500ECAOCING011
*EPA       Research  and
             Development
              HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
              FOR TRICHLOROANILINES
             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
                         DRAFT: DO NOT CITE OR QtW§E Environmental Protection Agency.
                                         Region V, Library
                                NnTTrF     230 South Dearborn Street
                                         Chicago, Illinois 60604
          This document Is a preliminary draft.  It has not been formally released
       by the U.S. Environmental Protection Agency and should not at this stage be
       construed to represent Agency policy.  It Is being circulated for comments
       on Its technical accuracy and policy Implications.

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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  from 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 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  RfO, 1s  an estimate of an
exposure  level   that  would  not  be  expected to  cause adverse  effects  when
exposure occurs  during a limited  time  Interval,  for  example,  one  that  does
not constitute a significant  portion of  the llfespan.  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.   A
carcinogenic  potency  factor,  or  q-j*  (U.S.  EPA,  1980), Is  provided  Instead.
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 1s  used  to determine the  quantity of a hazar-
dous substance for  which  notification 1s required In the  event of a release
as specified  under  the CERCLA.   These  two RQs (chronic toxlclty and cardno-
genldty) represent two of  six  scores developed (the remaining four reflect
1gn1tab1l1ty, reactivity,  aquatic  toxlclty, and  acute mammalian   toxldty).
Chemical-specific RQs  reflect the  lowest  of  these six primary criteria.   The
methodology  for  chronic  toxlclty  and  cancer-based  RQs  are  defined  In  U.S.
EPA, 1984a and 1986a,  respectively.
                                      111

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                              EXECUTIVE SUMMARY

    2,3,4-Tr1chloroan111ne,  2,4,5- and  2,4,6-tr1ch1oroan1l1ne  exist  1n the
solid phase  at  room temperature (Dean, 1985).   Aromatic  amines  are usually
weaker  bases  than  aliphatic  amines  but  undergo  many   similar   reactions
(Northcott,  1978).   CMR  (1986)  lists four suppliers for  2,4,5-tr1chloroan1-
llne and  two suppliers  each for 2,3,4- and 2,4,6-tr1chloroan1l1ne.  The U.S
EPA TSCA Production  File (U.S. EPA,  1977)  contains  production data  on  2,4,5-
and 2,4,6-tMchloroanlllne, but  contains  no Information  on  2,3,4-tMchloro-
anHlne.   Domestic  production  volume  data  for  recent  years  could  not  be
located  1n  the  available literature  as  cited 1n  Appendix A.   During  1983,
807  pounds   of  2,4,5-tr1chloroan1l1ne  was  Imported through  principal  U.S.
customs  districts  (USITC,  1984).   2,4,6-Tr1chloroan1l1ne  1s  used  as  an
Intermediate In the  manufacture  of benzene derivatives, Including  1,3,5-trl-
chlorobenzene,  in  the  formulation  of a fungicide  and  1n  the preparation  of
hexachlorodlphenyl urea  (Mitchell  et al., 1984).   It  may also be  used  as  a
dye and pigment  Intermediate (Society of  Dyers  and  Colorlst,  1971).
    Tr1chloroan1l1nes are weak  bases and  as  such,  may  be protonated  under
addle conditions and form  salts that are  more water soluble  than  the  parent
compound.  Variations  1n the behavior of  trlchloroanlllnes  may result  from
protonatlon.   In  air,  these compounds  are expected  to exist almost entirely
1n the  vapor phase  (E1senre1ch  et al.,  1981).   The estimated half-life for
2,3,4-,  2,4,5- and  2,4,6-tr1chloroan1l1ne  vapor  reacting with  photocheml-
cally  generated   hydroxyl  radicals  1n  the atmosphere  Is -3  weeks at  25°C
(U.S.  EPA,   1987).   Trlchloroanlllnes also have   the  potential  to  undergo
direct  photolysis  1n the atmosphere.  Small  amounts of  these compounds may
be removed  from   the atmosphere  by wet  deposition.  Reaction with  ozone  1s
                                      1v

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not  likely  to  be  environmentally relevant  (U.S.  EPA,  1987).   In  water,
tr1chloroan1!1nes  are  not  expected  to hydrolyze,  oxidize  or  bloaccumulate
significantly  1n  aquatic  organisms.   Photolysis,  physical  adsorption  to
suspended  solids  and   sediments,  and  volatilization  should  be  Important
removal  processes.   The  photolysis half-life of  2,4,6-trlchloroanlllne  In  a
surface  water exposed  to  mid-June  sunlight was  <1  day  (Dennis  et al.,  1983).
The half-life for  2,4f6-tr1chloroan1l1ne  volatilization  from water  1 m deep,
flowing  at  a  speed  of   1  m/sec,  with  a wind speed  of  3 m/sec  has  been
estimated  to be -19 days at 2Q°C  (see Section  2.2.7.).   Results  of  a  few
blodegradatlon  screening  studies  Indicate that trlchloroanlUnes may  not  be
readily  susceptible  to blodegradatlon and  that  the acclimation  period  before
blodegradatlon  may be 20-27  days (Mitchell  et al.,  1984; Freltag et  al.,
1985;  Janlcke and  HUge,  1980).   In  soil. 1t appears  that  trlchloroanlUnes
may  be  Immobilized  by  both  physical  adsorption  and  covalent   binding,
although some mobilization may occur 1n acidic  soils  from protonatlon.  Lack
of data  precludes  the  possibility of  predicting  the  Importance  of  chemical
and mlcroblal degradation processes In  the environment.   Volatilization from
wet and dry soil surfaces 1s not expected to be significant.
    TrlchloroanlUnes  may be  released  to  the environment 1n  the  effluent
from user  facilities  (Ellis et al., 1982).   They may be formed  as  a  result
of chlorinating wastewaters  that  contain  aniline   (Mitchell et  al.,  1984)  or
as a metabolite  of mlcroblal degradation  of  various  phenylurea  and  phenyl-
carbamate  herbicides  (Hwang  et   al.,   1985).    2,4,5-Tr1chloroan1l1ne  and
2,4,6-tr1chloroan1l1ne  were  Identified 1n  drinking water  and  1n  effluents
from advanced wastewater treatment plants  In  several  cities   In the  United
States   (Lucas,   1984);  however,  there  were  no   quantitative   data   1n  the
literature from  which  to  estimate  dally human  exposure  to   the  compounds
through the consumption of drinking water.

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    There was little  Information available concerning toxldty of  trlchloro-
anHlnes to  aquatic  organisms.   The  lowest reported toxic concentration was
0.8  mg/t 2,3,4-tr1chloroan1l1ne, a  96-hour  LC5Q  for  sand  shrimp,  Cranqon
sept1msp1nosa  (McLeese  et  al.,  1979).    A   study  1n  which  Photobacterlum
phosphoreum  was   exposed  to  four  tr1chloroanH1ne  Isomers  Indicated  that
2,4,5-tr1chloroan1l1ne was  most toxic,  followed  by  2,3,4-tr1chloroan1l1ne,
3,4,5-tr1chloroan1l1ne  and   2,4,6-tr1chloroan1l1ne,  which  was   least   toxic
(Oevlllers  et al., 1986).
    Pertinent data regarding  the  absorption,  distribution,  metabolism  or
excretion of  2,3,4-,  2,4,5- of  2,4,6-tr1chloroan1l1ne  could  not be located
1n the available literature  as  cited  In Appendix A.
    Administration of 2,4,6-tr1chloroan1l1ne  to  rats by  gavage  at doses of
160  or  800  mg/kg/day for  45   days,  or  4  or 40  mg/kg,  5 days/week  for  6
months,   produced   a   variety  of effects,  which  Include methemoglob1nem1a,
gross  hemorrhaglc/degeneratlve  alterations  In the  circulatory  system  and
altered  liver enzyme  activities (Sapegln et al.,  1985).  Also,  embryotoxlc-
Hy was reported at 4 mg/kg, and hlstologlcal  alterations  In  the testes were
reported  at  800   mg/kg.    The   validity  of  these  findings   1s  uncertain,
however, because of Inadequate  reporting  and discrepancies.
    2,4,6-Tr1chloroan1l1ne  hydrochlorlde  was  administered  to male  rats  1n
the diet at  TWA concentrations  of 1917  and  3833  ppm for 18  months  followed
by  6 months  observation  without  hlstopathologlcal  effects  (Welsburger  et
al.,  1978).   Dietary administration  of  6000 or  12,000  ppm  2,4,6-tMchloro-
anlUne hydrochlorlde to mice  for 18  months  followed  by 3 months observation
produced a dose-related,  statistically significant  Increase  1n  the Incidence
of vascular  tumors In male  mice (Welsburger  et al.,  1978);  hlstopathologlcal
effects  did not  occur In similarly  treated females.
                                      vl

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     Equivocal  results  were reported for 2,4,6-tr1chloroan1l1ne 1n mutagenlc-
 1ty assays with bacteria  (Zlmmer et  al.,  1980;  Sh1m1zu and Takemura, 1984).
 Chromosomal  aberrations  occurred  In the bone marrow cells of rats exposed by
 gavage to 40 mg/kg 2,4,6-tr1chloroan1l1ne, 5 days/week for 6 months  (Sapegln
 et al.,  1985).
     Information regarding  the toxic  or  carcinogenic  effects  of  2,3,4- or
 2,4,5-tr1chloroan1l1ne  could not be  located 1n  the  available literature as
 cited In Appendix  A.
     Because  2,4,6-tr1chloroan1l1ne  hydrochlorlde  Induced tumors 1n  one sex
 of one  species (limited  evidence)  1n  the  Welsburger  et al.  (1978) study,
 2,4,6-trlchloroanlllne  and  Us hydrochlorlde  are classified  In  the  EPA's
 Group C  weight  of  evidence category for  cardnogenlcHy.
     Values   for   q,*s   for   oral   exposure   of   2.9xlO~2    (mg/kg/day)'1
.2,4,6-tr1chloroap1l1ne     hydrochlorlde     and     3.4xlO~a      {mg/kg/day)'1
 2,4,6-trlchloroanlllne  were calculated  based  on  the  dose-response data for
 vascular tumors In  male mice.   Increased  lifetime  risk of  cancer  at   risk
 levels  of  10"5,   10"*   and   10"7  are  associated   with   drinking  water
 levels  of  1.2xlO'2,   1.2xlO~»  and   1.2xlO~*   mg/i  for  2,4,6-trlchloro-
 anHlne   hydrochlorlde  and   l.OxlO"2,   l.OxlO7"3  and   l.OxlO"4  mg/l  for
 2,4,6-trlchloroanlllne.    F    factors   of   1.82X10'1    (mg/kg/day)'1   for
 2,4,6-tr1chloroan1l1ne   hydrochlorlde   and   2.1&X10'1   (mg/kg/day)'1   for
 2,4,6-tr1chloroan1l1ne  were  also  calculated,  placing  these  chemicals In
          «
 Potency  Group  3,  which combined with  an  EPA  Group C  classification  gives
 these chemicals   a  LOU  Hazard  Ranking  under   CERCLA.    The  RQ  based on
 carclnogenlclty Is, therefore,  100  pounds.
    Data  were  Inadequate  to  derive  chronic  toxldty RQs  for 2,4.,6-trlchloro-
 anlUne  and  Us hydrochlorlde  and  to derive any  q,*s,  RfOs  or  RQs  for the
 other  Isomers.

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                             TABLE OF CONTENTS
                                                                       Page
1.  INTRODUCTION	     1

    1.1.   STRUCTURE AND CAS NUMBER	     1
    1.2.   PHYSICAL AND CHEMICAL PROPERTIES 	     2
    1.3.   PRODUCTION DATA	     4
    1.4.   USE DATA	     4
    1.5.   SUMMARY	     4

2.  ENVIRONMENTAL FATE AND TRANSPORT	     8

    2.1.   AIR	     8

           2.1.1.   Reaction with Hydroxyl Radicals 	     8
           2.1.2.   Reaction with Ozone 	     8
           2.1.3.   Photolysis	     8
           2.1.4.   Physical Removal Processes	     9

    2.2.   WATER	     9

           2.2.1.   Hydrolysis	     9
           2.2.2.   Oxidation 	     9
           2.2.3.   Photolysis	,	     9
           2.2.4.   Mlcroblal Degradation 	    10
           2.2.5.   B1oaccumulat1on 	    10
           2.2.6.   Adsorption	    11
           2.2.7.   Volatilization.	    11

    2.3.   SOIL	    12

           2.3.1.   Chemical Degradation	    12
           2.3.2.   Mlcroblal Degradation 	    12
           2.3.3.   Adsorption	    12
           2.3.4.   Volatilization	    12

    2.4.   SUMMARY	    13

3.  EXPOSURE	    15

    3.1.   WATER	    15
    3.2.   SUMMARY	    15

4.  AQUATIC TOXICITY	    17

    4.1.   ACUTE TOXICITY	    17
    4.2.   CHRONIC EFFECTS	    17
    4.3.   PLANT EFFECTS	    17
    4.4.   SUMMARY	   17

5.  PHARMACOKINETCS	   20

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                           TABLE OF CONTENTS (cont.)

                                                                        Page
 6.  EFFECTS	   21

     6.1.   SYSTEMIC TOXICITY	   21

            6.1.1.   Inhalation Exposures-	   21
            6.1.2.   Oral Exposures	   21
            6.1.3.   Other Relevant Information	   24

     6.2.   CARCINOGENICITY	   25

            6.2.1.   Inhalation	   25
            6.2.2.   Oral	   25
            6.2.3.   Other Relevant Information	   26

     6.3.   MUTAGENICITY	   26
     6.4.   TERATOGENICITY	   29
     6.5.   OTHER REPRODUCTIVE EFFECTS  	   30
     6.6.   SUMMARY	   30

 7.  EXISTING GUIDELINES AND STANDARDS	   32

     7.1.   HUMAN	   32
     7.2.   AQUATIC	   32

 8.  RISK ASSESSMENT	   33

     8.1.   CARCINOGENICITY	   33

            8.1.1.   Inhalation	   33
            8.1.2.   Oral	   33
            8.1.3.   Other Routes	   33
            8.1.4.   Height of Evidence	   33
            8.1.5.   Quantitative Risk Estimates  	   34

     8.2.   SYSTEMIC TOXICITY	   35

            8.2.1.   Inhalation Exposure 	   35
            8.2.2.   Oral Exposure	   35

 9.  REPORTABLE QUANTITIES 	   37

     9.1.   BASED ON SYSTEMIC TOXICITY  	   37
     9.2.   BASED ON CARCINOGENICITY	   39

10.  REFERENCES	   42

APPENDIX A:  LITERATURE SEARCHED	   50
APPENDIX B:  CANCER DATA SHEETS FOR  DERIVATION OF  q^	   53
APPENDIX C:  SUMMARY TABLE FOR 2,4,6-TRICHLOROANILlNE  AND
            2,4,6-TRICHLOROANILINE  HYDROCHLORIDE  	   54
                                      1x

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                               LIST OF  TABLES

No.                               Title                                Page

1-1     Physical Properties of Selected Tr1chloroan1l1ne  Isomers.  .  .     3

1-2     Production Data for 2,4,5- and  2,4,6-Tr1chloroan1l1ne  ....     5

4-1     Acute Tox1c1ty of TMchloroanlUne to Aquatic  Organisms  ...    18

6-1     Effects of Dally Gavage Exposure to 2,4,6-TMchloro-
        anlUne for 45 Days 1n Rats	    22

6-2     Effects of Dally Gavage Exposure to 2,4,6-Tr1chloroan1l1ne,
        5 Days/Week for 6 Months 1n Rats	    23

6-3     Incidence of Tumors In Male CD-I Mice Treated  with
        2,4,6-Tr1chloroan1l1ne Hydrochlorlde (97-99% pure) 1n  the
        Diet for 18 Months and Observed for an Additional 3 Months.  .    27

9-1     2,4,6-Tr1chloroan1l1ne and 2,4,6-Tr1chloroan111ne-HCl:
        Minimum Effective Dose (MED) and Reportable Quantity  (RQ)  .  .    38

9-2     Derivation of Potency Factor (F) for
        2,4,6-Tr1chloroan1l1ne Hydrochlorlde	    41

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                             LIST OF  ABBREVIATIONS

BCF                     Bloconcentratlon factor
bw                      Body weight
CAS                     Chemical Abstract Service
ECso                    Concentration effective to 50% of recipients
PEL                     Frank effect level
Koc                     Soil sorptlon coefficient
Kow                     Octanol/water partition coefficient
LCso                    Concentration lethal to 50% of recipients
1050                    Dose lethal to 50% of recipients
J.OAEL                   Lowest-observed-adverse-effect level
MED                     Minimum effective dose
NOAEL                   No-observed-adverse-effect level
ppm                     Parts per million
RfO                     Reference dose
RQ                      Reportable quantity
SGOT                    Serum glutamate oxaloacetate transamlnase
SGPT                    Serum glutamate pyruvate  transamlnase
TWA                     Time-weighted average
UV                      Ultraviolet
                                      x1

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                               1.   INTRODUCTION
 1.1.   STRUCTURE AND CAS NUMBER
    The  synonyms,  structures and CAS  Registry  numbers  for  2,3,4-,  2,4,5- and
 2.4,6-tr1chloroan1l1ne are as follows:
 2,3,4-TMchloroan1l1ne
    CAS Registry number:  634-67-3
    Synonyms:      2,3,4-tr1chlorobenzenam1ne;     2,3,5-tr1chlorophenylam1ne;
    l-am1no-2,3,4-tMchlorobenzene
    Structure:
                                             Cl
2,4,5-TrlchloroanlHne
    CAS Registry number:  636-30-6
    Synonyms:      2,4,5-tr1chlorobenzenam1ne;
    l-am1no-2,4,5-tr1chlorobenzene
    Structure:
              2,4,5-tr1chlorophenylam1ne;
0012d
-1-
05/01/87

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2,4,6-TMchloroan111ne
    CAS Registry number:   634-93-5
    Synonyms:   sym-tr1ch1oroan1Hne;  2,4,6-trlchlorobenzenamlne;  2,4,6-trl-
    chlorophenylamlne; 1-am1no-2,4,6-tr1chlorobenzene
    Structure:
                                 NH2
                                         Cl
                                 Cl
All of  the tr1chloroan111ne Isomers  have  a molecular weight  of  196.46 and
the empirical  formula C,H.C1.N.
1.2.   PHYSICAL AND CHEMICAL PROPERTIES
    The  selected  trlchloroanHlne  Isomers  are  solids  at  room temperature
(Dean, 1985).   2,3,4-Tr1chloroan1l1ne  1s  soluble  1n  alcohol  and 2.4,5-tr1-
chloroanlUne  1s soluble 1n alcohol  and  ether  (Weast,  1985).  Aromatic amines
are usually  weaker  bases  than  aliphatic  amines  but undergo  many similar
reactions (Northcott, 1978).  Amines can be readily converted to their  salts
by aqueous mineral adds or  carboxyllc  adds,  and aqueous hydroxyl Ions can
readily  convert these  salts back  to  the  free  amlne  (Morrison  and   Boyd,
1973).  When heated  to decomposition, tr1ch1oroan1Unes are expected to emit
toxic   chlorine and  NO  fumes   (Sax,  1984).    Physical  properties  for the
selected tr1chloroan1!1ne Isomers are listed In  Table  1-1.
0012d                               -2-                              05/01/87

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0012d
-3-
                                                                      05/12/87

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1.3.   PRODUCTION DATA
    Halogenated  anilines  are   usually  produced  by  the  reduction  of  the
corresponding  nltro  compounds   with  Iron  and  hydrochloric  add (KouMs  and
Northcott, 1963).  2,4,6-Tr1chloroan1l1ne can  be produced from  aniline  vapor
and chlorine  1n the  presence  of hydrogen  chloride  1n  an anhydrous  organic
solvent  (Northcott,  1978).  The  U.S.  EPA  TSCA Production  File  {U.S.  EPA,
1977)   contains  no production  data  on  2,3,4-tr1chloroan1l1ne;  data  for  the
other  two tr1chloroan1!1ne Isomers are  given 1n Table 1-2.
    CMR  (1986)  lists  four  suppliers  for  2,4,5-trlchloroanlllne  and  two
suppliers each  for  2,3,4- and  2,4,6-tr1ch1oroan1l1ne.   Domestic  production
volume data  for recent years could  not  be located  1n  the available  litera-
ture  as  cited  1n  Appendix A.   During  1983,  807  pounds of  2,4,5-trlchloro-
anlllne was  Imported through  principal  U.S.  customs districts (USITC,  1984).
1.4.   USE DATA
    2,4,6-Tr1chloroan1l1ne 1s used  as  an  Intermediate  1n the manufacture of
benzene derivatives,  Including  1,3,5-tr1chlorobenzene,  1n  the  formulation of
a fungicide  and 1n  the  preparation  of  hexachlorodlphenyl  urea  (Mitchell et
al.,  1984).   Tr1chloroan1l1nes  may  also  be used  as dye and pigment Inter-
mediates (Society of Dyers and Colourlsts, 1971; Dao et  al.,  1986).
1.5.   SUMMARY
    2,3,4-Tr1chloroan1l1ne,  2,4,5-  and  2,4,6-trlchloroanlllne  exist   1n  the
solid  phase  at  room  temperature  (Dean,  1985).  Aromatic amines  are  usually
weaker  bases  than  aliphatic   amines   but  undergo  many  similar  reactions
(Northcott,   1978).   CMR   (1986)  lists  four  suppliers   for  2,4,6-trlchloro-
anlllne and  two suppliers each for 2,3,4- and 2,4,6-tr1chloroan1l1ne.  The
U.S.  EPA  TSCA Production  File  (U.S.  EPA,  1977) contains  production  data on
0012d                               -4-                              05/12/87

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                               -6-
                                               05/01/87

-------
 2,4,5-  and  2,4,6-tr1chloroan1l1ne,  but  contains no Information on 2,3,4-tr1-
 chloroanlUne.   Domestic  production  volume  data  for recent  years  could not
 be  located  1n  the available literature  as dted 1n Appendix A.  During 1983,
 807  pounds  of  2,4,5-tr1chloroan1l1ne  was  Imported  through  principal  U.S.
 customs  districts  (USITC,  1984).    2,4,6-Tr1chloroan1l1ne  1s   used  as  an
 Intermediate  In  the manufacture of  benzene derivatives, Including 1,3,5-tM-
 chlorobenzene,  1n the formulation  of a fungicide and  1n  the preparation of
 hexachlorodlphenyl  urea  (Mitchell et al.,  1984).   It may  also  be  used  as a
 dye and pigment  Intermediate (Society of Dyers and ColouMsts, 1971).
0012d                               -7-                              05/12/87

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                     2.  ENVIRONMENTAL  FATE  AND  TRANSPORT

    TMchloroanlllnes  are  weak  bases  that  may be  protonated  under addle
conditions  to  form salts at  pH  values related to  their  pKa values.  These
salts are much more water soluble than the  parent compound.  Protonatlon can
alter the behavior of  a compound In water and soil,  for example, by  decreas-
ing volatilization as  well  as Increasing or  decreasing  adsorption  to soil,
sediments or suspended solids  1n  water.
2.1.   AIR
    Based on the  vapor pressures  listed  1n  Table 1-1, tr1chloroanH1nes are
expected  to exist  almost  entirely  1n  the vapor  phase   1n  the  atmosphere
(E1senre1ch et  al., 1981).
2.1.1.   Reaction  with  Hydroxyl   Radicals.  The   estimated   half-life  for
2,3,4-,  2,4,5-  and 2,4,6-tr1chloroan1l1ne vapor  reacting with photochenrtcally
generated hydroxyl radicals 1n the atmosphere 1s -3  weeks  using  an estimated
reaction  rate   constant  of  8.98xlO~"   cmVmolecule-sec   at   25°C   and   an
ambient   hydroxyl  radical  concentration   of   8.0x10s  molecules/cm3   (U.S.
EPA, 1987).
2.1.2.   Reaction  with Ozone.   Tr1chloroan1l1nes  are  not susceptible   to
oxidation by ozone'(U.S. EPA,  1987).
2.1.3.   Photolysis.    2,4,6-Tr1chloroan1l1ne that  was  adsorbed  to  silica
gel underwent  39.5X  degradation  (based  on  X  CO.  evolved) when  Irradiated
with  light  wavelengths  >290 nm  for   17   hours  (FreHag  et  al.,  1985).
2,3,4-Tr1chloroan1l1ne,   2,4,5-  and    2,4,6-tr1chloroan1l1ne   1n    methanol
strongly absorb UV light  1n the  environmentally significant wavelength  range
of >290 nm  (Sadtler,  1965,  1970. 1976).   These  data  Indicate that  tMchloro-
anlUnes may undergo direct photolysis  1n the troposphere.


0012d                               -8-                              05/12/87

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 2.1.4.   Physical  Removal  Processes.   Based  on  the  water   solubilities
 listed  1n  Table  1-1,  It appears that small amounts of  tr1chloroanH1nes may
 be removed from the atmosphere by wet deposition.
 2.2.   WATER
 2.2.1.   Hydrolysis.   Since  halogenated aromatlcs  and  aromatic  amines  are
 generally  resistant  to chemical hydrolysis (Lyman et al.t  1982),  tMchloro-
 anlUnes are  also expected to be resistant to  hydrolysis.   2,4,6-Trlchloro-
 anHlne In distilled water under ambient conditions at pH  5, 7  and 9  remained
 stable to chemical hydrolysis over a 2-week period (Dennis  et a!., 1983).
 2.2.2.   Oxidation.    2,4,6-Trlchloroanlltne    In   distilled   water   under
 ambient conditions  at pH  5,  7 and  9  remained  stable to chemical  oxidation
 over a 2-week period (Dennis et a!., 1983).
 2.2.3.   Photolysis.    2,3,4-,  2,4,5- and   2,4,6-tr1chloroan1l1ne   strongly
 absorb  UV  light   In  the  environmentally significant  range  (wavelengths  >290
 nm)  (Sadtler, 1965, 1970,  1976),  Indicating that  potential  exists for  direct
 photolysis   1n   aqueous    solution   for   these   compounds.    When   78   yg/l
 2,4,5-tr1chloroan111ne was  added  to fresh lake water samples  and Irradiated
 with 12 hours  of  sunlight followed by  12  hours of darkness,  28% degradation
 was  observed  1n   both  treated  and  untreated  water samples.   No  degradation
 was  observed  when samples were kept  1n the dark.  Therefore,  the estimated
 photolytlc half-life  of  2,4,5-tr1chloroan1l1ne  Is  -2  days.   Photochemical
 degradation  products  were presumed  to be chloroamlnophenol  and  catechols
 (Hwang et  al.,  1985).   When a  30 mg/l aqueous solution  of 2,4,6-tMchloro-
 anlUne  was   Irradiated  with  a  pyrex-flltered   mercury  vapor  lamp,   the
 photolysis  half-life  was  -7.5  hours.   Exposure of  the  aqueous  solution  to
 bright mid-June sunlight  resulted  1n a disappearance half-life  of  -20  hours
 (Dennis et al.,  1983).   Therefore,  photolysis  Is  an Important  fate process
 for trlchloroanlUne.

0012d                               -9-                              07/16/87

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2.2.4.   H1crob1al  Degradation.   In  short-term  degradation  studies  (<3
days)  with  moderately  eutrophlc  lake  water,  no  degradation of  2,4,6-tr1-
chloroanlUne was  observed  when the solution was  kept  In the dark, but 28%
of  the  compound  degraded  when the  solution  was  exposed  to 12  hours of
sunlight  and  12  hours  of  darkness   (Hwang  et  al.,   1985).    Based on
experimental   results,    H   was   speculated   that   photolysis    Initiates
transformation of  2,4,6-tr1chloroan1l1ne, followed by further  degradation to
C02  by  microbes  and  sunlight.  In  this  study, 19% of  the mineralization of
the  photoproducts was  attributed  to  mlcroblal   processes   (Hwang  et  al.,
1985).   Therefore,  the authors  concluded  that 2,4,6-tr1chloroan1l1ne  would
not  blodegrade  In natural  water  In 3 days, but  1t  would slowly  blodegrade
the  photodegradatlon  products  of  photolysis.   With  contaminated  surface
water  Mitchell   et   al.   (1984)   demonstrated   that   2,4,6-tr1chloroan1l1ne
required an approximate 20- to  27-day, lag period before  degradation would be
observed.   A  0.4%  degradation  (based  on  %  C02  evolved)  of   0.05  mg/i
2,4,6-tr1chloroan1l1ne  was  observed  after   5  days  Incubation 1n  activated
sludge  (Freltag   et   al.,  1985).   2,4,6-Tr1chloroan1l1ne was found  to be
resistant to blodegradatlon by activated sludge (Janlcke and  Hllge, 1980).
2.2.5.   Bloaccumulatlon.    BCFs  of 260  1n  algae,  Chlorella  fusca. and  330
1n  the  golden  1de,  Leudscus  Idus  melanotus.   have  been  measured  for
2,4,6-tMchloroanlHne  (Freltag  et  al.,   1985).    Based  on  the  log  KQw
values  listed  1n  Table 1-1,  BCFs  of  200,  247  and  279 were  estimated for
2,3,4-,  2,4,5- and  2,4,6-tr1chloroan1l1ne,  respectively,  using  the equation
log  BCF  =  0.76   log  KQW  - 0.23  (Lyman et  al.,  1982).   These  BCF  values
suggest  that bloaccumulatlon  of tr1chloroan1!1nes  1n  aquatic organisms would
be Insignificant.
0012d                               -10-                             07/16/87

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 2.2.6.   Adsorption.   In  treated  and untreated freshwater samples  that  were
 Irradiated  with  sunlight,  the  amount   of   2,4,6-tr1chloroan1l1ne  and  Its
 photoproducts  on  particles was  8.6 and  16.9%,  respectively (Hwang et  al.,
 1985).   Substituted and  unsubstHuted  aromatic  amines  have  been  found  to
 undergo  Irreversible  covalent  binding   with  humlc  substances  1n  aqueous
 solution.   Although  the presence of  chlorine In the ortho- position  to the
 aniline will  reduce  the  probability of  this  covalent  binding (Parrls,  1980),
 a  small  fraction  of tr1chloroan1!1ne 1n  natural water  may  undergo Irrevers-
 ible covalent  binding  with  humlc  substances  1n these  waters.  Based on these
 observations  and  the  estimated K    of  1540-1960  (Section  2.3.3.)  physical
 adsorption  and  covalent  binding to suspended  solids  and  sediments  should  be
 significant.
 2.2.7.   Volatilization.   Loss  of  2,4,6-tr1chloroan1l1ne  from  freshwater
 samples during  a  blodegradatlon screening study was  attributed  to volatili-
 zation.   A  50% loss was observed  after -20  days  (Mitchell et  al.,  1984).
 Henry's  Law  constant  for  2,4,6-tr1chloroan171ne  has  been  estimated  to  be
 2.7xlO~s  atm-ma/mol  when  a  vapor  pressure  of 3.3  mm Hg  at  20.5°C  and  a
 water  solubility  of 32 mg/i  at 19°C was used  (Dennis  et  al.,  1983).   Based
 on  this  value of   Henry's  Law  constant  the  volatilization  half-life  of
 2,4,6-tr1chloroan1l1ne volatilizing from water 1 m deep,  flowing  at a speed
 of 1 m/sec,  with  a  wind speed  of 3 m/sec has been  estimated to  be -19 days,
 using  the method  of Lyman  et  al.  (1982).   Protonatlon of tr1chloroanH1nes
 under  addle  conditions would  cause a  decrease  1n  the  volatility  of these
 compounds;  however,  1t  1s  not certain whether  protonatlon  would  be signifi-
cant under environmental conditions.
0012d                               -11-                             05/12/87

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2.3.   SOIL
2.3.1.   Chemical  Degradation.   Pertinent  data   regarding   the  chemical
degradation of tr1chloroanH1nes 1n  soil  could  not  be located 1n the avail-
able literature as cited In Appendix  A.
2.3.2.   H1crob1al Degradation.  Limited  data  are  available  regarding  the
blodegradatlon  of  trlchloroanlUnes  In  soil.    2,3,4-Trlchloroanlllne  was
transformed by purified  peroxldase  from an Isolated soil fungus, Geotrlchum
candldum;  however,   no   detectable  transformation  of  2,4,5- or  2,4,6-tr1-
chloroanlllne  was  observed* after  14 days.   None  of these  compounds  were
transformed by purified  aniline  oxldase extracted from G^. candldum  (Bartha,
1975; Bordeleau and  Bartha, 1972).
2.3.3.   Adsorption.    The  KQC  values   for   2,3,4-,   2,4,5-  and  2,4,6-tr1-
chloroanHlne were calculated  to be 1540, 1790  and  1960, respectively, using
the  log  K    values  listed  1n  Table  1-1 and  the linear regression equation,
log  KQc  »  0.544  log  KQW  *  1.377   (Lyman   et   al.f  1982).   These  KQc
values  Indicate   that  tr1chloroanH1nes  should have  low  mobility  1n  soil
(Swann  et  al.,   1983).   Thus,  It  appears  that these  compounds  would  be
Immobilized 1n soil  by physical adsorption and  partly  by covalent binding  as
observed with other  substituted amines  (ParMs,  1980).
2.3.4.   Volatilization.    Pertinent    data   regarding   volatilization    of
trlchloroanlUnes from soil could not be  located  In  the  available literature
as  cited  1n  Appendix A.   Based  on  the  expected  adsorption  and   covalent
binding  of tr1chloroanH1nes  to  soils  (see  Section  2.3.3.)  and  possible
protonatlon of these  compounds  1n  acidic soils, volatilization  from wet  and
dry soil surfaces 1s not expected to be  significant.
0012d
-12-
05/01/87

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 2.4.   SUMMARY
    Tr1chloroan1l1nes are weak bases and,  therefore, may  be  protonated  under
 addle conditions and form  salts  that  are  more  water  soluble than  the parent
 compound.   Variations  1n the  behavior  of  trlchloroanHlnes  may result  from
 protonatlon.   In  air,  these compounds  are  expected to exist  almost  entirely
 1n  the  vapor phase  (E1senre1ch  et  al.,  1981).   The estimated  half-life  for
 2,3,4-,  2,4,5- and  2,4,6-tr1chloroan1l1ne  vapor  reacting  with  photocheml-
 cally  generated  hydroxyl  radicals   In  the atmosphere  Is -3  weeks  at  25°C
 (U.S.  EPA,  1987).   TMchloroanlUnes  also   have  the potential  to  undergo
 direct photolysis  1n the atmosphere.  Small  amounts  of   these  compounds  may
 be  removed from  the  atmosphere  by  wet  deposition.   Reaction with  ozone  Is
 not  likely  to  be  environmentally   relevant  (U.S.  EPA,  1987).   In  water,
 tr1chloroanH1nes  are  not  expected  to  hydrolyze,  oxidize   or  bloaccumulate
 significantly  1n  aquatic  organisms.    Photolysis,  physical  adsorption  to
 suspended  solids  and  sediments,   and   volatilization  should  be  Important
 removal  processes.   The  photolysis  half-life of 2,4,6-tr1chloroan1l1ne  1n  a
 surface water exposed to  mid-June sunlight was  <1  day  (Dennis et  al., 1983).
 The half-life  for  2,4,6-tr1chloroan1l1ne volatilization  from water  1 m deep,
 flowing  at  a  speed  of   1  m/sec,  with  a  wind  speed  of 3 m/sec   has  been
 estimated  to  be -19  days  at  20"C  (see  Section 2.2.7.).   Results   of  a  few
 blodegradatlon  screening  studies  Indicate  that  tr1chloroanH1nes may  not  be
 readily  susceptible  to blodegradatlon and  that  the acclimation period before
 blodegradatlon  may  be 20-27  days  (Mitchell  et al.,  1984;  Freltag  et  al..
 1985;  Janlcke and  H1lge,  1980).   In soil,  1t appears  that  tr1chloroanH1nes
may  be  Immobilized  by  both  physical   adsorption  and  covalent   binding,
although  some mobilization may occur 1n  addle  soils  because of protonatlon.
0012d                               -13-                             05/12/87

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Lack of data precludes the possibility of predicting  the  Importance  of  chem-
ical and mlcroblal degradation processes 1n  the  environment.   Volatilization
from wet and dry soil  surfaces  1s  not  expected  to be  significant.
0012d                               -H-                              05/12/87

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                                 3.   EXPOSURE

    Pertinent data  regarding  human  exposure to tMchloroanlUnes by Inhala-
tion,  1ngest1on of  food or dermal contact could not be located 1n the avail-
able  literature  as  cited  In  Appendix A.   Tr1chloroan1l1nes  may  be released
to the environment  1n the  effluent from use facilities (Ellis et al., 1982).
Tr1chloroan1l1nes may be formed as a result of chlorinating wastewaters that
contain  aniline  (Mitchell et al.,  1984)  or  as  a metabolite  of  m1crob1al
degradation  of  various  phenylurea and  phenylcarbamate  herbicides  (Hwang et
al.. 1985).
3.1.   HATER
    2,4,5-Tr1chloroan1l1ne was  Identified  1n  drinking water  collected from
Cincinnati,  OH  (Oct. 1978)  and  Seattle,  WA  (Nov.  1976).   2.4,6-TMchloro-
anHlne  was  Identified  1n  drinking  water  collected from  PoplarvUle,  MS
                                                            •
(Mar. 1979); Cincinnati, OH (Oct. 1978 and  Jan. 1980); New Orleans, LA  (Jan.
1976);  Philadelphia,  PA  (Feb.  1976) and  Seattle, WA   (Nov.  1976)  (Lucas,
1984).   2,4,5-TMchloroan1l1ne was detected  1n treated  wastewaters obtained
from  Orange County,  CA (Jan.  1976),  and  2,4,6-tr1chloroan1l1ne  was   posi-
tively Identified 1n  treated  wastewaters obtained  from  Lake Tahoe, CA  (Oct.
1974);  Pomona,  CA  (Sept.  1974);  Orange  County,   CA  (Feb.   1976)  and   Wash-
ington,  DC  (May 1975)  (Lucas,  1984).  Tr1chloroan1l1ne  (Isomer not  speci-
fied)  was  qualitatively  Identified  In  the effluent  from  a publicly-owned
treatment works  1n  Sauget,  IL  (Ellis   et al.,  1982).
3.2.    SUMMARY
    TMchloroanlUnes may  be released  to  the environment   1n  the effluent
from user  facilities  (Ellis  et  al.,  1982).  They  may be formed as a  result
of chlorinating wastewaters that  contain aniline  (Mitchell  et al., 1984) or
0012d                               -15-                              05/12/87

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as a  metabolite  of m1crob1al degradation  of  various phenylurea and  phenyl-
carbamate herbicides (Hwang et al., 1985).   2,4,5- and 2,4,6-Tr1chloroan1l1ne
were  Identified  1n  drinking  water  and 1n effluents  from  advanced  wastewater
treatment  plants  1n  several  cities   1n  the  United States  (Lucas,  1984);
however,  there  were no  quantitative   data  1n the  literature from which  to
estimate  dally  human  exposure  to  the compounds  through  the consumption  of
drinking water.
0012d                                -16-                              05/12/87

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                             4.  AQUATIC TOXICITY
 4.1.   ACUTE TOXICITY
    Available  aquatic  toxlclty data for  the  trlchloroanlUnes  are  presented
 1n  Table  4-1.   For marine  species,  the lowest  reported  toxic  concentration
 was  0.8  mg/1  2,3,4-tr1chloroan1l1ne,  a  96-hour  LC5Q  for   sand  shrimp,
 Cranqon septlmsplnosa  (HcLeese et  al.,  1979).   Among  freshwater species,  the
 lowest  reported toxic  concentration was  1.96  mg/8,  2,4,5-tr1chloroan1l1ne,
 a  14-day   LC5Q for  gupples,   PoeclHa  retlculata  (Hermens  et al.,  1985).
 Available  Information  was  too  limited  to  generalize  about  the  relative
 tox1c1t1es of  the tr1chloroan1!1ne Isomers.
 4.2.   CHRONIC EFFECTS
    Pertinent  data   regarding   chronic  toxlclty  of  trlchloroanlUnes   to
 aquatic organisms could  not be located 1n  the  available  literature as cited
 1n Appendix A.
 4.3.   PLANT EFFECTS
    The only toxlclty data  available for  aquatic plants were  that  of Kn1e et
 al. (1983),  who reported that the EC,Q for  Inhibition  of  photosynthesis In
 Haematococcus  pluvlalls  was >12  mg/l   2,4,6-tr1chloroan1l1ne.   Devlllers et
 al. (1986)  conducted  tests  for Inhibition  of  luminescence  1n  PhotobacteMum
 phosphoreum exposed to  four trlchloroanlUne  Isomers.   The  most toxic Isomer
 was 2,4,5-tr1chloroan1l1ne  and  the least  toxic  was  2,4,6-trlchloroanlllne
 (see Table 4-1).
 4.4.   SUMMARY
    Limited  Information  was   available  concerning  toxlclty   of  tMchloro-
anHlnes  to  aquatic  organisms.   The lowest reported  toxic  concentration  was
0.8 mg/l  2,3,4-tr1chloroan1l1ne,  a 96-hour  LC5Q  for  sand shrimp,  Cranqon
septlmsplnosa  (HcLeese  et  al.,   1979).   A  study  1n  which  Photobacterlum
0012d                               -17-                             05/01/87

-------
























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phosphoreum  was  exposed  to  four  trlchloroanlUne  Isomers  Indicated  that
2,4,5-tr1chloroan1l1ne  was  most  toxic,  followed by  2,3,4-tr1chloroan1l1ne,
3,4,5-tr1ch1oroan1l1ne  and  2,4,6-tr1chloroan1l1ne,  which  was  least  toxic
(DevUlers et al., 1986).
0012d                               -19-                             05/01/87

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                             5.   PHARMACOKINETICS

    Pertinent  data regarding  the  absorption,   distribution,  metabolism  or
excretion of  2,3,4-,  2,4,5- of  2,4,6-tr1chloroan1l1ne  could not be  located
1n the available literature as  cited In Appendix A.
0012d                                -20-                              05/01/87

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                                  6.   EFFECTS
6.1.   SYSTEMIC TOXICITY
6.1.1.    Inhalation  Exposure.   Pertinent  data  regarding  the  effects  of
Inhalation  exposure to  the tr1chloroanH1nes  could  not  be  located  1n  the
available literature as cited In Appendix A.
6.1.2.    Oral Exposures.
    6.1.2.1.   SUBCHRONIC — Subchronlc   oral   studies  were   conducted   1n
which white  rats  were  exposed to 2,4,6-tMchloroanlHne at  doses  of 80,  160
or 800 mg/kg/day  for 45  days  or  0.4,  4 or 40 mg/kg, 5 days/week for 6 months
(Sapegln  et  al.,   1985).   The  compound  was  administered by  gavage  1n  8%
(45-day  study)  or  0.04, 0.4  and  4% (low-,  middle- and  high-dose  groups.
respectively; 6-month  study)  oil (type unspecified)  solutions  and doses  >8X
were  added   In  the  diet.   The  45-day study used  128  male  and  female rats
(number/sex  not Indicated)  and the  6-month  study used 180  rats (120 females,
60 males),  but  treatment and control  group  sizes,  and sex distribution were
not  specified.   The endpolnts  assessed  1n  these  studies were Incompletely
specified, but  the  results  (Tables 6-1  and 6-2)  Indicate that the emphasis
was  primarily on  determination  of  hematologlc, clinical  chemical  and gross
pathologic effects.   H1stolog1cal  examinations  appear to have been limited
to the testicles and ovaries (Section 6.5.).
    Confidence 1n  the  Sapegln et al.  (1985) study  1s  limited by Inadequate
reporting and discrepant  results.   The findings tabulated In  Tables 6-1  and
6-2  suggest  that  hemoglobin,  the vascular  system (hemorrhaglc/degeneratlve
effects)  and liver  (enzymatic   alterations)  were  affected  at  160  and  800
mg/kg In  the 45-day  study  and  4 and 40 mg/kg  1n the 6-month  study.  The
extent of  significant   treatment-related  effects  Is  unclear,   however,  as  p
0012d                               -21-                             05/12/87

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                                  TABLE 6-1

          Effects of Dally Gavage Exposure  to  2,4,6-TMchloroan1l1ne
                             for  45  Days  1n Rats3
    Dose
(mg/kg/day)
                       Response
    800
    160


     80
Depression (unspecified);  hair loss;  cyanosis;  hematurla;
decreased mean hemoglobin  concentration (p<0.02)b;
Increased number of red blood cells  (hypochromlc  and
polychromatophlllc); anlsocytosls  and po1k1locytos1s;
leukopenla (tendency);  Increased serum alanlne  amlno-
transferase (p<0.001)b; Increased  serum aspartate
amlnotransferase (p<0.02)b; decreased SGPT/S60T ratio;
Increased serum residual nitrogen  (p<0.001)b;  Increased
serum pyruvlc add (p<0.001)b; decreased serum  catalase
(p<0.001)b; decreased oxygen consumption (p<0.01)b;
decreased weight gain;  Increased relative weights of
heart, liver, kidneys and  spleen;  unspecified degenera-
tive alterations; hemorrhaglc areas  1n myocardium,  liver,
kidneys, brain and spleen; decreased lactate and succlnlc
dehydrogenase activities 1n liver  and kidneys

Effects similar to 800 mg/kg/day but less pronounced  (not
elaborated)

No significant effects
aSource: Sapegln et a!., 1985

Significant  change  when compared  with an
 reported, statistical method not reported
                         unspecified control  group;  data
QQ12d
                -22-
05/01/87

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                                   TABLE  6-2

          Effects of Dally Gavage Exposure  to  2,4,6-TMchloroanlHne,
                       5 Days/Week for  6  Months  1n  Ratsa
    Dose
 (mg/kg/day)
                        Response
   40
    4


    0.4
Increased methemoglobln concentration (p<0.02)b;  In-
creased number of red blood cells (hypochromlc);  anlso-
cytosls and po1k1locytos1s; retlculocytosls;  hypochromla;
Heinz bodies 1n erythrocytes; decreased oxygen consumption
(p<0.05)b; Impaired aqulsltlon of conditioned reflexes
(p<0.001)0; decreased weight gain 1n males; Increased
relative brain weight; decreased relative weight  of liver;
decreased succlnlc dehydrogena.se activity 1n  Hver;
decreased lactate dehydrogenase activity 1n Hver and
kidneys; unspecified degenerative alterations In  blood
vessels 1n the brain, liver and kidneys

Effects similar to 40 mg/kg but less pronounced (not
elaborated)

No significant effects
aSource: Sapegln et al., 1985

^Significant  change  when  compared  with an  unspecified control  group;  data
 reported, statistical method not reported
0012d
                 -23-
05/01/87

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values  were  reported for  only  some of  the  effects at  the  highest dose  1n
each  study 'and  results  at  the middle  doses  were reported to be similar  but
less pronounced.
    6.1.2.2.   CHRONIC — A  study  of   2,4,6-tr1chloroan1l1ne   hydrochloMde
was conducted  1n which  male  Charles River  rats were  treated  at  concentra-
tions of  3000 or  6000 ppm In the diet for 5 months followed by  1500 or  3000
ppm, respectively, for 13 months  (Welsburger et  al., 1978).  The TWA concen-
trations  were  1917  and  3833  ppm.  respectively.   Male  and female  CD-I  mice
were treated similarly at  levels  of 6000 or 12,000 ppm  for  18  months.   Mice
were observed for an additional  3 months and  rats for an  additional 6 months.
This study was  primarily  designed to assess  cardnogenlcUy (Section 6.2.2.).
Nonneoplastlc pathological  effects  of  treatment  did  not  occur   1n  either
species.  The  dosage  reduction   In  the  rat  experiment  was  due  to  a  >10%
decrease  1n weight gain below control weight gain  and  to Increased mortality
(effect not specified).
6.1.3.   Other   Relevant  Information.   Oral  administration of  single  doses
of  0.25  mmol/kg  (49.1   mg/kg)   2,4,6-trlchloroanHlne  1n   an  unspecified
vehicle  to  five cats produced mean methemoglobln percentages  of  35.9-43.7%
after 1-5 hours  (McLean  et al.,  1969).   The overall  mean of the  five post-
treatment hourly mean methemoglobln  percentages  was 38.8%, which 1s somewhat
less than that determined  for the same  molar  dose of  aniline (48.1%).   Adult
cats  were used  1n   this  study because  they are  particularly  sensitive to
methemoglobln  formation.    Eastman  Kodak   Company   (1970)   reported  that
2,4,6-tr1chloroan1l1ne 1s  not a   methemoglobln  Inducer  1n  rats,   but  addi-
tional  Information  was  not  provided.   Aniline  and many of  the  substituted
anilines  (Including  the  monochloroanllines  and  2,4- and 3,4-d1chloroan1l1ne)
produced  methemoglobln  In  cats   (McLean  et  al.,  1969).   U.S. EPA  (1984b)
considers all aniline compounds as potential methemoglobln Inducers.

0012d                               -24-                             07/16/87

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    The  acute oral  LDrQ of  2,4,6-tr1chloroan1l1ne  for rats  was  determined
 to  be between 1600 and 3200 mg/kg (Eastman Kodak Company, 1970).
 6.2.   CARCINOGENICITY
 6.2.1.    Inhalation.   Pertinent   data  regarding  the  carclnogenlcUy   of
 Inhaled  2,3,4-,  2,4,5- or  2,4,6-tr1chloroan1l1ne  could  not  be located 1n the
 available  literature as cited 1n Appendix A.
 6.2.2.    Oral.   The  cardnogenldty of  2,4,6-tr1chloroan1l1ne hydrochloMde
 was evaluated  by dietary administration 1n groups of  25,  six- to 8-week-old
 male Charles  River  rats, male CD-I mice and  female  CD-I mice (Welsburger et
 al.,  1978).   The purity  of the  test  chemical was determined by thin-layer
 chromatography and  Infrared spectra,  and  was  Inferred to be 97-99%.   Both
 species  were  treated at two  levels  that were  Intended  to  represent  the MTD
 and 1/2  MTD.   The rats were maintained  on  diets  containing compound concen-
 trations  of  3000 or  6000  ppm  for 5  months  followed  by  1500 or  3000 ppm,
 respectively,  for  13 months  (see Section  6.1.2.2.).   Male  and  female mice
 were treated  at  concentrations  of 6000 or  12,000  ppm for  18 months.  Groups
 of  25  untreated  male  rats  and mice  of each  sex served  as  controls.   Mice
 were  observed for  an  additional  3  months  and  rats   for  an additional  6
 months.   Necropsies,  which Included  hlstologlcal  examinations   of  grossly
 abnormal  organs  and  lung,  liver,  spleen,  kidney, adrenal,  heart,  bladder,
 stomach,  Intestine,   reproductive  organs   and  rat  pituitary  tissues,  were
 conducted  on  all  animals   that  died  after >6  months  of  treatment  and at
 termination of the study.   The emphasis  of  the study, however, was on deter-
mination  of  carclnogenlclty;  growth   and   survival  data were  not reported,
which precludes determining 1f a MTD was achieved.
0012d                               -25-                             05/12/87

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    2,4,6-Trlchloroanlllne  hydrochlorlde  Induced  a  dose-related,  statisti-
cally  significant  Increase In the  Incidence  of unspecified vascular  tumors
In male mice  (Welsburger et a!.,  1978).   As detailed  1n  Table  6-3,  Increased
Incidences of tumors 1n treated groups were statistically  significant  by  the
Fischer  Exact test  If  p<0.05 for  both  matched and  pooled control  groups.
Incidences of hepatocellular  carcinomas  were  also  Increased In  treated male
mice, but only 1n  the low-dose group when  compared with  pooled controls  (see
Table  6-3).   2,4,6-Trlchloroanlllne did  not  produce statistically  signifi-
cant  Increases   1n  tumor  Incidences   1n  the  female   mice  or  male  rats
(according to authors).
6.2.3.   Other  Relevant  Information.   The  Induction  of  both  tumors   and
methemoglob1nem1a by aniline  and  substituted  aniline  compounds 1s attributed
                •
to the  formation  of N-ox1d1zed metabolites  (Clayson  and  Garner,  1976;  U.S.
EPA, 1984b).  Evidence  for the carclnogenlcHy of aniline. (U.S.  EPA,  1985),
4-chloroan1l1ne  (NCI,  1979) and  other aromatic amines   (Clayson  and  Garner,
1976), and methemoglobln  Induction  by  2,4,6-tr1ch1oroan1l1ne (McLean  et  al.,
1969),  therefore,   provides   an  additional   Indication  of  the  potential
carclnogenlcHy  of 2,4,6-tr1chloroan1l1ne.
6.3.   HUTAGENICITY
    2,4,6-Tr1chloroan111ne  was  not  mutagenlc  for   Salmonella  typhlmurlum
strains TA100, TA98  or  TA1537  when  tested In  plate Incorporation assays  with
and without Aroclor  !254-1nduced  rat  liver  S-9 metabolic activation prepara-
tion  (Zlmmer  et  al..  1980).   Compound purity  was between -97  and  99%,  but
the doses  were  not  specified.   Liquid-suspension  assays  conducted  with  the
same  strains  of  S^ typhlmurlum  and  metabolic activation preparations  were
also negative (Zlmmer et al., 1980).
0012d                               -26-                             07/16/87

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                                   TABLE  6-3

            Tumor Incidence In Male CD-I  Mice Treated with Dietary
                   2,4,6-TMchloroanlllne Hydrochlorlde for
             18 Months and Observed for an Additional 3 Monthsa»b
Dose
(ppm)
Oc
Qd
6,000
12,000
. of
09
6,000
12,000
Target Organ
vascular system
vascular system
vascular system
vascular system
liver
liver
liver
liver
Tumor Type
NR
NR
NR
NR
hepatocellular
carcinoma
hepatocellular
carcinoma
hepatocellular
carcinoma
hepatocellular
carcinoma
Tumor Incidence
(p value)
5/99
2/16
10/18
(p<0. 025)6
12/16
(p<0.025)e
7/99
1/16
5/18
(p<0.025)n
1/16
(NS)
0012d
-27-
05/01/87

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                              TABLE 6-3 (cont.)
Strengths of study:
        QUALITY OF  EVIDENCE

The compound was  administered  by a  relevant  route of
exposure at  two  dose levels for a  significant  portion
of the  Hfespan with  an  additional  observation  period.
Female  CD-I  mice  and  male  Charles River  rats  were
similarly  tested,  but data  were not reported  because
of negative  results.   The extent of hlstopathologlcal
examination  was   adequate.    Appropriate   statistical
analyses were performed.
Weaknesses of study:
Overall adequacy:
Small number  of  animals were  evaluated.
of vascular tumors were not specified.

Adequate
The  type(s)
aSource: Welsburger et al., 1978

bPur1ty  (97-99%);  not   reported   specifically  for   2,4,5-tr1chloroan1l1ne
 hydrochlorlde

cPooled  controls  from untreated  diet control  groups  of  similarly  designed
 18-month experiments with  other  aromatic amines or derivatives  In  the same
 study.

Hatched controls

6S1gn1f1cantly  different  from matched  and  pooled control  groups,  Fisher
 Exact test

^Pooled controls

^Simultaneous controls

"Significantly different from pooled control group only. Fisher Exact test

NR » Not reported; NS * not specified
0012d
              -28-
    05/12/87

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     In  a  study  1n  which  the  mutagenlclty  of  2,4,6-tr1chloroan1l1ne  was
 evaluated  with  S.  typhlmurlum strains  TA98,  TA100 and TA1538 and Escher1ch1a
 coll  strains WP2uvrA  and  HP2uvra/pKm  by the  pre-1ncubat1on  (liquid suspen-
 sion) method (Sh1m1zu and Takemukra, 1984), mutagenlclty  was  reported  1n S..
 typhlmurlum  or  E..  coll.  but  the species and  stra1n(s)  other  than  S. typhl-
 murlum  TA98  were not  specified.   Mutagenlclty of 2,4,6-tr1chloroan1l1ne was
 also demonstrated 1n  a fluctuation test conducted with S.  typhlmurlum TA98.
    Rats  exposed to  2,4,6-tr1chloroan1l1ne  by gavage at  40 mg/kg,  5  days/
 week for  6 months  showed a statistically significant Increase 1n the number
 of bone marrow  cells  containing  lacunae and chromosomal  aberrations  (1.6 vs.
 0.4X  1n  unspecified  controls)  (Sapegln et  al.,  1985).   Treatment-related
 clastogenlc  effects  did  not  occur 1n  rats  similarly treated with  4 or 0.4
 mg/kg.  Limited  additional  Information  was  available regarding the design of
 this Inadequately reported study (see Section  6.1.2.1.).
 6.4.   TERATOGENICITY
    Rats were exposed to  2,4,6-tr1ch1oroan1l1ne by gavage at doses of 0.4, 4
 and  40  mg/kg,  5 days/week  for  6 months (Sapegln  et  al.,  1985)  (see Section
 6.1.2.1.).   A  teratogenldty  study was conducted  at  "the  end of the 6-month
 experiment."  Additional  Information regarding  the  design of the teratology
 study was  not  reported,  but  1t  may be  Inferred that  mating  and gestation
 occurred  during the  6-month  exposure  period since  the  4  mg/kg  dose was
 reported to  be embryotoxlc; evidenced  by an Increase 1n pre- and postlmplan-
 tatlon  fetal mortality,  massive  hematomas  In  the  abdominal  cavity  and a
decrease In  the  number of  fetuses/female.   The significance of these effects
 1s difficult to ascertain  since further details  (Incidences  of embryotoxlc
effects  at 4 mg/kg  dose,  effects on the dam,  and effects  on at the  40 mg/kg
dose) were not reported.   Teratogenldty was not  reported.


0012d                               -29-                              05/12/87

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6.5.   OTHER REPRODUCTIVE EFFECTS
    A  subchronlc  toxIcHy  study  was conducted  In which  rats  were  exposed
dally  by  gavage to  2,4,6-tr1ch1oroan1l1ne  at concentrations of  80, 160  or
800 tug/kg  for  45 days  (Sapegln  et  a!., 1985).  H1stolog1cal examination  of
the testes  showed  a  decrease In the weight  "coefficients" and  volume of  the
testicles, and an  Increase  1n  the number of  tubules  with  desquamated sperma-
togenlc epithelium at 800 mg/kg.  These effects were  attributed to  a general
toxic  effect  and did not occur  at  160 or  80 mg/kg.  H1stolog1cal  or  func-
tional  alterations  In  the  ovaries  did not  occur  at  any dose.  In  another
experiment  that  was  summarized 1n  the same  report, rats  were exposed  to
2,4,6-tMchloroanlllne  by gavage at doses  of 0.4,  4  and 40 mg/kg,  5  days/
week  for  6 months.  Treatment at any  dose  1n this study  had no significant
effect  on   "the  morphofunctlonal  Indices"  1n  the testes  or   ovaries;  this
appears  to  refer  to   histology,  spermatogenesls  and ovogenesls.   Limited
additional  Information  regarding  the design  of  the  studies 1s  presented  In
Section 6.1.2.1.
6.6.   SUMMARY
    Administration of  2,4,6-tr1chloroan1l1ne to rats  by  gavage at  doses  of
160 or 800 mg/kg/day for  45 days, or 4 or  40 mg/kg,  5 days/week for 6 months
produced  a  variety  of  effects.  Including  methemoglob1nem1a,   gross  hemor-
rhaglc/degeneratlve alterations  1n  the circulatory  system and  altered  liver
enzyme activities  (Sapegln  et  al.,  1985).   Also,  embryotoxldty was reported
at  4  mg/kg and hlstologlcal alterations  1n the testes were reported at 800
mg/kg.   However,  because  of   Inadequate   reporting  and discrepancies  the
validity of these findings  1s uncertain,.
0012d                               -30-                              05/12/87

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     2,4,6-Tr1chloroan1l1ne  hydrochloMde was  administered  to  male  rats  1n
 the  diet at TWA  concentrations  of  1917 and 3833 ppm  for  18 months followed
 by  6  months  observation  without  hlstopathologlcal  effects  (Welsburger  et
 al.,  1978).   Dietary  administration  of 6000 or  12,000  ppm 2,4,6-trlchloro-
 anHlne  hydrochloMde  to mice  for 18  months followed by 3 months observation
 produced  a  dose-related,  statistically significant  Increase In the Incidence
 of vascular  tumors  1n  male  mice  (Welsburger et  al., 1978); hlstopathologlcal
 alterations  did not occur 1n similarly  treated females.
    Equivocal  results  were  reported for 2,4,6-tr1chloroan1l1ne In mutagenlc-
 Hy assays  with  bacteria (Zlmmer et  al., 1980;  Shlmlzu and Takemura, 1984).
 Chromosomal  aberrations occurred  1n the bone marrow cells of rats exposed by
 gavage to 40 mg/kg  2,4,6-tr1chloroan1l1ne,  5 days/week for 6 months (Sapegln
 et al., 1985).
    Information  regarding  the toxic  or carcinogenic  effects  of  2,3,4- or
 2,4,5-tr1chloroan1l1ne  could  not be  located In  the available  literature as
 cited 1n Appendix A.
0012d                               -31-                             05/12/87

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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,  FAQ/WHO  ADIs,  EPA or FDA  toler-
ances  for  raw agricultural commodities  or  foods,  and  ACGIH,  NIOSH or  OSHA
occupational exposure  limits  could  not be  located  In the available  litera-
ture as cited 1n Appendix  A.
7.2.   AQUATIC
    Guidelines and  standards  for  the protection of  aquatic organisms  from
the  effects of  trlchloroanlUnes   could  not  be  located  1n  the  available
literature as cited 1n Appendix  A.
0012d                               -32-                             05/01/87

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                              8.  RISK ASSESSMENT
 8.1.    CARCINOGENICITY
 8.1.1.    Inhalation.    Pertinent   data  regarding   the   carclnogenldty   of
 Inhaled  2,3,4-,  2,4,5-  or  2,4,6-tr1chloroan1l1ne could  not be located In the
 available  literature as cited 1n Appendix A.
 8.1.2.    Oral.   The carclnogenldty  of  2,4,6-tr1chloroan1l1ne hydrochlorlde
 was  evaluated by dietary  administration  to groups  of  25 six- to 8-week-old
 male  Charles  River  rats,  male  CD-I mice  and  female CD-I  mice (Welsburger et
 al.,  1978).   The rats  were  maintained on  diets  containing  compound concen-
 trations  of  3000 or 6000  ppm for  5 months  followed by 1500  or  3000 ppm for
 13 months  (TWA 1917 or 3833 ppm).  The  rats  were observed for an additional
 6  months.  Both  sexes  of  mice were  treated at  concentrations  of  6000 or
 12,000  ppm for  18 months  and observed for an additional  3 months.  Groups of
 25 untreated  male rats  and mice of each sex served  as controls.  As detailed
 1n   Section   6.2.2.   and   Table  6-3,  2,4,6-tr1chloroan1l1ne  hydrochlorlde
 Induced  a dose-related, statistically significant  Increase  1n the Incidence
 of unspecified  vascular tumors  1n  the male  mice.  Incidences of hepatocelTu-
 lar carcinomas were also  Increased In treated male mice  but only In the  low-
 dose  group when  compared  with  pooled controls.   Statistically  significant
 Increases  1n  tumor Incidences 1n the  female mice or  male  rats did not occur.
 8.1.3.   Other  Routes.    Pertinent data  regarding  the  carclnogenldty  of
 Inhaled  2,3,4-,  2,4,5- or 2,4,6-tr1chloroan1l1ne  by routes  other  than  oral
 could not  be  located 1n the available  literature as  cited 1n Appendix A.
 8.1.4.   Weight  of  Evidence.   2,4,6-Tr1chloroan1l1ne  hydrochlorlde produced
 vascular  tumors  and  an equivocal  Increase In  hepatocellular  carcinomas  1n
male  CD-I  mice,  but no  Increase In  the  Incidence  of  tumors  1n  female  CD-I
mice  or  male  Charles  River  rats   (Welsburger  et  al.t 1978).   Since  tumors
0012d                               -33-                              05/12/87

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occurred  1n  one  species  and sex In a single study, and because  the  study  Is
limited by small group sizes,  these data  are  Interpreted  as  limited  evidence
of  carc1nogen1c1ty.   Thus,  2,4,6-tr1chloroan1l1ne  and Its hydrochlorlde are
classified as EPA Group C (U.S. EPA,  1986b).
    The  Induction  of both  cardnogenlclty  and methemogloblnemla by  aniline
and  substituted  aniline  compounds   are  attributed   to   the   formation   of
N-ox1d1zed   metabolites   (Clayson  and   Garner,  1976;   U.S.   EPA,   1984b).
Evidence   for   the   cardnogenlclty   of   aniline    (U.S.    EPA,    1985),
4-chloroan1l1ne  (NCI,  1979) and other  aromatic amines (Clayson and  Garner,
1976), and methemoglobln  Induction by 2,4,6-tr1chloroan1l1ne (McLean  et a!.,
1969),  therefore,   provides   an  additional   Indication   of   the   potential
cardnogenlclty  of  2,4,6-trlchloroanlllne  and  the  hydrochlorlde,  but not
enough to raise the EPA classification.
8.1.5.   Quantitative Risk Estimates.
    8.1.5.1.    INHALATION — Lack  of   pertinent  Inhalation  data   precludes
derivation of a q,* for Inhalation exposure.
    8.1.5.2.    ORAL — A  q,*  for  oral  exposure  to   2,4,6-trlchloroanlUne
hydrochlorlde can  be calculated by using  the   Incidences   of vascular  tumors
In  the  male  mice  from the  Welsburger  et al.  (1978)  study.   The mice  were
exposed to 2,4,6-tr1chloroan1l1ne hydrochlorlde at  dietary concentrations  of
6000 and  12,000 ppm  for  18 months  followed  by an observation period of 3
months. Expanding  the exposures  over  a  21-month  period   by multiplying  the
dietary levels by  18  months/21  months yields  TWA exposure levels of 5143 and
10,286  ppm.   Using  the  TWA dietary  concentrations  and   the  standard  mouse
food consumption estimate of 0.13 kg  food/kg  bw/day,  the  dally doses for the
low- and  high-dose  groups  are  calculated to  be  669 and  1337  mg/kg/day,
respectively.   Using  these  doses  with  the   corresponding   vascular  tumor
Incidences and the computerized multistage model  developed by  Howe and Crump

0012d                               -34-                             07/16/87

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 (1982),   the  unadjusted  q.,*  1s  calculated  to  be   1.4625xlO~3   {mg/kg/
 day)'1   (Appendix B).   This  q,*   may   be  conservative  as  the  numbers   of
 animals  used  In  the  multistage  calculation were relatively  small.  The  human
 q-j*,  calculated  by   multiplying  the  unadjusted  q-j*  by  the   cube  root   of
 the  ratio  of  assumed  human  body weight  (70  kg)  to assumed animal  body weight
 (0.03 kg)  and  by  the cube  of  the  ratio  of  assumed mouse llfespan  (24 months)
 to  experiment  duration (21  months)  1s 2.9xlO~2  (mg/kg/day)"1.   Assuming
 that  a  70  kg human  consumes  2  I/day,  the concentrations  of  2,4,6-tr1-
 chloroanlUne  hydrochloMde  1n  drinking  water  associated  with  Increased
 lifetime   risk  of   cancer  at  risk  levels  of  10~3,  10~»  and  10~7  are
 1.2xlO"2,  1.2xlO~3 and 1.2x10"* mg/l,  respectively.
    A   q.,*   for   2,4,6-tr1chloroan1l1ne   of  3.4x10"*   (mg/kg/day)'1   Is
 calculated  by multiplying  the  q,*  for the  hydrochlorlde by  the  ratio  of
 the  molecular  weight of the  hydrochlorlde  (232.92)  to the molecular weight
 of  2,4,6-tr1chloroan1l1ne  (196.46).   The concentrations  of  2,4,6-tMchloro-
 anlllne  In drinking  water  associated  with  Increased lifetime risk of cancer
 at   risk   levels   of  10~9,  10~»  and  10"7  are   l.OxlO"2,   1.0xlO~»  and
 l.OxlO"4 mg/l.
 8.2.   SYSTEMIC TOXICITY
 8.2.1.   Inhalation  Exposure.   Pertinent   data  regarding  the  effects   of
 Inhalation  exposure  to  the tr1chloroan1!1nes could  not be  located In  the
 available  literature  as cited In Appendix A.
 8.2.2.   Oral Exposures.
    8.2.1.1.   LESS  THAN LIFETIME  EXPOSURES  (SUBCHRONIC)  —  Administration
of 2,4,6-tMchloroanlHne  to  rats by gavage  at  160 or 800 mg/kg/day for  45
days or  4  or  40  mg/kg, 5 days/week for  6 months  produced methemogloblnemla,
gross  hemorrhaglc/degeneratlve  alterations   In  the circulatory  system  and
0012d                               -35-                             07/16/87

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altered  liver  enzyme  activities  (Sapegln  et  al.,  1985).   Also,  embryo-
toxldty was  reported  at 4 mg/kg  administered 5 days/week for 6 months  and
testlcular effects were  reported at 800 mg/kg/day.  There  were  no effects at
80 mg/kg/day for 45 days  or 0.4 mg/kg/day,  5 days/week  for  6 months.
    Because effects  at  4 mg/kg, 5  days/week  for 6 months  and  160  mg/kg/day
for 45  days  were  reported  to  be similar but  less  pronounced than  those at
the high  doses,  these   doses  appear   to  be  LOAELs.   The  lack of  specific
Information,   however,  precludes evaluation  of  these dose effects   or  dose-
response relationships. . Assessment of the  results  1s further complicated by
a  lack  of survival  data,   the  occurrence   of  an 80 mg/kg/day  NOAEL  In  the
45-day study, a  40 mg/kg,  5 days/week PEL  In  the 6-month  study and  the fact
that pathological effects were  not observed  1n rats  treated with  TWA dietary
concentrations of  1917  and 3833 ppm  [-96  or  192 mg/kg/day 2,4,6-trlchloro-
anlllne hydrochlorlde (-81  or  162  mg/kg/day 2,4,6-tr1chloroan1l1ne)  assuming
5X  body  weight  dally  food consumption]  for  18  months  (Helsburger  et al.,
1978)   (see  Section 6.1.2.2.).   Thus,  a  subchronlc  oral  RfD  cannot  be
calculated for   2,4,6-tr1chloroan1l1ne.  Calculation  of  RfDs  for  2,3,4- or
2,4,5-tr1chloroan1l1ne  1s precluded by a lack of toxlclty data.
    8.2.2.2.    CHRONIC   EXPOSURES — The  only   chronic  study  of   2,4,6-tr1-
chloroanlUne was  the dietary study using  rats and  mice  by Welsburger et al.
(1978)  (see   Section  8.1.2.).    Nonneoplastlc   pathological  effects  did  not
occur  In either  species.  The dosage  reduction In the  rat experiment was due
to a  >10X  decrease In weight  gain and Increased mortality.   Because of the
positive cardnogenlcHy results  In mice,  however, 1t 1s  not appropriate to
derive a  chronic oral  RfD  for  2,4,6-tr1chloroan1l1ne.   Calculation of  RfDs
for the other Isomers Is precluded by lack of  data.
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                           9.  REPORTABLE QUANTITIES
 9.1.    BASED  ON  SYSTEMIC  TOXICITY
    Chronic  (Welsburger et al.,  1978),  subchronlc  and reproductive (Sapegln
 et  al.,  1985)  studies  are available  for  2,4,6-tr1chloroan1l1ne,  but  Inade-
 quacies  preclude use of these data  for the calculation of an RQ (Table 9-1).
    Welsburger   et  al.   (1978)  administered  2,4,6-tr1chloroan1l1ne  hydro-
 chloride 1n  the diet to  groups  of  25  male Charles  River rats at TWA concen-
 trations of  1917 or 3833  ppm for  18 months  followed by 6 months observation
 or  to  groups  of  25 male and 25  female CD-I mice at  6000 or 12,000 ppm for 18
 months  followed  by 3 months observation (see Section 6.2.2.).  Nonneoplastlc
 pathological  effects of  exposure  were  not  observed,  but  the  reduction In
 dosage   In  the  rat  groups  was  due  to  a  >10% weight  gain  reduction and
 mortality.   The effect pertinent  to  the  dose reductions was  not specified
 further,  thus precluding  calculation of an RQ.
*            "             •
    Gavage  studies were  conducted  1n which  white  rats  were  treated   with
 2,4,6-trlchloroanlllne  at concentrations  of  80, 160  or  800  mg/kg/day  for 45
 days or  0.4,  4  or 40 mg/kg, 5 days/week for 6 months (Sapegln et al., 1985).
 Various  effects  were  attributed to treatment,  Including methemoglob1nem1a,
 apparent  hepatic damage  and widespread  gross hemorrhaglc  and degenerative
 alterations at  the highest  or  middle  doses or  both 1n  each experiment  (see
 Section  6.1.2.1.).   Additionally, embryotoxlclty was  reported  at  4 mg/kg, 5
 days/week 1n  the 6-month  study  and  testlcular  effects  (apparent atrophy and
 spermatogenlc  epithelium  desquammatlon)  at  800  mg/kg/day  1n   the  45-day
 study.   The  significance  of these  effects  cannot  be  established, however,
 because  of  low confidence  In the study resulting  from  Inadequate reporting
 of  experimental  design and results,  and  apparent  discrepancies  within the
 study  (Sapegln  et al., 1985) and with the  Welsburger  et  al. (1978) study.


 0012d                                -37-                             07/16/87

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                                   TABLE  9-1
        2,4,6-Trlchloroanlllne  and  2,4,6-Tr1chloroan1l1ne Hydrochlorlde
           Minimum Effective  Dose  (MED) and  Reportable  Quantity  (RQ)

Route:
Dose:
Effect:
Reference:
RVd:
RVe:
Composite Score:
RQ:                     Data are Insufficient for deriving an RQ.
0012d                               -38-                             07/16/87

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 Interpretation  of   the  Sapegln  et  al.  (1985)  study  1s  complicated  by
 unexplained  proximity  of the  80  mg/kg/day NOAEL In  the  45-day  study to the
 40  mg/kg,  5  days/week  PEL  In the  6-month study, by uncertainty regarding the
 MED  for  an  effect  since  effects  at   the  middle  doses were  Inadequately
 documented  (similar  to but  less  pronounced  than the high doses),  by a lack
 of  hemorrhaglc/degeneratlve  and  testlcular  alterations  1n  rats  that  were
 maintained on  diets  that  provided 96 or 192 mg/kg/day 2,4,6-trlchloroanlHne
 hydrochlorlde  (81 or  162  mg/kg/day 2,4,6-tr1chloroan1l1ne)  for  18 months
 (Welsburger  et al.,  1978)   (see  Section 6.1.2.2.),  and  by  the  unexplained
 Indication  that   the  testlcular  effects  were due  to a  general  rather  than
 specific toxic effect.  The  embryotox1c1ty reported at  4 mg/kg has uncertain
 significance because H was  not reported at  40 mg/kg and additional  Informa-
 tion regarding experimental  design or  the results  was  not  reported.  Calcu-
 lation  of  an RQ  from  the  effects reported by Sapegln  et al. (1985), there-
 fore, 1s precluded by low confidence 1n  the study.
 9.2.   BASED ON CARCINOGENICITY
    The   carclnogenlcHy   of   2,4,6-tr1chloroan1l1ne   hydrochlorlde   was
 evaluated by dietary administration  to  groups of 25, six- to 8-week-old male
 Charles River  rats,  male  CD-I mice and female CD-I mice (Welsburger et al.,
 1978).   The  rats  were maintained  on  diets containing  TWA  concentrations of
 1917 or 3833  ppm for  18  months  followed by a 6-month  observation period.
 Both sexes of  mice  were treated at concentrations  of 6000 or 12,000 ppm for
 18 months  and  observed for  an additional 3  months.  Groups  of  25 untreated
male rats  and  mice of each  sex  served  as controls.  As  detailed In Section
6.2.2.   and  Table  6-3,  2,4,6-tr1chloroan1l1ne hydrochlorlde  Induced a  dose-
related, statistically  significant Increase  1n  the Incidence of unspecified
vascular tumors  1n  the male mice.  Incidences  of  hepatocellular carcinomas


0012d                               -39-                              07/1b/87

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were  also Increased  1n  treated male  mice,  but only  1n  the  low-dose  group
when  compared  with pooled controls.   Statistically  significant  Increases  In
tumor  Incidences   1n  the  female  mice  or  male  rats . did  not occur.   Since
tumors  occurred  1n one  species and  sex  1n  a  single  study,   these  data  are
Interpreted  as  limited evidence of  carc1nogen1dty  and are  consistent  with
an EPA Group C classification (U.S. EPA, 1986b).
    An  F  factor  for  oral exposure  to 2,4,6-tr1chloroan1l1ne hydrochlorlde
can be  calculated using  the  Incidences  of vascular  tumors 1n the  male  mice
from  the  Welsburger  et al.  (1978)  study.   Multiplying the exposure of  6000
and 12,000  ppm by 18  months/21  months and by  the standard mouse  food  con-
sumption  estimate of 0.13 kg food/kg bw/day,  the dally  doses  for  the  low-
and high-dose  groups are  calculated  to be  669 and  1337  mg/kg/day, respec-
tively  (Table  9-2).   Using   these  doses,  the  corresponding  vascular  tumor
Incidences and the computerized multistage model developed by Howe  and Crump
                                                                          «
(1982),  the  unadjusted  1/ED1Q  Is   calculated to  be  9.1754x10""  (mg/kg/
day)"1.   The  adjusted  I/ED™  (F  factor)  for  humans,  calculated  by  multi-
plying  the unadjusted  T/ED-m  by  the  cube  root  of  the  ratio of  assumed
human body weight  (70 kg) to assumed mouse body  weight  (0.03 kg)  and by the
cube of  the  ratio of mouse  llfespan (24 months)  to experiment  duration (21
months),   Is    1.82X10"1   (mg/kg/day)"1.     An   F   factor   of   2.16X10"1
(mg/kg/day)"1   for  2,4,6-trlchloroanlllne  1s   calculated  by  multiplying the
F  factor  for  the hydrochlorlde  by the  ratio  of  the molecular weight of the
hydrochlorlde     to    the   molecular   weight    of   2,4,6-tr1chloroan1l1ne
(232.92/196.46).   These  F  factors  place  2,4,6-tr1chloroan1l1ne  and  the
hydrochlorlde   1n  Potency Group 3.   An  EPA   Group C  chemical   that  Is  1n
Potency Group  3  ranks LOW 1n the  Hazard  Ranking  Scheme under CERCLA.  A LOW
hazard ranking 1s assigned an RQ of 100.


0012d                               -40-                             07/16/87

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                                   TABLE  9-2
                       Derivation of Potency Factor (F)
                   for 2,4,6-TMchloroan1l1ne HydrochloMde
Reference:
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:
Duration of treatment:
Duration of study:
Ufespan of animal:
Target organ:
Tumor type:
Experimental doses/exposures:
Transformed doses: .
(mg/kg/day)
Tumor Incidence:
Unadjusted 1/EOi0:
Adjusted 1/EO]0:
(F Factor)
Welsburger et a!., 1978
oral
mouse
CD-I
male
diet
0.03 kg (assumed)
18 months
21 months
24 months (assumed)
vascular system
not specified
0, 6000, 12,000 ppm
0, 669, 1337

2/16, 10/18, 12/16
9.1754xlO"» (mg/kg/day)"1
1.82X10"1 (mg/kg/day)"1
0012d
  -41-
07/16/87

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                               10.  REFERENCES

Bartha,  R..   1975.   M1crob1al  transformations  and environmental fate of  some
phenylamlde herbicides.  Rocz.  Glebozn.   26:  17-24.

Bordeleau,  L.M.  and  R.  Bartha.    1972.    Biochemical   transformations   of
herbicide-derived anilines:  Requirements of  molecular  configuration.   Can.
J. Micro.  18(12):  1873-1882.

Brooke,  L.T.,  D.J.  Call, D.L.  Gelger and  C.E.  Northcott, Ed.  1984.   Acute
tox1cH1es of  organic chemicals  to fathead  minnows  (Plmephales  promelas).
University of Wisconsin,  Superior,  UI.   p.  136.

Clayson,  O.B.  and   R.C.  Garner.   1976.  Carcinogenic  aromatic amines.   In.:
Chemical Carcinogens, ACS Monograph 173, C.E. Searle, Ed.  American  Chemical
Society, Washington, DC.

CMR  (Chemical   Marketing   Reporter).    1986.   1978  OPO   Chemical   Buyers
Directory, 74th ed.   Schnell Publishing Co.,  New York.   p.  707.

Dao, T.H., D.  Bouchard,  J. Mattlce  and T.L.  Lavy.  1986.   Soil  sorptlon of
aniline  and  chloroanlUnes: Direct  and Indirect  concentration  measurements
of the absorbed phase.  Soil Sc1.  141(1):  26-30.

Dean, J.A., Ed.  1985.   Lange's  Handbook of  Chemistry,  13th  ed.   McGraw-Hill
Book Co., New York.   p. 7-652.
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-------
 Dennis,  H.H.,  Jr.,  E.P.  Burrows  and  B.A.  S1gg1ns.   1983.   Environmental  fate
 of  2,4,6-trlchloroanlllne  chemical   and   physical  pathways.   Army  Medical
 B1oeng1neer1ng  Research  and Development Lab, Fort  DetMck,  MD.   56  p.   NTIS
 AD-A133  937.

 Devlllers,  J.,  P.  Chambon,  D.   Zakarya  and M.  Chastrette.   1986.   A  new
 approach  1n ecotoxlcologlcal QSAR studies.  Chemosphere.  15(8): 993-1002.

 Eastman  Kodak  Company.   1970.   Toxldty  and  Health  Hazard Summary.   OPTS
 Public Files, U.S. EPA, Washington, DC.  F1che No. OTS0509455.

 Elsenrelch,  S.J.,  B.B.  Looney and  J.D.  Thornton.   1981.   Airborne  organic
 contaminants  of the Great  Lakes  Ecosystem.   Environ.  Sc1.  Technol.   15(1):
 30-38.

 Ellis,  D.D.,  C.M.  Jone, R.A.  Larson  and D.J.  Schaeffer.   1982.   Organic
 constituents  of  mutagenlc   secondary  effluents  from  wastewater  treatment
 plants.  Arch. Environ. Contam. Toxlcol.  11: 373-382.

 Freltag,  D.,   L.  Ballhorn,   H.  Geyer  and  F.  Korte.   1985.   Environmental
 hazard profile  of organic chemicals.   An  experimental  method for the assess-
ment  of   the  behavior  of  organic chemicals  1n  the  ecosphere  by means  of
 simple  laboratory  tests  with  carbon-14-labeled  chemicals.   Chemosphere.
14(10): 1589-1616.

Hansch, C. and  A.J. Leo.  1985.   Medchem  Project  Issue #26.   Pomona College,
Claremont, CA.
0012d                               -43-                             07/16/87

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Hermens,  J.,  P.  Leeuwangh and A.  Musch.   1985.   Joint tox1c1ty of mixtures
of groups  of  organic  aquatic  pollutants  to the guppy  (Poecllla  retlculata).
Ecotoxlcol. Environ. Saf.  9(3):  321-326.

Howe,  R.B.  and   K.S.  Crump.   1982.   GLOBAL 82.   A  Computer  Program  to
Extrapolate  Quantal  Animal  Toxldty  Data  to Low  Doses.   Prepared  under
Contract  No.  41USC252C3.   Office  of  Carcinogen  Standards,  OSHA, U.S.  Dept.
of Labor, Washington,  DC.

Hwang, H.M.,  R.E.  Hodson and R.F.  Lee.   1985.  Photochemical and  mlcroblal
degradation of 2,4,5-tr1chloroan1l1ne  1n  a freshwater lake.   Appl.  Environ.
Wcroblol.  50: 1177-1180.

Janlcke,  W.   and  G.  HUge.   1980.   Measurement  of   the  b1oe!1m1nat1on  of
chloroanllines.  Eighth paper on the  behavior  of  synthetic  organic  compounds
during wastewater treatment.   Gass  Wasserfach Wasser  Abwasser.  121: 131-135.

Knle, J., A.  Halke, I. Juhnke and  W.  Schiller.  1983.   Ergebnlsse der Unter-
suchungen  von  chemlschen  Stoffen mlt vler  Blotests.   Deutsche Gewasserkund-
llche mttellungen.  27:  77-79.

KouMs,  C.S.  and  J.  Northcott.    1963.   Aniline.   l£: Klrk-Othmer Encyclo-
pedia of  Chemical  Technology,  Vol.  2,  2nd ed.,  A. Stander,  Ed.   John Wiley
and Sons, New York.  p. 423.
0012d                               -44-                             07/16/87

-------
 Lucas,  S.V.  1984.   GC/MS Analysis  of  Organic*  In  Drinking Water  Concen-
 trates  and Advanced Haste Treatment  Concentrates:  Vol.  2.   Computer-Printed
 Tabulations of Compound Identification Results for Large-Volume Concentrates.
 Columbus  Labs.   Health  Eff.  Res.  Lab.   p. 397.   EPA 600/1-84-0208.   NTIS
 PB85-128239.

 Lyman,  H.J.,  H.F.  Reehl  and  D.H.  Rosenblatt.   1982.   Handbook of  Chemical
 Property  Estimation Methods.  McGraw-Hill Book  Co.,  New  York.  p.  2-13,  4-9,
 5-5, 7-4,  15-13, 15-21, 15-27.

 McLean,  S.,  G.A. Starmer  and J.  Thomas.   1969.   Methemoglobln  formation  by
 aromatic amines.  J. Pharm. Pharmacol.  21(7): 441-450.

 McLeese,  D.W.,   V.   ZHko  and  H.R.  Peterson.    1979.   Structure-lethality
 relationships for  phenols, anilines  and  other  aromatic compounds  1n  shrimp
 and clams.  Chemosphere.  8(2):  53-57.

 Mitchell,  W.R.,  S.H.  Hoke and  A.B. Rosencrance.   1984.  M1crob1al  degrada-
 tion of  2,4,6-tr1chloroan1l1ne  1n aquatic samples  and laboratory  enrichment
 cultures.  NTIS/AO-A143 286/3.

 Morrison,  R.T. and  R.N.  Boyd.  1973.  Organic  Chemistry, 3rd ed.   Allyn and
 Bacon,  Inc.  p.  730, 751.

NCI  (National  Cancer  Institute).   1979.   Bloassay  of  £-Chloroan1l1ne  for
possible  cardnogenlcHy.   NCI  Cardnogenesls  Tech.  Rep.   Ser.  No.  189.
 [Also publ. as DHEW (NIH) 79-1749.]
0012d                               -45-                             07/16/87

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Neely,  W.B.  and  G.E.  Blau.   1985.   Environmental  Exposure from  Chemicals.
CRC Press Inc., Boca Raton, FL.   p.  31.

Northcott, J.   1978.   Amines,  aromatic (aniline).  ln_: K1rk-0thmer  Encyclo-
pedia of Chemical Technology, Vol 2,  3rd  ed.,  M.  Grayson  and  0.  Eckroth,  Ed.
John Wiley and Sons, New York.   p.  309-313.

ParMs,  G.E.   1980.   Covalent  binding of  aromatic  amines  to  humates.   1.
Reactions  with  carbonyls  and  qulnones.   Environ.  Scl.  Technol.    14(9):
1099-1106.

Sadtler.   1965.   Standard UV  Spectra  No.  7882.   Sadtler  Research  Lab.,
Philadelphia, PA.

Sadtler.   1970.   Standard UV  Spectra No.  16958.  Sadtler  Research  Lab.,
Philadelphia, PA.

Sadtler.   1976.   Standard UV  Spectra No.  24088.  Sadtler  Research  Lab.,
Philadelphia, PA.

Sapegln, O.I., I.P.  Fomochkln,  G.T.  Pls'ko, V.V. Swlstov  and  N.P. Barsukov.
1985.   Setting  health  and  safety  standards  for  permissible  levels  of
trlchloroanlllne  1n  water  reservoirs.  G1g.  Sanlt.   3:  83-84.   (In Russian
with English translation)

Sax, N.I.  1984.  Dangerous  Properties  of Industrial Materials,  6th ed.  Van
Nostrand Relnhold Co., New York.  p. 2618.


001Zd                               -46-                             07/16/87

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 Shlmlzu,  H.  and  N.  Takemura.   1984.  Hutagenlclty  of  some aniline  deriva-
 tives.   ITK  Proc.  nth Int.  Congr.  Occup. Health  Chem.   Ind.   p.  497-506.
 (CA 103:155574J)

 Society  of  Dyers  and ColouMsts.   1971.   Colour Index, 3rd ed.   The  Society
 of Dyers and Colourlsts, England.

 Swann, R.L., O.A.  Laskowskl, P.J.  McCall, K. Vander  Kuy  and H.J.  Dlshburger.
 1983.   A rapid method  for  the  estimation  of  the  environmental  parameters
 octanol/water  partition coefficient,  soil  sorptlon constant,  water  to  air
 ratio and water solubility.  Res.  Rev.  85:  17-28.

 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 In  the Preparation  of
 Health  Effect   Assessment   Chapters  of  the Consent Decree Water  Criteria
 Documents.  Federal Register.  45(231): 49347-49357.

 U.S. EPA.  1984a.   Methodology and  Guidelines  for  Reportable Quantity Deter-
 minations Based on  Chronic Tox1c1ty 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,
Washington,  DC.

U.S.   EPA.   1984b.    Aniline   and   Chloro-,   Bromo-  and/or  NHroanlUnes;
Response  to  the   Interagency  Testing Committee.   Federal  Register.   49:
 108-126.

0012d                               -47-                             07/16/87

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U.S.  EPA.    1985.   Health  and  Environmental  Effects Profile  for Aniline.
Prepared by  the Office of Health and  Environmental  Assessment,  Environmental
Criteria and Assessment Office, Cincinnati, OH for  the Office of  Solid Waste
and Emergency Response, Washington,  DC.

U.S.  EPA.   1986a.   Methodology for  Evaluating Potential Cardnogen1c1ty  1n
Support of  Reportable Quantity Adjustments  Pursuant  to  CERCLA Section  102.
Prepared by  the Office  of  Health  and  Environmental  Assessment,  Carcinogen
Assessment Group,  Washington, DC for  the Office of  Solid Waste  and Emergency
Response,  Washington,  DC.

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

U.S.  EPA.  1987.  Graphical  Exposure  Modeling System (GEMS).   Fate of  Atmo-
spheric Pollutants (FAP).  Office of  Toxic  Substances, U.S.  EPA,  Washington,
DC.

USITC  (U.S.  International Trade  Commission).  1984.   Imports  of  Benzenold
Chemicals  and Products.  1983.  USITC Publ. 1548,  Washington, DC.

Weast,  R.C.   1985.    CRC  Handbook  of Chemistry and  Physics,  66th ed.   CRC
Press, Inc., Boca  Raton,  FL.  p.  C-74.

Welsburger,  E.L.,  A.B. RussMeld, F.  Homburger, et  al.   1978.   Testing of 21
environmental  aromatic amines  or  derivatives  for  long   term  toxlclty  or
cardnogenlclty.  J.  Environ. Pathol. Toxlcol.  2: 235-258.


0012d                               -48-                             07/16/87

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 Zlmmer,  0.,  J.   Mazurek,  G.  Petzold  and  B.K.  Bhuyan.   1980.   Bacterial
 mutagenlcHy  and  mammalian cell  DNA damage  by  several  substituted  anilines.
 Mutat Res.  77: 317-326.
0012d                               -49-                             07/16/87

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                                  APPENDIX A

                              LITERATURE SEARCHED



    This  HEED  Is  based  on  data  Identified  by  computerized   literature

searches of the following:


         TSCATS
         CASR online (U.S. EPA Chemical  Activities  Status  Report)
         TOXLINE
         TOXBACK 76
         TOXBACK 65
         RTECS
         OHM TADS
         STORET
         SRC Environmental Fate Data Bases
         SANSS
         AQUIRE
         TSCAPP
         NTIS
         Federal Register


These searches  were  conducted 1n  January, 1987.   In addition,  hand  searches
                                 •            "            *

were made of  Chemical  Abstracts  (Collective Indices 5-9), and  the following

secondary sources should be reviewed:


    AC6IH (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).
    1986-1987.  TLVs: Threshold Limit Values for  Chemical Substances  1n
    the  Work  Environment  adopted  by  ACGIH with  Intended Changes  for
    1986-1987.  Cincinnati. OH.  Ill 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.O.  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.O.  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.
0012d                               -50-                             07/16/87

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     Grayson,  H.  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.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.  WHO,  IARC, 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.
     SRI   International,   Menlo   Park,  CA.    EPA   600/6-84-010.   NTIS
     PB84-243906.

     NTP  (National  Toxicology Program).  1986.   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).   1986.   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.

     U.S. EPA.   1985.   CSB  Existing Chemical  Assessment Tracking System.
     Name  and  CAS  Number  Ordered  Indexes.   Office  of  Toxic Substances,
    Washington, DC.

     USITC  (U.S.   International  Trade  Commission).   1985.   Synthetic
     Organic Chemicals.   U.S. Production  and  Sales,  1984,  USITC Publ.
     1422. Washington. DC.

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

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

    Worthing,   C.R.  and S.B. Walker,  Ed.   1983.   The  Pesticide Manual.
    British Crop Protection Council.  695 p.
0012d                               -51-                             07/16/87

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    In addition,  approximately  30  compendia  of aquatic  toxlclty data were

reviewed. Including the following:


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

    Johnson,  W.W.  and  M.T. Flnley.   1980.   Handbook  of  Acute  Toxldty
    of  Chemicals   to   Fish  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
    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.
0012d                               -52-                             07/16/87

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                                  APPENDIX B
                   Cancer Data Sheets for Derivation of q-|*
Compound:  2,4,6-Trlchloroanlllne hydrochloMde
Reference:  Welsburger et al., 1978
Specles/straln/sex:  mouse, CD-I, male
Route/vehicle:  oral, diet
Length of exposure (le) » 18 months
Length of experiment (Le) » 21 months
Llfespan of animal (L) = 24 months
Body weight = 0.03 kg (assumed)
Tumor site and type:  vascular system (not specified)
Exposure
ppm (TWA) a
0
5,143
10,286
Unadjusted
Human q-j* =
Transformed Doseb
(mg/kg/day)
0
669
1337
qT* - 1.46251x10"" (mg/kg/day)"1
. 2.895567x10"' (mg/kg/day)"1
Incidence
No. Responding/No. Tested
2/16
10/18
12/16

a6000 or 12,000 ppm x 18 months/21 months
blt Is assumed that mice consume 0.13 kg food/kg bw/day
0012d                               -53-                             07/16/87

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