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                                  DISCLAIMER

    This report  1s  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.
                                      11

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                                   PREFACE
    Health and  Environmental  Effects  Documents  (HEEDs) 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  emer-
gency 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 1n this  document
and  the  dates  searched  are  Included In  "Appendix: Literature  Searched."
Literature search material  Is  current up to 8  months previous  to the  final
draft date  listed  on  the front  cover.   Final  draft  document  dates  (front
cover) reflect the date the document 1s  sent  to  the  Program Officer (OSWER).

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

    In the case of  suspected  carcinogens,  RfDs  are  not  estimated.   Instead,
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.

    Reportable quantities  (RQs)  based on both chronic toxldty  and  cardno-
genlclty are derived.   The RQ Is used to determine  the quantity  of a hazard-
ous 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  carclno-
genldty) represent two  of six  scores developed (the  remaining  four reflect
1gn1tab1l1ty,   reactivity,  aquatic  toxldty,  and  acute mammalian  toxldty).
Chemlcal-spedf 1c  RQs  reflect the lowest of  these six  primary criteria.   The
methodology for chronic  toxldty and  cancer based  RQs  are defined  1n  U.S.
EPA, 1984 and  1986a, respectively.
                                      111

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                              EXECUTIVE SUMMARY

    4-Chlorobenzotr1fluor1de Is a  colorless  liquid at ambient  temperatures,
with an  aromatic  odor .(Hawley,  1981;  Boudaklan,  1980).   It 1s  practically
Insoluble In water (Elanco  Products Company, 1984).  This  compound  undergoes
easy nitration  and  nucleophHlc  substitution  reactions   (Boudaklan,  1980).
Currently,  Occidental  Petroleum  Corp.  of  Niagara Falls,  NY,   1s  the  only
major manufacturer of  this  chemical  1n  the United States  (SRI,  1987;  USITC,
1987).   Data regarding the  current U.S. production volume  are not available,
although -10-50 million pounds was produced In  1977  (U.S.  EPA,  1977).   It  1s
produced  from  the   reaction   of  4-chlorobenzotr1chlor1de  and   anhydrous
hydrogen  fluoride.   This  chemical 1s  used primarily  as  an Intermediate  In
the manufacture of certain dyes,  drugs  and herbicides  (Boudaklan,  1980).
    Of   the  three   likely  chemical processes  that may  lead to  the loss  of
4-chlorobenzotr1fluor1de  in the  atmosphere,  neither  direct -photolysis  nor
Us  reaction  with atmospheric  0_ 1s  significant (Atkinson et al.,  1985).
                                 0
Its reaction with photochemlcally produced HO radical  has  a  rate  constant  of
2.3xlO~13  cm3/molecule-sec   (Atkinson  et  al.,   1985).   Assuming  the  atmo-
spheric   concentration of  HO  radical   as 10*  radicals/cm3,  the   lifetime
of this  compound  In  the air has  been estimated to be -50 days  (Atkinson  et
al.,  1985).   Therefore,    the  compound   1s  expected  to  persist   1n   the
atmosphere.   In water,  photolysis of the  chemical  1s  not  Important  (Elanco
Products  Co.,  1983a).    Although   the  rates   of  aerobic  and   anaerobic
blodegradatlon of  the compound 1n water could not  be  determined,  these rates
are  slower  than  the  volatilization  rate  (Elanco Products  Co.,  1983b,c,d).
From the  value  of the  ratio  of  the volatilization  rate  of the compound  to
the  oxygen  reaeratlon rate  determined  experimentally  (Elanco  Products  Co.,
                                      1v

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1983d)  and  the  values  of oxygen  reaeratlon  rates 1n  a  few  natural  waters
(Thomas, 1982),  the  half-life  for  volatilization of the compound  from water
has been  estimated  to be  1-6  days.   The K    value of 420-490  In  sediments
                                           oc
(Elanco  Products  Co.i   1983e)   Indicates   that   the  compound   will   sorb
moderately  to  suspended solids  and  sediments  In  natural  waters.   Based  on
the experimentally  determined BCF  of 122-202  1n  blueglll sunflsh,  Lepomls
macrochlrus  (Elanco  Products  Co.,  1984),  the  compound Is  not expected  to
bloconcentrate significantly  1n  aquatic  organisms.  From  the  data  available
In  aquatic  studies,   1t  can be  predicted  that  photolysis In  soil will  be
unimportant, and some  loss  of  the  compound will occur  from the soil  surface
because of  volatilization,  although  the  volatilization process will  become
less  Important  as  the  soil  depth Increases.   The K   value  of 510-530  1n
soil  (Elanco  Products  Co.,  1983e)  Indicates  that  the compound  may  leach
through some soils, particularly soil from Improper disposal sites.   No data
regarding the blodegradabllHy of ;the compound  In soil  are  available.
    There 1s a paucity  of data on the levels  of 4-chlorobenzotrlfluorlde  1n
environmental media.   This compound was qualitatively  detected  1n  water from
Lake Ontario at  Niagara  River  (Great Lakes Water  Quality  Board, 1983). The
source of the  compound  1n the water was possibly  the  nearby manufacturer  of
the chemical.  Mauser and  Bromberg (1982) reported the qualitative detection
of  this compound In  the sedlment/son/water  samples collected  from contami-
nated areas  of  Love  Canal,  Niagara  Falls.   Bass  and  yellow perch  collected
from Niagara  River  and  analyzed  1n  1978 contained 4-chlorobenzotr1fluor1de
1n the concentration range 0.17-2.0 ppm.  The  compound was  not detected at a
later date  (1980),   however,  at  a  detection   limit  of 0.01  ppm In  various
samples of  fish  (walleye, brown  trout  and sucker)  from  Lake   Erie and Lake
Ontario  near  the  suspected  contaminated  areas   (Occidental  Chem.   Corp.,

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1980b).  Cacco and Ferrari (1982) reported the detection  of  this  compound  at
a level of 1 ppm  In  groundwater  near  an  Improper  disposal site near  Vlcenza,
Italy.
    Exposure of rainbow  trout  and blueglll sunflsh  to  4-chlorobenzotrlfluo-
rlde  generated 96-hour  LC5Q  values  of  13.5  and  12.0  (10.3-13.9)  mg/l,
respectively (Union  Carbide  Environmental  Services,  1979b).   Exposure  of  D.
magna   to   4-chlorobenzotr1f1uor1de   generated  a   48-hour   LC^n   of   12.4
(10.7-14.5) mg/l (Union Carbide Environmental  Services,  1979c).
    The  concentration  of  4-chlorobenzotr1fluor1de   that  produced   chronic
effects 1n  aquatic  organisms  was  ~l-2 orders of  magnitude lower than  that
produced for acute effects.  The MATC for fathead minnow eggs  was >0.54 but
<1.4  mg/l  4-chlorobenzotr1fluor1de.   The  MATC for  |).  magna  was >0.03  and
<0.05  mg/l  4-chlorobenzotrlfluorlde   (Union  Carbide  Environmental  Services,
1979d).
    The  single  study  of  [l*C]-4-chlorobenzotr1fluor1de  metabolism  using
rats  (Qulstad  and Mulholland*  1983)  Indicated that the compound  1s  absorbed
and excreted readily, predominantly as the parent  compound.  The  major  route
of  excretion  was  through  expired  air,  which  accounted   for  62-82% of  the
dose.    Urinary   metabolites    Identified   were    the    glucuronldes    of
d1hyclroxybenzotr1fluor1de   and   4-chloro-3-hydroxybenzotr1fluor1de,   which
accounted  for  <2.7  and  4.'4%  of the  dose,   respectively.   A  minor  urinary
metabolite,  the  mercaptuMc  add   conjugate   of  4-chlorobenzotr1fluor1de
accounted for 0.1-0.2% of the dose.
    Minimal to moderate renal  tubular degeneration was  observed  In male rats
treated by gavage with 4-chlorobenzotr1fluorlde at doses  >40 mg/kg/day  for 3
months  (Arthur  and  Probst,  1983).   CentMlobular hypertrophy of the  liver
was  observed  In male  rats  at  4-chlorobenzotr1fluor1de doses  >150  mg/kg/day
                                      v1

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and  1n  female  rats at 500  mg/kg/day.   No significant effects were  observed
1n rats  treated  for 3 months  by  gavage with 4-ch1orobenzotr1f1uor1de at  10
mg/kg/day.
    In contrast  to the- Arthur and  Probst  (1983)  study, hlstologlcal  kidney
and  liver  effects were  not  observed  1n  a  2-generat1on  study  1n which
Sprague-Dawley rats were  treated  by gavage with  4-chlorobenzotr1fluor1de  at
doses <45  mg/kg/day for  >90 days  (Hooker  Chemical  Corp.,  1981).   4-Chloro-
benzotrlfluoMde .  treatment   did   not  have  any  effect   on   reproductive
parameters.
    A  Russian  study   (Rapoport   et  al.,   1986}   reported   that   Inhalation
exposure  of  rats  to 4-chlorobenzotr1fluor1de at  concentrations >20.5 mg/m3
for  120  hours  resulted  1n  changes 1n  blood  analyses, motor  activity and
muscle strength.   Significant  changes  were not observed In  rats exposed  at
5.5 mg/m3 for 120 hours.
    Hooker  Chemical Corp.  (1979a)  reported a   4-hour  LC™  for  4-chloro-
benzotrlfluorlde  1n Sprague-Dawley  rats  of  33  mg/m3.  The oral  LD5Q for
4-chlorobenzotr1fluorlde  1n  Sprague-Dawley  rats  was  reported  as >5.0 ml/kg
(6.7  g/kg)  (Hooker  Chemical   Corp.,   1985a),  while  the   dermal   LD5Q   In
rabbits  was  reported  to  be >2.0  mil/kg (2.7 g/kg)  (Hooker  Chemical  Corp.,
1985b).
    Except  for   positive  results  1n  assays of  unscheduled  DMA  synthesis
(Benlgnl  and Dogl1ott1, 1980) and  sister chromatld exchange  (Hooker  Chemical
Corp., 1979c),  results of  mutagenldty  assays  of  4-chlorobenzotr1flubr1de
have been negative.
    4-Chlorobenzotrlfluorlde  has   not   been  tested  for cardnogenldty   or
teratogenldty.

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    Pertinent guidelines  and  standards,  Including EPA ambient water  and  air
quality  criteria,  drinking  water  standards,   FAO/WHO  ADIs,   EPA  or  FDA
tolerances  for  raw agricultural  commodities  or foods,  and  ACGIH, NIOSH  or
OSHA  occupational  exposure  limits  were  not   located  In   the  available
literature cited 1n Appendix A.
    Because  of  the lack  of  data  concerning  carc1nogen1c1ty  In  humans  and
animals,  4-chlorobenzotr1fluor1de  can   be  classified   as  an  EPA  Group  D
chemical.  The derivation of  carcinogenic potency  factors  and  a  cancer-based
RQ  1s  precluded by the  lack of  cardnogen1c1ty  data.   Based on  the Hooker
Chemical Corp.  (1981)  2-generatlon study using rats, subchronlc  and  chronic
oral RfDs for 4-chlorobenzotr1fluor1de of 0.2 mg/kg/day  (11 mg/day)  and 0.02
mg/kg/day  (1  mg/kg)  were  calculated.   Because of  the  lack  of  supporting
studies, confidence  1n the oral  RfDs  1s  low.   A chronic  toxlclty  RQ  for
4-chlorobenzotrlfluorlde  of  1000 was calculated  from the Arthur  and Probst
(1983) 90-day rat study.
                                     vlll

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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	     3

2.  ENVIRONMENTAL FATE AND TRANSPORT	     4

    2.1.   AIR	     4
    2.2.   WATER	     5
    2.3.   SOIL	     6
    2.4.   SUMMARY	  .     7

3.  EXPOSURE.	  .     9

4.  AQUATIC TOXICITY	    10

    4.1.   ACUTE TOXICITY	    10
    4.2.   CHRONIC EFFECTS	    11
    4.3.   PLANT EFFECTS	    11
    4.4.   SUMMARY.	    11

5.  PHARMACOKINETCS	    13

    5.1.   ABSORPTION 	  ...................    13
    5.2.   DISTRIBUTION	    13
    5.3.   METABOLISM	    14
    5.4.   EXCRETION	    14
    5.5.   SUMMARY	    15

6.  EFFECTS	    16

    6.1.   SYSTEMIC TOXICITY	    16

           6.1.1.   Inhalation Exposure 	    16
           6.1.2.   Oral Exposure	    16
           6.1.3.   Other Relevant Information	    17

    6.2.   CARCINOGENICITY	    19

           6.2.1.   Inhalation	    19
           6.2.2.   Oral	    19
           6.2.3.   Other Relevant Information	    19

    6.3.   MUTAGENICITY	    19
    6.4.   TERATOGENICITY	    22
    6.5.   OTHER REPRODUCTIVE EFFECTS 	    22
    6.6.   SUMMARY	    23
                                     1x

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                           TABLE  OF  CONTENTS  (cont.)

                                                                        Page
 7.  EXISTING GUIDELINES AND STANDARDS 	   25

     7.1.   HUMAN	   25
     7.2.   AQUATIC. .  :	   25

 8.  RISK ASSESSMENT	   26

     8.1.   CARCINOGENICITY	   26

            8.1.1.    Weight of Evidence.  .	   26
            8.1.2.    Quantitative Risk Assessment	   26

     8.2.   SYSTEMIC TOXICITY	   26

            8.2.1.    Inhalation Exposure  	  	   26
            8.2.2.    Oral Exposure ......"	   26

 9.  REPORTABLE QUANTITIES 	   29

     9.1.   BASED ON SYSTEMIC TOXICITY	   29
     9.2.   BASED ON CARCINOGENICITY	   29

10.  REFERENCES	   32

APPENDIX A: LITERATURE  SEARCHED. ....	   40
APPENDIX B: SUMMARY TABLE FOR 4-CHLOROBENZOTRIFLUORIDE  	   43

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                               LIST  OF TABLES

No.                               Title                                Page

6-1     Mutagenldty Testing of 4-Ch1orobenzotr1fluor1de	   20

9-1     Composite Scores  for the Oral ToxUHy  of
        4-Chlorobenzotr1fluor1de (97% Pure)  1n  Corn 011 Using
        Male F344 Rats.	   30

9-2     4-Chlorobenzotr1fluor1de:  Minimum Effective Dose  (MED)
        and Reportable Quantity (RQ)	   31
                                     x1

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                             LIST  OF  ABBREVIATIONS

ADI                     Acceptable dally Intake
BCF                     B1oconcentrat1on factor
CAS                    -Chemical Abstract Service
CS                      Composite score
DNA                     DeoxyMbonuclelc acid
Koc                     Soil sorptlon coefficient standardized
                        with respect to organic carbon
Kow                     Octanol/water partition coefficient
                        Concentration lethal to 50% of recipients
                        Dose lethal to 50% of recipients
LOAEL                   Lowest-observed-adverse-effect level
MATC.                    Maximum allowable toxicant  concentration
MED                     Minimum effective dose
NOAEL              -     No-observed-adverse-effect  level
ppm                     Parts per million
RBC                     Red blood cell
RfD                     Reference dose
RQ                      Reportable quantity
RV(j                     Dose-rated value
RVP                     Effect-rated value

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                              1.  INTRODUCTION
1.1.   STRUCTURE  AND  CAS  NUMBER
    4-Chlorobenzotr1fluor1de  Is   also  known  as  l-chloro-4-{tr1fluoromethyl)
benzene;     (p-chlorophenyl )tr1fluoromethane;      4-chloro-a-a-a-tMf luoro-
toluene; p-chlorobenzotMfluoMde;  and p-chlorotr1fluoromethylbenzene  (HSDB,
1988)..  The structure, molecular formula, molecular weight  and  CAS  Registry
number for  this  compound  are as  follows:
                                C\
Molecular formula:   C^H.CIF-
                     74    3
Molecular weight:   180.56
CAS Registry number:   98-56-6
1.2.   PHYSICAL AND CHEMICAL PROPERTIES
    4-Chlorobenzotr1fluor1de  1s a  colorless  liquid at  ambient  temperatures
(Boudaklan,  1980),  with an aromatic odor  (Hawley,  1981).   It  1s  not  soluble
1n  water but   Is  soluble  1n  n-hexane  (Elanco   Products  Company,   1984).
Selected physical properties of  this compound are as follows:

Melting point:          -36.0°C                           Hawley,  1981
Boiling point:          138.6°C                           Hooker Chems.  and
         ^                                              Plastics  Corp.,  1980
Density:               1.338 g/cm3 at 25°C               Boudaklan, 1980
Vapor pressure:        7.86 mm  Hg at 25°C                Hooker Chems.  and
                                                        Plastics  Corp.,  1980
Water solubility:       29.1 mg/l at 23°C                 Hooker Chems.  and
                                                        Plastics  Corp.,  1980
Odor threshold:        50% panel members at 0.63         Occidental Chems.
                       mg/m3 and 100% at 0.8 mg/m3       Corp., 1980a
Oil Id                               -1-                              04/19/88

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•Log  Kow:                3.52                               Elanco  Products
                                                          Company,  1984
 Conversion              1  ppm = 7.51 mg/m3 at  20°C
 factor  1n air:          and 760 mm Hg
     4-Chlorobenzotr1fluor1de  undergoes  several  chemical reactions. Nitration
 of  this compound yields  n1tro-subst1tuted  products that are  used as  Inter-
 mediates  1n the production  of  dyes, germicides  and  herbicides.   Because of
 the  strong electron-withdrawing effect, this compound also undergoes nucleo-
 ph1!1c  substitution  reactions (Boudaklan, 1980).
 1.3.    PRODUCTION DATA
     According  to EPA's  TSCA  production file  (U.S.   EPA,  1977),  the  major
 producer  of 4-chlorobenzotr1fluor1de 1n the United States In 1977 was  Hooker
 Chems.  and  Plastics Corp.  of  Niagara  Falls,   NY.   This   company  produced
 between 10 and  50  million  pounds of  the compound In  1977.   At  least  three
 companies  Imported  this chemical  1n the United  States  during the same year
.(U.S.  EPA, 1977).   More  recent data (USITC, 1987;  SRI,  1987) Indicate that
 Occidental  Petroleum  Corp.   at Niagara  Falls,   NY,   the  parent   company  of
 Hooker  Chems.  and  Plastics  Corp., Is  the only  current major manufacturer of
 the  chemical  1n  the United  States.   It  1s produced  from the  reaction  of
 4-chlorobenzotr1chlor1de  and   anhydrous  hydrogen  flourlde   under  high  or
 atmospheric  pressure   conditions  (Boudaklan,   1980)  or  the  reaction  of
 4-chlorotoluene with hydrogen fluoride  (HSDB, 1988).
 1.4.    USE  DATA
     4-Chlorobenzotr1fluor1de  Is used  as  an  Intermediate  In  the manufacture
 of  certain dyes,  drugs, herbicides  and  germicides  (Boudaklan, 1980).   It 1s
 also used  as a solvent and a  dielectric  fluid (Hawley,  1981).
Ollld                               -2-                              04/19/88

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1.5.   SUMMARY
    4~Chlorobenzotr1fluor1de  1s  a colorless liquid  at  ambient temperatures,
with  an  aromatic  odor  (Hawley,  1981;  Boudaklan,  1980).   It  Is  practically
Insoluble  1n  water (Elanco  Products  Company,  1984).   This compound undergoes
easy  nitration  and  nucleophlUc  substitution  reactions  (Boudaklan,  1980).
Currently,  Occidental   Petroleum  Corp.  of  Niagara  Falls,  NY,  Is  the  only
major manufacturer of  this  chemical  1n  the United  States (SRI,  1987;  USITC,
1987).   Data  regarding  the  current U.S.  production  volume are not available,
although -10-50  million pounds was produced  In  1977 (U.S. EPA, 1977).   It Is
produced   from  the  reaction  of   4-chlorobenzotr1chlor1de   and  anhydrous
hydrogen  fluoride.  This chemical  1s  used primarily  as  an  Intermediate 1n
*the manufacture  of certain dyes, drugs and herbicides (Boudaklan, 1980).
01 lid                               -3-                              05/10/88

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                     2.  ENVIRONMENTAL FATE AND TRANSPORT
2.1.   AIR
    The  fate  of  4-chlorobenzotr1fluor1de  In  the  gas phase  was studied  by
Atkinson et al. (1985) and  the  results  were  applied  to assess Us fate under
atmospheric  conditions  (Occidental  Chem.  Corp.,  1984).   Later,  the  same
study  was  published  In  the  open  literature  (Atkinson  et  al.,   1985).
Although  the  study  did  not  directly  determine the  photolytlc  fate  of  the
compound,  the  upper  limit for  photolytlc  rate was Indirectly determined  to
be  2.7xlO~6/  sec  at  a  light  Intensity  -1.5  times   higher   than  solar
radiation.  Therefore,  the  lower limit  for  photolytlc lifetime  (lifetime  =
1/R,)  under  atmospheric  conditions  was  estimated to  be  6.5 days.   Since
the  compound  exhibits Its  first absorption  band 1n  the wavelength  region*
230-280  nm and   shows  no  detectable  absorption  at  wavelengths  >280  nm,
Atkinson  et  al.  (1985)   concluded  that atmospheric  photolysis   1s  probably
unimportant  compared  with   other   loss   processes.   The  same  conclusion
regarding  the  significance  of  photolysis  can  be reached  from   the  aquatic
photolysis study (Section 2.2.).
    The  rate  constants for  the vapor  phase  reaction of  HO  radical  and  0_
with    4-chlorobenzotr1fluor1de   at   23°C  are   2.3xlO~i3   cm3/molecule-sec
and  <5xlO~21   cm3/molecule-sec,  respectively  (Atkinson  et al.,  1985).   If
the  dally average   atmospheric  concentrations  of HO  radical  and  0«  are
assumed   to   be   10*  radicals/cm3   and  7.2X1011   molecules/cm3,   respec-
tively, the corresponding lifetimes will be  50  days and  >8.8  years  (Atkinson
et al.,  1985).  Therefore,  1n the absence of  any  other  faster loss  process,
the lifetime of this  compound 1n  the  atmosphere will  be  close to 50  days  and
1t will be very persistent 1n the ambient atmosphere.
Ollld                               -4-                              05/10/88

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2.2.   WATER
    There 1s a paucity of data  In  the  open  literature  regarding the fate and
transport of 4-chlorobenzotr1fluor1de  1n water.  The data  reported  here  were
obtained  from  the public  files section of  the reports  of  the major  manu-
facturer  as  submitted to  EPA's Office  of  Toxic  Substances  (OTS)   under  8D
submission rules.
    The  photolytlc  fate  of  this  chemical  1n water was  reported  by  Elanco
Products  Co.  (1983a).  When  a  10 ppm aqueous solution  of  the chemical  In
sealed and sterilized glass tubes  was  exposed  to natural  light  for  <28 days,
no  degradation  was  observed  and  almost  100% of  the  compound  remained  un-
altered.  Therefore,  1t was  concluded  that  the compound  Is  not photolablle.
The  aerobic  and  anaerobic   blodegradatlon  of  4-chlorobenzotr1fluor1de  1n
water was also  reported  by  Elanco Products  Co.  (1983b,c).   When microorgan-
isms  from soil  and   raw  domestic sewage acclimatized to  4-chlorobenzotrl-
fluorlde were used as mlcroblal  Inoculum for  aerobic blodegradatlon study In
flasks  with  attached  CO '  traps,  only  13%  of   the  Initial  theoretical
compound  could   be   accounted   for   on  day   0,   presumably  because   of
volatilization.   By  the  fifth  day,  only 2%  of  the compound remained.   The
report  concluded that  the  high  volatility  of  the compound   precluded  the
determination  of  Us aerobic   blodegradatlve  fate.   Similarly,  when  the
compound  was  Inoculated  with   anaerobic  dlgestor  sludge  under  anaerobic
conditions  for  >59   days,  1t  was determined  that  the   compound  might  be
Inhibitory to anaerobic microorganisms for a  period of 17  days  at an Initial
concentration   of   50    mg   C/l.     No   conclusion   regarding   anaerobic
blodegradatlon   of   4-chlorobenzotr1fluor1de   could  be   drawn  from  these
experiments,  however, because  the  control   experiments   showed  unexplained
high losses of the compound  (77%), possibly  resulting  from undefined abiotic
reactions.

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    The  loss  of 4-ch1orobenzotr1fluor1de  from water because  of  volatiliza-
tion  was reported  by  Elanco Products  Co.  (1983d).  With  a 10  ppm  aqueous
solution of the  compound,  the average ratio of  compound  volatilization rate
to oxygen reaeratlon  rate  was determined to be  0.64 at ambient temperature.
If 1t  Is assumed that  the  oxygen  reaeratlon  rates  from a pond, a  river and a
lake   are 0.19/day, 0.96/day and 0.24/day, respectively  (Thomas,  1982),  the
estimated   volatilization  half-lives  from these water  bodies would  be -1-6
days.  Therefore,  H  can  be  concluded  that  volatilization  of the  compound
from  water  1s an  Important  process.   The sorptlon  of  the  compound  by soil
and  sediment  was  also reported by  Elanco Products  Co.  (1983e).   WHh sandy
loam  soil of  1.2%  organic  matter  content and  clay  loam soil of 3.1% organic
matter content,  the authors  of this  report  estimated the soil K    value  to
range  between  510  and 530.   The  K    value 1n sediments  of  3.0-3.2% organic
matter content was  -420-490.   Therefore,  the compound  Is expected  to remain
moderately sorbed to most soils and  sediments.
    Bloconcentratlon by Blueglll  sunflsh,  Lepomls  macrochlrus.  was  tested  In
a static nonaerated system 1n the presence of 0.025-0.25 ppm 4-chlorobenzo-
trlfluorlde  for  <48 hours  (Elanco Products  Co., 1984).  A  steady-state  BCF
of 122-202  was  estimated,  Indicating that the compound  will  not  bloconcen-
trate significantly 1n aquatic organisms.
2.3.    SOIL
    Data  regarding   the   fate  of  4-chlorobenzotr1flour1de   In   soil  are
extremely limited.   As discussed  1n  Section  2.2.,  the  K    value  for this
compound In  soil  has  been experimentally determined  to be  510-530  (Elanco
Products Co.,  1983e).  From  this moderate  K   value,  It   can be  predicted
that   4-chlorobenzotr1fluor1de may leach significantly from  some soils 1f  the
blodegradatlon rate 1n the soil 1s slower  than the Infiltration rate.  Since
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the  compound  was  detected  In  a  groundwater   1n  Italy  near  an  Improper
disposal site  (Cacco  and  Ferrari, 1982),  It  Is  likely that  blodegradatlon,
at least 1n  soils that contain high concentrations of  the  compound,  will  not
be  fast.    Based on  data  provided  In  Section  2.2.,  photolysis  on  soil
surfaces will  probably  be unimportant,  and  some loss  of  the compound  will
occur from soil  surfaces as a result of  volatilization.  Volatilization  loss
from  soil  will  become  Increasingly  less Important,  however,  as  the  soil
depth Increases.  Based on  the data available  regarding  Us  fate In  water,
It  1s  likely  that   the  compound  will  be persistent  1n  most  soils.   The
absorption  of  the  compound   from soil  and   the  subsequent  possibility  of
translocatlon  to upper  parts  of  plants  were studied  by  Cacco  and  Ferrari
(1982),  who demonstrated that the translocatlon of the  compound  from root to
leaves  of  grass  and  legumes  1s rapid;  however,  the compound  1s metabolized
rapidly  1n legumes  but not  1n grass.
2.4.   SUMMARY
    Of  the  three likely  chemical processes  that  may  lead  to  the  loss  of
4-chlorobenzotrlfluoMde 1n  the  atmosphere,  neither  direct  photolysis  nor
Us  reaction  with  atmospheric  ()„ Is  significant  (Atkinson  et  al.,  1985).
Its reaction with photochemlcally produced HO radical  has  a  rate constant of
2.3xlO~13   cm3/molecule-sec   (Atkinson  et  al.,   1985).   Assuming  the  atmo-
spheric    concentration  of  HO  radical  as 106  radicals/cm3,  the  lifetime
of this compound 1n  the air  has  been  estimated  to  be -50 days  (Atkinson et
al.,  1985).   Therefore,  the  compound   Is  expected  to  persist In  the  atmo-
sphere.    In  water,  photolysis of  the  chemical  1s   not  Important   (Elanco
Products Co., 1983a).  Although the rates  of  aerobic and anaerobic blodegra-
datlon  of  the compound In  water  could  not  be  determined,  these  rates  are
slower  than  the  volatilization  rate  (Elanco  Products  Co., 1983b,c,d).   From
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the  value  of the  ratio  of the  volatilization rate  of  the compound  to  the
oxygen  reaeratlon  rate  determined  experimentally  (Elanco  Products  Co.,
1983d)  and  the values  of oxygen  reaeratlon  rates 1n  a few  natural  waters
(Thomas, 1982), the  half-life  for  volatilization of  the  compound  from water
has  been  estimated to be  1-6  days.  The K    value of 420-490  1n  sediments
                                           oc
(Elanco  Products   Co.,   1983e)   Indicates   that   the   compound   will  sorb
moderately to  suspended  solids  and sediments In  natural waters.   Based  on
the  experimentally determined BCF  of 122-202  In  Blueglll  sunflsh,  Lepomls
macrochlrus.  (Elanco  Products  Co.,  1984),  the compound  1s  not  expected  to
bloconcentrate significantly  1n  aquatic  organisms.   From  the  data  available
1n  aquatic  studies,  1t  can be  predicted that  photolysis  1n  soil will  be
unimportant,  and  some  loss  of  the compound will occur  from  the soil surface
because of  volatilization,  although  the  volatilization  process  will  become
less  Important  as  the  soil  depth  Increases.   The K    value  of  510-530  1n
soil  (Elanco Products  Co.,  1983e)  Indicates that   the  compound  may  leach
through some soils, particularly soil from Improper disposal  sites.  No data
regarding the b1odegradab1!1ty of the compound 1n soil are available.
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                                 3.   EXPOSURE

    There Is a paucity  of  data on the levels of  4-chlorobenzotMfluor1de  1n
environmental media.  This compound was qualitatively detected  1n  water  from
Lake Ontario at Niagara  River  (Great Lakes Water Quality  Board,  1983).  The
source of the compound  1n  the  water  was possibly the nearby  manufacturer  of
the chemical.  Hauser and Bromberg (1982)  reported  the  qualitative detection
of this  compound  1n the sediment/sol I/water samples collected  from contami-
nated areas  of  Love Canal, Niagara  Falls.   Bass  and yellow  perch collected
from Niagara  River  and  analyzed  1n  1978  contained  4-chlorobenzotr1fluor1de
1n the concentration range 0.17-2.0 ppm.  The compound  was  not  detected  at a
later date  (1980),  however, at a detection  limit  of  0.01  ppm  1n  various
samples   of  fish  (walleye, brown  trout  and sucker)  from  Lake Erie  and  Lake
Ontario   near  the   suspected   contaminated  areas  (Occidental  Chem.  Corp.,
1980b).-  Cacco and  Ferrari (1982) reported  the detection  of. this  compound  at
a level  of 1 ppm 1n groundwater  near an  Improper  disposal site  near Vlcenza,
Italy.
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                             4.  AQUATIC TOXICITY
4.1.   ACUTE TOXICITY
    The acute  toxldty  of 4-chlorobenzotr1fluor1de to aquatic  organisms  was
assessed for two  species  of  fish (rainbow trout,  Salmo  galrdnerl.  and  blue-
gill sunflsh,  Lepomls  macrochlrus)  and a macrolnvertebrate  (the  crustacean,
Daphnla maqna).   Exposure of  rainbow  trout  to 4-chlorobenzotr1fluor1de  In
static  acute  toxldty  tests  produced  nominal  24-,  48-,  72- and  96-hour
LCrQ   estimates   of  13.5  mg/l   (Union  Carbide  Environmental   Services,
1979a).  Confidence  limits  were  not  generated because  of  a lack  of  Inter-
mediate levels  of mortality.   No deaths  were  observed at 10 mg/8,  4-chloro-
benzotMfluorlde,  and   100%  mortality  was  observed   at  18  mg/i  for   each
observation period.  The test  was conducted 1n  reconstituted  water at  12°C.
    Exposure of  blueglll  sunflsh  to 4-chlorobenzotr1fluor1de  1n static  acute
toxldty tests  produced nominal  24-,  48-, 72- and 96-hour  LC5Q  values  with
95%  confidence   limits  of   19.1    (15.9-22.9),   13.5   (11.5-15,8),   12.7
(11.4-14.1)  and  12.0   (10.3-13.9)   mg/S.,   respectively    (Union   Carbide
Environmental  Services,  1979b).   No  deaths   were  observed  at  5.6   mg/8.
4-chlorobenzotr1fluor1de  after   96   hours.    The  test  was   conducted   1n
reconstituted water at  22°C.
    Exposure  of   0_.  maqna   to   4-chlorobenzotr1fluor1de   In  static   acute
toxldty  tests  produced  nominal  24-  and 48-hour  LCSQ estimates  with  95%
confidence  limits of  13.2  (11.4-15.2)  and  12.4  (10.7-14.5)  rag/i.  respec-
tively  (Union  Carbide  Environmental  Services,  1979c).    No   deaths   were
observed at  5.6 mg/l 4-chlorobenzotr1fluor1de  after  either  24 or 48  hours
of exposure.  The test  was conducted In well  water at  21°C.
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4.2.   CHRONIC EFFECTS
    The  chronic  toxlclty  of  4-chlorobenzotr1fluor1de  to aquatic  organisms
was  assessed  for  a  single  species  of   fish  (fathead  minnow,  Plmephales
promelas)  and   the   macrolnvertebrate,   D.   maqna.    Percentage  hatch  and
survival of  fathead  minnow embryos  exposed  to  4-chlorobenzotrlfluorlde were
used  to estimate  a   31-day  MATC  of >0.54  but <1.4  mg/l  (EG&G  Bionomics,
1981).   Fathead  minnow eggs  were exposed  to 4-chlorobenzotr1fluor1de  1n  a
flowthrough  system using  well  water  at   a  temperature  of  25°C.   Measured
concentrations of  4-chlorobenzotr1fluor1de were used  to calculate  the MATC
value.
    The  chronic  effects  of exposure of D_. maqna to  4-chlorobenzotr1fluorlde
were  assessed  by generating 4-,  7-,  14-  and 21-day LC5Q  estimates  with 95%
confidence   limits   of   0.163  (0.120-0.222),  0.150   (0.105-0.214),  0.073
(0.05-0.107)  and  0.071   (0.047-0.107)  mg/l,  respectively   (Union  Carbide
Environmental  Services,   1979d).    In  addition,  brood   size   of  -actively
reproducing  D. maqna  adults exposed to 4-chlorobenzotr1fluor1de was used to
estimate  a  21-day MATC  of  >0.03 but  <0.05 mg/l  4-chlorobenzotr1fluor1de.
The test was  conducted  1n  well  water  under  flowthrough  conditions  at a mean
temperature  of  20.8°C.   Measured  concentrations of  4-chlorobenzotr1fluor1de
were used to calculate the  MATC  and LC5Q values.
4.3.   PLANT EFFECTS
    There were no  studies  Identified that addressed the  effects  of exposure
of aquatic plants to  4-chlorobenzotr1fluor1de.
4.4.   SUMMARY
    Exposure of  rainbow  trout and blueglll  sunflsh  to 4-chlorobenzotrlfluo-
rlde  generated  96-hour  LC5Q  values  of   13.5  and  12.0  (10.3-13.9)  mg/l,
respectively  (Union  Carbide Environmental Services,  1979b).  Exposure  of J).
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magna   to   4-chlorobenzotr1fluor1de  generated   a   48-hour  LCc0   of   12.4
(10.7-14.5) mg/8, (Union Carbide Environmental Services, 1979c).
    The  concentration  of  4-chlorobenzotr1fluor1de  that  produced  chronic
effects  In  aquatic organisms  was  ~l-2 orders  of magnitude  lower  than that
produced for acute  effects.   The MATC for fathead  minnow eggs  was  >0.54 but
<1.4 mg/l  4-chlorobenzotr1fluor1de.  The  MATC  for  D. maqna  was  >0.03  and
<0.05  mg/l  4-chlorobenzotr1fluor1de  (Union  Carbide  Environmental  Services,
1979d).
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                             5.   PHARMACOKINETICS
5.1.   ABSORPTION
    A   metabolism   study   of    [CF3-l4C]-4-chlorobenzotr1fluor1de,    which
found  radioactivity  In  the expired  air  and  urine  of  male  and   female
Sprague-Oawley  rats  treated  at  doses  of  1   or 104  mg/kg  (In  corn  oil),
Indicated  that   the  compound  1s  absorbed  from  the  gastrointestinal  tract
(Qulstad and  Mulholland,  1983).   Within 4  days  of  dosing,  radioactivity  In
the expired air  and  urine of treated rats accounted for  68-82% and 6-15%  of
the dose,  respectively,  with the total by  both routes ranging from  76-88%.
Only  2-4%  of  the  dose  was  found  In  the  feces.    Analysis  of  blood  for
radioactivity Identified  a  peak  concentration  of  ~0.05  ppm,  1  hour  after
dosing,  suggest- 1ng  that  absorption  from the  gastrointestinal  tract was
rapid.
5.2.   DISTRIBUTION
    Four  days  after'  rats  of  both  s.exes  were  given  a  gavage  dose  of
[CF,-lAC]-4-chlorobehzotr1fluor1de  1n  corn oil  (1   or  104  mg/kg),  -1%  of
   0
the radioactivity remained  In  the carcass,  except for  selected tissues  (see
below)  (Qulstad  and  Mulholland,   1983).   Analysis  of organs  and  tissues,
Including  the spleen,  fallopian  tubes  and ovaries,  testes,  pancreas,  lungs,
kidney,  brain,   heart,   muscles,   fat,  liver,   hide,  stomach  and  Intestines,
revealed slightly higher  levels of  radioactivity  1n tissues  from  female rats
compared with male rats.  The radioactivity 1n the  tissues  was  Identified  as
4-chlorobenzotr1fluor1de,  and   tissue   concentrations    ranged   from   <1-16
yg/kg  following  a 1  mg/kg  dose,  and  <40-371  yg/kg  following  a 104  mg/kg
dose.   The only  exception was abdominal fat from female,  but not  male,  rats,
which  contained  higher  levels  of  radioactivity:   104  yg/kg following a  1
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mg/kg  dose  and  1420  yg/kg  following  a 104  mg/kg  dose.  Approximately  90%
of  the  radioactivity  1n the abdominal  fat  was Identified as  4-chlorobenzo-
trlfluoMde.
5.3.   METABOLISM
    In  a   metabolism  study  of   [CF3-14C]  4-chlorobenzotr1fluor1de   where
rats  were   treated  orally,  Qulstad and  Mulholland  (1983)  found  that  the
compound was not metabolized extensively.  At  a dose  of  1  mg/kg,  -15% of  the
dose was metabolized.  Analysis of  radioactivity  1n the  expired air  revealed
that  unmetabollzed  [l4C]-4-chlorobenzotr1fluor1de accounted  for  a  majority
of  the  62-82% of  the dose  recovered,  with  negligible amounts recovered  as
"CO-.   At   least   56%  of   the  radioactivity  found  1n   the   feces   was
unmetabollzed 4-chlorobenzotr1fluor1de;  the  remaining radioactivity was  not
Identified.   The major  urinary metabolites Identified were  the glucuronldes
of  dlhydroxybenzotrlfluorlde  and  4-chloro-3-hydroxybenzotr1fluor1de,  which
accounted .for <2.7   and  4.4%  of   the  total   dose,   respectively.   A  minor
metabolite,   the  mercaptuMc  add  conjugate  of  4-chlorobenzotr1fluor1de,
accounted for  0.1-0.2% of the  total  dose,  respectively.  Because  4-chloro-
benzolc add  and Us conjugates were  not  detected  In the urine,  the  Inves-
tigators concluded  that  the CF- moiety  was   stable  to  hydrolysis.   Little
                                o
difference  In qualitative or quantitative metabolism  between male  and  female
rats was observed.
5.4.   EXCRETION
    Four  days  after  rats were  given  a single  oral dose  of  [CF3-14C]-4-
chlorobenzotrlfluorlde  1n  corn oil  at 1  (four females,  two  males) or  104
mg/kg  (two  females), 62-82% of  the dose  was recovered  In  the expired  air
(Qulstad and Mulholland, 1983).  Analysis of  air  resulted  In  recovery  of  35%
of  the  radioactivity  before  the  rats  defecated;  this   suggested   that
pulmonary excretion was rapid, and  confirmed  that the radioactivity  had  been
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expired and had  not  volatilized  from the feces.  Radioactivity  recovered  1n
the feces  accounted  for 2.6-3.5%  of the dose,  while urinary  radioactivity
accounted  for  13.6-14.9% of  the dose  following treatment  at  1 mg/kg,  and
5.9% of  the dose at  104 mg/kg.   Total  recoveries  ranged from  79-90%.   The
Investigators  stated that the relatively low recoveries were a  reflection  of
                                 r-
difficulties In the  radloassay of volatile  [l4C]-4-chlorobenzotr1fluor1de.
5.5.   SUMMARY
    The  single  study  of   [l4C]-4-chlorobenzotr1fluor1de  metabolism  using
rats (Qulstad and Mulholland,  1983)  Indicated  that the compound  1s  absorbed
and excreted readily,, predominantly as Ihe  parent compound.   The major route
of  excretion  was through  expired  air,  which  accounted   for  62-8254  of  the
dose.     Urinary   metabolites   Identified  were    the    glucuronldes    of
d1hydroxybenzotr1fluor1de   and   4-chloro-3-hydroxybenzotr1fluor1de,   which
accounted  for  <2.7   and 4.4%  of the  dose, respectively.   A minor  urinary
metabolite,  the  mercaptuMc  acid  conjugate   of  4-chlorobenzotr1fluor1de,
accounted for  0.1-0.2% of the dose.
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                                  6.   EFFECTS
6.1.   SYSTEMIC TOXICITY
6.1.1.   Inhalation  Exposure.   Pertinent  data  regarding  the  toxldty   of
4-chlorobenzotrifluoride   following    subchronlc   and   chronic   Inhalation
exposure were not located 1n the available literature dted 1n Appendix A.
6.1.2.   Oral Exposure.
    6.1.2.1.   SUBCHRONIC — In a 3-month  study,  groups  of 15 F344 rats/sex
(5-6  weeks  old)  were  treated  dally  by gavage with  4-chlorobenzotr1fluor1de
(97.7% pure) 1n corn oil at doses of  0,  10,  40,  150  or  500 mg/kg/day  (Arthur
and Probst,  1983).   One male.rat at  10 mg/kg/day and  two male rats  at  500
mg/kg/day died.  No significant dose-related physical or  behavioral signs  or
ophthalmic  changes  were noted.   Transiently  significant reductions  1n  body
weight gain were observed  1n all  dose  groups,  with body  weight gain 1n males
at  500  mg/kg/day  consistently  below controls. Food  Intake of  all  4-chloro-
benzotrlfluorlde-treated  rats  was   depressed   throughout   the  study, . the
largest  decrease  being observed 1n  males  at  500  mg/kg/day.   The  only
significant hematology  changes  noted  were 1n high-dose male  rats,  which  had
a  statistically  significant (p<0.05)  decrease  In total  erythrocytes and  a
shift  toward an  Increase  In   neutrophlls  and  a decrease   In  lymphocytes.
Results of  clinical  chemistry  analyses revealed  slightly  elevated  levels  of
serum  urea   nitrogen  1n male   rats  treated  at   150  and  500 mg/kg.    Total
blllrubin  was  Increased  In   both   male  and   female  rats  at  500   mg/kg.
UMnalysIs  Indicated  mild  prbtelnurla  In  both  sexes at  150 and 500  mg/kg.
Determinations  of  hepatic  p-nltroanlsole  0-demethylase  activity   showed
significantly (p<0.05) greater  levels  In males at 40, 150 and 500 mg/kg/day,
and  1n  females at  500  mg/kg/day.   At necropsy, relative liver and  kidney
weights  were  significantly   (p<0.05)  Increased  "at   the   higher   doses"
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(presumably 150 and  500  mg/kgj.   Thyroid weights were slightly  Increased  In
treated rats,  with  significant  Increases (p<0.05)  1n  females at 40 and  500
mg/kg.  Slightly Increased adrenal weights were  observed  1n males at  150  and
500 mg/kg/day  and  1n  females at  500  mg/kg/day.   Hlstologlcal  examinations
revealed renal  tubular degeneration  In  one  low-dose male rat  (10 mg/kg/day)
and In  all  male rats  treated at  doses >40 mg/kg/day.   The severity of  the
renal   lesions   was  dose-related,   ranging  from  minimal   (decreased  cellular
height,   Increased   cytoplasmlc   basophlUa,    Increased  hyaline   droplet
formation)  to   moderate  (Increased  number  of   necrotlc  cortical epithelial
cells, and  prominent hyaline  casts 1n  tubules  of the outer zone medulla  and
occasionally  In  the  cortex).   Tubular  degeneration  was  not  observed  In
female rats or  1n any  male controls.   Centrllobular  hypertrophy  was  observed
In the  livers  of  all males and one  female  rat treated at  150 mg/kg/day  and
1n all  rats  treated  at  500 mg/kg/day.  CentMlobular  hypertrophy  was  not
observed 1n control  rats.  Among  high-dose rats,  the effect-on  the  liver" was
slightly  more  prominent  1n males   than  1n   females.    The  Investigators
concluded  that  rats  tolerated   the  10  mg/kg  dose  for  90  days   without
significant toxlclty.
    6.1.2.2.   CHRONIC  -- Pertinent   data   regarding    the   toxlctty    of
4-chlorobenzotr1fluor1de following chronic oral  exposure  were  not located  In
the available literature cited In  Appendix A.
6.1.3.   Other  Relevant   Information.   Hooker  Chemical   Corp.    (1979a)
reported  a  4-hour  LC5Q  of  33.0  mg/m3  for  4-chlorobenzotMfluorlde   1n
Sprague-Dawley  rats  (male and  female).  No mortality occurred at  6.03  or
20.8  mg/m3.   According  to  the   Investigators,  signs  of  Irritation  during
the   exposure   (redness   around    the   eyes,   excessive   lacrlmatlon,   nasal
discharge)  occurred  at  concentrations  >20.8   mg/m3, and lung  discoloration
on necropsy was observed  In all exposure  groups.  These  results  suggest that

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pulmonary  Irritation  may  be  an  Important  component   1n  the  toxlclty  of
4-chlorobenzotr1fluor1de following Inhalation exposure.
    In a Russian study  (Rapoport  et  al.,  1986),  male nonpurebred albino male
rats  (numbers  unspecified)  were exposed  to  4-chlorobenzotr1fluor1de  at 5.5,
20.5,  71.6  or  440  mg/m3,  continuously  for   120  hours.   The  rats  were
observed for  at least  115 days  following exposure.   Examinations  Included
body  weight,  muscular  strength  (grasping  reflex),  blood  analyses (RBC  and
leukocyte  counts,   hematocrlt,  content  of  hemoglobin   In  one  erythrocyte,
liver function, chollnesterase and lactate  dehydrogenase) and  studies of  the
nervous  system ("summation-threshold Index,"  motor  activity).  Exposure  at
440  and  71.6  mg/m3  resulted   1n   a  change  In  "practically  all  of  the
parameters   studied."   The  20.5  mg/m3   concentration   was  considered  the
"minimally   effective"  concentration,  while  5.5  mg/m3 was  considered  the
"subthreshold."  The results,   which are  difficult  to  Interpret, are  pre-
sented as  time of  onset of  significant  changes  1n  parameters.   In  general,
time  of  onset  of  significant  effects   Increased with decreasing  exposure
concentration.   The   study  does  not   relate  exposure   concentration   to
Incidence or severity of effects.
    The  oral   LD5Q   for   4-chlorobenzotr1fluor1de  In   Sprague-Dawley  rats
(male and  female)  was  reported  as  >5.0 ml/kg  (6.7 g/kg) (Hooker  Chemical
Corp., 1985a).   At a  dose  of  5  ml/kg  (6.7 g/kg),  2/8 male  and  0/8 female
rats died during the 14-day observation period.
    The  dermal  LD5Q  1n  New  Zealand White  rabbits  was  reported to  be >2.0
ml/kg  (2.7  g/kg)  (Hooker  Chemical  Corp.,  1985b).   4-Chlorobenzotr1fluor1de
was  applied  to shaved  abraded  skin  (back)  and  the  test area was  occluded.
Only  one dose was  studied; at  2  ml/kg (2.7  g/kg),  0/5 male  and  1/5 female
rabbits died during the 14-day  observation period.
Ollld                               -18-                             05/10/88

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6.2.   CARCINOGENICITY
6.2.1.   Inhalation.    Pertinent  data   regarding   the  carclnogenldty   of
4-chlorobenzotr1fluor1de following  Inhalation  exposure were  not  located  In
the available literature cited 1n Appendix  A.
6.2.2.   Oral.  Pertinent  data  regarding  the  carclnogenldty  of  4-chloro-
benzotr1fluor1de following  oral  exposure were not  located  In  the available
literature cited 1n Appendix A.
6.2.3.   Other  Relevant  Data.   Hooker  Chemical  Corp.  (1980)  reported  that
4-chlorobenzotr1fluor1de   tested  negative   for    cell   transformation   In
Balb/C3T3 cells.  The compound (purity unspecified) was added to the  culture
medium at  concentrations of  0.1-40  nl/mi, which  allowed  80 to  50% of  the
cells to survive.   The study  did  not  report whether an activating  system was
used.  Lilly  Research Laboratories (1983a) also found  that  4-chlorobenzotr1-
fluoride  (97% pure)  tested  negative  for  cell  transformation  In Balb/C3T3
cells." ' This-study  was  conducted 1n  the presence  of  S-9,  with-the  compound
added  to  the  .culture  medium at  concentrations   of   10-300  pg/l.   Reduced
survival   was   observed   at  300  jig/mi,  a   concentration  at  which   the
compound was not completely mlsdble  with the  culture  medium.
6.3.   MUTAGENICITY
    Data  regarding   the   mutagenldty   of   4-chlorobenzotr1fluor1de   are
presented In  Table  6-1.   4-Chlorobenzotr1fluor1de  tested negative 1n  assays
for reverse mutation  In Salmonella typhlmurlum (Haworth et  a!., 1983;  Hooker
Chemical   Corp., 1978a).    Urine  from  mice  treated  with   4-chlorobenzotrl-
fluoMde  also  tested  negative  1n  assays  for   reverse  mutation   1n  S.
typhlmurlum  (Hooker   Chemical Corp.,  1979b).  Negative  results   have  been
reported  for  4-chlorobenzotr1fluoMde   1n  assays   for reverse  mutation  In
Saccharomvces  cerevlslae.  DNA repair  1n  Escher1ch1a  coll  (Hooker  Chemical
01 lid                               -19-                             05/10/88

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                   TABLE 6-1



Nutagenlclty Testing  of 4-Chlorobenzotrtfluoride
Assay
Reverse
nutation
Reverse
nutation
Reverse
nutation
(urine assay)
Reverse
mutation
DMA repair
test
Forward
nutation
Unscheduled
DNA synthesis
Chromosome
aberrations
Indicator Purity
Organlsn
Salmonella 96X
typhlmurlum
TA1535. TA1537.
TA9B. TA100
S. typhlmurluro NR
TA1535. TA1537.
TA98, TA100
S. typhlmurlun NR
TA1535. TA1537.
TA98. TA100
Saccharoroyces NR
cerevlslae D4
Escherlchla NR
coll U3HO/po1A+.
P3478/polA-
L5178Y mouse NR
1 ymphoma
EUE cells NR
Chinese hamster NR
ovary cells
Application Concentration
or Dose
pre Incubation 10-1000 pg/plate
plate 0.01-10 pi/plate
Incorporation
male CO-1 nice 0.1, 0.2 or 0.3
treated by gavage nt urine/plate
for 2 days at 50,
167 or 500 rag/kg/
day; urine tested
for nutagenlclty
by plate Incor-
poration
plate 0.1-10 vft/plate
Incorporation
spot test 0.01-10 |ii/plate
(check) (check)
added to 3.13-50 nl/rot
culture medium
NR NR
added to 29.99-130 nt/mt .
cultures
Activating
System
»S-9
»S-9
i deconjuga-
tlng enzyme.
B-glucuront-
dase, before
urine was
added to
plate
± S-9
»S-9
±S-9
NR
±S-9
Response Comment
NC
NC
= Urine was collected
overnight (16 hours);
the tine between dosing
and urine collection
was not stated.
NC
NC
= Concentrations of >78
nfc/nl were highly
toxic to mouse lymphoma
cells.
» Study was available only
as an abstract, which
did not further describe
the cells used or the
study protocol.
Cells treated for 12
hours collected at 14 or
24 hours, cytotoxlclty
at 90 nft/mt.
Reference
Haworth et al.,
1983
Hooker Chemical
Corp.. 1978a
Hooker Chemical
Corp.. 1979b
Hooker Chemical
Corp., 1978a
Hooker Chemical
Corp.. 1978a
Hooker Chemical
Corp.. 1978b
Benign) and
Dogllottl. 1980
Lilly Research
Laboratories.
19B3b

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                                                                          TABLE!
                                                               (cont.)
Assay
Sister
chromatld
exchange
Indicator Purity Application
Organism
LS178 mouse NR added to
lymphoma cells culture medium
Concentration
or Dose
0.0025. O.OOSO,
0.0100, 0.0200,
0.0400 |il/ml
Activating
System
iS-9
Response Comment
t Without activation, re-
sults were significant
at all concentrations.
Ulth activation, results
were significant at 0.0025
0.0100 and 0.0200 vl/ml
(not dose-related)
Reference
Hooker Chemical
Corp.. 1979c
t
    Chromosome
    aberrations
bone marrow
cells of rats
NR
gavage dose
0.5. 1.7 or 5.0
ml/kg
NA
Analyses were completed
6, 24 and 48 hours after
a single gavage dose.
Lilly Research
Laboratories,
1983c
    NA -  Not  applicable;  NC = no comment; NR = not reported
a
CO

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Corp.,  1978a),  forward  mutation  In  mouse lymphoma  cells  (Hooker  Chemical
Corp.,  1978b),  and  chromosome  aberrations  In Chinese  hamster ovary  cells
(Lilly  Research  Laboratories,  1983b)  and  rat  bone  marrow  cells  (Lilly
Research   Laboratories,    1983c).     The   only   positive    results    for
4-chlorobenzotr1fluor1de were  1n an assay  for unscheduled DNA  synthesis  1n
EUE cells  (cells  were  not  further described)   (Benlgnl and  Dogl1ott1,  1980),
and  In  an assay  for  sister  chromatld  exchange  1n mouse  lymphoma  cells
(Hooker Chemical Corp., 1979c).
6.4.   TERATOGENICITY
    Pertinent data  regarding the  teratogenlcity  of  4-chlorobenzotr1fluor1de
were not located 1n the available literature cited 1n  Appendix A.
6.5.   OTHER REPRODUCTIVE EFFECTS
    Hooker Chemical  Corp.   (1981)  reported  results  of a  2-generatlon  repro-
ductive study 1n  which groups  of 20 Sprague-Dawley rats/sex  were  treated  by
gavage with  4-chlorobenzotr1fluor1de  (97% pure)  1n corn  oil at doses  of  0,
5,  15  or  45  mg/kg/day.  The  parental generation  was  treated  for  4  weeks
before mating,  throughout   reproduction,  and  through  the  weaning  of the  F.
generation.  The  F,  generation was culled  to  10  pups/Utter on day  14,  and
was  treated   for  90  days  postweanlng.   Offspring   were  not  examined  for
malformations.    No   treatment-related  mortalities,   behavior  changes   or
consistent  treatment-related  changes  1n  weight  gain and  food  consumption
were  observed  1n the  F_  or   F,   rats.   No  significant  treatment-related
changes  In  hematology  and clinical   chemistry  were  noted  in  F_  or  F,
rats.  Treatment  of  rats with  4-chlorobenzotr1fluor1de  had no effect on  the
number  of  pups/Utter,  pup surv1vabH1ty  or  length of  gestation  period.
Body weight  of  female  pups from rats  treated  at 45  mg/kg/day  was  signifi-
cantly (p<0.05) decreased  compared with  controls on  day 1 after  birth.   On
day  4,  body  weights  of  offspring (males  and females)  were  significantly

Ollld                               -22-                             05/10/88

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(p<0.05)  Increased  compared  with  controls  1n  all  treatment  groups.   At
necropsy,  no  dose-related  gross  lesions  were  observed  1n  the  FQ  rats.
Hlstologlcal  examinations  were  not  completed.   In   the   F.   generation,
determination  of  organ  weights   revealed   a   nonsignificant   dose-related
Increase In  mean  liver  weights  and  mean I1ver-to-body weight ratios  1n both
sexes.   Hlstologlcal  examinations  of major  tissues  and  organs   completed  on
F,  controls  and  on   rats   treated  at  45  mg/kg/day  did  not  reveal  any
treatment-related effects.
6.6.   SUMMARY
    Minimal to moderate renal tubular degeneration was observed  1n  male rats
treated by gavage with 4-chlorobenzotr1fluor1de at doses >40  mg/kg/day  for  3
months  (Arthur  and Probst,  1983).   CentMlobular hypertrophy  of  the  Hver
was  observed 1n  male rats  treated with  4-chlorobenzotr1fluor1de  doses  at
>150 mg/kg/day and  In female rats  at 500 mg/kg/day.  No significant  effects
were   observed   In   rats    treated   for    3    months    by    gavage   with
4-chlorobenzotr1fluor1de at  10 mg/kg/day.
    In contrast  to  the Arthur and  Probst  (1983) study, hlstologlcal  kidney
and  liver   effects  were  not  observed  1n   a 2-generat1on  study  In  which
Sprague-Dawley rats were  treated by gavage  with  4-chlorobenzotr1fluor1de  at
doses <45  mg/kg/day  for >90  days  (Hooker  Chemical  Corp., 1981).   4-Chloro-
benzotr1fluor1de  treatment   did  not  have any  effect  on   reproductive
parameters.
    A  Russian  study   (Rapoport  et  al.,   1986)  reported  that  Inhalation
exposure of  rats to  4-chlorobenzotr1fluoMde at concentrations  >20.5  mg/m3
for  120  hours  resulted  1n  changes 1n  blood analyses,  motor   activity  and
muscle strength.  Significant changes  were  not  observed 1n  rats exposed  at
5.5 mg/m3 for 120 hours.
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    Hooker  Chemical  Corp.  (1979a)  reported  a   4-hour  LC5Q  for  4-chloro-
benzotMfluoride  1n  Sprague-Dawley  rats  of  33  mg/m3.   The oral  LD5Q  for
4-chlorobenzotr1fluor1de 1n Sprague-Dawley  rats  was  reported  as >5.0  mi/kg
(6.7  g/kg)  (Hooker   Chemical   Corp.,   1985a),   while  the   dermal   LD™   1n
rabbits was  reported to  be >2.0  ml/kg (2.7 g/kg)  (Hooker Chemical  Corp.,
1985b).
    Except  for  positive  results  1n  assays of  unscheduled  DNA  synthesis
(Benlgnl and Dogllottl, 1980) and  sister chromatld exchange  (Hooker  Chemical
Corp.,  1979c),  results of  mutagenlclty assays  of  4-chlorobenzotr1fluor1de
have been negative.
    4-Chlorobenzotr1fluor1de  has   not   been  tested  for  carclnogenlclty   or
teratogenldty.
Ollld                               -24-                             04/19/88

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                    7.  EXISTING GUIDELINES AND STANDARDS
7.1.   HUMAN
    Pertinent guidelines and  standards,  Including  EPA ambient water and  air
quality criteria, drinking water standards,  FAO/WHO  ADIs,  EPA or FDA  toler-
ances  for  raw agricultural commodities  or  foods,  and  ACGIH,  NIOSH or  OSHA
occupational  exposure  limits  were  not  located  In  the available literature
dted 1n Appendix A.
 *2.   AQUATIC
    Pertinent guidelines  and  standards  for  the protection  of aquatic  life
from exposure to  4-chlorobenzotr1fluor1de were not located 1n the  available
literature cited 1n Appendix A.
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                             8.  RISK ASSESSMENT
8.1.   CARCINOGENICITY
    Pertinent data regarding the cardnogenlcHy  of  4-chlorobenzotr1fluor1de
were not located In the available  literature cited 1n Appendix  A.
8.1.1.   Weight  of Evidence.   As  a  result of  a  lack of  data  concerning
cardnogenlclty  In  humans  and  animals,   4-chlorobenzotrlf luorlde   can   be
classified as an EPA Group D chemical (U.S.  EPA,  1986b), not classifiable  as
to human cardnogenlclty.
8.1.2.   Quantitative  Risk  Estimates.    The   derivation   of  carcinogenic
potency  factors  for  4-chlorobenzotr1fluor1de  1s  precluded  by  the  lack  of
cardnogenlclty data.
8.2.   SYSTEMIC TOXICITY
8.2.1.   Inhalation Exposure.  The derivation  of  Inhalation  risk assessment
values  for  4-chlorobenzotrlfluorlde  Is  precluded  by the  lack of  subchronlc
and chronic Inhalation studies.
    An  LCgg  study  using rats (Hooker Chemical  Corp., 1979a)  suggested  that
pulmonary  Irritation  may  be  an   Important component  1n  the  toxlcity  of
4-chlorobenzotr1fluor1de  following  Inhalation  exposure.    The   only   other
Inhalation study,  a  Russian  study  (Rapoport et al.,  1986), reported  changes
1n blood  analyses,  motor  activity and muscular  strength  In rats  exposed  to
4-chlorobenzotr1fluor1de   continuously   at  >20.5   mg/m3   for  120   hours.
Significant effects  were  not observed In  rats exposed to  4-chlorobenzotrl-
fluorlde at 5.5 mg/m3 for  120 hours.
8.2.2.   Oral Exposure.
    8.2.2.1.   LESS  THAN   LIFETIME  EXPOSURES -- In  the  90-day  study  by
Arthur  and  Probst  (1983), F344 rats  were  treated  by gavage  with 4-chloro-
benzotrlfluorlde  In  corn  oil  at   0,  10,  40,  150  or  400  mg/kg/day.   No
Oil Id                               -26-                             05/10/88

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significant  treatment-related  effects  were observed  at  10  mg/kg/day.   In
male rats treated at >40 mg/kg/day, renal  tubular  degeneration  was  observed,
with severity  Increasing  from minimal  effects  at  40  mg/kg/day to  moderate
effects  at  150  mg/kg/day.   CentMlobular  hypertrophy  In  the  liver  was
observed 1n all male rats and 1n  one  female rat  at 150 mg/kg/day,  and 1n all
rats at 400 mg/kg/day.
    The only  other  study  of sufficient  duration  for risk assessment  1s  the
                                                              »
2-generat1on study  using  Sprague-Dawley rats (Hooker  Chemical  Corp.,  1981).
In  this  study,  no  significant  treatment-related  effects on  reproduction  or
h1stolog1cal  changes  were noted  1n  rats  treated  by  gavage  with  4-chloro-
benzotrlfluorlde  In corn  oil  at  0,  5,  15 or  45 mg/kg/day.   The FQ  rats
were treated  for  4  weeks  before mating, through  mating  and weaning,  and the
F,  were  treated  for  90 days  after  weaning.  A   nonsignificant  dose-related
Increase In liver weights  was noted In F, rats.
    A 3-month rat study  (Arthur  and Probst, -1983)  Indicated  that  the kidney
and  liver  are the  target  organs  of  4-chlorobenzotr1fluor1de  toxldty.   The
LOAEL  found  1n  this study was  40 mg/kg/day, a  dose at which  minimal  renal
tubular degeneration 1n male rats was observed.  The highest  NOAEL  below the
40 mg/kg/day  LOAEL  Is  the  15 mg/kg/day  dose from the  2-generat1on  rat study
(Hooker Chemical  Corp.,  1981).   A  subchronlc  oral RfD  of 0.2  mg/kg/day,  or
11 mg/day for a 70  kg  human,  1s  calculated from  the NOAEL of  15 mg/kg/day by
dividing the  NOAEL  by an uncertainty  factor of  100,  10  to extrapolate from
animals to humans, and 10 to protect sensitive  Individuals.
    Confidence  In this  RfD  1s  low.   The studies  useful  for  risk  assessment
are  limited  to two  rat  studies.    These studies  Indicate a  possible strain
difference; one study  reported  renal  tubular degeneration In  male  F344 rats
treated with  4-chlorobenzotr1fluor1de  at  40 mg/kg/day  (Arthur and  Probst,
Ollld                               -27-                             05/10/88

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1983), but no  treatment-related effects were  observed  In  Sprague-Dawley rats
In a  2-generat1on  study  at  45 mg/kg/day  (Hooker  Chemical  Corp.,  1981).  Low
confidence 1n   the subchronlc RfD  1s  also  Indicated because of  the  lack  of
teratogenlclty studies.
    8.2.2.2.    CHRONIC EXPOSURES  -- Chronic  oral  studies  of  4-chlorobenzo-
trlfluorlde were  not  available.   A  chronic  oral  RfD of 0.02 mg/kg/day or  1
mg/day for a  70 kg human can be  derived  by dividing the  subchronlc  oral RfD
by an additional  uncertainty  factor  of  10  to  extrapolate from  subchronlc
exposure.
    Confidence 1n  this RfD Is low.   There are only two rat studies available
concerning the  toxldty  of   4-chlorobenzotr1fluor1de,  and  they   Indicate  a
possible strain difference In the  development  of  renal  tubular  degeneration.
Ollld                               -28-                             05/10/88

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                          9.  REPORTABLE QUANTITIES
9.1.   BASED ON SYSTEMIC TOXICITY
    The  only  study  reporting   effects   following  subchronlc   exposure   to
4-chlorobenzotr1fluor1de 1s  the  3-month  study  by  Arthur  and Probst  (1983).
As  discussed 1n  Section 6.1.2.1.  and summarized  In Table  9-1,  male  rats
treated by  gavage with  4-chlorobenzotr1fluor1de 1n corn oil at  a  dose  of  40
mg/kg/day developed  minimal  renal  tubular  degeneration,  while  rats  treated
at  150  mg/kg/day  developed  protelnurla,   mild to  moderate  renal  tubular
degeneration and  centrllobular   hypertrophy  of  the  liver.   As   Indicated  In
Table 9-1,  the animal doses of 40 and  150  mg/kg/day  correspond  to  human MEDs
of  43  and  149  mg/day,  and  RV.s  of  3.0  and  2.2,  respectively.   The  most
appropriate  RV    for  minimal  renal  tubular degeneration  observed  at  the
lower  dose   Is  3,  and   the  RV    for  renal  tubular  degeneration  associated
with  mild  protelnurla   1s   7.    Multiplication of  the  RV.s  by   the   RV s
yields  CSs   of  9.0  and  15.4  for  minimal  renal  tubular  degeneration  and
tubular degeneration associated  with protelnurla,  respectively.  Th-e  highest
CS, 15.4, 1s the most appropriate basis for the  RQ  of 1000  (Table 9-2).
9.2.   BASED ON CARCINOGENICITY
    Pertinent data  concerning  the  carclnogenldty  of  4-chlorobenzotMfluo-
rlde were  not  located.   Except  for an assay for  sister chromatld  exchange
(Hooker Chemical  Corp., 1979c)   and  an assay for  unscheduled DMA  synthesis
(Benlgnl  and Dogl1ott1, 1980),  mutagenlcHy assays  have  reported  negative
results (see Section 6.3.).  The  lack of  data concerning the  carclnogenldty
of  4-chlorobenzotr1fluor1de  In  either humans or  animals  Indicates that  the
compound should be  classified as an EPA Group  D chemical  (U.S.  EPA,  1986b),
not  classifiable  as  to  human  carclnogenldty.   Hazard  ranking  based  on
carclnogenldty 1s not  possible.
Oil Id                               -29-                             05/10/88

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o
I
                                                                            TABLE 9-1


                          Composite Scores  for  the Oral Toxlclty of 4-Chlorobenzotrlfluorlde (97X Pure) In Corn Oil Using Hale F344 Rats*
No. at
Start
15
15
Average
Body Ue1ghtb
(kg)
0.25
0.2
Dose/Exposure
40 rog/kg/day
by gavage for
3 months
150 mg/kg/day
by gavage for
3 months
Animal Dose
(rog/kg/day)
40
150
Equivalent
Human NEDC
(rog/day)
43
149
RVd Effect RVe
3.0 Minimal renal tubular 3
degeneration
2.2 Mild protelnurla. renal 7
tubular degeneration
and centrllobular hyper-
trophy of the liver
CS RQ
9 1000
15.4 1000
         aSource: Arthur and Probst. 1903


         Estimated from graphs


         cAnimal  dose  multiplied by the cube root of  the  ratio  of animal to reference human body weight  (70 kg)  and by 70 kg to express human  NED In

          tng/day, and  divided by an uncertainty factor of 10 to expand  from subchronlc  to  chronic  exposure.
ca
CD

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                                  TABLE 9-2
                           4-ChlorobenzotMfluoride
           Minimum  Effective Dose (MED) and Reportable Quantity (RQ)
Route:                  oral
Dose*:                  149
Effect:                 mild  protelnurla,  renal  tubular  degeneration,
                        centrllobular  hypertrophy of  the liver
Reference:              Arthur and Probst,  1983
RVd:   -                 2.2
RVe:.                    7
Composite Score:        15.4
RQ:                     1000
*Equ1valent human dose
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                                10.   REFERENCES

Arthur, B.H. and K.S. Probst.   1983.  A  subchronlc  study  1n Fischer 344 rats
given  dally gavage  doses  of  4-chlorobenzotrlfluorlde (PCBTF).   Toxicology
Division,  Lilly  Research Laboratories,  Division of  E11  Lilly and  Company,
Greenfield, IN.  U.S. EPA/OPTS Public Files.   Microfiche #OTS0507306.

Atkinson,  R.,  S.  Aschmann,  A.  Winer and  J.  Pitts, Jr.   1985.   Atmospheric
gas phase  loss  processes for chlorobenzene,  benzotrlfluorlde,  and  4-chloro-
benzotrlfluorlde,   and  generalization of  predictive   techniques  for  atmo-
spheric  lifetimes  of aromatic  compounds.   Arch.  Environ. Contam.  Toxlcol.
H(4): 417-425.

Benlgnl, 4. and E.  Dogllottl.   1980.  UDS studies  on  selected  environmental
chemicals.  Mutat.  Res.   74:  217.

Boudaklan,  M.M.   1980.   Fluorlnated  aromatic   compounds.   In.:  Kirk-Othmer
Encyclopedia of Chemical Technology,  3rd ed., Vol.  10,  M.  Grayson,  Ed.   John
WHey and Sons, New York, NY.  p. 901, 912, 921-925, 936.

Cacco,  G.  and  G.  Ferrari.   1982.  Absorption  and  translocatlon of  4-{tr1-
fluoromethyljchlorobenzene 1n  soil  and  crops.   J. Agrlc.  Food  Chem.   30:
196-197.

EG&G  Bionomics.   1981.   The  toxlclty of  parachlorobenzotrlgluorlde  (PCBTF)
to  fathead  minnow   (Plmephales  promelas)   embryos   and   larvae.    Report
#BW-81-3-838 (OTS0508145).
Ollld                               -32-                             04/19/88

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Elanco Products  Company.   1983a.   Photolysis of  p-chlorobenzotr1fluoMde  In
water.   Prepared by  Lilly Res.  Labs.,  Greenfield,  IN.   USEPA/OPTS  Public
Files, 80 Submission.   Microfiche  #OTS 0507306.

Elanco   Products   Company.   1983b.   Aerobic   aquatic  blodegradatlon   of
4-chlorobenzotr1fluor1de.    Prepared   by  Lilly  Res.  Labs.,  Greenfield,  IN.
USEPA/OPTS Public Files,  80 Submission.  Microfiche #OTS 0507306.

Elanco Products  Company.   1983c.  Anaerobic  blodegradatlon  of  4-chlorobenzo-
tr1fluor1de.   Prepared by  Lilly  Res.  Labs.,  Greenfield,  IN.   USEPA/OPTS
Public Files, 80 Submission.  Microfiche  #OTS: 0507306.

Elanco Products  Company.    1983d.    Volatilization rate of  p-chlorobenzotr1-
fluorlde from water.   Prepared  by Lilly  Res. Labs., Greenfield,  IN.   USEPA/
OPTS Public Files, 80  Submission.   Microfiche #OTS 0507306.

Elanco Products  Company.   1983e.   Absorption of  p-chlorobenzotr1fluor1de  on
soil  and  sediment.   Prepared by  Lilly Res.  Labs.,  Greenfield,  IN.   USEPA/
OPTS Public Files, 80  Submission.   Microfiche #OTS 0507306.

Elanco Products  Company.    1984.   Bloconcentratlon of  14C-p-chlorobenzotM-
fluorlde by blueglll 1n a  static  test system.   Prepared by  Lilly  Res.  Labs.,
Greenfield,  IN.   USEPA/OPTS  Public  Files,   80  Submission.   Microfiche  #OTS
0507307.

Great Lakes Water Quality Board.  1983.  An  Inventory  of  chemical substances
Identified  1n  the Great  Lakes  ecosystem.   Vol.  1 - Summary.   Report  to  the
Great Lakes Water Quality Board.  Windsor Ontario. Canada,  p.  12, 59,  90.

Ollld                               -33-                              04/19/88

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Mauser,  T.R.  and  S.M.  Bromberg.   1982.   EPA's  monitoring  program at  Love
Canal 1980+.  Environ. MonH.  Assess.   2:  249-271.

Hawley,  G.G.,  Ed.   1981.   The Condensed  Chemical  Dictionary,  10th ed.   Van
Nostrand Relnhold Co., New York,  NY.   p.  235.

Haworth,  S.,   T.   Lawlor,  K.  Mortlemans,  W.  Speck  and  E.  Zelger.    1983.
Salmonella mutagenldty  test results for  250 chemicals.   Environ. Mutagen.
Suppl.  1: 3-5, 8-9, 16-21, 41, 51,  78.

Hooker  Chemical  Corp.  1978a.  Mutagenldty  evaluation of  parachlorober.zo-
trlfluorlde  (PCBTF)  1n  the  Ames  Salmonella/mlcrosome plate  test.    Final
Report.  Submitted  by Litton Blonetlcs, Inc., Kensington, MD.  U.S. EPA/OPTS
Public Files.   Microfiche #OTS0508133.

Hooker  Chemical  Corp".  1978b.  Mutagenldty  evaluation of  parachlorobenzo-
trlfluorlde In the  mouse  lymphoma  forward  mutation  assay.   Final  report.
Submitted  by  Litton Blonetlcs, Inc., Kensington,  MD.  U.S.  EPA/OPTS  Public
Files.  Microfiche #OTS0508135.

Hooker  Chemical  Corp.    1979a.    An  acute   Inhalation  toxldty   study  of
parachlorobenzotMfluorlde In  the rat.   Prepared  by  B1o/dynam1c  Inc.  U.S.
EPA/OPTS Public Files.  Microfiche #OTS0508137.

Hooker  Chemical  Corp.  1979b.  Mutagenldty  evaluation of  parachlorobenzo-
trlfluorlde 1n a In v1vo/Ui  vitro urine assay.   Final  Report.   Submitted  by
LHton  Blonetlcs,   Inc.,  Kensington,  MD.   U.S.   EPA/OPTS   Public   Files.
Microfiche #OTS0508139.
01 lid                               -34-                             04/19/88

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Hooker  Chemical  Corp.   1979c.  MutagenlcHy  evaluation of  parachlorobenzo-
trlfluorlde (PCBTF)  In  the  sister chromatld  exchange  assay  1n L5178Y mouse
lymphoma  cells.   Final  report.   Submitted  by  LHton  B1onet1cs,  Inc.,
Kensington, MO.  U.S. EPA/OPTS Public  Files.   Microfiche #OTS0508136.

Hooker  Chemical  Corp.   1980.   Evaluation of  p-chlorobenzotr1fluor1de  In  the
In  vitro  transformation  of   BALB/3T3  cells  assay.   Submitted   by   LHton
Blonetlcs,  Inc.,  Kensington,   MD.   U.S.  EPA/OPTS  Public Files.   Microfiche
#0150508144.

Hooker  Chemical  Corp.   1981.   Modified  90-day gavage and reproduction study
1n  rats  PCBTF.   Conducted  by Elars  Bioresearch Laboratories,  Inc.,  Fort
Collins, CO.  U.S. EPA/OPTS  Public Files.   Microfiche #OTS0508148.
Hooker Chemical  Corp.   1985a.  Acute  oral  toxicity  (LD5Q)  1n albino  rats.
Prepared  by  Raltech .Scientific .Services,  Inc., Madison,  HI.  U.S.  EPA/OPTS
Public Files.  Microfiche #OTS508138.
Hooker  Chemical   Corp.    1985b.   Acute  dermal  toxldty  (LDro)  In  albino
rabbits.  Prepared  by  Raltech Scientific  Services,  Inc.,  Madison, HI.  U.S.
EPA/OPTS Public Files.   Microfiche #OTS508134.

Hooker Chej^s. and Plastics Corp.  1980.  Solubility  of  p-chlorobenzotrifluo-
rlde  1n  water.   USEPA/OPTS  Public  Files, 80  Submission.   Microfiche  #OTS
0508143.
Ollld                               -35-                             04/19/88

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•HSDB  (Hazardous Substances  Data  Bank).   1988.  Office  of Toxic Substances,
 U.S.  EPA, Washington, DC.  Online retrieval January 21,  1988.

 Lilly  Research Laboratories.   1983a.   Evaluation  of compound  #38502 1n  the
 BALB/C-3T3  Neoplastlc  transformation assay with an Aroclor-lnduced rat  liver
 mlcrosomal  (S9)  metabolic  activating system.   Submitted by Arthur D. Little,
 Incorporated,   Cambridge,   MA.    U.S.  EPA/OPTS  Public  Files.   Microfiche
 #OTS0507306.

 Lilly  Research  Laboratories.   1983b.   Chromosome  aberrations  1n  Chinese
 hamster  ovary  cells:  Test article compound 38502,  Lot  No. 633F02.   Prepared
 by  Microbiological Associates,  Bethesda.,  MD.   U.S.  EPA/OPTS  Public Files.
 Microfiche  #OTS0507306.

 Lilly  Research Laboratories.  1983c.  Activity  of  compound 38502 (T2025) 1n
 the  acute  Vn  vivo cytoqenetlc  assay  In male and  female  rats.   Prepared by
 Microbiological  Associates,  Bethesda,  MD.   U.S.   EPA/OPTS  Public  Files.
 Microfiche  #OTS0507306.

 Occidental  Chem.  Corp.   1980a.   Odor  threshold  studies  on eleven chemicals.
 Prepared  by Arthur D.  Little, Inc.,  Cambridge, MA.  USEPA/OPTS  Public Files,
 8D Submission.  Microfiche #OTS 0205957.

 Occidental  Chem. Corp.   1980b.   Analysis  of  fish samples from Lakes  Erie  and
 Ontario  for chlorinated  benzotrlfluorldes  as  contaminants.  Analyzed by FDA,
 Washington,  DC.   USEPA/OPTS  Public   Files,  80  Submission.   Microfiche  #OTS
 0507284.
Ollld                               -36-                             04/19/88

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Occidental  Chem.  Corp.   1984.   Loss  processes for  4-chlorobenzotr1fluor1de
under  atmospheric  conditions.   Prepared  by  R.  Atkinson  et al.,  Univ.  of
Calif., Riverside, CA.   USEPA/OPTS  Public Files, 80 Submission.   Microfiche
#OTS 0507309.

Qulstad,  G.B.  and  K.M.   Mulholland.   1983.   Metabolism of  p-chlorobenzotr1-
fluorlde by rats.  J.  Agrlc.  Food Chem.   31(3): 585-589.

Rapoport,  K.A.,  L.A.  Teplklna,  Y.G.  Fel'dman,  et  al.   1986.   Setting  the
limits  for  parachlorobenzotrlfluorlde  In  atmospheric air.   Gig. Sanlt.   10:
82-83. -(Russian translation)                                            ;

SRI  (Stanford  Research  Institute).    1987.    1987   Directory   of  Chemical
Producers.   United  States  of  America.   SRI  International,  Menlo  Park,  CA.
p. 533.  .                                                         •      .

Thomas,  R.G.   1982.   Volatilization  from water.  In:  Handbook of  Chemical
Property  Estimation  Methods.  Environmental  Behavior  of Organic  Compounds,
W.J. Lyman et al.,  Ed.   McGraw H111  Publishers,  New  York, NY.   p.  15-20.

Union  Carbide  Environmental  Services.  1979a.   The  acute toxldty  of  para-
chlorobenzotrlfluorlde  to  the  rainbow  trout,  Salmo  galrdnerl Richardson.
UCES Project No. 11506-81-08 (OTS 0508140).

Union   Carbide   Environmental  Services.    1979b.    The   acute   toxldty  of
parachlorobe/izotrlfluoMde  to  the  blueglll   sunflsh,  Lepomls macrochlrus
Raflnesque.  UCES Project No. 11506-81-07 (OTS 0508149).
Ollld                               -37-                             04/19/88

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Union  Carbide  Environmental  Services.   1979c.   The   acute   toxlclty   of
parachlorobenzotrlfluoMde to  the water  flea.  Daphnla  maqna Straus.   UCES
Project No. 11506-81-06 (OTS  0508141).

Union  Carbide  Environmental  Services.   1979d.   Daphnla  maqna chronic  study
testing  parachlorotrlfluorlde  (97%  active  Ingredient).   UCES  Project  No.
11507-18 (OTS 0508142).

U.S.  EPA.   1977.   Computer  print-out  of non-confidential  production  data
from TSCA Inventory.  OPTS,  CID,  U.S.  EPA, Washington,  DC.

U.S.  EPA.   1980.   Guidelines  and  Methodology  Used  1n   the  Preparation  of
Health  Effect  Assessment Chapter  of  the  Consent  Decree  Water  Criteria
Documents.   Federal Register.  45(31):  49347-49357.

U.S.  EPA   1984.   Methodology and  Guidelines  for  Reportable  Quantity  Deter-
minations Based on  Chronic Toxldty  Data.  Prepared by the Office of  Health
and Environmental  Assessment,  Environmental  Criteria  and Assessment  Office,
Cincinnati, OH  for  the Office of  Solid  Waste and  Emergency  Response,  Wash-
ington, DC.

U.S.  EPA.   1986a.   Methodology  for Evaluating CardnogenlcHy 1n  Support  of
Reportable Quantity Adjustment Pursuant  to CERCLA Section 102.   Prepared  by
the  Office of  Health and  Environmental   Assessment,  Carcinogen  Assessment
Group,  Washington,  DC for  the  Office   of  Solid  and  Emergency  Response,
Washington, DC.
01 lid                               -38-                             05/10/88

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U.S.  EPA.   1986b.    Guidelines   for  Carcinogen  Risk  Assessment.   Federal
Register.  51(185):  33992-34003.

USITC  (U.S.  International  Trade  Commission).    1987.    Synthetic  Organic
Chemicals.   United  States  Production  and  Sales,  1986.   USITC Publ.  1892,
Washington, DC.  p.  31, 41.
Ollld                               -39-                             05/10/88

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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)
              HSDB


These searches were conducted 1n  October  1987,  and the  following  secondary

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

    ACGIH  (American  Conference  of Governmental  Industrial  Hyglenlsts).
    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.

    Clayton,   G.D.  and  F.E.  Clayton,  Ed.   1982.   Patty's  Industrial
    Hygiene  and  Toxicology,   3rd  rev.  ed., Vol.  2C.   John  WHey  and
    Sons, NY.  p.  3817-5112.
01 lid                               -40-                             04/19/88

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

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

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

    Jaber, H.M.,  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.   1984.   Dangerous  Properties of  Industrial  Materials,  6th
    ed.  Van  Nostrand Relnhold Co.,  NY.

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

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

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

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

    Worthing, C.R.  and S.B. Walker, Ed.   1983. .The Pesticide  Manual.
    British  Crop Protection  Council.   695 p.

    Wlndholz, M., Ed.  1983.   The Merck  Index,  10th  ed.   Merck and Co.,
    Inc., Rahway, NJ.
Ollld                               -41-                             04/19/88

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    In  addition,  approximately  30  compendia of  aquatic  toxldty  data  were

reviewed. Including the following:


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

    Johnson,  W.W.  and H.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.  Dept.  Interior, Fish  and  Wildlife
    Serv. Res. Publ. 137,  Washington, DC.

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

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

    Schneider, B.A.   1979.  Toxicology  Handbook.   Mammalian and Aquatic
    Data.  Book 1: Toxicology  Data.   Office  of  Pesticide  Programs,  U.S.
    EPA, Washington, DC.   EPA 540/9-79-003.  NTIS PB 80-196876.
Ollld                               -42-                             04/19/88

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                                                       A90 days
15 mg/kg for
>90 days
NOAEL
NOAEL
                                            ID

                                            ID

                                            ID
0.2 mg/kg/day or
11 mg/day for a
70 kg human

0.02 mg/kg/day or
1 mg/day for a 70
kg human

ID
Hooker Chemical
Corp., 1981
Hooker Chemical
Corp., 1981
       REPORTABLE QUANTITIES

       Based  on  chronic  toxlcity:


       Based  on  Carclnogenlclty:
            1000


            ID
                                                       Arthur and
                                                       Probst, 1983
CO
00      ID  =  Insufficient data

-------