ECAO-CIN-G101
                                                    FINAL DRAFT
       environmental Protection                                ECAO-C IN-G1 01
                                                    May, 1990
       Research  and
       Development
       HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
       FOR BROMOCHLOROMETHANE
      Prepared for
       OFFICE OF SOLID WASTE AND
       EMERGENCY RESPONSE
      Prepared  by
      Environmental Criteria and Assessment Office
      Office of Health and Environmental Assessment
      U.S. Environmental Protection Agency
      Cincinnati, OH  45268    &•& M&MMf&A'fateto* 'Agency
                                  Region 5, Library 
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                                  DISCLAIMER

    This report  Is  an external draft  for  review purposes only and  does  not
constitute  Agency  policy.   Mention of  trade  names  or  commercial  products
does not constitute endorsement or recommendation for use.

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                                    PREFACE

    Health  and  Environmental  Effects Documents (HEEOs) are  prepared  for  the
Office  of  Solid  Waste and Emergency Response  (OSWER).  This  document series
1s  Intended  to support  listings  under  the  Resource Conservation and Recovery
Act  (RCRA)  as  well  as  to  provide  health-related  limits  and  goals  for
emergency   and   remedial   actions   under   the   Comprehensive  Environmental
Response,   Compensation  and   Liability   Act   (CERCLA).    Both   published
literature  and  Information  obtained  for   Agency  Program  Office   files  are
evaluated  as  they  pertain  to  potential   human  health,  aquatic  life  and
environmental  effects  of  hazardous  waste  constituents.   The  literature
searched  for  In  this  document  and  the   dates  searched  are  Included  In
"Appendix;  Literature  Searched."  Literature  search material  1s  current  up
to  8  months  previous  to the  final draft  date listed on the  front cover.
Final  draft  document  dates  (front  cover)   reflect  the date  the document  Is
sent to the Program Officer  (OSWER).

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

    In  the  case  of  suspected  carcinogens,  a carcinogenic  potency  factor,  or
q-j*  (U.S.  EPA,  1980),  1s  provided.   These potency  estimates are  derived
for both  oral and  Inhalation  exposures where  possible.   In  addition,  unit
risk estimates for air  and  drinking water   are  presented  based on  Inhalation
and oral data, respectively.  An  RfO may also  be derived  for the noncarclno-
genlc health effects  of compounds that  are  also carcinogenic.

    Reportable   quantities   (RQs)   based   on   both   chronic   toxlclty  and
carclnogenlclty are derived.  The RQ Is used  to determine the quantity of a
hazardous  substance  for  which  notification  Is  required   1n  the event  of a
release  as   specified   under   the  Comprehensive  Environmental   Response,
Compensation  and Liability  Act  (CERCLA).    These  two RQs  (chronic  toxldty
and carclnogenlclty)  represent  two  of  six  scores  developed  (the remaining
four reflect  IgnltabllHy, reactivity,  aquatic  toxlclty,  and acute mammalian
toxlclty).   Chemical-specific  RQs  reflect  the  lowest of these six  primary
criteria.   The  methodology  for  chronic toxlclty  and cancer based  RQs  are
defined 1n U.S. EPA,  1984 and 1986a, respectively.
                                      111

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                               EXECUTIVE SUMMARY

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

                                      1v

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Levels  of 0.2-0.4  ppt  have been  Identified  1n  air over  the  Atlantic  Ocean
(Class  and BallschmHer,  1988),  while  levels  of  2.4-2.9  ppt were detected In
the  Alaskan   Arctic (Rasmussen  and  Khalll,  1984).  Bromochloromethane  has
also been  Identified In  air  samples  collected near  a hazardous waste site In
New Jersey (Lareglna et  al.,  1986).   It  has been suggested that the presence
of  bromochloromethane  In marine water and  air may  be  due, In  part,  to  Us
blogenlc  formation  In  algae,  followed by  release  to seawater, with  subse-
quent  volatilization  (Class and  BallschmHer,  1988).  The  classic  haloform
reactions  responsible  for  the  formation  of  chloroform and other halomethanes
during  chlorlnatlon of  drinking water  will  not produce  bromochloromethane
(NAS, 1980).
    Summarized  toxldty  data  for  bromochloromethane consisted of a NOEL of
80  mg/i  for  fathead   minnows,   P.   promelas.   and  an  LC5Q   (duration  not
reported)  of  >80  mg/l  (U.S.  EPA,   1987).     Bromochloromethane  has  been
found  1n  tissues of rainbow trout,   S.  galrdnerl.   from  the  Colorado  River.
The estimated whole-fish concentration was 8 v9/l (H1att, 1983).
    Bromochloromethane  1s  rapidly  absorbed  by  rats  In  a blphaslc  manner
following acute  Inhalation  exposure  (Gargas and  Andersen,  1982), but quanti-
tative  data are  not available  regarding  the extent  of Inhalation exposure or
the rate  or  extent  of  oral exposure.  There  appears to  be some distribution
of  bromide  to  the brain  of  dogs   during  subchronlc  Inhalation  exposure
(Svlrbely et  al., 1947).   Rat  t1ssue:blood  partition coefficients  (Gargas et
al., 1986a,b) suggest  that  bromochloromethane will  distribute more readily
                                               
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CO^  and  hallde (Gargas  et  al.,  1986a).   It  Is proposed  that  a portion of
the  oxldatlve  pathway also  yields a  significant  amount  of  C0_ (Gargas et
al.,1986a).  Information regarding the  rate and  extent  of  bromochloromethane
excretion was not  located 1n the  literature cited 1n  Appendix  A.
    Acute  Inhalation  LC5Qs  for  mice  for   7-hour   exposures   ranged   from
2268-2995  ppm  (Svlrbely et  al.,  1947;  Hlghman et  al.,  1948).  Exposure  to
5000 ppm  (26,460  mg/m3) for 7 hours  was  not  lethal  for  rats (Torkelson et
al., 1960).  Rats  survived  a single oral  dose  of  5  g/kg,  and all rats  died
within 24  hours  after a dose  of 7 g/kg  (Torkelson  et  al., 1960).  An  oral
L05Q  of   -4300 mg/kg was  determined  for mice  (Svlrbely  et   al.,  1947).
Signs  and  pathological  effects  of  acute Inhalation  and   oral  exposure to
bromochloromethane are similar;  principal  effects  Include  CNS depression and
degeneration of the liver.
    Subchronlc  Inhalation studies  of  bromochloromethane have been  conducted
with rats,  mice,   guinea pigs,  rabbits  and  dogs  (Torkelson et al.,  1960;
MacEwen et al., 1966;  Svlrbely et  al.,  1947;  Hlghman et al.,  1948).   Concen-
trations  ranged from 370 ppm  (rats)   to  ~1000 ppm  (all species);  exposures
were usually 5-7  hours/day,  5  days/week ranging from 14 weeks to  ~6  months.
Generally, minor  effects such as  decreased  body weight,  Increased  relative
liver and kidney weight  and  reversible  liver  and kidney hlstologlcal  altera-
tions occurred at concentrations >500  ppm 1n  most  species.  Torkelson et al.
(1960)  found that  relative  liver weight was  Increased  In  rats at  concentra-
tions of  370 ppm with  hlstologlcal  effects  occurring at  490 ppm.   Exposure
to  1000  ppm caused death and  marked  liver injury  1n mice (Hlghman  et  al.,
1948).   Information regarding  the  chronic Inhalation toxlclty,  subchronlc  or
chronic  oral  toxldty  or   teratogenldty of   bromochloromethane  were  not
located.    Decreased  spermatogenesls  and flbrosls occurred  1n the  tubules  of
                                      v1

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

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pathological  effects  of acute  Inhalation  and  oral  exposure to  bromochloro-
methane are  similar;  principal  effects Include CNS depression and  degenera-
tion of the liver.
    The  cardnogenlcUy  of  bromochloromethane  has   not   been  evaluated.
Bromochloromethane was  mutagenlc  In  Salmonella  typhlmurlum and  Escherlchla
coll bacteria  (Simmon,  1976;  Simmon  et  al.,  1977;  Osterman-Golkar  et  al.
1983;  Strobe!  and Grummt,  1987) and  Induced  SCE  and  chromosome  aberrations
1n Chinese hamster cells In vitro (Strobel  and  Grummt,  1987).
    An  RfD  for  subchronlc  Inhalation exposure  of  4  mg/m3 was  based  on  a
NOAEL  associated  with  slightly  elevated liver weight  but no effect  on  body
weight  In female  rats  exposed Intermittently for 195 days  (Torkelson  et  al.,
1960).   This  study also  served as  the  basis  for  an  RfD.  of  0.4 mg/ma  for
chronic  Inhalation  exposure.   Oral   data  were not  sufficient   for  deriving
route-specific RfD values; therefore,  the  NOAEL from the  Inhalation  study In
female  rats by Torkelson et  al. (1960) served as  the  basis for an RfD  of  1
mg/kg/day  for  subchronlc  oral   exposure   and  an RfD  of  0.1  mg/kg/day  for
chronic oral  exposure.  An  RQ   for  noncancer  chronic  toxlclty  of 1000  was
based  on  the  occurrence of  liver  lesions  In rats exposed  by  Inhalation  for
114 days.
    Bromochloromethane  1s classified  In EPA  Cancer  Group  D (Not  Classifiable
as  to  Human  CardnogenlcUy} because  of  lack  of cardnogenlcUy  data;  this
lack of data  precludes  calculation  of   a  carcinogenic   potency  factor  or
cancer-based RQ for bromochloromethane.

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                              TABLE  OF  CONTENTS
                                                                       Page
1.  INTRODUCTION	     1

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

2.  ENVIRONMENTAL FATE AND TRANSPORT	     3

    2.1.   AIR	     3
    2.2.   WATER	     3

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

    2.3.   SOIL	     5

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

    2.4.   SUMMARY	     6

3.  EXPOSURE	     7

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

4.  ENVIRONMENTAL TOXICOLOGY	    10

    4.1.   AQUATIC TOXICOL06Y 	    10

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

    4.2.   TERRESTRIAL TOXICOLOGY 	    11

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

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                          TABLE  OF  CONTENTS  (cont.)

                                                                       Page
    4.3.   FIELD STUDIES	    11
    4.4.   AQUATIC RISK ASSESSMENT	    11
    4.5.   SUMMARY	    12

5.  PHARMACOKINETCS	    13

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

6.  EFFECTS	    19

    6.1.   SYSTEMIC TOXICITY	    19

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

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

7.  EXISTING GUIDELINES AND STANDARDS 	    34

    7.1.   HUMAN	    34
    7.2.   AQUATIC	    34

8.  RISK ASSESSMENT	    35

    8.1.   CARCINOGENICITY	    35

           8.1.1.   Inhalation	    35
           8.1.2.   Oral	    35
           8.1.3.   Other Routes	    35
           8.1.4.   Weight of Evidence	    35
           8.1.5.   Quantitative Risk Estimates 	    35
                                              *
    8.2.   SYSTEMIC TOXICITY	    35

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

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

5.  PHARMACOKINETCS	   13

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

6.  EFFECTS	   19

    6.1.   SYSTEMIC TOXICITY	   19

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

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

7.  EXISTING GUIDELINES AND STANDARDS 	   34

    7.1.   HUMAN	   34
    7.2.   AQUATIC	   34

8.  RISK ASSESSMENT	   35

    8.1.   CARCINOGENICITY	   35

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

    8.2.   SYSTEMIC TOXICITY	"*	   35

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

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                           TABLE  OF  CONTENTS  (cont.)

                                                                        Page

 9.  REPORTABLE QUANTITIES 	   45

     9.1.   BASED ON SYSTEMIC TOXICITY 	   45
     9.2.   BASED ON CARCINOGENICITY	   49

10.  REFERENCES	   51

APPENDIX A: LITERATURE SEARCHED	   61
APPENDIX B: SUMMARY TABLE FOR BROMOCHLOROMETHANE 	   64
APPENDIX C: DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO
            BROMOCHLOROMETHANE 	   65

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

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                             LIST  OF  ABBREVIATIONS
AEL                Adverse-effect  level
A/G                Albumin/globulin
CAS                Chemical Abstract Service
CNS                Central nervous system
CO                 Carbon monoxide
C02                Carbon dioxide
CS                 Composite score
DWEL               Drinking water  equivalent level
PEL                Frank-effect level
GSH                Reduced glutathlone
HA                 Health advisory
HEC                Human equivalent concentration
HEO                Highest effective dose
Km                 Concentration 1n air at which uptake occurs at one-half
                   the maximum rate
Koc                Soil sorptlon coefficient standardized with respect
                   to organic carbon
Kow                Octanol/water partition coefficient
LC5Q               Concentration lethal to 50% of recipients
                   (and all other  subscripted concentration levels)
1050               Dose lethal to  50% of recipients
LDU                Log dose units
LED                Lowest effective dose
                                               i
LOAEL              Lowest-observed-adverse-effect level
MED                Minimum effective dose
NOAEL              No-observed-adverse-effect level
NOEL               No-observed-effect level
                                      xll

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                         LIST OF  ABBREVIATIONS  (cont.)
PEL                Permissible exposure limit
ppb                Parts per billion
ppm                Parts per million
ppt                Parts per trillion
RfD                Reference dose
RQ                 Reportable quantity
RV(j                Dose-rating value
RVe                Effect-rating value
SCE                Sister chromatic! exchange
SGOT               Serum glutamlc oxaloacetlc transamlnase
SGPT               Serum glutamlc pyruvlc transamlnase
SIC                Sister chromatic! exchange, Chinese hamster cells l£ vitro
STEL               Short-term exposure limit
TLV                Threshold limit value
TLV-STEL           Threshold limit value-Short-term exposure limit
TWA                Time-weighted average
UV                 Ultraviolet
Vmax               Maximum rate of uptake

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                               1.  INTRODUCTION
 1.1.   STRUCTURE AND CAS NUMBER
    Bromochloromethane  1s   the  common  name  for  the  chemical  known  by  the
 synonyms  chlorobromomethane,  methylene chlorobromlde, fluorocarbon 1011  and
 Halon  1011  (Chemllne,  1989).   The   structure,  molecular  weight,  empirical
 formula and CAS Registry number for bromochloromethane are as follows:

                                       Br
                                        I
                                    Cl-C-H
                                        I
                                       H

 Molecular weight:  129.39
 Empirical formula:  CH.BrCl
 CAS Registry number:  74-97-5
 1.2.   PHYSICAL AND CHEMICAL PROPERTIES
    Bromochloromethane  1s   a  clear,   colorless  liquid  with  a  sweet  odor
 (Stenger,  1978).   It  Is   completely  mlsdble  with  most  common  organic
 solvents.  Selected physical properties of bromochloromethane are as follows:
     Melting point:
     Boiling point:
     Density (25°C):
     Water solubility
       at 25°C:
     Vapor pressure
       at 25"C:
       at 15.72*C:
     Log Kow:
     A1r odor threshold:
     Water odor threshold:
-87.95°C
68.06°C
1.923 g/cm*

16.7 g/l

147.2 mm Hg
93.34 mm Hg
1.41
400 ppm
200 ppm
Rlddlck et al., 1986
Rlddlck et al., 1986
Rlddlck et al., 1986
Tewarl et al., 1982
Rlddlck et al., 1986
McDonald et al., 1959
Tewarl et al., 1982
Amoore and Hautala, 1983
Amoore and Hautala, 1983
0316d
     -1-
                     01/17/90

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Bromochloromethane 1s nonflammable and does  not  have  a flash point (Hawley,
1981; Dean, 1985).
1.3.   PRODUCTION DATA
    Recent production figures for bromochloromethane are not available.  The
public  portion  of  the  U.S.  EPA TSCA  Production File  for 1977  lists  Dow
Chemical (Midland, MI) as a manufacturer of  1-10  million pounds and Bruckman
Laboratories, Inc. (Memphis, TN) as a manufacturer of  10-100 thousand pounds
(U.S. EPA, 1977).
    The 1989 Directory of  Chemical  Producers (SRI,  1989)  lists Ethyl Corpo-
ration  (Magnolia,  AK)  as  a  current  manufacturer   of  bromochloromethane.
USITC (1988) lists Dow Chemical  as  a  manufacturer  during 1987.
    Bromochloromethane  Is   prepared   by    reacting   dlchloromethane  with
anhydrous  aluminum  bromide  (treatment  wUh  bromine  and  aluminum)  or  by
reaction  with   hydrogen  bromide   In  the  presence  of  an  aluminum  hallde
catalyst, followed by water washing and  distillation  (Stenger,  1978).
1.4.   USE DATA
    Bromochloromethane  1s   used  mainly  as   a  fire-extinguisher   fluid  1n
aircraft  and  portable extinguishers  (Stenger, 1978).   It  Is  also  used In
chemical synthesis (Kuney,  1988).
1.5.   SUHHARY
    Bromochloromethane  1s   a  clear,  colorless   liquid  wHh  a  sweet  odor
(Stenger,  1978).   It  Is   completely  mlsdble   wHh  most  common   organic
solvents  (Stenger,  1978) and  soluble 1n water to the  extent of 16.7 g/l at
25°C  (TewaM et al., 1982).  Current production  figures  are  not  available.
Recent  manufacturers  of bromochloromethane  Include  Dow  Chemical  and Ethyl
Corporation  (USITC,  1988;  SRI,  1989).  Bromochloromethane  1s  used mainly as
a  fire-extinguisher  fluid  In aircraft  and  portable extinguishers  (Stenger,
1978).  It 1s also used In  chemical synthesis (Kuney,  1988).

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                     2.  ENVIRONMENTAL FATE AND TRANSPORT
2.1.   AIR
    The relatively high vapor pressure  of  bromochloromethane  (147.2 mm  Hg  at
25°C)  Indicates  that  1t probably  exists  almost entirely  In  the  vapor  phase
1n  the ambient atmosphere  (Elsenrelch  et a!.,  1981).   Using the method  of
Atkinson  (1987),  the  rate  constant  for  the  vapor-phase reaction of  bromo-
chloromethane   with   atmospheric  HO-   can   be   estimated  at   9.55xlO~14
cmVmolecule-sec  at  25°C.   This  rate  constant corresponds  to  a  half-life
of  -168  days,  assuming  an  average  atmospheric H0«  concentration of  5xl05
molecules/cm3.
    Bromochloromethane  does not  absorb  UV   light  at  >290  nm  (Cadman and
Simons,  1966).   Therefore,  direct photolysis  will  not  occur 1n  the  tropo-
sphere.  However,  the  relatively long half-life predicted  for reaction with
HO*  suggests  that some  bromochloromethane may eventually diffuse Into  the
stratosphere, where direct  photolysis  can destroy the compound.   Based on a
half-life of  168 days and  a tropospheMc-to-stratospherlc turnover  time  of
30  years,   -2% of  tropospherlc  bromochloromethane  will   diffuse Into  the
stratosphere.
    Pertinent data regarding the physical  removal  of  bromochloromethane from
the  atmosphere were  not  located In  the  literature cited  In  Appendix  A.
Bromochloromethane's  water   solubility  of  16,700 rog/i  at  25°C  (TewaM  et
a!.,  1982)   suggests   that  physical  removal  by wet deposition  (rainfall.
dissolution  Into  clouds,  etc.)  Is possible.   However,  the  significance  of
physical removal cannot be verified because of  lack of experimental data.
2.2.   WATER
2.2.1.   Hydrolysis.    The  hydrolysis   half-life  of  bromochloromethane has
been  estimated at  -44  years  at  25°C  and  pH 7  (Mabey  and  Mill,  1978).
Therefore,  hydrolysis  1s not environmentally significant.
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2.2.2.   Photolysis.   UV  spectra,  as  determined  by  Cadman  and  Simons
(1966), predict that direct photolysis of  bromochloromethane has no  signifi-
cance 1n the environment since no absorption occurs at  >290 nm.
2.2.3.   Mlcroblal Degradation.  Tabak et  al.  (1981)  studied the  blodegrad-
abinty of  114  organic  priority pollutants on the  U.S.  EPA  Priority  Pollut-
ants  List  to ascertain m1crob1al  degradation  and acclimation periods.   The
Bunch and  Chambers  static  culture flask blodegradablllty  screening  test  was
performed  under  a  set  of  controlled  experimental  conditions  that  Included
the  following  parameters:   5  and  10  mg/i  concentrations   of   the   test
compound,  5 mg/i  of yeast  extract  In  the synthetic  medium,  7-day  static
Incubation  at 25°C  In  the  dark followed by  three  weekly subcultures  (total-
Ing 28 days  of  Incubation), and  Incorporation  of  settled domestic  wastewater
as the mlcroblal  Inoculum.   With respect  to  bromochloromethane,  100% loss of
compound was  observed  after  the  first  7-day Inoculation  period  and  after
each  subsequent  subculture.   The  results  Indicated significant  blodegrada-
tlon with rapid adaptation.
2.2.4.   Volatilization.   Based  upon  a  water  solubility  of   16,700  mg/i
and a vapor  pressure of 147.2 mm Hg at 25°C  (see  Section  1.2.),  the Henry's
Law   constant   for   bromochloromethane  can   be   estimated  to   be   0.0015
atm-mVmol.   A  Henry's  Law  constant  of  this   magnitude  Indicates   that
volatilization  from  environmental  waters  may  be  significant  and  rapid
(Thomas, 1982).   Using  a model  river  estimation  method (Thomas,  1982),  the
volatilization half-life of bromochloromethane,from a  river  1 m deep flowing
1   m/sec with a  wind  velocity  of  3 m/sec  1s  -4  hours.   The  estimated
volatilization half-life from a model environmental pond  1s -47  hours  (U.S.
EPA,  1986b).   These estimates Indicate that  volatilization  Is  a significant
environmental fate process  for bromochloromethane.


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 2.2.5.   Adsorption.   KOC  estimates  presented   1n  Section  2.3.1.  predict
 that  bromochloromethane  1s  not tightly  bound  to  soil  through  adsorption.
 Therefore,  It  Is  likely  that  adsorption of  bromochloromethane  1n  sediments
 does  not  compete with volatilization  or  blodegradatlon  In the disappearance
 of bromochloromethane from the aquatic environment.
 2.3.   SOIL
 2.3.1.   Adsorption/Leaching.   Pertinent  data  regarding  the  leaching  of
 bromochloromethane  1n  soil  were  not  located   In  the  available   literature
 dted  1n  Appendix  A.   A  K    value  of  21  can  be  estimated  using  a  water
 solubility  of  16,700  mg/l  and  the  following   regression-derived equation
 (Lyman,  1982):  log  KQC   =   3.64-0.55  log   (water  solubility).   This  K
 value Indicates very high soil mobility (Swann et a!., 1983).
 2.3.2.   H1crob1al  Degradation.   Pertinent  data  regarding  the  mlcroblal
 degradation of bromochloromethane  In soil were  not  located In the available
 literature cited  In  Appendix A.  The  blodegradatlon  results  of  Tabak et al.
 (1981)  discussed  In  Section  2.2.3.   suggest  that  blodegradatlon  of bromo-
 chloromethane  1n  soil  may  be significant.   Since no  other processes  are
 expected  to degrade  bromochloromethane  1n  soil   to  a  significant  degree,
 blodegradatlon  1s  probably  the ultimate  degradation  process,  although  the
 degradation rate of this process cannot be quantified.
 2.3.3.   Volatilization.   The  relatively  high  vapor  pressure   of  bromo-
 chloromethane  (147.2  mm  Hg  at  25°C)  suggests  significant  evaporation from
 dry  surfaces.   In  moist  soils, evaporation may  still  be  significant near
 soil  surfaces,  although  leaching may diminish  the  relative  significance of
 volatilization.
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2.4.   SUMMARY
    Bromochloromethane  1s   expected   to  degrade  relatively  slowly  1n  the
atmosphere.  Using the method of Atkinson  (1987), the  half-life  with  respect
to  HO-  reaction  can be  estimated  at  -168 days.  This  suggests  that -2%  of
tropospherlc  bromochloromethane  will  diffuse  Into  the  stratosphere  and  be
destroyed by direct photolysis.  Physical  removal from  the  atmosphere by  wet
deposition may be  possible, but Us  relative  significance 1s not  known.   A
single blodegradatlon  study (Tabak et a!., 1981) suggested that  blodegrada-
tlon  of  bromochloromethane  1s  an   Important  environmental   fate  process.
Volatilization  from  water   and  soil  surfaces  Is  a  major   fate  process.
Volatilization half-lives of 4 and 47 hours were estimated  for  a model  river
(1 m deep)  and  for an environmental  pond, respectively (Thomas,  1982;  U.S.
EPA, 1986b).  Bromochloromethane may  leach readily  1n soils, based  upon  an
estimated K   value  of 21   (Swann  et  a!.,  1983).  Aquatic  hydrolysis 1s  not
environmentally  significant (Mabey  and Mill,  1978).
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                                 3.  EXPOSURE
3.1.   WATER
    Bromochloromethane was  tentatively  Identified  1n  a  drinking water  sample
collected  In  Philadelphia,  PA,   1n  August  1976,  and  In  drinking  water
concentrates collected from New Orleans,  LA,  In  January 1976 (Suffet et al.,
1980; Lucas, 1984).
    Kaiser  et  al.  (1983)  collected  water  samples  from 95  stations on Lake
Ontario  and  16 stations  on the  lower  Niagara River 1n 1981  for  analysis  of
volatile  halocarbons.   Bromochloromethane  was  detected In  one sample  at  a
level of  10 ng/i  and  In  14 samples  at trace levels  (detection limit  equals
1 ng/l).
    Bromochloromethane was  qualitatively  detected  1n  seawater collected from
the Narragansett  Bay,  RI,  1n  1979-1980 (Wakeham et al.,  1983).   Monitoring
of  the  north  and south  Atlantic  Ocean  1n 1985  yielded  a  baseline  bromo-
chloromethane  concentration of  0.02  ng/l  (Class  and  Ballschmlter,  1988).
These Investigators  detected  the blogenlc  presence of  bromochloromethane  In
specific  algae that  occur 1n  the Atlantic  Ocean, and  suggested  that  the
occurrence  of  bromochloromethane  1n  marine  water and air  may  result,  1n
part, from biological emissions from these algae.
    Zoeteman et al.  (1981) detected a  bromochloromethane  concentration of 8
ug/l In a contaminated groundwater sample from the Netherlands.
    Halomethanes,   such  as  bromodlchloromethane,  chlorodlbromomethane  and
trlhalomethanes,  have been  detected  1n drinking waters  and  other  waters
during chlorlnatlon  (Allgeler  et al.,  1980;  Arguello et al.,  1979; Oore  et
al., 1982; Gould  et  al.,  1983).   Although bromlnatlon can  occur when natural
bromide  1s present In the water, the classic haloform  reactions responsible
for the  formation of  chloroform  and  other halomethanes during chlorlnatlon
will not produce bromochloromethane (NAS, 1980).

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3.2.   FOOD
    Pertinent data  regarding  the food monitoring of  bromochloromethane were
not located 1n the available literature cited 1n Appendix A.
3.3.   INHALATION
    The   average   concentrations  of   bromochloromethane  In  ambient   air
monitored throughout 1983 near Point  Barrow, AL  (In  the  Arctic) were  2.4-2.9
ppt (Rasmussen  and  Khalll,  1984).  The  higher  concentrations were found  In
the  winter   and   spring  when  the Arctic  haze  was   observed.   The  authors
suggested that the bromochloromethane  1n the Arctic  air  was  primarily due to
transport from anthropogenic sources.   Experimental  evidence  to support  this
was not given.
    Bromochloromethane  was   Identified  (detection   limit  of  0.1  ppb)   In
ambient  air   samples  collected  near  a  hazardous  waste   site  1n  New  Jersey
(Lareglna et  al., 1986).  The  actual  concentrations  1n  the  samples were  not
reported.
    Mean  bromochloromethane  concentrations  of  0.2-0.4  ppt were measured in
the air  over  the open Atlantic  Ocean (30°S-40°N) during  monitoring  In  1985
(Class  and  BallschmHer,  1988).  Bromochloromethane was  also  detected  in
open seawater and 1n macro algae collected  near  various  sampling  sites.   The
presence  of  bromochloromethane  In marine  air  may  be due,  In part,   to  Us
blogenlc  formation  In algae,  followed by   release  to seawater, with subse-
quent volatilization.  Monitoring of  baseline  concentrations  In  seawater  and
air tend to support  this supposition.
3.4.   DERMAL
    Pertinent  data   regarding  the  dermal   monitoring of  bromochloromethane
were not located 1n  the available literature cited 1n Appendix A.
0316d                               -8-                              01/17/90

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3.5.   SUMMARY
    Bromochloromethane has  been detected  1n  drinking  water (Suffet et  al.,
1980;  Lucas,  1984),  groundwater  (Zoeteman  et al.,  1981),  Lake Ontario  and
Niagara  River  water   (1-10  ng/i)  (Kaiser  et al.,  1983),  and  open  seawater
from   the  Atlantic  Ocean   (0.02   ng/4)   (Class   and   BalIschmlter,   1988).
Levels of  0.2-0.4 ppt have  been  Identified  1n  air  over the  Atlantic  Ocean
(Class and BallschmHer, 1988), while  levels  of  2.4-2.9  ppt were  detected In
the  Alaskan  Arctic  (Rasmussen  and KhalU,  1984).   Bromochloromethane  has
also been  Identified In air  samples collected near  a hazardous waste site 1n
New Jersey (Lareglna et al.,  1986).   It  has  been  suggested  that the  presence
of  bromochloromethane  In  marine water and  air may  be  due, In part,  to  Us
blogenlc  formation  1n  algae,  followed by release  to  seawater, with  subse-
quent  volatilization  (Class  and  Ballschmlter,  1988).   The  classic  haloform
reactions  responsible for the  formation  of  chloroform  and  other halomethanes
during chlorlnatlon  of drinking  water  will  not  produce  bromochloromethane
(NAS, 1980).
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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  \n  fathead  minnows,  Plmephales promelas.  exposed  to  80  mg/i  bromo-
chloromethane.   The  1C.- (duration  not  reported) for  this  species was  >80
mg/i.  No study details were provided.
4.1.2.   Chronic Effects on Fauna.
    4.1.2.1.   TOXICITY — Pertinent  data  regarding  the  effects of  chronic
exposure  of  aquatic  fauna  to  bromochlormethane  were  not   located  In  the
available literature cited In Appendix A.
    4.1.2.2.   BIOACCUMULATION/BIOCONCENTRATION — Hlatt   (1983)    detected
the  presence  of  bromochloromethane  In  tissues of rainbow trout,  Salmonella
qalrdnerl.  collected  from  the  Colorado  River  and  reported   an  estimated
whole-fish concentration of 8 yg/l.
4.1.3.   Effects on Flora.
    4.1.3.1.   TOXICITY — Pertinent  data  regarding  the  toxic  effects  of
exposure  of  aquatic  flora  to  bromochloromethane were not  located in  the
available literature cited In Appendix A.
    4.1.3.2.   BIOCONCENTRATION ~ Pertinent  data regarding  the  bloconcen-
tratlon potential of  bromochloromethane  1n  aquatic flora were not  located In
the available literature cited In Appendix A.
4.1.4.   Effects  on  Bacteria.   Pertinent   data  regarding  the  effects  of
exposure  of  aquatic  bacteria to bromochloromethane  were not  located  1n the
available literature dted in Appendix A.
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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  1n  the
available literature cited In Appendix A.
4.2.2.   Effects  on   Flora.    Pertinent   data  regarding  the   effects   of
exposure of  terrestrial  flora to bromochloromethane were not  located  In  the
available literature cited 1n Appendix A.
4.3.   FIELD STUDIES
    Pertinent  data  regarding the effects  of bromochloromethane  on  flora  and
fauna  1n  the  field  were not  located In   the  available literature  dted  1n
Appendix A.
4.4.   AQUATIC RISK ASSESSMENT
    The lack of  pertinent  data regarding  the  effects  of  exposure of aquatic
fauna and flora  to  bromochloromethane precluded the development  of  a  fresh-
water criterion  by  the  method of  U.S.  EPA/OWRS (1986).   Data  required  for
the  development   of  a  freshwater  criterion   Include  the  results   of  acute
assays with  a  salmon Id fish species, a warmwater  fish species,  a third fish
species or  an  amphibian,  planktonlc and   benthlc  crustaceans, an  Insect,  a
nonarthropod and  nonchordate  species and  an Insect or  species from a  phylum
not previously  represented.   The development  of a  freshwater  criterion will
also require data from chronic toxldty tests with  two species  of fauna  and
one  species  of  algae  or  vascular  plant   and  at least  one bloconcentratlon
study.
                                               v
    The lack of  pertinent  data regarding the  effects  of  exposure of aquatic
fauna and  flora  to  bromochloromethane  prevented the development  of a salt-
water criterion  by  the  method of  U.S.  EPA/OWRS (1986).   Data  required  for
the development of a saltwater  criterion  Include the results of acute assays
with two chordate species, a  nonarthropod and  nonchordate  species, a mysld

0316d                               -11-                             02/13/90

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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/i  for   fathead   minnows,  P.   promelas.  and  an  LC5Q  (duration  not
reported)  of  >80  mg/l  (U.S.  EPA,  1987).   Bromochloromethane has been  found
In  tissues  of  rainbow  trout, S.  qalrdnerl.  from  the  Colorado River.   The
estimated  whole-fish concentration  was 8 vg/l  (Hlatt,  1983).
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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  tn  a
closed  Inhalation  chamber  (Gargas  and Andersen,  1982).   Chamber concentra-
tion disappearance curves  Indicated that  absorption was blphaslc, consisting
of a rapid  equilibrium phase  that was  completed  1n 70-110 minutes and a slow
phase  that  was nearly  linear  after   this  time.   The  rapid uptake  phase
reportedly  represents  Initial  blood-.gas equilibrium.   The slow uptake phase,
reportedly  representing  metabolism  and loading Into poorly perfused tissues,
was a composite  of a  saturable process, which  predominated at low concentra-
tions, and  a  first-order  process.   Kinetic  constants  were determined for the
saturable  process;  these  Included  a K   of  91  ppm  (482  mg/m3)  and  a
V     of  10.5  mg/kg/hour.   Similar  data  were   reported  In  other  studies
(Andersen et al.,  1980;  Gargas and  Anderson, 1982).  Gargas et al. (1986a,b)
simulated  the  mixed  uptake kinetics of bromochloromethane In rats,  using a
physiologically-based  pharmacoklnetlc  model.    Information   regarding  the
extent  of   respiratory  absorption  from  Inhaled  bromochloromethane was  not
located In the available literature.
    Quantitative  oral absorption   data  were  not  located for  bromochloro-
methane.   The occurrence  of   systemic  effects  1n rats  and  mice  following
acute oral  exposure  to bromochloromethane (Section 6.1.3.) provides qualita-
tive evidence of gastrointestinal absorption.
    Male F344 rats were exposed to  2500-40,000 ppm  (13,230-211,681  mg/m*}
bromochloromethane In  air  for  4 hours 1n  dermal  vapor  absorption chambers
without  significant   Inhalation exposure  (McOougal  et  al.,  1985).   Blood
concentrations  of  bromide  showed  that absorption  of  bromochloromethane was


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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/cma/hour  was  calculated.
5.2.   DISTRIBUTION
    Svlrbely et al.  (1947) exposed  20 male  rats,  3  male  rabbits and 2 female
dogs  (strains  not  specified) to  -890 ppm (4710 mg/m3)  bromochloromethane
for 7  hours/day,  5  days/week for  14 weeks.   Both  total  and  organic  (vola-
tile)   bromide  were  elevated   1n  the  blood  and brain of the treated animals,
compared  with  unexposed  controls,  following  the  last  7-hour   exposure.
Levels of  total  bromide 1n the  blood  were  6-8 times greater   than  levels  In
the brain.   Similarly,  levels   of  organic   bromide  In  the blood  were  8-12
times greater than levels 1n  the brain.
    Rat  blood:a1r  and  rat t1ssue:blood  partition  coefficients  for  bromo-
chloromethane  have  been  determined   as   follows:   blood:a1r  (41.5^0.9),
fat:blood (325±3), 11ver:blood (29.2+0.5)  and muscle:blood (11.1+1.8).
    Pertinent data  regarding  the distribution of  bromochloromethane follow-
ing oral  exposure  were not  located  1n  the  available  literature  cited  In
Appendix A.
5.3.   METABOLISM
    Concentrations  of   Inorganic  bromide  Increased In  the  blood  of  rats,
guinea pigs, rabbits and dogs as a result  of  subchronlc  Inhalation exposure
to  bromochloromethane   (Svlrbely  et   al.,   1947;  Torkelson   et  al.,  1960;
MacEwen  et   al.,   1966)   (Section  6.1.1.1.).    Carboxyhemoglobln  levels
Increased 1n  male Long-Evans rats  given  a  single  IntraperHoneal  Injection
of  3.0  mmol  l*C-bromochloromethane/kg  (388.2  mg/kg) 1n  corn oil  (Kublc  et
al.,  1974).   These data  and  studies of  other dlhalomethanes  Indicate  that
bromochloromethane  Is   metabolized  by  two major   pathways:  an  oxldatlve,
cytochrome  P-450  mediated  pathway  yielding  CO  and  hallde   using putative


0316d                               -14-                             02/13/90

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 formyl  hallde  Intermediates,  and  a glutathlone-dependent  cytosollc  pathway
 producing  CO^  and  hallde (Gargas  et  al.,  1986a).   Based  on  physiological
 pharmacoklnetlc  analysis  of  plasma bromide  and  carboxyhemoglobln concentra-
 tions  In  rats  pretreated  with  pyrazole (which Inhibits mlcrosomal oxidation)
 and  2,3-epoxypropanol  (which  depletes  glutathlone)  and  exposed  to  bromo-
 chloromethane  by Inhalation,  Gargas  et  al.  (1986a)  concluded  that  bromide
 was  the preferred leaving group  1n the oxldatlve mechanism, resulting In the
 formation of  formyl  chloride rather  than formyl  bromide.   They proposed that
 a  significant  portion (-20-30X)  of the putative  formyl chloride Intermediate
 may  react with  GSH  and other cellular  nucleophlles,  Instead of spontaneously
 decomposing  to CO.    According  to  these  Investigators,  this portion  of the
 oxldatlve  pathway  probably  yields C0~;  a larger proportion  of  the  formyl
 chloride  Intermediate  decomposes   to  CO  when   cellular   GSH   1s  depleted.
 Metabolic  pathways   of   bromochloromethane  and  other  dlhalomethanes  are
 presented 1n Figure 5-1.
    Gargas  et  al.   (1986a)  evaluated  the  kinetics  of  bromochloromethane
metabolism, using 4-hour  Inhalation  studies with male F344 rats.  Gas uptake
 (disappearance)  was  determined during exposure  to  200-4000 ppm (1058-21,168
 mg/m3)  In  a   closed  exposure  chamber,  and  plasma  bromide  levels  and
 carboxyhemoglobln  levels  were  determined  following  exposure  to  constant
 concentrations  of   51-2006 ppm  (270-10,616  mg/m').   The  gas  uptake  data
 Indicated   that  metabolism   comprises   both  first-order   and   saturable
 components;  similar data  were found  In other,  studies  (see  Section  5.1.).
 The oxldatlve pathway was high affinity  and low capacity, with production of
 CO saturable  at bromochlormethane  concentrations greater  than ~200 ppm; the
maximum percent  carboxyhemoglobln  saturation  attained  was ~9X.   The maximum
0316d                               -15-                             02/13/90

-------
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0316d
                                  FIGURE 5-1
            Proposed Pathways for D1 halomethane (CH2X2) Metabolism
                         Source:   Gargas et  al.,  1986a
-16-
01/17/90

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


0316d                                -17-                              02/13/90

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period.   Information  regarding  the  rate  and  extent  of  bromochloromethane
excretion was not located In the available literature cited 1n Appendix  A.
5.5.   SUMMARY
    Bromochloromethane  1s   rapidly  absorbed  by rats  In  a   blphaslc  manner
following acute  Inhalation  exposure  (Gargas  and Andersen,  1982),  but quanti-
tative data are  not available  regarding  the  extent  of  Inhalation  exposure or
the rate  or  extent  of oral exposure.  There  appears  to  be some distribution
of  bromide  to   the  brain  of  dogs  during   subchronlc  Inhalation  exposure
(Svlrbely et al., 1947).   Rat  t1ssue:blood  partition coefficients  (Gargas et
al.,  1986a,b)  suggest that  bromochloromethane  will distribute more readily
to  fat  than  to  liver or  muscle.   Available  data  Indicate that bromochloro-
methane 1s metabolized by  two  major  pathways:  an oxldatlve,  cytochrome  P-450
mediated  pathway yielding  CO and  hallde  (putative  formyl  hallde  Inter-
mediate)  and  a   glutathlone  (GSH)-dependent  cytosollc pathway  producing C0~
and hallde  (Gargas  et  al., 1986a).   It  Is  proposed  that a portion  of the
oxldatlve  pathway  also  yields  a   significant amount  of   C0_  (Gargas  et
al.,1986a).  Information regarding  the rate and extent of bromochloromethane
excretion was not located In the literature cited 1n Appendix A.
0316d                               -18-                             02/13/90

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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-extinguishing
agent  had  gastrointestinal Irritations  (e.g.,  vomiting,  stomach  pains)  and
manifestations of  CNS  Involvement  (e.g.,  headache,  loss of  consciousness).
Acute  Inhalation  lethality  data  for  bromochloromethane are summarized  1n
Table  6-1.   These  data suggest  that mice  are more  susceptible than  rats
since  7-hour  exposures  resulted 1n  LC^s of  2268-2995  ppm  (12,000-15,850
mg/m3)  for  mice  (Svlrbely  et  al.,  1947;  Hlghman  et  al., 1948),  and  7-hour
exposures  to  5000  ppm  (26,460  mg/m3)  were not  lethal  for  rats  (Torkelson
et  al.,  1960).   Death was  often delayed In the mice  but generally  occurred
during treatment  1n the rats  exposed  to 10,000 ppm.  Signs  observed  1n  the
mice and rats  Indicated CNS toxlclty; these  Included  restlessness,  muscular
twitching,   uncoordinated movements,  labored respiration and  narcosis  1n  the
mice (Svlrbely et al.,  1947),  and drowsiness  and unconsciousness  In  the rats
(Torkelson et al.,  1960).
    Hlghman  et  al.  (1948) exposed  Swiss mice  (sex  not  reported)   to  7-17
mg/i  (7000-17,000   mg/m*   or  1323-3212  ppm)   bromochloromethane  by  Inhala-
tion 7  hours/day  on  1-5  successive  days.  H1stolog1cal  examination of  79
mice  Immediately  following  exposure showed   changes  that  Included  fatty
degeneration  of  the  liver after  single  exposures  of >7  mg/i  and  kidneys
after  single  exposures  of  >12 mg/i.   These effects were most  severe within
24  hours  of  exposure and  were  minimal   or  absent after  72 hours.   H1sto-
logUal examinations  were  conducted  on  groups  of  four  to five  female  rats
(strain not  reported) 24  hours  following Inhalation  exposure  to 600-40,000


0316d                               -19-                             05/17/90

-------
ppm  (113-7559  mg/m3)  bromochloromethane  for  durations  of  7-0.025  hours,
respectively   (Torkelson   et   al.,   1960).   Unequivocal   alterations   were
observed  only  In  the  liver  (small vacuoles  1n parenchyma  not typical  of
fatty  degeneration,  often accompanied   by   Increased  liver  weight).   The
minimum  concentration  producing  hepatic  effects after  7-hour   exposure  was
1500  ppm (7938 mg/m3);  exposure to  600  ppm (5175 mg/m»)  for  7  hours  did
not  produce   hepatic  effects  and  exposure  to  800  ppm (4234  mg/m3)  for  7
hours produced equivocal  hepatic histologlcal alterations.
    6.1.1.2.   ORAL EXPOSURE — Acute  oral toxldty data  are available  for
rats  and  mice.    Torkelson  et  al. (1960)  fed  (apparently by gavage)  an
unspecified  series of  single  doses  of   bromochloromethane  In  corn  oil  to
groups  of  five male  rats.  Observation  for 14  days   showed  that  all  rats
survived a dose of 5  g/kg and  all  rats died  within  24  hours  after  a  dose of
7  g/kg.   Additional  Information   regarding  this  study  was  not  reported.
Groups  of   10 mice  (strain  and  sex  not reported)  were  fed   (method  not
reported)  single   doses  of 500-4400  mg/kg  bromochloromethane   1n  olive  oil
(Svlrbely  et al.,  1947).  The  LD5Q  (6-day observation)  was   -4300  mg/kg.
Signs showing  dose-related CNS depression were  observed  at >500 mg/kg,  but
pathological  examinations  were not conducted and the  lowest  dose  producing
death was  not reported.   In  a related  study,  unspecified  numbers  of Swiss
mice  (sex  not  reported)  were   administered  single  gavage  doses of 0,  500,
3000  or  4500 rag/kg bromochloromethane In olive oil (Hlghman  et al.,  1948).
Histologlcal  examinations  conducted   <96 hours  after treatment  showed  no
                                               \
significant changes at 500 mg/kg.
    Effects  occurring at  >3000  mg/kg   Included  death,  pronounced  hepatic
hlstopathology  and other  pathological  changes   similar  to  those  resulting
from  acute  Inhalation  exposure.    Mice   killed  24  hours  after  the   Initial
0316d                               -20-                             05/17/90

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-21-
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exposure  had  severe  effects,  which Included  focal  subcapsular  necrosis  in
the  liver  (12/50),  hydropic  degeneration  1n the liver (5/50) and  hemoglobin
casts 1n a  few  renal  tubules  (8/32).   These effects  were  generally absent  or
slight In mice surviving >48 hours.
    Hlghman et  al.  (1948) also  treated  a group of  -32  Swiss mice  (sex  not
reported) with single gavage doses  of  3000  mg/kg bromochloromethane 1n  olive
on  on  1-10 consecutive  days.   Several  mice  were  sacrificed after each  of
the 10 doses.  Hlstologlcal examination of  mice that  died  or  were  sacrificed
showed fatty  degeneration of the liver,  kidney  and sometimes heart.   Other
hepatic  effects   Included   subcapsular   necrosis    (23/32  mice),   hydropic
degeneration  (8/32  mice)  and an  Increased  number  of mononuclear  perlportal
cells (8/32 mice).   Effects were most severe  24-48 hours after the Initial
dose and became  slight  after  80 hours.  Opacity of  the eyes  was observed  In
5/19 mice surviving <3 days.
    Occluded  dermal  application   of  bromochloromethane   (5000   mg/kg)   to
clipped skin of  five  rabbits  resulted In burns and  denaturatlon of the skin
with four  surviving after  24  hours (Torkelson  et  al.,  1960).  Application
without occlusion caused only slight defatUng.
6.1.2.    SUBCHRONIC.
    6.1.2.1.   INHALATION EXPOSURE  — Groups of  20  male and  20  female rats
were exposed  to  nominal  concentrations of 0,  500 or  1000 ppm bromochlorome-
thane  (490  ppm  [2593  mg/m«]   or   1010  ppm  [5345  mg/m»]  actual  average
concentrations)  7  hours/day for  79-82 exposures In  114  days (Torkelson  et
al.,  1960).   These  concentration   correspond   to  0,   166.97-173.31  and
344.18-357.25 mg/kg/day assuming  a  body  weight of 0.35 kg,  a breathing rate
of  0.223  m'/day and  a  50% absorption  of  the  Inhaled  dose.    Because  no
effects were observed  In  male  rats  at  166.97-173.31  mg/kg/day,  a group of 10


0316d                               -22-                             05/17/90

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

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


0316d                               -24-                             05/17/90

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 7  hours/day,  5  days/week  for  79-82 exposures  In  114 days.   These  dose
 correspond  to  0,  137.93-143.16  and  284.32-295.09  mg/kg/day assuming  a  body
 weight  of  3.8  kg, a breathing rate of 2  mVday and a 50%  absorption  of  the
 Inhaled  dose.    Evaluations  of  body  weight,  survival  and  pathology  were
 conducted  as  1n  the  rat  study.   Blood  bromide  and  blood  nitrogen  were
 determined  In  all treated and control  rabbits except one  treated  female In
 the  137.93-143.16  mg/kg/day  group.   Hematologlcal   examinations  were  not
 performed.   The hlstologlcal  examinations  showed  testlcular alterations  in
 one  of  the males  exposed  to  284.32-295.09 mg/kg/day  (Section 6.5.).   Blood
 bromide  levels  were elevated  1n both sexes  at both  exposure levels.   Both
 sexes  appeared  to  have  elevated  liver  weights,  but the  small numbers  of
 rabbits  Involved  precluded  definitive  analysis.    Results  of  the  blood
 nitrogen determinations were not  reported.
    Torkelson et al. (1960) also exposed  one  male  and one  female dog (strain
 not  reported)  to 0 or  370  ppm  (1958 mg/m*)  bromochloromethane  7 hours/day,
 5 days/week  for  135 exposures  In 195 days.   These  doses correspond to 0 and
 66.93 mg/kg/day  assuming  a body weight of 12.7 kg, a breathing  rate  of 4.3
mVday  and  a   50% absorption of  the  Inhaled  dose.   Evaluations  of  body
weight,  survival,   blood  bromide,   blood   nitrogen  and   hematology  were
 conducted  as   In  the  rat   study.   Pathological   examinations   were  not
performed.  The only effect reported was  elevated blood bromide levels.
    Groups of  50 male  and  50 female  albino  rats  (descendants  of  germ-free
Wlstar  rats) were exposed  to  nominal  concentrations  of  500  or   1000  ppm
bromochloronethane 6 hours/day,  5  days/week for 6 months for  a  total  of 124
exposures  (MacEwen  et  al.,  1966).   Actual measured  concentrations averaged
 515  and  1010   ppm  (2725  and  5345 mg/m1),  respectively.    These  doses
correspond to 0,  149.51 and 293.26 mg/kg/day  assuming an average body weight


0316d                               -25-                             05/17/90

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of  0.35  kg,  a  breathing  rate of  0.223  mVday and a  50% absorption of the
Inhaled dose.  Fifty chamber air-exposed male rats served as  controls.  Body
weight,  serum  bromide  levels and survival  were evaluated  throughout the
treatment period.   After  2 and 4  months  of exposure, groups  of  10 rats  In
each  treatment  group and  five control  rats  were subjected  to white  blood
cell  count  and clinical  chemistry determinations and  sacrificed  for  organ
weight  and   histologlcal   examinations.   The  remainder  of  the   rats  were
evaluated at the  termination  of  treatment.   The clinical tests consisted  of
SGOT,  SGPT,  total  protein,  albumin  and  A/G ratio.   It  1s  not   specified
whether  organs  other   than  Hver,   kidney  and   spleen were  weighed and
hlstologlcally  examined.   The only  effect  attributable  to  treatment  was a
significantly (p<0.01) dose-related  decreased  body weight gain 1n male rats
at  >149.51   mg/kg/day,  the  magnitude  of   which   Increased  with   increasing
duration of  exposure.   Blood  bromide levels  were  Increased at both  concen-
trations throughout  the  treatment  period.   The investigators  indicated that
similar  levels  of  blood   bromide  1n humans  may   produce mild sedation  and
suggested that lethargy and altered  eating habits may have  been responsible
for the reduction In body weight  gain.
    HacEwen  et  al.  (1966)  also exposed four male  and  four female beagle dogs
to  0,  515  or 1010  ppm  (2725  or  5345 mg/m'}  bromochloromethane 6  hours/day,
5 days/week  for  6 months  for  a  total of 124 exposures.  These doses  corre-
spond  to  0,  79.45  and  155.84 mg/kg/day assuming  an  average body  weight  of
12.7  kg,  a  breathing  rate  of   4.3 m»/day  and  a  50% absorption  of  the
                         9
Inhaled dose.  Toxldty was evaluated as In  trie  rat  study  wUh the addition
of  other clinical  chemistry tests.  Evaluations were performed on  groups  of
two  treated  and  one control  dog  after  2 and  4 months  and  on  the remaining
0316d                               -26-                             05/17/90

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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 a!.,  1947).  The measured concentration was  generally 11% lower
than  the  calculated  value  (I.e.,  890  ppm   or 4710  mg/m3).   This   dose
corresponds to 299.20  mg/kg/day  assuming an average body weight  of 0.35  kg,
a  breathing  rate  of  0.223  mVday   and a  50%  absorption  of  the  Inhaled
dose.  A control  group appears  to have  been  used, but  specific  Information
was not  reported.   Weight gain and  survival throughout  treatment, histology
after  67 exposures  (19  rats)  and  bromide  levels  In  the  blood and  brain
Immediately after  the  last  exposure were  evaluated.   It  Is  not Indicated
whether  tissues  other  than  liver and  spleen  were hlstologlcally examined.
Effects  consisted  of  a  slight  Increase of  hemoslderln In  the   spleen  and
Increased concentrations of  bromide In the blood  and brain.
    Svlrbely et  al.  (1947)  also exposed three  male  rabbits and  two  female
dogs  (strains not  reported)  to 1000  ppm  bromochloromethane  (measured concen-
tration  ~890  ppm  [4710 mg/m*])  7 hours/day,  5  days/week for  14  weeks.   In
rabbits  this dose  corresponds  to  247.16 mg/kg/day  assuming an average body
weight of 3.8 kg,  a  breathing rate  of 2 mVday  and a 50% absorption  of  the
Inhaled dose.   In  dogs  this  dose corresponds to  158.99  mg/kg/day  assuming an
average  body  weight  of 12.7 kg, a  breathing  rate of  4.3  m'/day and  a  50%
absorption of the  Inhaled dose.   Toxldty was evaluated  as  In  the rat study
with  the addition  of hematologlcal examinations  1n  both  species at "regular"
Intervals, liver function evaluation (bromsulfaleln excretion) and  urlnaly-
s1s In  dogs  at  "regular" Intervals  and blood   Inorganic bromide determina-
tions   1n dogs  throughout the  treatment period.   Effects  consisting of  a
0316d                               -27-                             05/17/90

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slight  Increase of  hemoslderln  1n  the spleen and kidneys and an  increase  In
fat  In  the  kidneys occurred  In  the  dogs.  Inorganic bromide accumulated  1n
the  blood of  the  dogs  throughout  treatment  (terminal  concentrations  were
-300-360 mg/dl).
    Hlghman et al.  (1948) exposed  100  Strain  A  mice  (sex  not  reported,  age 2
months) and 45 C3H  mice  (sex  not reported,  age  3-7  months)  to 1000  ppm (5292
mg/m3)  bromochloromethane.   Use  of  control   groups  was   not   Indicated.
Exposures were  administered 5 times/week  with  occasional  long rest  periods
of  unspecified  frequency   and  duration  when  necessary,  as  Indicated  by
mortality  and  abnormal  general  condition.    Calculation   of   a   dose  1n
mg/kg/day  1s  uncertain  given  these  experimental   conditions.    Surviving
Strain A mice each  received a  total  of 64 exposures  of  3-7  hours  In a period
of ~5 months  (approximately  143.97-335.93 mg/kg/day corresponding  to 3  or  7
hour  dosing  schedule  and  assuming  an average  body weight  of  0.03 kg,  a
breathing rate  of  0.039 m'/day  and  a 50% absorption  of  the  Inhaled  dose;
surviving C3H mice each received a  total  of  49 exposures of 3-7 hours  In a
period of 4 months  (approximately  150.43-351  mg/kg/day  corresponding  to  3  or
7  hour  dosing schedule  and  assuming  an  average body weight  of  0.03  kg,  a
breathing rate  of  0.039 mVday  and  a 50%  absorption of the  Inhaled dose).
Most of the  mice  died at unspecified. Irregular  Intervals  during treatment,
and  some  died   or   were   sacrificed at  unspecified   intervals  following
treatment.   A  total  of  21 mice  (one Strain A  and  20 CjH)  survived  until
terminal  sacrifice  at 13-16  months  of age.  HlstologUal  examinations  were
conducted on  mice  that  were  sacrificed  and  some (number  unspecified)  that
died.   The  mice  that  died  during  exposure  generally  showed slight  fatty
changes 1n  the  liver and  kidneys.   Extensive tubular necrosis of  the Inner
zone of the  renal cortex was observed 1n  two strain  A  mice that  died during


0316d                                -28-                             05/17/90

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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 In  the mice  that survived until
 terminal sacrifice.
    6.1.2.2.   ORAL  EXPOSURE — Pertinent  data  regarding   subchronlc  oral
 exposure of humans  or  animals to  bromochloromethane  were  not located 1n the
 available  literature cited 1n Appendix A.
 6.1.3.   Chronic
    6.1.3.1.   INHALATION  EXPOSURE — Pertinent data  regarding  the  chronic
 Inhalation  exposure of  humans  or  animals  to bromochloromethane were  not
 located 1n the available literature cited 1n Appendix A.
    6.1.3.2.   Oral  Exposure —  Pertinent  data  regarding  the  subchronlc  or
 chronic oral  exposure of  humans  or  animals  to bromochloromethane were  not
 located In the available literature cited In Appendix A,
 6.2.   CARCINOGENICITY
    Pertinent  data  regarding  the  carclnogenlclty of  bromochloromethane  to
 humans or  animals  following  exposure by Inhalation,  oral  or other routes of
 exposure were not located In the available literature cited  1n Appendix A.
 6.3.   GENOTOXICITY
    Data from genotoxlclty  tests  with  bromochloromethane  are  presented  1n
 Table  6-2.   Consistently  positive  results  were  observed  1n  the  reverse
mutation test in Salmonella  typhlmurlum (Simmon  et  al., 1977;  Strobel  and
 Grummt, 1907; Osterman-Golkar et  al.,  1983).    Metabolic  activation  was  not
 required but  Increased the  response  1n  TA98 and  TA100 (Strobel and Gruramt,
 1987).  Positive results  were  also observed  In  the  reverse  mutation  and
 lambda prophage  Induction  tests  1n Escher1ch1a coll (Osterman-Golkar et al.,
 1983).  Negative results were observed  In the  mltotlc  recombination  test In


0316d                               -29-                              08/20/90

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Saccharomyces  cerevlslae   (Simmon,   1976).    In   the   only  mammalian   test
located,  bromochloromethane  Induced  SCEs   and  chromosomal  aberrations  1n
Chinese hamster FAF cells (Strobe! and Grummt, 1987).
6.4.   DEVELOPMENTAL TOXICITY
    Pertinent  data  regarding  the  developmental   toxldty of  bromochloro-
methane were not located 1n the available literature cited  1n Appendix A.
6.5.   OTHER REPRODUCTIVE EFFECTS
    Torkelson  et  al.   (1960)  exposed groups  of  10 male guinea  pigs  (strain
not  reported)  to   0,  490  or  1010  ppm  bromochloromethane  7   hours/day,  5
days/week  for  79-82  exposures  1n 114  days  (see  Section  6.1.1.1.).   These
dose  correspond  to 0, 124.79-129.53 and  257.23-267.00  mg/kg/day assuming an
average body  weight of  0.84  kg,  a  breathing rate  of  0.4 mVday and  a 50%
absorption  of the Ihnaled  dose.   H1stolog1cal  examination  of  the  testes
showed  decreased   spermatogenesls  In the tubules  and  flbrosls  1n  numerous
tubules with   only  germinal  epithelium   remaining  1n   the  other  tubules  at
257.23-267.00  mg/kg/day.   The   average  testes-to-body  weight  ratio  was
decreased at  257.23-267.00  mg/kg/day (0.38  vs.  0.46 at 0  and   124.79-129.53
mg/kg/day),  but  statistical  significance  was  not reported.   Reproductive
function was not evaluated.
    Torkelson  et al.  (I960) also exposed groups of  two male rabbits (strain
not  reported)  to  0,  490  or 1010  ppm  (2593 or  5345 mg/m")  bromochloro-
methane  7  hours/day,  5  days/week  for   79-82 exposures   In  114 days  (see
Section   6.1.1.1.).    These  doses   correspond   to  0,   137.93-143.16  and
284.32-295.09  ng/kg/day  assuming an average  body weight  of  3.8  kg,  a
breathing  rate of 2  m'/day  and a 50% absorption  of  the  Ihnaled  dose.
H1stolog1cal examination  showed  testlcular  tubule  changes, characterized by
decreased  spermatogenesls  with  replacement   flbrosls 1n  one of the rabbits


0316d                               -31-                             08/20/90

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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  In
the 284.32-295.09 mg/kg/day group  (0.08) was  lower  than  the  ratios  for  the 0
and   137.93-143.16  mg/kg/day   groups   (0.16  and   0.17,   respectively).
Reproductive function was not evaluated.
6.6.   SUMMARY
    Inhalation  LCrQs  for  mice   for  7-hour exposures  ranged  from  2268-2995
ppm (Svlrbely  et  al.,  1947; Hlghman  et al.,  1948)  and exposure  to  5000  ppm
(26,460  mg/m3) for  7  hours  was  not  lethal  for  rats  (Torkelson  et  al.,
1960).  Rats survived a  single  oral  dose of  5 g/kg, and all  rats  died within
24 hours  after  a  dose  of 7 g/kg (Torkelson  et al., 1960).  An oral  L0-n  of
-4300  mg/kg was  determined for  mice  (Svlrbely  et al.,  1947).   Signs  and
pathological effects  of  acute  Inhalation  and oral  exposure to  bromochloro-
methane are  similar;  principal  effects Include CNS depression and  degenera-
tion of the liver.
    Subchronlc  Inhalation  studies  of bromochloromethane  have  been  conducted
with  rats,  mice,  guinea pigs,  rabbits and  dogs   (Torkelson  et  al.,  1960;
MacEwen et al., 1966; Svlrbely  et  al.,  1947;  Hlghman  et al., 1948).   Concen-
trations  ranged  from  66.93  mg/kg/day  (dogs)  to  728.88 mg/kg/day  (mice);
exposures were  usually  5-7 hours/day,  5 days/week  ranging  from  14  weeks  to
-6  months.    Generally,  minor   effects   such  as   decreased   body  weight,
Increased relative  liver and kidney  weight  and reversible  liver and kidney
hlstologlcal alterations occurred  at  concentrations >500  ppm 1n most species
                                              T
evaluated for  these  endpolnts.   Torkelson  et al. (1960)  found that relative
liver  weight  was  Increased  In  rats  at concentrations of  125.96 mg/kg/day.
With hlstologlcal  effects  occurring  at  166.97-173.31  mg/kg/day,  exposure to
1000 ppm  (143.97-335.93  mg/kg/day) caused death  and marked liver  Injury In


0316d                               -32-                             08/20/90

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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  toxlclty or  teratogenldty
of  bromochloromethane  were  not  located.   Decreased  spermatogenesls   and
flbrosls  occurred  In  the  tubules  of the  testes  of  guinea pigs and  rabbits
that   were   subchronkally   exposed   to  344.18-357.25  and   257.23-267.00
mg/kg/day  respectively,  to  bromochloromethane by  Inhalation  (Torkelson  et
al., 1960).  The functional significance of these  effects  was not  evaluated.
    The   cardnogenldty   of   bromochloromethane  has   not  been   evaluated.
Bromochloromethane was  mutagenlc  1n Salmonella  typh1mur1um and  EscheMchla
coll  bacteria  (Simmon et  al.,  1977; Osterman-Golkar  et  al.,  1983;  Strobel
and  Grummt,  1987)  and   Induced  SCE and chromosome aberrations  1n  Chinese
hamster cells jjn vitro (Strobel and Grummt, 1987).
0316d                               -33-                             08/20/90

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                     7.   EXISTING  GUIDELINES AND STANDARDS
7.1.   HUMAN
    ACGIH  (1989)  recommends  a  TLV-TWA   of  200  ppm  (1058  mg/m»)  and  a
TLV-STEL of  250  ppm (1320 mg/m3)  for  occupational exposure  to  bromochloro-
methane, but  deletion  of the  STEL  1s  proposed.    The  recommendation  for  the
TLV-TWA  Is  based  primarily  on the  subchronlc  animal  studies evaluated  1n
Section  6.1.1.1.  (ACGIH, 1986).   OSHA  (1989) has  promulgated a PEL  of  200
ppm (-1050 mg/m3) for occupational exposure to bromochloromethane.
    Based on  Inhalation toxlclty  data,  U.S.  EPA  (1988)  has  derived  1-day,
10-day,  longer-term  (child)  and longer-term (adult) drinking  water  HAs of 50
mg/a,   50   mg/l,   13.1  mg/l   and   45.7   mg/l,    respectively,   for   bromo-
chloromethane.   U.S.  EPA (1988)  also  calculated  a  provisional  DWEL  of  4.6
mg/l for bromochloromethane.
7.2.   AQUATIC
    Guidelines  and  standards  for  the  protection  of  aquatic  life  from
exposure to   bromochloromethane were not  located  1n the available literature
dted In Appendix A.
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                              8.   RISK ASSESSMENT
8.1.   CARCINOGENICITY
8.1.1.   Inhalation.   Pertinent   data   regarding   the  cardnogenldty  of
bromochloromethane  to humans  or  animals  by  Inhalation  exposure  were  not
located  1n  the  available  literature  cited  1n  Appendix  A.   Bromochloromethane
has   not   been   scheduled  for  cardnogenldty  testing  by   the   National
Toxicology Program (NTP,  1989).
8.1.2,   Oral.   Pertinent  data  regarding  the  cardnogenldty  of   bromo-
chloromethane to  humans or  animals by oral exposure were  not  located  1n  the
available literature cited In Appendix A.
8.1.3.   Other  Routes.    Pertinent  data  regarding  the  cardnogenldty  of
bromochloromethane to humans or animals by other routes  of exposure  were  not
located 1n the available literature dted In  Appendix A.
8.1.4.   Height of Evidence.   Pertinent  cardnogenldty  data for humans  and
animals were  not  located  1n  the  available  literature dted In Appendix A;
therefore,  bromochloromethane  1s  categorized  1n U.S.  EPA  we1ght-of-evidence
Group  D  (Not  Classifiable  as  to  Human  Cardnogenldty)  using the U.S.  EPA
(1986c) classification scheme.
8.1.5.   Quantitative  Risk   Estimates.    Derivation   of   a   cardnogendc
potency  factor  for  bromochloromethane  Is  precluded  by  the  lack  of  appro-
priate data.
8.2.   SYSTEHIC TOXICITY
8.2.1.   Acute Exposure.
    8.2.1.1.   INHALATION — Acute    Inhalation     lethality    data     for
bromochloromethane are  summarized  1n Table  6-1.    These  data suggest  that
mice are more susceptible to bromochloromethane exposure  by  Inhalation than
are rats.  Hallmarks of CNS toxldty 1n  mice  and  rats  Includes restlessness,


0316d                               -35-                              08/20/90

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muscular  twitching,  uncoordlnatedmovements,   labored  respiration,  narcosis
(mice), drowsiness  (rats) and  unconsciousness  (rats).   Hlghman  et  al.  (1948)
demonstrated  fatty  degeneration of  the  liver  In  Swiss mice after  a  single
expousre  >7  mg/i bromochloromethane  and degeneration  of  the  kidneys  after
a  single  exposure to >12 mg/t bromochloromethane.  Torkelson  et  al.  (1960)
demonstrated  that  liver  and  kidney  degeneration  1n  rats  occured  after  a
single  7   hour  expousure  to  1500  ppm,  equivocal  results  at  800  ppm,  no
degeneration at 600 ppm bromochloromethane.
    8.2.1.2.   ORAL — Torkelson  et  al.  (1960)  determines   that  a  7   g/kg
dose of bromochloromethane  was lethal  to all  rats  within  24  hours of  dosing
but  that   all  rats  survived  a dose  of 5  g/kg.   Svlrbely  et  al.  (1947)
determined a  6-day  LD,.. to  be 4300  mg/kg 1n mice.  Signs of  CNS  depression
were  observed at  doses >  500 mg/kg.   Hlghman  et al. (1948) demonstrated
effects 1n  mice  at  > 3000  mg/kg  Including  pronouned  hepatic hlstopathology
and other acute pathological changes.  Mice  killed 24  hours  after  dosing had
severe   effects    Including   focal    subcapsular   necrosis    and   hydropic
degeneration  of   the  liver  and hemoglobin  casts  1n  a  few  renal  tubules.
These effects were generally absent or slight 1n mice surviving >48 hours.
    Occluded  dermal  application  of  5000  mg/kg  bromochloromethane to  the
clipped  skin of  five  rabbits resulted  1n  burns and  denaturatlon of  the
skin.  Application without occlusion only caused slight defattlng.
8.2.2.   Subchronlc Exposure.
    8.2.2.1.   IMHALATIOH — Sufficient  data  *re  available  for  derivation
of  a  subchronic  Inhalation  RfD   for   bromochloromethane.   Inhalation  RfD
derivation  Involves  evaluating  the  quality  of  the   Inhalation exposure-
response data, converting  exposure  concentrations associated with effects  in
0316d                               -36-                             08/20/90

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animals  to  human  equivalent  concentrations  and  dividing these by uncertainty
factors  and modifying factors.  For gases  such  as  bromochloromethane,  which
produce  systemic  effects and  reach steady  state  within the  dally  exposure
length,  HECs  are  calculated by adjusting  the animal  exposure concentrations
to  equivalent  continuous  exposure concentrations  and  multiplying  by  the
ratio  of the blood/gas  partition  coefficient  1n the experimental animal  to
that 1n  humans.
    Evidence  for  rapid  attainment  of  steady state  with  bromochloromethane 1s
provided by  Gargas  and  Andersen   (1982),  who  found that  the  rapid  uptake
phase  1n  rats was   completed 1n  70-110  minutes   (see Section  5.1.).   A
blood/gas partition  coefficient  for bromochloromethane  of  41.5  was  reported
for  rats (see Section  5.2.),  but  not  for  humans.   Insufficient data  for  a
blood/gas partition  coefficient for bromochloromethane  was  found for  humans;
therefore,  the ratio  of  the  animal  to  human blood/gas partition coefficients
1s assumed  to be  1.   Therefore,  HECs   (Human equivalent concentrations)  for
extraresplratory  effects   from   bromochloromethane  are  Identical   to  the
adjusted animal exposure concentration.
    Torkelson et  al.  (1960)  exposed 10 female  rats  (strain not reported) to
370  ppm  (1958 mg/m*) bromochloromethane  7 hours/day  for  135  exposures  1n
195 days, and groups of  20  rats/sex  (strain not reported)  to 490  ppm (2593
mg/m') or  1010 ppm   (5345  mg/m")  bromochloromethane 7 hours/day for  79-82
exposures  1n 114  days.  These  doses  correspond   to  125.96  mg/kg/day  (370
ppm);  166.97-173.31  mg/kg/day (490  ppm);  and * 344.18-357.25  mg/kg/day (1010
ppm) assuming an  average body weight  of  0.35 kg, a  breathing rate  of 0.233
mVday and   a 50*  absorption of  th  Inhaled dose.   Effects attributed  to
treatment   Included   Increased   I1ver-to-body   weight    ratios   at   >125.96
mg/kg/day,   liver  hlstologlcal   alterations   (e.g.,   slight  flbrosls  and


0316d                               -37-                             08/20/90

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vacuollzatlon)  In  females  at  166.97-173.31  mg/kg/day  and  both  sexes  at
344.18-357.25 mg/kg/day  and  Increased  kidney-to-body  weight  ratio  In both
sexes  at  344.18-357.25   mg/kg/day.   Abnormal  hematology.  Increased   blood
nitrogen levels,  decreased  body  weight  gain or symptoms of bromlsm were  not
observed at  any  of the exposure  concentrations.   As the  Increased relative
liver  weight  was  not  accompanied  by  hlstologlcal  alterations  or   other
effects  at  125.96 mg/kg/day,  this  concentration  represents  a  NOAEL  and
166.97-173.31 mg/kg/day  1s  the  lowest  LOAEL  (Recs. #1  and 2, Appendix  C).
Dogs  (I/sex)  were also exposed  to 370  ppm (1958 mg/m")  bromochloromethane
7  hours/day  for  135  exposures  1n  195  days.   This  exposure corresponds to
66.93 mg/kg/day assuming an average bodw weight of  12.7  kg,  a  breathing rate
of  4.3 mVday  and a  50X  absorption  of  the  Inhaled  dose.   There  were no
effects  on  body   weight,  blood  nitrogen   or   hematology,  but  hlstologlcal
examinations  and   organ  weight  measurements were  not  performed.  Although
66.93 mg/kg/day 1s  a  NOEL 1n dogs (Rec. #7, Appendix C),  this  value  1s not
suitable for  quantitative  risk assess- ment because of the small number of
animals and lack of histology.
    Albino rats (50/sex/concentrat1on)  and beagle dogs  (4/sex/concentrat1on)
were  exposed  to  515  or  1010 ppm  (2725  or  5345 mg/m")  bromochloromethane  6
hours/day  for  124  exposures  1n  6 months  (MacEwen  et  a!.,  1966).  In rats
these doses  corresponds  to 149.51 and  293.26 mg/kg/day assuming  an  average
body  weight  of  0.35 kg,  a breathing   rate  of  0.223  mVday  and  a  50%
absorption of  the  Inhaled  dose.   In beagle dogs these doses  correspond to
79.45 and  155.84  «g/kg/day  respectively, assuming an average  body weight of
12.7  kg,  a   breathing  rate  of  4.3 mVday  and  a  50%  absorption  of  the
Inhaled dose.  Decreased body weight gain  In male rats  at >149.51 mg/kg/day,
possibly from  lethargy associated with  elevated blood  bromide concentration,
was  the  only effect  attributed  to treatment.  Hlstologlcal  examinations of

0316d                               -38-                             08/20/90

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 the   liver   and   other   tissues,   organ   weight   measurements   and  clinical
 chemistry  evaluations  (Including  SCOT and SGPT) were  unremarkable.   In  this
 study,  149.51 mg/kg/day  1s  considered  a  LOAEL  associated  with  reduced growth
 rate  1n rats possibly from bromide-Induced lethargy (Rec.  #8, Appendix C).
    Twenty  male   rats  (Rec. #10,  Appendix  C),  two female  dogs  (Rec.  #12,
 Appendix  C) and  three  male  rabbits  (Rec. #11,  Appendix  C)   (strains  not
 reported)  were  exposed  to  890 ppm (4710 mg/m3)  bromochloromethane  (nominal
 concentration)  7  hours/day,  5  days/week  for  67  exposures   (-14  weeks)
 (Svlrbely  et al.,  1947).  In rats this  dose corresponds  to  299.20 mg/kg/day
 assuming  an average  body  weight of  0.35  kg,   a  breathing  rate of  0.223
 m'/day  and  a   50%  absorption of  the  Inhaled  dose.   In  dogs  this  dose
 corresponds  to 158.99  mg/kg/day  assuming an average body  weight of  12.7 kg,
 a  breathing rate of  4.3 m»/day  and  a  50%  absorption of the  Inhaled dose.
 In  rabbits  this   dose  corresponds to  247.16  mg/kg/day  assuming  an  average
 bodw  weight  of  3.8 kg,  a breathing  rate of 2.0 m'/day and  a  50* absorption
 of  the  Inhaled  dose.   Slightly  Increased  hemoslderln occurred 1n  the  rats
 (spleen) and  dogs (spleen  and kidneys), and  Increased fat occurred  1n the
 kidneys  of dogs.   Other hlstologlcal  alterations  such  as  liver were  not
 observed and body weight measurements (all  species),  liver  function evalua-
 tion  (dogs,  rabbits)  and urlnalysls  (dogs,  rabbits) were unremarkable.   The
 247.16  mg/kg/day  concentration,  therefore, 1s  a  NOEL   In  rabbits  and  the
 299.20 mg/kg/day Is a LOAEL 1n rats and  158.99 mg/kg/day 1s a LOAEL 1n dogs.
    Guinea  pigs  (I0/sex/concentrat1on) (Rec. f3, Appendix C),  mice  (10/sex/
concentration)  (Rec. #4, Appendix C)  and rabbits (2/sex/concentrat1on) (Rec.
#5, Appendix C)   were  exposed to 0,   490  or 1010  ppm (2593 or  5345  mg/m*)
bromochlormethane 7 hours/day  for 79-82 exposures  In  114 days  (Torkelson  et
al.,  1960).  In  guinea  pigs these doses correspond to 0.  124.79-129.53 and
257.23-267.00 mg/kg/day respectively,  assuming  an average  body weight  of

0316d                               -39-                             08/20/90

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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 1s a LOAEL  In the guinea pigs and the  340.67-353.59
mg/kg/day concentration  1s  a  LOAEL 1n mice, associated  with decreased body
weight,  Increased relative liver and  kidney weights and neutrophHla (female
guinea pigs).  Adverse effects 1n rabbits were  limited to testlcular lesions
at the 284.32-295.09 mg/kg/day  level
    One  hundred  Strain A  mice  and  45  C3H  mice (sexes  not reported) were
exposed  for  3-7  hours/day to  1000 ppm  (5292  mg/m*)  bromochloromethane  for
<64 exposures 1n 5 months  (<143.97-335.93 mg/kg/day assuming an average body
weight of 0.03 kg,  a  breathing rate  of 0.039  mVday  and  a 50% absorption
of the  Inhaled  dose) and  49 exposures 1n 4 months (150.43-351.00 mg/kg/day
assuming  an average  body  weight  of  0.03  kg,  a  breathing rate  of  0.039
mVday and  a 50% absorption of  the  Inhaled dose), respectively (Hlghman et
al.,   1948).    The  exposures   were   administered   5   days/week  but  were
Interrupted   by occasional  long  rest periods  (duration and  frequency  not
reported) when necessary,  as  Indicated by  mortality or  abnormal general
condition.  Host of  the mice (numbers  not  reported) died  during the  exposure
period and  the mice that died  generally had  slight  fatty  changes   1n  the
liver  and  kidneys.  The  exposure schedule  was  not  reported   In  sufficient
detail   to   permit   consideration  of   this  study  for   quantitative  risk
assessment.


0316d                               -40-                             08/20/90

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    Acute  toxldty  data  Indicate  that  the critical  effects  of exposure  to
bromochloromethane   appear  to   be  CNS   Involvement  and   hepatotoxIcHy
(Rutsteln,  1963;  Svlrbely  et  al.,  1947;  Torkelson  et  al.,  1960).   In  the
subchronlc  Inhalation  studies, reduced  rate of  body weight  gain and elevated
liver  weight  were  the  first effects reported  at  the  lower  concentrations.
In  the absence  of  histopathologlcal alteration  or biochemical evidence  of
organ  damage  or  Impaired  function,  elevated  liver  weight   alone  may  be
considered  a   nonadverse  effect.    Similarly,  a  slight  reduction   1n  growth
with no evidence  of  organic  Injury or compromised function  may be  considered
nonadverse.   Several   studies,  however, have  shown  that  bromide  1on Is  a
consistent  metabolite   of  bromochloromethane   1n   the  mammalian  species
studied, and  that blood levels of  bromide Increase 1n a dose-related manner
1n  animals  exposed  by  Inhalation  (Svlrbely  et al.,  1947;  Torkelson  et al.,
1960;  MacEwen  et al.,  1966; Gargas et al.,  1986a).  MacEwen  et  al.  (1966)
postulated  that   the  reduced body  weight  gain observed  In rats  exposed  to
bromochloromethane may  have  resulted from  lethargy Induced  by elevated blood
bromide  levels.   The  conservative  approach,  therefore,   1s  to  consider
reduced body weight gain  a potentially  adverse effect of Inhalation exposure
to bromochloromethane.
    Reduced body  weight  gain  was  reported  1n all species  studied  (except
rabbits)  1n the  subchronlc  Inhalation studies  reviewed herein.   The NOAEL
for this  effect   1n  rats  was the 125.96 mg/kg/daylevel  In  the 195-day study
(Rec.  #1,  Appendix  C)  by  Torkelson et  al. (I960).  Using  this NOAEL  and  an
uncertainty  factor  of  1000  (10  to  reflect  uncertainties associated  with
estimating a human equivalent  concentration from  animal exposure data, 10  to
reflect uncertlntles  associated  with extrapolation from a  subchronlc study
of  chronic  toxldty  endpolnts,  and  10  to  protect  the  most  sensitive


0316d                               -41-                             08/20/90

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Individuals) a  chronic  RfD of 1.26E-02 mg/kg/day  Is  calculated.   Confidence
In  the  key study  1s  low because of  the  relatively  small number  of  animals
and  lack  of treated males  at  the lowest  (NOAEL)  concentration.   Confidence
1n  the  data base and RfD  are low because  of  the lack  of  developmental  and
reproductive  data   and  the  lack of  adequate  evaluation of  the  effect  of
bromochloromethane  (elevated  blood bromide  levels)   on  CMS function,  which
could be the critical effect of exposure.
    Two previous  risk  assessments of bromochloromethane  have  been performed
by  the  U.S. EPA.   An RfD  was not calculated  1n a Health  and  Environmental
Effects Profile  (U.S.   EPA,  1985) because  the  Torkelson  et  al.  (1960)  rat
study  was   considered  Inadequate.  It  did not  clearly  define  a  NOAEL  for
liver effects  and  did not  test  males at the  NOAEL concentration.   The same
NOAEL,  however,  was considered sufficient basis  for  deriving  drinking water
longer-term  HAs  and  a   provisional  DWEL  for  bromochloromethane  (U.S.  EPA,
1988).
    8.2.2.2.   ORAL — Information  on   the   subchronlc  oral   toxlclty   of
bromochloromethane  was  not located.   Acute exposure  data,  however,  Indicate
that the critical  effects  of  both Inhalation  and oral exposure are CNS signs
and  hepatotoxlclty.    In   addition,   the  critical   effects   of  subchronlc
Inhalation  exposure  to  bromochloromethane  are  reduced  body  weight  and
hepatotoxlclty.  The respiratory  tract  does  not appear to  be  the  target
organ for  Inhalation exposure  to bromochloromethane.  The data  reviewed 1n
Section  5.3.  suggest  that  metabolism  Involving dehalogenatlon would  be
                                               \
expected  with  either   route  of  exposure.   Therefore.  1n the   absence  of
subchronlc  oral  data,  U  1s  appropriate  to use  Inhalation  toxlclty data to
derive a subchronlc oral RfO for bromochloromethane.
0316d                               -42-                             08/20/90

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

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This RfO  1s  the  same as a previously  derived  RfD  of 0.13 mg/kg/day used  to
calculate  a  provisional   DWEL  for   lifetime   exposure   (U.S.   EPA,   1988).
Confidence 1n the key study Is  low (see  Section  8.2.1.1.),  and  confidence  1n
the data base and RfD are  low  because of  the lack of  oral  toxldty  data.
0316d
.44.                             08/20/90

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                           9.   REPORTABLE  QUANTITIES
9.1.   BASED 0* SYSTEMIC TOXICITY
    The  toxldty  of  bromochloromethane Is discussed 1n  Chapter  6,  and Inha-
lation data suitable  for  RQ  derivation are summarized  1n Table 9-1.  Chronic
Inhalation data and oral data useful for RQ derivation are not available.
    As  shown   1n  Table 9-1,  subchronlc  Inhalation exposure  to  bromochloro-
methane  produced  decreased body  weight  gain  1n  rats,  mice  and  guinea  pigs
(MacEwen  et  al.,  1966;  Torkelson  et  al.,  1960),  Increased  relative  organ
weights  (liver and/or kidneys) In  rats,  mice and  guinea  pigs (Torkelson et
al.,  1960), hlstologlcal alterations 1n the  liver  1n  rats  (Torkelson et al.,
1960) and  kidneys  In dogs (Svlrbely et al.,  1947), Increased hemoslderln 1n
the spleen of  rats (Svlrbely et al.,  1947)  and  testlcular effects  1n guinea
pigs  and  rabbits  (Torkelson  et al.,  1960).   Death 1n mice  (Hlghman et al.,
1948) was  not  Included  because the exposure protocol  was  not  presented 1n
sufficient detail from which  to estimate a transformed animal  dose.
    Derivations of  CSs for  bromochloromethane,  based on  the lowest equiva-
lent  human dose  associated with  each  effect 1n Table 9-1,  are  presented 1n
Table 9-2.   Changes  1n  body  and  organ  weights  are assigned an  RV   of 4.
The  most  appropriate RV   for  the  kidney  hlstologlcal  alterations  1s  5
because  the  effects   were  slight  and reversible.  Lesions In   the  liver
Included flbrosls, which  may not  be reversible;  liver  lesions were assigned
an  RV  of  6.   Increased  hemoslderln  warrants  an RV   of   1 since hematln
      e                                                 e
formation  1s most appropriately  viewed  as  a Biochemical  effect.   The  most
appropriate RV  for  the  testlcular alterations  1s 6  because 1t  cannot be
determined 1f  the effects were sufficient  to  Impair  fuctlon.   Five  of  the
six CSs  correspond  to an  RQ  of  1000.   The highest  CS  (12.22)  for  liver
lesions   1n rats  {Torkelson  et al., 1960)  1s used as  the basis for  the RQ
0316d                               -45-                             08/20/90

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-------
 (Table  9-3).   This  RQ  1s  the  same as  a previously  derived  RQ (U.S. EPA,
 1985),  but  the previous evaluation did  not  evaluate  the studies by  HacEwen
 et al.  (1966) and Svlrbely et al. (1947).
 9.2.    BASED ON CARCINOGENICITY
    Pertinent  data   regarding  the  cardnogenldty  of bromochloromethane  to
 humans  or  animals  by Inhalation, oral  or other routes of exposure were  not
 located  1n  the  available  literature cited  1n Appendix  A.   Because  of  the
 lack  of cardnogenldty data,  bromochloromethane 1s categorized 1n U.S.  EPA
 we1ght-of-ev1dence  Group  D  (Not  Classifiable  as to  Human  Cardnogenldty).
 Chemicals  In  EPA  Group  0  are  not  ranked  for  cancer  hazard  or assigned
 cancer-based RQs.
0316d                               -49-                             08/20/90

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                                   TABLE  9-3
                              Bromochloromethane
           Minimum  Effective  Dose  (MED) and Reportable Quantity  (RQ)


Route:                  Inhalation
Species/Sex:            rat/female
Dose*:                  203.65
Duration:               114 days (79-82 exposures, 7 hours/day)
Effect:                 h1sto!og1cal lesions  In liver
RVd:                    2.04
RVe:                    6
CS:                     12.22
RQ:                     1000
Reference:              Torkelson et a!., 1960

*Equ1valent human dose
0316d                               -50-                             08/20/90

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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  Hyg1en1sts).   1989.
Threshold  Limit  Values  and  Biological  Exposure  Indices  for  1989-1990.
Cincinnati, OH.   p. 16, 46.

Allgeler,  G.O.,  R.L.  Mulllns,  Jr.,  D.A.  Wilding,  J.S.  Zogorskl and  S.A.
Hubbs.    1980.    TMhalomethane  levels  at   selected   water   utilities  1n
Kentucky, USA.  Environ. Sc1. Res.  16: 473-490.

Amoore, J.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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Andersen, M.E., N.L. Gargas, R.A.  Jones and L. Jenkins, Jr.  1980.  Determi-
nation of  the  kinetic  constants for metabolism of  Inhaled toxicants  in vivo
using gas uptake measurements.   Toxlcol. Appl.  Pharmacol.  53(1):  100-116.
                                              4
Arguello, M.O., C.O. Chriswe11,  J.S.  Fritz  et al.   1979.  Tr1halomethanes 1n
water: A report on  the occurrence,  seasonal variation 1n concentrations, and
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0316d                               -51-                             08/20/90

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Atkinson, R.   1987.  A  structure-activity  relationship  for  the  estimation  of
the  rate  constants for  the  gas-phase reaction  of  OH radicals with  organic
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Cadman, P.  and J.P. Simons.   1966.   Reactions  of  hot halomethyl  radicals.
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Chemllne.   1989.   Chemical Information Service  (CIS).   On-line  computer  data
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Class,  T.H.  and  K. BallschmHer.   1988.    Chemistry  of   organic  traces  1n
air.   VIII.  Sources and distribution of  bromo- and bromochloromethanes  1n
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35-46.

Crockett,  P.W.,  B. K1l1an,  K.S.  Crump  and R.B.  Howe.   1985.   Descriptive
Methods for  Using  Data  from Dissimilar  Experiments to Locate  a  No-Adverse-
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Company,  Inc.  under Contract  No.  68-01-6807 for Environmental Criteria and
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Dean, J.A.  1985.   Lange's Handbook  of Chemistry, 13th  ed.   McGraw-Hill  Book
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Dore,  M., N.  Merlet,  J. De  Laat  and   J.  Golchon.   1982.   Reactivity  of
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0316d                                -52-                             08/20/90

-------
 Ourkln,  P. and  H.  Meylan.   1989.   Users  Guide for  D2PLOT:  A  Program for
 Dose/Duration  Graphs  Version  2.00.   Prepared by  Chemical  Hazard Assessment
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 E1senre1ch,  S.J.,  B.B.  Looney and  D.J.  Thornton.   1981.   Airborne organic
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 Gargas,  M.I.  and  M.E.  Andersen.   1982.   Metabolism of  Inhaled bromlnated
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 Gargas,  M.L.,  H.J.  Clewell,  II  and M.E.  Andersen.   1986a.   Metabolism of
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 Gould, J.P.,  R.E.  Ramsey, M.  G1abba1  and  F.G.  Pohland.   1983.  Chapter 36.
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0316d                               -53-                             08/20/90

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

H1att,  M.H.   1983.   Determination  of  volatile  organic  compounds  1n  fish
samples by vacuum distillation and fused  silica capillary gas  chromatography-
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Hlghman, B., J.L. Svlrbely,  W.F.  von Oettlngen, M.C.  Alford and  L.J.  Pecora.
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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.U. Anders,  R.R.  Engel, C.H.  Barlow and  M.S.  Caughey.   1974.
Metabolism of dlhalomethanes  to  carbon  monoxide.   I. In. vivo  studies.   Drug
Metab. Dlspos.   2(1):  53-57.

Kuney,  J.H.   1988.   Chemcyclopedla 1989.    Volume  7.   American  Chemical
Society, Washington, DC.  p.  179.

Lareglna.  J.,  J.W.  BozzelH,  R. Markov  and. S. Glantl.   1986.   Volatile
organic  compounds at  hazardous  waste  sites and  a sanitary  landfill  1n New
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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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concentrates.   EPA-600/1-84-020A.   NTIS PB85-128221.  Columbus  Labs.  Health
Eff. Res. Lab., Columbus, OH.  p. 144, 174, 255.

Lyman,  W.J.    1982.   Adsorption  coefficient  or   soils  and  sediments,   in:
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Mabey,  W.  and  T.   Mill.   1978.   Critical  review of  hydrolysis of  organic
compounds  1n water   under  environmental   conditions.   J.  Phys. Chem.  Ref.
Data.  7: 383-415.

MacEwen, J.D.,  J.M.  McNerney, E.H.  Vernot  and D.T. Harper.   1966.   Chronic
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Mantel,  N.   and M.A.  Schnelderman.    1975.    Estimating   "safe"  levels,  a
hazardous undertaking.  Cancer Res.   35: 1379-1386.

McDonald, R.A.,  S.A. Shrader and  O.R.  Stull.   1959.   Vapor pressures and
freezing points of 30 organlcs. J. Chem. Eng. Data.  4: 311-313.

McOougal, J.N., 6.U.  Jepson,  H.3. Clewell  and  M.E.  Andersen.  1985.   Dermal
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0316d                               -55-                             08/20/90

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NAS  (National  Academy  of Science).  1980.   Drinking  Hater  and Health.   Vol
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NTP (National Toxicology Program).   1989.   Management  Status  Report.   7/7/89.

OSHA  (Occupational  Safety   and  Health  Administration).   1989.   29  CFR  Part
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Osterman-Golkar,  S., S. Hussaln, S. Halles,  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.   KhalH.  1984.   Gaseous  bromine  1n the  Arctic and
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Rlddlck,  J.A., H.B. Bunger  and  T.K. Sakano.   1986.  Organic  solvents:  Physi-
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Rutsteln,  H.R.   1963.   Acute  chlorobromomethane  toxldty.   Arch.  Environ.
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Simmon,  V.F.   1976.   .In  Vitro Microbiological  MutagenlcUy  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
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 Strobe!,  K. and  T. Grummt.   1987.   Aliphatic  and  aromatic  halocarbons  as
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 Suffet,  I.H.,  L.  Brenner  and  P.R.  Cairo.   1980.   GC/MS  Identification  of
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 Svlrbely, J.L., B.  Hlghman,  H.C. Alford and  W.F. von Oettlngen.  1947.  The
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0316d                               -57-                             08/20/90

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Swann,  R.L.,   D.A.   Laskowskl,   P.J.  McCall,   K.   Vander   Kuy  and   H.J.
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Tabak, H.H., S.A.  Quave,  c.I.  Mashnl  and E.F.  Barth.   1981.   B1odegradab1l-
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Tewarl,  Y.B.,  M.M.  Miller, S.P.  Waslk   and  O.E.  Martlre.   1982.   Aqueous
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0316d                               -58-                             08/20/90

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 U.S.  EPA.   1986
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U.S.  EPA.    1988.   Drinking  Water  Health  Advisory  for  Bromochloromethane.
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U.S.  EPA/OWRS.    1986.   Guidelines  for  Deriving Numerical  National  Water
Quality  Criteria  for  the  Protection  of  Aquatic Organisms  and Their  Uses.
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volatile organic  compounds 1n  Narragansett Bay Rhode Island.   Can.  J.  Fish
Aquat. Sd.  40:  304-321.

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

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                                  APPENDIX A

                              LITERATURE SEARCHED



    This  HEED  Is  based  on  data  Identified  by  computerized  literature

 searches of the following:


              CHEMLINE
              TSCATS
              CASR online (U.S. EPA Chemical Activities Status Report)
              TOXLINE
              TOXLIT
              TOXLIT 65
              RTECS
              OHM TADS
              STORET
              SRC Environmental Fate Data Bases
              SANSS
              AQUIRE
              TSCAPP
              NTIS
              Federal Register
              CAS ONLINE (Chemistry and Aquatic)
              HSD8
              SCISEARCH
              Federal Research 1n Progress


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

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

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

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

    Clayton,  G.D.  and  F.E.  Clayton,  Ed.   1981.  Patty's  Industrial
    Hygiene  and Toxicology,  3rd rev.  ed.,  Vol.  2B.   John Wiley  and
    Sons, NY.  p. 2879-3816.
0316d                               -61-                             08/20/90

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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, M. and  D.  Eckroth,  Ed.   1978-1984.  K1rk-0thmer  Encyclo-
    pedia of Chemical Technology,  3rd ed.  John  WHey and  Sons,  NY.   23
    Volumes.

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

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

    Jaber,  H.M.,  W.R.  Mabey,  A.T.  L1eu,  T.W.   Chou and  H.L.  Johnson.
    1984.   Data  acquisition   for  environmental  transport  and  fate
    screening  for compounds  of Interest  to  the Office  of  Solid Waste.
    EPA  600/6-84-010.    NTIS  PB84-243906.    SRI  International,   Menlo
    Park, CA.

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

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

    Sax, I.N.   1964.  Dangerous Properties of  Industrial  Materials,  6th
    ed.  Van Nostrand Relnhold Co.,  NY.

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

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

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

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

    Wlndholz,  M.,  Ed.  1983.   The Merck  Index,  10th  ed.  Merck  and Co.,
    Inc., Rahway,  NO.

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

-------
     In  addition,  approximately  30 compendia of  aquatic toxldty  data  were

reviewed.  Including the following:


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

     Johnson,  W.W.  and  M.T.  Flnley.   1980.  Handbook of  Acute  Toxldty
     of  Chemicals  to  F1sh  and  Aquatic   Invertebrates.    Summaries  of
     Toxldty  Tests  Conducted  at  Columbia National  Fisheries  Research
     Laboratory.   1965-1978.   U.S. Oept.  Interior,  F1sh  and  Wildlife
     Serv.  Res. Publ. 137, Washington, DC,

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

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

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

-------
















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

-------
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   (Inhalation Exposure)
                  e.wi            e.ei             e.i

                   HUHRN EOUIU DURflTIQN (fraction  Hftspan)

                             DWELO? HEIHOD
   Key:
F
L
n
N
FEL
LOAEL
NOAEL
NOEL
       Solid lint • Advtrse Effects  Boundary   %
       Dashed lint • No Advtrst  Efftcts Boundary
                                   FIGURE C-1

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

-------
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                         0061            0.01             0.1

                         HUhflH EOUIU OURflTION (fraction 1 if wan)

                               CENSORED DRIB METHOD
  Key:
        F

        L
        n

        N
PEL

LOAEL
NOAEL

NOEL
       Solid line . Adverse Effects Boundary
       Dashed line • Mo Adverse Effects  Boundary
                                   FIGURE  C-2


           Dose/Duration  -  Response Graph for Inhalation  Exposure to
                    Bromochloromethane: Censored Data Method
                      (Expanded Experimental Concentration)
0316d
                                   -67-
                                                          08/20/90

-------
      1000000
        1688
           6.0601
          19
  (Inhalation Exposure)
BCrtlNHRL D2
             0.061            1.61             6.1
              HUHRN EQUIU OURRTIQN (fraction 1 if wan)

                        IMUOOPHEIHOO
   Key:
        F
        L
        n
        N
FEL
LOAEL
NOAEL
NOEL
       Solid line - Adverse Effects  Boundary
       Dashed line - Ho Adverse Effects  Boundary

                                   FIGURE C-3

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

-------
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                          HUMflN EQUUI DUBflTlON (fraction lifttpan)
(Inhalation Exposure)             CENSORED DflTfl METHOD
  BOIINHflL D2;
    Key:
          F
          L
          n
          N
FEL
LOAEL
NOAEL
NOEL
        Solid  line  •  Adverse Effects Boundary
        Dashed  line • No Adverse Effects  Boundary
                                    FIGURE C-4

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

-------
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                                                                -K-
HUHflH EQUIU DUWTIOH (friction lifwpan)

          DWELOP NEIHOO
                                                                     j	I
                                                                          8.81
  Key:    F . FEL
         N . NOEL

      Solid lint - Advtrst  Effects Boundary
      Dashed line . No Adverse  Effects Boundary
                                     FIGURE C-5

     Dose/Duration - Response Graph  for  Oral  Exposure to Bronochloromethane:
                                  Envelope Method
  03164
                                       -70-
                                                                         08/20/90

-------
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       1688
 BCI10RRL D2
 (Oral Exposure)
                    •HIS
                                                                  46-
                                                                       J	L
                                                                             e.ei
               HUttflN EQUIU DUBflTION (fraction liftspan)

                    CENSORED MIR METHOD
   Key:    F » PEL
           N . NOEL

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

        Response  Graph for Oral  Exposure to Bromochloromethane;
                  Censored  Data  Method
0316d
                                      -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) 1s  drawn  by  Identifying  the
lowest  adverse  effect  dose  or  concentration  at  the  shortest  duration  of
exposure at which  an  adverse effect occurred.  From  this  starting  point,  an
Infinite line  1s  extended  upward,  parallel  to the dose axis.   The starting
point  Is  then  connected to  the  lowest  adverse effect  dose  or  concentration
at  the  next  longer duration of  exposure  that has  an adverse effect dose  or
concentration  equal   to  or   lower  than  the  previous  one.   This process  1s
continued  to  the  lowest  adverse  effect  dose  or  concentration.   From  this
point,  a  line  parallel  to  the duration  axis  Is  extended Infinitely to  the
right.  The adverse effects  region lies  above the adverse  effects boundary.
    Using the envelope method, the  no adverse effects boundary  (dashed  line)
1s  drawn  starting with  the  point  representing   the  highest  no  adverse
effects  dose  or  concentration.    From  this  point,  a  line  parallel to  the
duration axis  1s  extended  to  the  dose  or concentration axis.   The starting
point 1s then connected  to the next equal or lower no adverse effect dose or
concentration at  a longer duration of  exposure.   When this process can  no
longer  be  continued,  a  line parallel  to  the dose or  concentration axis  1s
dropped  to the  duration axis.   The no adverse effects  region lies  below the
no  adverse  effects   boundary.   At  either  ends  of  the   graph  between  the
adverse  effects and no  adverse effects  boundaries  are  regions  of ambiguity.
                                               * *
The area (1f any)  resulting  from Intersections of  the adverse effects and no
adverse effects boundaries Is defined as  the region of contradiction.
    In the censored data method,  all  no  adverse effect points located 1n the
region  of  contradiction are  dropped from  consideration  and the  no adverse
effects  boundary  1s  redrawn  so  that   H  does  not  Intersect   the  adverse

0316d                               -72-                             08/20/90

-------
 effects  boundary,  and no region of  contradiction  Is  generated.   This method
 results  1n  the most conservative definition of the no adverse effects region.
     Figures  C-l  and  C-3 present the Inhalation dose/duration-response graphs
 generated  by the envelope method.   The adverse effects  boundary  1s defined
 by  the LOAEL for  liver  hlstologlcal alterations  1n  mice (Rec.  #17), LOAELs
 for  kidney  hlstologlcal  alterations 1n dogs  (Rec. #12),  reduced body weight
 and  elevated organ  weights  1n guinea  pigs   (Rec.  #3),   liver  hlstologlcal
 alterations  1n rats  (Rec.  #2)  and  for  reduced body weight 1n rats (Rec. #8).
 Using  the  envelope  method  (Figures C-l  and C-4),  the  no  adverse effects
 boundary  1s defined  by  the  acute  NOEL for mortality 1n  rats  (Rec.  #14), a
 NOAEL  for  slightly  Increased  hemoslderln In  the  spleen  of  rats  (Rec.  #10)
 and  a  NOAEL for  Increased  liver  weight  1n  rats  (Rec.  #1).  Using   the
 censored data method  (Figures  C-2 and  C-4),  the no  adverse effects  boundary
 Is  defined  by  the  NOEL for  liver hlstologlcal  alterations 1n  rats  (Rec.
 #16),  the  NOEL  1n rabbits  (Figure C-2.  Rec.  #5)  or dogs  (Figure C-4,  Rec.
 #7) and  the  NOAEL  for liver  hlstologlcal  alterations In rats (Rec. #1).   The
 subchronlc  and  chronic  RfDs  for  bromochloromethane  are  based  on  the  NOAEL
 for liver hlstologlcal alterations  1n rats (Rec. #1).
    Figures  C-5 and  C-6  present the oral  dose/duration-response graphs.   The
 adverse  effects  boundary 1s  defined by FfLs  for mortality 1n rats (Rec.  #1)
 and mortality 1n mice (Recs. #3,  4 and 6).  In  Figure C-5 (envelope  method),
 the no adverse effects  boundary 1s  defined by the NOEL for mortality In rats
 (Rec.  #2)  and the NOEL  for  mortality and hlsiopathology  1n  mice (Rec. #5).
 Using  the censored data  method  (Figure C-6),  the no adverse effects  boundary
 Is defined  by a single  value,  the NOEL  for  mortality  and hlstopathology in
mice  (Rec.  #5).    Figures  C-5  and  C-6 emphasize  that additional  oral  data
 (I.e.,  for  longer  duration  exposures)  are   needed  to  Identify a  maximal
 region of no adverse effects.
0316d                                -73-                              08/20/90

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

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

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




Species:
Sex:
Effect:
Route:

Rats
Female
NOAEL
Inhalation

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

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

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

-------
 RECORD 12:     Species:   Rats        Body Weight:  0.35 kg
               Sex:       Both        Reported Dose:  2593 mg/m3
               Effect:    LOAEL       Converted Dose:  166.97-173.31 mg/kg/day
               Route:     Inhalation  Exposure Period:  114 days
                                      Duration Observation:  114 days

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

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

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

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

Number Exposed:     20       20       20
Number Responses:   NR       NR       NR
Type of Effect:     WGTIN    WGTIN    WGTOC
SHe of Effect:     LIVER    KIDNY    BODY
Severity Effect:    4        4,4

10/sex,  79-82 exposures.   Exposure  concentrations:   2593 and
5345 mg/m*  (490 and 1010  ppm).   Effect on  kidney  weight only
1n  males.    No  effects   on   histology   or  blood  nitrogen.
Testlcular effects  (decreased  weight,  spermatogenesls) at 5345
mg/m» (257.23-267.00 mg/kg/day).

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

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

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

               Number  Exposed:     10       10       10
               Number  Responses:   NR       NR       NR
               Type of  Effect:     WGTOC    WGTIN     WGTIN
               SHe of  Effect:     BODY     LIVER     KIONY
               Severity  Effect:    444

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

Citation:      Torkelson et a!., 1960
RECORD #5:




Species:
Sex:
Effect:
Route:

Rabbits
Both
NOEL
Inhalation

Body Weight: 3.8 kg
Reported Dose: 2593 mg/m3
Converted Dose: 137.93-143.16 mg/kg/day
Exposure Period: 114 days
Duration Observation: 114 days
Comment:
Citation:
                        Molecular Weight:  129.39
                        Inhalation hours/day:   7.00
                        Inhalation days/week:  4.8509-5.0351
                        Inhal. Exp. days:  79.00-82.00
                        Assumed Absorption Inhalation:  50%

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

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

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

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

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

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

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

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




Species:
Sex:
Effect:
Route:

Dogs
Both
NOEL
Inhalation

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

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

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

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RECORD #8:
Comment:
Citation:
Species:   Rats            Body Weight:   0.32 kg
Sex:       Both            Reported Dose:   2725  mg/m3
Effect:    LOAEL           Converted Dose:   149.51  mg/kg/day
Route:     Inhalation      Exposure Period:         6 months
                           Duration Observation:   6 months

                           Molecular Weight:  129.39
                           Inhalation hours/day:  6.00
                           Inhalation days/week:  4.8222
                           Inhal. Exp. days:  124.00
                           Assumed Inhalation Absorption:   50X

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

50/sex.   Exposure concentrations:  2725 and 5345  mg/m3  (515
and 1010 ppm}  (149.51  and  293.26 mg/kg/day, respectively).   No
effect  on  body  weight  1n  females.  No  effect on  histology,
organ weights or clinical chemistry at either exposure level.

MacEwen et al., 1966
RECORD #9:




Species:
Sex:
Effect:
Route:

Dogs
Both
NOEL
Inhalation

Body Weight: 12.7 kg
Reported Dose: 5345 mg/m3
Converted Dose: 155.84 mg/kg/day
Exposure Period: 6 months
Duration Observation: 6 months
Comment:
                                          Molecular We1ght:l29.39
                                          Inhalation hours/day:  6.00
                                          Inhalation days/week:  4.8222
                                          Inhal. Exp. days:  124.00
                                          Assumed Inhalation Absorption:
                                                           50%
Citation:
Number Exposed:     8
Number Responses:   0
Type of Effect:
Site of Effect:
Severity Effect:    3

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

MacEwen et al., 1966
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:  50X

Number Exposed:     20
Number Responses:    NR
Type of Effect:     OTHER
SHe of Effect:     SPLEN
Severity Effect:    1

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

Svlrbely et al., 1947
RECORD #11:




Species:
Sex:
Effect:
Route:

Rabbits
Male
NOEL
Inhalation

Body Weight: 3.8 kg
Reported Dose: 4710 mg/m1
Converted Dose: 247.16 mg/kg/day
Exposure Period: 14 weeks
Duration Observation: 14 weeks
Comment:
Citation;
                                          Molecular Weight:  129.39
                                          Inhalation hours/day:  7.00
                                          Inhalation days/week:  4.7857
                                          Inhal. Exp. days:  67.00
                                          Assumed Inhalation Absorption:
                                                           50%
Number Exposed:     3
Number Responses:   0
Type of Effect:
SHe of Effect:
Severity Effect:    3

Exposure concentration  1s equivalent  to 890  ppm.  Histology
evaluated after 67 days.   No  effect  on  histology,  weight gain,
hematology, liver function or urlnalysls.

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

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

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

Number Exposed:     2
Number Responses:   NR
Type of Effect:     DEGEN
SHe of Effect:     KIDNY
Severity Effect:    5

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

Svlrbely et al., 1947
RECORD #13:




Species:
Sex:
Effect:
Route:

Rats
Both
PEL
Inhalation

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

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

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

-------
 RECORD #14:
Comment:


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

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

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

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

Torkelson et al., 1960
RECORD #15:




Species:
Sex:
Effect:
Route:

Rats
Female
LOAEL
Inhalation

Body Weight: 0.35 kg
Reported Dose: 1500 ppm
Converted Dose: 105.37 mg/kg/day
Exposure Period: 0.29 days
Duration Observation: 1 day
Comment:
Citation:
                                          Molecular Weight:
                                          Inhalation hours/day:   7.00
                                          Inhalation days/week:   1.00
                                          # Inhal. Exp. days:
                                          Assumed Inhalation Absorption:
                                                           SOX
Number Exposed:     4
Number Responses:   NR
Type of Effect:     DE6EN
SUe of Effect:     LIVER
Severity Effect:    5

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

Torkelson et al., 1960
0316d
                     -81-
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:   50X

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

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

Citation:      Torkelson et a!., 1960
RECORD #17:
Comment:
Species:
Sex:
Effect:
Route:
Mice
NR
LOAEL
Inhalation
Citation;
                            Body Weight:  0.03 kg
                            Reported Dose:  7 mg/i
                            Converted Dose:  189.62 mg/kg/day
                            Exposure Period:  0.29 days
                            Duration Observation:  1 day

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

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

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

Hlghman et al., 1948
0316d
                     -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:    PEL           Converted Dose:  325.78 mg/kg/day
Route:     Inhalation    Exposure Period:  0.29 days
                         Duration Observation:  6 days

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

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

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

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

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




Species:
Sex:
Effect:
Route:

Rats
Hale
PEL
Gavage

Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Dura tlonObser vat Ion:
0.35 kg
7000 mg/kg/day
7000 mg/kg/day
1 day
1 day
Comment:


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

All rats died within  24  hours  of treatment. Dose administered
1n corn oil apparently by gavage.

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

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

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

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

               Approximate  LDso-   Doses  ranging  from  500-4400  mg/kg/day
               administered In corn oil  apparently  by  gavage  to  groups  of 10
               animals.

               Svlrbely et al.. 1947
RECORD |4: Species: Mice
Sex: NR
Effect: PEL
Route: Gavage

Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
NR
NR
DEATH
BODY
10
0.03 kg
3000 mg/kg/day
3000 mg/kg/day
1 day
12 days





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

               Hlghman et al., 1948
0316d
                                    -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 16:




Species:
Sex:
Effect:
Rout:e

Mice
NR
PEL
Gavage

Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
0.03 kg
3000 mg/kg/day
3000 mg/kg/day
5 days
5 days
Comment:
Citation:
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

Death In unspecified  number  of  32  mice that were given single
doses 1n  olive oil on  1  to 10  consecutive days.   H1stolog1c
examination  showed effects  Including  fatty degeneration  of
the liver and kidney and liver subcapsular necrosis.

Hlghman et al., 1948
NR = Not reported
0316d
                     -85-
                                           08/20/90

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 A

 J
 D
 C
      18080 "
       1880
             Bronoch1orone thane
                                                        r    i     i   r
          8.881
         3
 (Oral Exposure)
BCMORRL D2
                    •N5
                                                                 -K-
                                                                   i    i   i
                                                                           e.8i
HUKRN EQUIV DURRTION (fraction 1 if wan)

     CENSORED DATR KETHOD
   Key:    F  . FEL
           N  . NOEL

        Solid Hne - Adverse Effects  Boundary  *
        Dashed Hne « No Adverse  Effects Boundary
    Dose/Duration  -
                                   FIGURE C-6

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

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

0316d                               -72-                             08/20/90

-------
effects boundary,  and  no region of contradiction  1s  generated.   This  method
results 1n the most conservative definition of the no adverse effects region.
    Figures C-l  and  C-3 present the Inhalation dose/duration-response graphs
generated  by  the envelope method.  The  adverse effects boundary  1s defined
by  the  LOAEL  for  liver  hlstologlcal  alterations  In  mice  (Rec.  #17),  LOAELs
for kidney hlstologlcal  alterations 1n dogs  (Rec. #12),  reduced body weight
and  elevated  organ  weights   1n guinea  pigs   (Rec.  #3),   liver  hlstologlcal
alterations 1n rats  (Rec. #2)  and  for  reduced body weight In rats (Rec. #8).
Using  the envelope  method   (Figures  C-l  and C-4),   the  no  adverse effects
boundary  1s  defined  by  the  acute  NOEL for mortality 1n  rats (Rec. #14),  a
NOAEL  for slightly  Increased  hemosldeMn  In  the  spleen  of  rats  (Rec.  #10)
and  a  NOAEL  for  Increased  liver  weight  In rats  (Rec.  #1).  Using  the
censored  data method  (Figures  C-2 and C-4),  the  no  adverse effects  boundary
Is  defined by  the  NOEL for  liver hlstologlcal  alterations 1n  rats  (Rec.
#16),  the NOEL  1n rabbits  (Figure C-2,  Rec.  #5)  or dogs  (Figure C-4,  Rec.
#7) and the NOAEL  for  liver  hlstologlcal alterations In rats (Rec. #1).  The
subchronlc and  chronic  RfOs  for  bromochloromethane  are  based  on the  NOAEL
for liver hlstologlcal alterations 1n rats  (Rec. #1).
    Figures C-5 and  C-6  present the oral dose/duration-response  graphs.   The
adverse effects  boundary Is  defined by FRs  for  mortality 1n rats (Rec.  #1)
and mortality 1n mice  (Recs. #3,  4 and 6).  In Figure C-5 (envelope  method),
the no adverse effects  boundary 1s  defined by the NOEL for mortality 1n rats
(Rec. #2)  and the NOEL  for  mortality and  hlsiopathology  1n  mice (Rec.  #5).
Using the censored data  method  (Figure C-6),  the no  adverse effects  boundary
1s  defined by a single  value,  the NOEL for  mortality  and hlstopathology In
mice  (Rec.  #5).   Figures  C-5  and  C-6 emphasize  that additional oral  data
(I.e.,  for  longer  duration  exposures)  are   needed  to  Identify a  maximal
region of no  adverse  effects.
0316d                               -73-                             08/20/90

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

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

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




Species:
Sex:
Effect:
Route:

Rats
Female
NOAEL
Inhalation

Body Weight: 0.35 kg
Reported Dose: 1958 mg/m9
Converted Dose: 125.96 mg/kg/day
Exposure Period: 195 days
Duration Observation: 195 days
Comment:
                                       Molecular Weight:  129.39
                                       Inhalation hours/day:   7.00
                                       Inhalation days/week:   4.8461
                                       Inhal. Exp. days:  135.00
                                       Assumed Inhalation Absorption:
                                                        50%
Citation:
Number Exposed:     10
Number Responses:   NR
Type of Effect:     WGTIN
Site of Effect:     LIVER
Severity Effect:    4

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

Torkelson et a!., 1960
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 Dose:  166.97-173.31  mg/kg/day
               Route:     Inhalation  Exposure Period:  114 days
                                      Duration Observation:  114 days

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

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

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

Citation:      Torkelson et al., 1960
RECORD #3:
Species:
Sex:
Effect:
Route:
Guinea pigs Body Weight: 0.64 kg
Both Reported Dose: 2593 mg/m3
LOAEL Converted Dose: 124.29-129.53 mg/kg/day
Inhalation Exposure Period: 114 days
Duration Observation: 114 days
Comment:
Citation:
                       Molecular Weight:  129.39
                       Inhalation hours/day:  7.00
                       Inhalation days/week:  4.8509-5.0351
                       Inhal. Exp. days:  79.00-82.00
                       Assumed Inhalation Absorption:  50%

Number Exposed:     20       20       20
Number Responses:   NR       NR       NR
Type of Effect:     W6TIN    WGTIN    WGTDC
Site of Effect:     LIVER    KIDNY    BODY
Severity Effect:    4        4,4

10/sex,  79-82  exposures.   Exposure  concentrations:  2593  and
5345 mg/m'  (490 and 1010  ppm).   Effect on kidney  weight only
1n  males.   No  effects  on  histology   or   blood  nitrogen.
Testlcular effects  (decreased  weight,  spermatogenesls)  at 5345
mg/m» (257.23-267.00 mg/kg/day).

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

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

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

               Number  Exposed:     10       10        10
               Number  Responses:   NR       NR        NR
               Type  of  Effect:     WGTDC    WGTIN     WGTIN
               SHe  of  Effect:     BODY      LIVER     KIDNY
               Severity  Effect:    444

Comment:       79-82  exposures.   Exposure  concentrations:  2593  and  5345
               mg/m3  (490  and  1010  ppm)   (340.67-353.59  and   702.22-728.88
               mg/kg/day).  Same  effects  at   2593  mg/m8.   No  effects  on
               histology.   Other endpolnts  not  examined.

Citation:       Torkelson et al.. 1960
RECORD #5:




Species:
Sex:
Effect:
Route:

Rabbits
Both
NOEL
Inhalation

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


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


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

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

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

Torkelson et al., 1960
0316d
                     -76-
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RECORD #6:     Species:   Rabbits     Body Weight:  3.8 kg
               Sex:       Male        Reported Dose:  5345 mg/m"
               Effect:    LOAEL       Converted Dose:  284.29-295.09 mg/kg/day
               Route:     Inhalation  Exposure Period:  114 days
                                      Duration Observation:  114 days

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

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

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

Citation:      Torkelson et a!., 1960
RECORD #7:




Species:
Sex:
Effect:
Route:

Dogs
Both
NOEL
Inhalation

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

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

Torkelson  et al.. 1960
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                     -77-
08/20/90

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RECORD #8:
Comment:
Citation:
Species:   Rats            Body Weight:   0.32  kg
Sex:       Both            Reported Dose:   2725 mg/m3
Effect:    LOAEL           Converted Dose:   149.51  mg/kg/day
Route:     Inhalation      Exposure Period:         6 months
                           Duration Observation:    6 months

                           Molecular Weight:   129.39
                           Inhalation hours/day:   6.00
                           Inhalation days/week:   4.8222
                           Inhal.  Exp.  days:   124.00
                           Assumed Inhalation  Absorption:   50%

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

50/sex.   Exposure  concentrations:  2725 and  5345  mg/m3  (515
and 1010 ppm)  (149.51  and  293.26  mg/kg/day, respectively).   No
effect  on  body  weight  1n  females.  No  effect  on histology,
organ weights or clinical chemistry at  either  exposure level.

MacEwen et al., 1966
RECORD #9:




Species:
Sex:
Effect:
Route:

Dogs
Both
NOEL
Inhalation

Body Weight: 12.7 kg
Reported Dose: 5345 mg/ma
Converted Dose: 155.84 mg/kg/day
Exposure Period: 6 months
Duration Observation: 6 months
Comment:
Citation;
                                          Molecular We1ght:l29.39
                                          Inhalation hours/day:   6.00
                                          Inhalation days/week:   4.8222
                                          Inhal.  Exp.  days:   124.00
                                          Assumed Inhalation Absorption:
                                                           50%
Number Exposed:     8
Number Responses:   0
Type of Effect:
SHe of Effect:
Severity Effect:    3

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

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

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

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

Number Exposed:     20
Number Responses:   NR
Type of Effect:     OTHER
Site of Effect:     SPLEN
Severity Effect:    1

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

Svlrbely et al., 1947
RECORD #11:




Species:
Sex:
Effect:
Route:

Rabbits
Male
NOEL
Inhalation

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

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

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

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

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

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

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

Svlrbely et al., 1947
RECORD #13:




Species:
Sex:
Effect:
Route:

Rats
Both
FEL
Inhalation

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

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

Torkelson et al.. 1960
                                                        50%
expanded  over  24
 Deaths  generally
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:  50X

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

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

Torkelson et al., 1960
       24
RECORD #15:




Species:
Sex:
Effect:
Route:

Rats
Female
LOAEL
Inhalation

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

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

Torkelson et al., 1960
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:
               SHe of  Effect:
               Severity Effect:     3

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

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




Species:
Sex:
Effect:
Route:

Mice
NR
LOAEL
Inhalation

Body Weight: 0.03 kg
Reported Dose: 7 mg/l
Converted Dose: 189.62 mg/kg/day
Exposure Period: 0.29 days
Duration Observation: 1 day
Comment:
Citation;
                                           Molecular Weight:
                                           Inhalation hours/day:   7.00
                                           Inhalation days/week:   1.00
                                           # Inhal.  Exp.  days:
                                           Assumed Inhalation Absorption:
                                                            50%
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     DEGEN
SHe of Effect:     LIVER
Severity Effect:    5

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

Hlghman et al., 1948
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:    PEL           Converted Dose:  325.78 mg/kg/day
Route:     Inhalation    Exposure Period:  0.29 days
                         Duration Observation:  6 days

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

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

Concentration  not  expanded  over 24  hours.  LC 59 after  72-hour
observation.   A similar value  was  reported by Hlghman  et  al.
(1948).   LC50S  after  8,  24  and  48  hours   observation  were
2995, 2504 and  2436 ppm, respectively.

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

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




Species:
Sex:
Effect:
Route:

Rats
Male
PEL
Gavage

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


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

All rats died within  24  hours  of treatment.  Dose administered
1n corn oil apparently by gavage.

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

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RECORD #2:
Comment:
Species:
Sex:
Effect:
Route:
Rats
Hale
NOEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
                                        Duration Observation:  14 days
0.35 kg
5000 mg/kg/day
5000 mg/kg/day
1 day
               Number Exposed:     5
               Number Responses:   0
               Type of Effect:
               Site of Effect:
               Severity Effect:    10
Comment: No deaths. See previous record.
Citation: Torkelson et al., 1960
RECORD #3: Species: Mice
Sex: NR
Effect: PEL
Route: Gavage
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
NR
NR
DEATH
BODY
10
0.03 kg
4300 mg/kg/day
4300 mg/kg/day
1 day
6 days

Approximate  LDsQ.   Doses  ranging  from  500-4400  mg/kg/day
administered In corn oil  apparently  by  gavage  to  groups  of 10
animals.
Citation:
RECORD *4:
SvUbely
Species:
Sex:
Effect:
Route:
et al.. 1947
Mice
NR
PEL
Gavage

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

0.03 kg
3000 mg/kg/day
3000 mg/kg/day
1 day
12 days
Comment:
Citation:
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

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

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

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RECORD #5:
Comment:

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

Hlghman et al., 1948
RECORD #6;
Comment:
Species:
Sex:
Effect:
Rout:e
Mice
NR
PEL
Gavage
               Number Exposed:
               Number Responses:
               Type of Effect:
               Site of Effect:
               Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
                    NR
                    NR
                    DEATH
                    BODY
                    10
0.03 kg
3000 mg/kg/day
3000 mg/kg/day
5 days
5 days
Citation:
Death In unspecified  number  of  32 mice that were given  single
doses 1n  olive oil on  1  to 10  consecutive days.  H1stolog1c
examination  showed effects  Including  fatty  degeneration of
the liver and kidney and liver subcapsular  necrosis.

Hlghman et al., 1948
NR = Not reported
                                              tfJ. &tvJfomncnt^t Protection Agency
                                              Region 5, library (PL-12J)
0316d
                     -85-
                                           08/20/90

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