECTION  AGENCY
             CINCINNATI, OH 45268

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-------
                                   TECHNICAL REPORT DATA
                            (Fleatt read Instructions on the revtru before completing/
 , REPORT NO.
 EPA/600/8-91/016
3. RECIPIENT'S ACCESSION NO.
  PB91-213702
 . TITLE AND SUBTITLE

 Health  and Environmental Effects Document for
 Bromochloromethane
                                                            S. REPORT DATE
6. PERFORMING ORGANIZATION CODE
7. AUTHOHISI
                                                            B. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
                                                            10. PROGRAM ELEMENT NO.
                                                            11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
                                                            13. TYPE OF REPORT AND PERIOD COVERED
 Environmental  Criteria and Assessment  Office
 Office of  Research and Development
 U.S. Environmental Protection Agency
 Cincinnati.  OH  45268	
14. SPONSORING AGENCY CODE

   EPA/600/22
15. SUPPLEMENTARY NOTES
16. ABSTRACT
      Health and Environmental Effects Documents  (HEEDS) are prepared for  the  Office of
 Solid Waste and Emergency Response (OSWER).   This document series is intended to
 support listings under the Resource Conservation and Recovery Act (RCRA)  as well as
  o provide health-related limits and goals for emergency and remedial actions under
  he Comprehensive Environmental Response, Compensation and Liability Act  (CERCLA).
 Both published literature and information obtained from Agency Program Office files
 are evaluated as they  pertain to potential human health, aquatic life and environmen-
 tal effects of hazardous  waste constituents.
      Several quantitative estimates are presented provided sufficient data are
 available.  For systemic  toxicants, these include Reference Doses (RfDs)  for  chronic
 and subchronic exposures  for both the inhalation and oral exposures.  In  the  case  of
 suspected carcinogens,  RfDs may not be estimated.   Instead, a carcinogenic potency
 factor, or q^*f is provided.  These potency estimates are derived for both oral  and
 inhalation exposures where possible.   In addition, unit risk estimates for air and
 drinking water are presented based on inhalation and oral data, respectively.
 Reportable quantities  (RQs) based on both chronic toxicity and carcinogenicity are
 derived.  The RQ is used  to determine the quantity of a hazardous substance for
 which notification is  required in the event of a release as specified under CERCLA.
17.
                                KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
                                              b.lDENTIFIERS/OPEN ENDED TERMS  C.  COSATI Field/Group
  DISTRIBUTION STATEMENT
                                              19. SECURITY CLASS (Thit Report)
                                                 Unclassi fied
              21. NO. OF PAGES
                 98
                                              20. SECURITY CLASS (This page/
                                                 Unclassified
                                                                         22. PRICE
EPA form 2220-1 .(R«v. 4-77)   PREVIOUS COITION i« OBSOLCTE

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i

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    In  addition,  approximately  30  compendia of  aquatic  toxlclty data  were

reviewed, Including the following:


    Battelle's  Columbus  Laboratories.   1971.   Water  Quality  Criteria
    Data  Book.   Volume  3.  Effects  of  Chemicals  on   Aquatic  Life.
    Selected  Data  from the  Literature  through  1968.  Prepared  for  the
    U.S. EPA under Contract No. 68-01-0007.  Washington,  DC.

    Johnson,  W.W.  and M.T.  Flnley.   1980.  Handbook of  Acute  Toxlclty
    of  Chemicals   to  Fish  and   Aquatic   Invertebrates.   Summaries  of
    Toxlclty  Tests  Conducted  at Columbia  National Fisheries  Research
    Laboratory.   1965-1978.   U.S.  Dept.  Interior, Fish  and  Wildlife
    Serv. Res. Publ.  137,  Washington, DC.

    McKee, J.E. and  H.W.  Wolf.  1963.  Water Quality Criteria,  2nd  ed.
    Prepared  for   the  Resources  Agency  of  California,  State  Water
    Quality Control Board.  Publ. No. 3-A.

    Plmental, 0.   1971.   Ecological  Effects  of  Pesticides on Non-Target
    Species.  Prepared for the U.S.  EPA, Washington, DC.   PB-269605.

    Schneider, B.A.   1979.   Toxicology  Handbook.   Mammalian  and Aquatic
    Data.  Book 1: Toxicology  Data.   Office  of  Pesticide  Programs, U.S.
    EPA, Washington,  DC.   EPA 540/9-79-003.  NTIS PB 80-196876.
0316d                               -63-                             08/20/90

-------



















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0316d
-64-
08/20/90

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                                  APPENDIX C
       DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO BROHOCHLOROHETHANE
C.I.   DISCUSSION
    Dose/duration-response graphs  for  Inhalation  and  oral  exposure  to bromo-
chloromethane generated  by the  method  of Crockett  et  al. (1985)  using  the
computer  software  by Durkln  and Heylan  (1989)  developed  under  contract  to
ECAO-C1nc1nnat1  are  presented  In Figures  C-l to  C-6.   Data  used  to generate
these  graphs  are  presented  In Section  C.2.   In  the  generation  of  these
figures,  all  responses  are  classified  as  adverse  (FEL,  AEL  or  LOAEL)  or
nonadverse  (NOEL  or  NOAEL) for  plotting.  The  ordlnate expresses Inhalation
exposure  1n  either of  two ways.  In  Figures  C-l and  C-2,  the experimental
concentration,  expressed as  mg/m3,  was  multiplied  by the  time parameters
of  the  exposure protocol  (e.g., hours/day  and days/week), and  Is  presented
as  expanded  experimental   concentration  [expanded  exp cone   (mg/m3)].   In
Figures C-3 and C-4, the expanded experimental  concentration  was multiplied
by  the animal  Inhalation  rate  1n  mVday  and  divided by  the  animal  body
weight  In kg  to  calculate a  dally  dose In  mg/kg/day.  The dally  dose  was
then  multiplied by  the  cube  root  of  the  ratio of  the animal:human  body
weight  to  adjust  for  species  differences   In  metabolic   rate  (Mantel  and
Schnelderman,  1975).  The  result was multiplied by  an absorption  coefficient
of  0.5  to adjust  to  an  equivalent absorbed  dose and  then multiplied  by  70
kg, the reference  human  body  weight, to express the human equivalent dose as
mg/day  for  a  70  kg  human  [human  equlv dose (mg/day)].   For  oral  exposure,
the ordlnate  expresses  dose as  human  equivalent dose.  The  animal  dose,  1n
mg/kg/day,  1s multiplied by  the cube  root of  the ratio of  the animal:human
body  weight  to adjust  for  species  differences  In  basal  metabolic  rate
0316d                               -65-                             08/20/90

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       180000
    0



    I
    ft,
    X
    C
    H
    a
    ft.
    x
    hi
          108
            8.0601
   BCMINHRL.D2
   (Inhalation Exposure)
                   0.601            0.61             6.1

                         EQUIU DURflTlON (fraction lifespan)

                             ENVELOP  METHOD
   Key:
F

I

n

N
FEL

LOAEL

NOAEL

NOEL
       Solid line - Adverse Effects Boundary
       Dashed line -  No Adverse Effects Boundary
                                    FIGURE C-l


           Dose/Duration  - Response Graph  for  Inhalation Exposure  to
   Bromochloromethane:  Envelope Method  (Expanded  Experimental Concentration)
0316d
                            -66-
                                                          08/20/90

-------
  B

  I
  U

  0
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  ft,
  X
  fi
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  X
  hi
       1800 •:
        166
             Bronochloronethane
                       13
                       14
                       18
           8.6601
 BCHINHRL.D2
 (Inhalation Exposure)
                                                        —«1
                                                  i   i  i  i i i it
                  0.081            e.ei             e.i
                  HUMfiN EQUIU DURATION (fraction lifespan)
                        CENSORED Dfllfl KEIHOD
  Key:
F
L
n
N
FEL
LOAEL
NOAEL
NOEL
      Solid line - Adverse  Effects Boundary
      Dashed line - No Adverse  Effects Boundary
                                    FIGURE C-2

           Dose/Duration - Response Graph  for Inhalation Exposure to
                    Bromochloromethane: Censored Data  Method
                      (Expanded Experimental  Concentration)
031 od
                            -67-
                                                          08/20/90

-------
   A
   3
   I
   0
   Q
   U
   z
   I
        1086
           e
  BCMINHHL.D2
  (Inhalation Exposure)
                  e.eei            e.ei             e.i
                  HUNflN EQUIU DURflUON (fraction lifespan)
                            EHUZLOP METHOD
   Key:
F
L
n
N
FEL
LOAEL
NOAEL
NOEL
       Solid Hne • Adverse  Effects  Boundary
       Dashed line - No Adverse  Effects  Boundary

                                   FIGURE C-3

           Dose/Duration - Response  Graph for Inhalation Exposure  to
          Bromochloromethane: Envelope Method (Human Equivalent Dose)
0316d
                           -68-
                                                         08/20/90

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  A
  J

  1

  C
  v
  0
  0

  D
  M
          0.8801
          3
 (Inhalation Exposure)
BCMINHflL.D2
            e.eei            e.ei             e.i
                 EQUIU DURflllON (fraction lifespan)
                 CENSORED DflTR METHOD
    Key:
          F
          L
          n
          N
PEL
LOAEL
NOAEL
NOEL
        Solid Hne « Adverse  Effects Boundary
        Dashed Hne - No Adverse  Effects Boundary
                                   FIGURE C-4

           Dose/Duration  -  Response  Graph for Inhalation  Exposure to
       Bromochloromethane:  Censored Data Method  (Human Equivalent Dose)
0316d
                                    -69-
                                                        08/20/90

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 i
 t
 V
 W
 0
 C

 I
      1800

                                                                 -F6-
                   m
         e.eei
         I
(Oral Exposure)
                                                                           B.81
BCMORRL.D2
HUMflN EQUIU DURRTION (fraction lifespan)
          ENVELOP METHOD
 Key:
         F » FEL
         N - NOEL
      Solid line - Adverse  Effects Boundary
      Dashed line - No Adverse Effects Boundary
                                     FIGURE C-5

     Dose/Duration - Response Graph  for  Oral Exposure to Bromochloromethane:
                                  Envelope Method
 0316d
                                       -70-
                                               08/20/90

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 1
 hi
 0)
 0
 a
 M
 £


 Z
       1808
             Bronochlorone thane
           1.081



 (Oral Exposure)
BCI10RRI.D2
                                                                       J	I
                                                                            8.61
HUHRN EQUIU DURRTION (fraction lifespan)

      CENSORED Dfllfl HETKOD
   Key:    F » PEL
           N » NOEL


        Solid line • Adverse  Effects Boundary
        Dashed Une • No Adverse Effects Boundary
    Dose/Duration -
                                   FIGURE C-6


                    Response Graph  for  Oral Exposure  to  Bromochloromethane:
                              Censored Data Method
0316d
                                      -71-
                                                                         08/20/90

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(Mantel  and  Schnelderman, 1975).   The result  1s  then multiplied by  70 kg,
the  reference  human  body weight,  to  express  the  human equivalent dose  as
mg/day for a 70 kg human  [human equlv dose (mg/day)].
    The  adverse  effects  boundary  (solid  line)  Is  drawn by  Identifying the
lowest  adverse effect  dose  or  concentration  at  the  shortest duration  of
exposure at which  an  adverse effect occurred.   From this  starting point,  an
Infinite line  Is  extended upward,  parallel  to  the  dose axis.   The  starting
point  Is  then  connected  to  the  lowest adverse  effect  dose  or  concentration
at  the next  longer duration  of  exposure  that has an adverse effect dose  or
concentration  equal   to  or  lower  than the  previous one.   This  process  1s
continued  to  the  lowest  adverse  effect  dose  or  concentration.  From  this
point, a  line  parallel  to the duration  axis  Is extended Infinitely  to the
right.  The adverse effects region lies above the adverse effects boundary.
    Using the envelope method, the no  adverse effects boundary  (dashed line)
Is  drawn  starting with   the  point  representing  the   highest  no  adverse
effects  dose  or  concentration.    From this  point,  a  line  parallel  to the
duration axis  1s  extended to  the  dose or concentration axis.   The  starting
point  1s then connected to the next equal or lower no adverse effect dose or
concentration at  a longer  duration of exposure.   When this process  can  no
longer be  continued,  a  line parallel  to  the  dose or  concentration axis  1s
dropped to the duration  axis.  The no adverse  effects  region  lies below the
no  adverse effects   boundary.   At  either  ends of  the graph  between  the
adverse effects and no  adverse effects boundaries are  regions  of  ambiguity.
The area (If any)  resulting  from  Intersections  of  the adverse effects  and no
adverse effects boundaries 1s defined as the region of contradiction.
    In the censored data  method,  all no adverse effect points located  1n the
region of  contradiction  are  dropped  from consideration  and the  no  adverse
effects  boundary   Is  redrawn  so  that 1t   does  not  Intersect  the  adverse
0316d
-72-
08/20/90

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effects boundary, and  no  region of contradiction 1s generated.   This  method
results 1n the most conservative definition of the no adverse effects region.
    Figures C-l and C-3 present the  Inhalation dose/duration-response  graphs
generated by  the  envelope method.  The  adverse effects boundary  Is  defined
by the  LOAEL  for  liver hlstologlcal  alterations  In mice  (Rec.  #17),  LOAELs
for kidney hlstologlcal alterations  In  dogs (Rec. #12), reduced  body  weight
and  elevated  organ weights   1n  guinea   pigs   (Rec.   #3),   liver  hlstologlcal
alterations In rats {Rec. #2) and  for reduced  body  weight  1n rats (Rec.  #8).
Using  the envelope method   (Figures  C-l  and  C-4), the  no adverse  effects
boundary  1s  defined  by the  acute  NOEL  for mortality  1n  rats (Rec. #14),  a
NOAEL  for  slightly Increased hemosldeMn  In  the  spleen  of rats  (Rec.  #10)
and  a  NOAEL  for  Increased  liver  weight  In rats  (Rec.  #1).   Using  the
censored data method  (Figures C-2 and C-4), the  no  adverse effects boundary
1s defined  by  the NOEL  for liver  hlstologlcal  alterations  In  rats  (Rec.
#16),  the  NOEL  1n rabbits  (Figure C-2,  Rec.  #5)  or dogs  (Figure  C-4,  Rec.
#7) and the NOAEL for  liver  hlstologlcal  alterations 1n rats (Rec. #1).   The
subchronlc and  chronic RfDs  for  bromochloromethane are  based on  the  NOAEL
for liver hlstologlcal alterations In rats (Rec. #1).
    Figures C-5 and C-6 present the  oral  dose/duration-response  graphs.   The
adverse effects boundary  1s  defined  by  FELs for  mortality 1n  rats (Rec. #1)
and mortality 1n mice  (Recs.  #3,  4 and  6).  In Figure C-5 (envelope method),
the no adverse effects boundary Is defined by  the NOEL for mortality 1n rats
(Rec.  #2)  and the NOEL for  mortality and hlstopathology  1n mice (Rec.  #5).
Using  the censored data method  (Figure C-6),  the  no adverse effects boundary
Is defined by a single value,  the NOEL  for mortality  and hlstopathology 1n
mice  (Rec.  #5).   Figures  C-5  and C-6   emphasize  that additional  oral  data
(I.e.,  for   longer  duration  exposures)   are   needed  to  Identify a  maximal
region of no adverse effects.

0316d                               -73-                             08/20/90

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C.2.   DATA USED TO GENERATE OOSE/DURATION-RESPONSE GRAPHS

C.2.1.   Inhalation Exposure.
Chemical Name:
CAS Number:
Document Title:

Document Number;
Document Date:
Document Type:
   Bromochloromethane
   74-97-5
   Health and Environmental Effects Document on
   Bromochloromethane
   Pending
   Pending
   HEED
RECORD #1 :




Species:
Sex:
Effect:
Route:

Rats
Female
NOAEL
Inhalation

Body Weight: 0.35 kg
Reported Dose: 1958 mg/m3
Converted Dose: 125.96 mg/kg/day
Exposure Period: 195 days
Duration Observation: 195 days
Comment:
                                       Molecular Height:  129.39
                                       Inhalation hours/day:  7.00
                                       Inhalation days/week:  4.8461
                                       Inhal. Exp. days:  135.00
                                       Assumed Inhalation Absorption:
                                                        50?4
Citation:
Number Exposed:     10
Number Responses:   NR
Type of Effect:     HGTIN
Site of Effect:     LIVER
Severity Effect:    4

Concentrations  studied:  1958,  2593  and  5345  mg/m3  (370,  490
and  1010 ppm  or  125.96,  -170.14,  -350.69 mg/kg/day).   Both
sexes  treated   at    higher   concentrations.    No  effects  on
histology, hematology, blood nitrogen or body weight.

Torkelson et al., 1960
0316d
                     -74-
08/20/90

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RECORD #2:     Species:   Rats        Body Weight:   0.35 kg
               Sex:       Both        Reported Dose:   2593 mg/m3
               Effect:     LOAEL       Converted Oose:   166.97-173.31  mg/kg/day
               Route:     Inhalation  Exposure Period:   114 days
                                      Duration Observation:  114 days

                                      Molecular Weight:   129.39
                                      Inhalation hours/day:  7.00
                                      Inhalation days/week:  4.8509-5.0351
                                      Inhal.  Exp. days:   79.00-82.00
                                      Assumed Inhalation Absorption:   50%

               Number Exposed:     40
               Number Responses:    NR
               Type of  Effect:     PROLF
               SHe of  Effect:     LIVER
               Severity Effect:    5

Comment:       20/sex,   79-82  exposures.    See  previous  record.    Effects
               Included  slight   bile  duct    proliferation,    slight   portal
               flbrosls and  occasional  vacuollzatlon.   Similar effects  with
               cloudy  swelling   1n   liver   In  both  sexes   at   5345  mg/m3
               (344.18-357.25 mg/kg/day}.

Citation:      Torkelson et al.f  1960
RECORD #3:
Species:
Sex:
Effect:
Route:
Guinea pigs Body Weight: 0.84 kg
Both Reported Dose: 2593 mg/m3
LOAEL Converted Dose: 124.29-129.53 mg/kg/day
Inhalation Exposure Period: 114 days
Duration Observation: 114 days
Comment:
Citation:
                       Molecular Weight:  129.39
                       Inhalation hours/day:   7.00
                       Inhalation days/week:   4.8509-5.0351
                       Inhal. Exp. days:  79.00-82.00
                       Assumed Inhalation Absorption:  50%

Number Exposed:     20       20       20
Number Responses:   NR       NR       NR
Type of Effect:     WGTIN    WGTIN    WGTDC
SHe of Effect:     LIVER    KIDNY    BODY
Severity Effect:    444

10/sex,  79-82  exposures.   Exposure  concentrations:   2593  and
5345 mg/m3  {490 and 1010  ppm).   Effect on kidney  weight  only
In  males.   No  effects  on   histology   or   blood  nitrogen.
Testlcular effects  (decreased  weight,  spermatogenesls) at  5345
mg/m3 {257.23-267.00 mg/kg/day).

Torkelson et al., 1960
0316d
                     -75-
08/20/90

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RECORD #4:
Comment:
Citation:
Species:   Mice        Body Weight:  0.03 kg
Sex:       Female      Reported Dose:  5345 mg/m3
Effect:    LOAEL       Converted Dose:  702.22-728.88 mg/kg/day
Route:     Inhalation  Exposure Period:  114 days
                       Duration Observation:  114 days

                       Molecular Weight:  129.39
                       Inhalation hours/day:  7.00
                       Inhalation days/week:  4.8509-5.0351
                       Inhal, Exp. days:  79.00-82.00
                       Assumed Inhalation Absorption:  50%

Number Exposed:     10       10       10
Number Responses:   NR       NR       NR
Type of Effect:     WGTDC    WGTIN    WGTIN
Site of Effect:     BODY     LIVER    KIONY
Severity Effect:    444

79-82  exposures.   Exposure  concentrations:   2593   and  5345
mg/m3  {490  and  1010  ppm)   (340.67-353.59  and  702.22-728.88
mg/kg/day).  Same   effects   at   2593  mg/m3.    No  effects   on
histology.  Other endpolnts not examined.

Torkelson et al., 1960
RECORD #5:




Species:
Sex:
Effect:
Route:

Rabbits
Both
NOEL
Inhalation

Body Weight: 3.8 kg
Reported Dose: 2593 mg/m3


Converted Dose: 137.93-143.16 mg/kg/day
Exposure Period: 114 days
Duration Observation: 114 days


Comment:
Citation:
                        Molecular Weight:  129.39
                        Inhalation hours/day:  7.00
                        Inhalation days/week: 4.8509-5.0351
                        Inhal. Exp. days:  79.00-82.00
                        Assumed Absorption Inhalation:  SOX

Number Exposed:     4
Number Responses:   0
Type of Effect:
SHe of Effect:
Severity Effect:    3

2/sex,  79-82 exposures.   Exposure concentrations:   2593  and
5345   mg/m3    (490    and   1010   ppm)   (137.93-143.16   and
284.32-295.09   mg/kg/day,   respectively).    No   effects   on
histology, organ weight, body weight or blood nitrogen.

Torkelson et al., 1960
0316d
                     -76-
08/20/90

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RECORD #6:     Species:   Rabbits     Body Weight:   3.8 kg
               Sex:       Male        Reported Dose:   5345 mg/m3
               Effect:    LOAEL       Converted Dose:   284.29-295.09  mg/kg/day
               Route:      Inhalation  Exposure Period:   114 days
                                      Duration Observation:  114  days

                                      Molecular Weight:  129.39
                                      Inhalation hours/day:  7.00
                                      Inhalation days/week:  4.8509-5.0351
                                      Inhal.  Exp. days:  79.00-82.00
                                      Assumed Inhalation Absorption:   50%

               Number  Exposed:     2
               Number  Responses:   1
               Type of Effect:     DEGEN
               SHe of Effect:     TESTE
               Severity Effect:    6

Comment.:       See previous record. Decreased  spermatogenesls  1n tubules with
               flbrosls 1n 1  of 2 males.  Decreased relative testes weight.

Citation:      Torkelson et al., 1960
RECORD #7:




Species:
Sex:
Effect:
Route:

Dogs
Both
NOEL
Inhalation

Body Weight: 12.7 kg
Reported Dose: 1958 mg/m3
Converted Dose: 66.93 mg/kg/day
Exposure Period: 195 days
Duration Observation: 195 days
Comment:
Citation:
                                      Molecular Weight:  129.39
                                      Inhalation hours/day:  7.00
                                      Inhalation days/week:  4.8462
                                      Inhal. Exp. days:  135.00
                                      Assumed Inhalation Absorption:
                                                       50%
Number Exposed:     2
Number Responses:   0
Type of Effect:
SHe of Effect:
Severity Effect:    4

I/sex.  370  ppm equivalent concentration.  No  effect on body
weight, blood  nitrogen  or  hematology.   Pathological  examina-
tions not performed.

Torkelson et al., 1960
0316d
                     -77-
08/20/90

-------
RECORD #8;
Comment:
Citation:
Species:   Rats            Body Weight:  0.32 kg
Sex:       Both            Reported Dose:  2725 mg/m3
Effect:    LOAEL           Converted Dose:   149,51  mg/kg/day
Route:     Inhalation      Exposure Period:         6 months
                           Duration Observation:   6 months

                           Molecular Weight:  129.39
                           Inhalation hours/day:  6.00
                           Inhalation days/week:  4.8222
                           Inhal. Exp. days:  124.00
                           Assumed Inhalation Absorption:   5054

Number Exposed:     100
Number Responses:   NR
Type of Effect:     WGTDC
SHe of Effect:     BODY
Severity Effect:    4

50/sex.   Exposure concentrations:  2725 and  5345  mg/m3  {515
and 1010 ppm)  (149.51  and  293.26 mg/kg/day, respectively).   No
effect  on  body  weight  In  females.   No effect on  histology,
organ weights or clinical chemistry at either exposure level.

MacEwen et al., 1966
RECORD #9:




Species:
Sex:
Effect:
Route:

Dogs
Both
NOEL
Inhalation

Body Weight: 12.7 kg
Reported Dose: 5345 mg/m3
Converted Dose: 155.84 mg/kg/day
Exposure Period: 6 months
Duration Observation: 6 months
Comment:
Citation:
                                          Molecular We1ght:129.39
                                          Inhalation hours/day:   6.00
                                          Inhalation days/week:   4.8222
                                          Inhal.  Exp. days:   124.00
                                          Assumed Inhalation Absorption:
                                                           50%
Number Exposed:     8
Number Responses:   0
Type of Effect:
Site of Effect:
Severity Effect:    3

4/sex.  Dogs were exposed  to  0,  515  or  1010 ppm (2725 or  5345
mg/m3)   bromochloromethane   (79.45   and   155.84   mg/kg/day,
respectively).   No  effect   on   body  weight,   organ  weight,
histology or clinical chemistry.

MacEwen et al., 1966
0316d
                     -78-
08/20/90

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RECORD #10:
Comment:
Species:
Sex:
Effect:
Route:
Rats
Male
NOAEL
Inhalation
Citation:
Body Weight:  0.35 kg
Reported Dose:  4710 mg/m3
Converted Dose:  299.20 mg/kg/day
Exposure Period:  14 weeks
Duration Observation:  14 weeks

Molecular Weight:  129.39
Inhalation hours/day:  7.00
Inhalation days/week:  4.7857
Inhal. Exp. days:  67.00
Assumed Inhalation Absorption:  50%
Number Exposed:     20
Number Responses:   NR
Type of Effect:     OTHER
Site of Effect:     SPLEN
Severity Effect:    1

890  ppm  equivalent   concentration.   Histology  was  evaluated
after  67  exposures.    Increased   hemoslderln  1n  spleen.   No
other effect on  histology or  weight  gain.   Other  endpolnts  not
evaluated.

Svlrbely et al., 1947
RECORD #11:




Species:
Sex:
Effect:
Route:

Rabbits
Male
NOEL
Inhalation

Body Weight: 3.8 kg
Reported Dose: 4710 mg/m3
Converted Dose: 247.16 mg/kg/day
Exposure Period: 14 weeks
Duration Observation: 14 weeks
Comment:
Citation:
                                          Molecular Weight:   129.39
                                          Inhalation hours/day:   7.00
                                          Inhalation days/week:   4.7857
                                          Inhal.  Exp. days:   67.00
                                          Assumed Inhalation Absorption:
                                                           50%
Number Exposed:     3
Number Responses:   0
Type of Effect:
SHe of Effect:
Severity Effect:    3

Exposure  concentration  Is  equivalent  to  890  ppm.   Histology
evaluated after  67  days.   No  effect  on histology,  weight gain,
hematology, liver function or urlnalysls.

Svlrbely et al., 1947
0316d
                     -79-
                                           08/20/90

-------
RECORD #12:
Comment:
Citation:
Species:   Dogs            Body Weight:   12.7 kg
Sex:       Female          Reported Dose:  4710 mg/m3
Effect:    IOAEL           Converted Dose:   158.99 mg/kg/day
Route:     Inhalation      Exposure Period:  14 weeks
                           Duration Observation:  14 weeks

                           Molecular Weight:  129.39
                           Inhalation hours/day:  7.00
                           Inhalation days/week:  4.7857
                           Inhal. Exp. days:  67.00
                           Assumed Inhalation Absorption:   50%

Number Exposed:     2
Number Responses:   NR
Type of Effect:     DEGEN
Site of Effect:     KIONY
Severity Effect:    5

890  ppm  equivalent   concentration.   Histology  was  evaluated
after 67  exposures.  Increased  fat  1n the kidneys and Increased
hemoslderln  In  the  kidneys  and spleen.   No effect  on  weight
gain, hematology, liver function or. urlnalysls.

Svlrbely et al., 1947
RECORD #13:




Species:
Sex:
Effect:
Route:

Rats
Both
PEL
Inhalation

Body Weight: 0.35 kg
Reported Dose: 10000 ppm
Converted Dose: 702.45 mg/kg/day
Exposure Period: 0.29 days
Duration Observation: 14 days
Comment:
Citation:
                                       Molecular Weight:  129.39
                                       Inhalation hours/day:  7.00
                                       Inhalation days/week:  1.00
                                       # Inhal. Exp. days:
                                       Assumed Inhalation Absorption:
                                                        50*
Number Exposed:     20
Number Responses:   11
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

Single  7-hour  exposure.   Concentration  not  expanded  over  24
hours.   6/10  males  and 5/10  females  died.   Deaths  generally
occurred during exposure to anesthesia.

Torkelson et al., 1960
0316d
                     -80-
08/20/90

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RECORD #14:
Comment:


Citation:
Species:   Rats         Body Weight:   0.35 kg
Sex:       Both         Reported Dose:   5000 ppm
Effect:    NOEL         Converted Dose:   351.23 mg/kg/day
Route:     Inhalation   Exposure Period:   0.29 days
                        Duration Observation:  14 days

                        Molecular Weight:
                        Inhalation hours/day:  7.00
                        Inhalation days/week:  1.00
                        # Inhal. Exp.  days:
                        Assumed Inhalation Absorption:   50%

Number Exposed:     22
Number Responses:   0
Type of Effect:
Site of Effect:
Severity Effect:    10

Single  7-hour  exposure.  Concentration  not  expanded  over 24
hours.  0/11 males and 0/11  females died.

Torkelson et aK, 1960
RECORD #15:




Species:
Sex:
Effect:
Route:

Rats
F ema 1 e
LOAEL
Inhalation

Body Weight: 0.35 kg
Reported Dose: 1500 ppm
Converted Dose: 105.37 mg/kg/day
Exposure Period: 0.29 days
Duration Observation: 1 day
                                          Molecular Weight:
                                          Inhalation hours/day:    7.00
                                          Inhalation days/week:    1.00
                                          # Inhal. Exp. days:
                                          Assumed Inhalation Absorption:
                                                           50%
               Number Exposed:     4
               Number Responses:   NR
               Type of Effect:     DEGEN
               Site of Effect:     LIVER
               Severity Effect:    5

Comment:       Minimum concentration producing unequivocal hepatic  effects  24
               hours after  7-hour  exposure.  Concentration  not  expanded over
               24  hours.    Effects   Included  small  vacuoles  not   typical  of
               fatty degeneration often accompanied by Increased liver weight.

Citation:      Torkelson et al., 1960
0316d
                     -81-
08/20/90

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RECORD #16:    Species:   Rats             Body Weight:   0.35 kg
               Sex:       Female           Reported Dose:  600 ppm
               Effect:    NOEL             Converted Dose:   42.15 mg/kg/day
               Route:     Inhalation       Exposure Period:  0.29 days
                                           Duration Observation:  1  day

                                           Molecular Weight:
                                           Inhalation hours/day:  7.00
                                           Inhalation days/week:  1.00
                                           # Inhal. Exp.  days:
                                           Assumed Inhalation Absorption:   50%

               Number Exposed:     4
               Number Responses:   NR
               Type of Effect:
               Site of Effect:
               Severity Effect:    3

Comment:       Maximum concentration that did not produce hepatic hlstologlcal
               effects 24 hours after  a  single 7-hour  exposure. Concentration
               not expanded over 24 hours.

Citation:      Torkelson et al., 1960
RECORD #17:




Species:
Sex:
Effect:
Route:

Mice
NR
LOAEL
Inhalation

Body Weight: 0.03 kg
Reported Dose: 7 mg/s.
Converted Dose: 189.62 mg/kg/day
Exposure Period: 0.29 days
Duration Observation: 1 day
Comment:
Citation:
                                           Molecular Weight:
                                           Inhalation hours/day:  7.00
                                           Inhalation days/week:  1.00
                                           # Inhal. Exp. days:
                                           Assumed Inhalation Absorption:
                                                            SOX
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     DEGEN                                    9
Site of Effect:     LIVER
Severity Effect:    5

Single  7-hour  exposure.   1323 ppm  equivalent  concentration.
Concentration not expanded  over  24 hours.   Fatty degeneration.
Effect  observed  In  mice  exposed  to  concentrations  of  7-17
mg/ma for 1-5 days but was minimal/absent after 72 hours.

Hlghman et al., 1948
0316d
                     -82-
08/20/90

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RECORD #18:
Comment:
Citation:
Species:   Mice          Body Weight:  0.03 kg
Sex:       NR            Reported Dose:  2273 ppm
Effect:    FEL           Converted Dose:  325.78 mg/kg/day
Route:     Inhalation    Exposure Period:  0.29 days
                         Duration Observation:  6 days

                         Molecular Weight:
                         Inhalation hours/day: 7.00
                         Inhalation days/week: 1.00
                         # Inhal. Exp.  days:
                         Assumed Inhalation Absorption:  50%

Number Exposed:     NR
Number Responses:   NR
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

Concentration  not  expanded  over 24  hours.  LC 50 after 72-hour
observation.    A  similar value  was  reported by Hlghman  et  al.
(1948).   LCsQS  after   8,  24  and  48   hours  observation  were
2995, 2504 and 2436 ppm, respectively.

Svlrbely et al., 1947
C.2.2.  Oral Exposure.
Chemical Name:    Bromochloromethane
CAS Number:
Document Title:

Document Number;
Document Date:
Document Type:
   74-97-5
   Health and Environmental Effects Document on
   Bromochloromethane
   Pending
   Pending
   HEED
RECORD #1:




Species:
Sex:
Effect:
Route:

Rats
Male
FEL
Gavage

Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
DuratlonObservatlon:
0.35 kg
7000 mg/kg/day
7000 mg/kg/day
1 day
1 day
Comment:


Citation:
Number Exposed:     5
Number Responses:   5
Type of Effect:     DEATH
S1te~of Effect:     BODY
Severity Effect:    10

All rats died within  24  hours  of  treatment.  Dose administered
In corn oil apparently by gavage.

Torkelson et al., 1960
0316d
                     -83-
08/20/90

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RECORD #2:
Species:
Sex:
Effect:
Route:
Rats
Hale
NOEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
0.35 kg
5000 mg/kg/day
5000 mg/kg/day
1 day
                                        Duration Observation: 14 days
               Number Exposed:     5
               Number Responses:   0
               Type of Effect:
               SHe of Effect:
               Severity Effect:    10
Comment:
Citation:
RECORD #3:

No deaths. See previous record.
Torkelson et al. , 1960
Species: Mice Body Weight:
Sex: NR Reported Dose:
Effect: PEL Converted Dose:
Route: Gavage Exposure Period:
Duration Observation:
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10

0.03 kg
4300 mg/kg/day
4300 mg/kg/day
1 day
6 days

Comment:       Approximate  1059.   Doses  ranging  from  500-4400  mg/kg/day
               administered 1n corn oil  apparently by  gavage  to  groups  of 10
               animals.
Citation:
RECORD #4:
Svlrbely
Species:
Sex:
Effect:
Route:
et al., 1947
nice
NR
PEL
Gavage

Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:

0.03 kg
3000 mg/kg/day
3000 mg/kg/day
1 day
                                        Duration Observation:  12 days

               Number Exposed:     NR
               Number Responses:   NR
               Type of Effect:     DEATH
               Site of Effect:     BODY
               Severity Effect:    10

Comment:       Single doses of  500,  3000 and  4500  mg/kg  were  administered In
               corn oil.  12/50 mice  that  died  or  were killed at two highest
               doses  showed  subcapsular   necrosis  In   liver.   8/32  showed
               hemoglobin casts 1n renal tubules.

Citation:      Hlghman et al., 1948
0316d
                     -84-
                                           08/20/90

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RECORD |5:
Comment:

Citation:
Species:
Sex:
Effect:
Route:
Mice
NR
NOEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
0.03 kg
500 mg/kg/day
500 mg/kg/day
1 day
                                        Duration Observation:  12 days
                                   NR
                                   NR
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
See previous record.  No effect on mortality or histology.

Hlghman et al., 1948
RECORD #6:
Comment:
Species;
Sex:
Effect:
Rout:e
Mice
NR
PEL
Gavage
               Number Exposed:
               Number Responses:
               Type of Effect:
               Site of Effect:
               Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
                    NR
                    NR
                    DEATH
                    BODY
                    10
0.03 kg
3000 mg/kg/day
3000 mg/kg/day
5 days
5 days
Citation:
Death In unspecified number  of  32  mice  that were given single
doses 1n  olive  oil on  1  to 10 consecutive days.   Hlstologlc
examination  showed effects  Including  fatty  degeneration  of
the liver and kidney and liver subcapsular  necrosis.
                                                 t
Hlghman et al.,  1948
NR = Not reported
0316d
                     -85-
                                           08/20/90

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