FINAL DRAFT
               United States       •                              FrAn_niil fifl?ft
               Environmental Protection                               L  I  ,;!:!
               Aaency                                        Harch, 1988
SEPA       Research  and
               Development
               HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
               FOR P-CHLORO-M-CRESOL
               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                           DRAFT: DO NOT CITE OR QUOTE
                                  NOTICE

           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.
             U,S. Environmental Protection
             fteffc" 5, Library (PL-12J)
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                                             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
Is Intended to support listings under  the  Resource Conservation and Recovery
Act  (RCRA) as  well as to provide health-related limits and goals  for emer-
gency  and  remedial actions  under  the Comprehensive  Environmental  Response,
Compensation  and   Liability  Act  (CERCLA).   Both  published literature  and
Information obtained for  Agency Program Office  files are evaluated  as  they
pertain to potential human health, aquatic  life  and environmental  effects of
hazardous waste constituents.   The  literature searched for  In  this document
and  the  dates  searched   are  Included 1n  "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  RfD, Is  an estimate of  an
exposure  level  that would  not  be expected  to  cause adverse  effects  when
exposure occurs during a  limited  time  Interval  I.e., for  an  Interval  that
does  not  constitute a  significant portion  of the  Ufespan.  This  type  of
exposure estimate  has  not been  extensively used,  or rigorously defined  as
previous risk assessment  efforts have  focused  primarily on lifetime exposure
scenarios.  Animal data  used  for  subchronlc  estimates  generally  reflect
exposure durations of  30-90  days.   The general  methodology  for  estimating
subchronlc RfDs Is  the same  as  traditionally  employed for  chronic  estimates,
except that subchronlc  data are utilized  when available.

    In the case of suspected carcinogens,  RfDs are  not estimated.   Instead,
a  carcinogenic potency   factor,  or   q-j*   (U.S.  EPA,  1980a)  Is , provided.
These  potency  estimates  are  derived for both  oral and Inhalation  exposures
where possible.  In addition, unit risk  estimates  for air  and drinking water
are presented  based on  Inhalation and  oral  data,  respectively.

    Reportable quantities  (RQs)  based  on both chronic toxlclty and carclno-
genlclty  are   derived.    The  RQ  1s  used   to  determine  the  quantity of  a
hazardous substance for   which  notification 1s  required   1n the event  of  a
release as specified under the  Comprehensive  Environmental Response,  Compen-
sation and  Liability  Act (CERCLA).   These two  RQs  (chronic toxlclty  and
carclnogenlclty) represent  two  of six scores  developed (the remaining  four
reflect  1gn1tab1l1ty,  reactivity,  aquatic toxlclty,  and   acute  mammalian
toxlclty).   Chemical-specific  RQs reflect  the lowest of  these six  primary
criteria.  The  methodology  for  chronic  toxlclty  and cancer based  RQs  are
defined 1n U.S. EPA, 1984 and 1986a,  respectively.
                                      111

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                              EXECUTIVE SUMMARY

    p-Chloro-m-cresol 1s  a white  to slightly  pinkish crystalline  compound
that Is odorless when very pure,  but usually has a  phenolic  odor  (Wlndholz,
1983; Hawley,  1981).  It  1s freely  soluble  1n  common organic  solvents,  but
only very  slightly  soluble  (3850 ppm  at 20"C)  1n  water {Wlndholz,  1983).
p-Chloro-m-cresol  Is not  currently manufactured  In  the  United States on  an
Industrial  scale;  however,  H  1s  Imported (U.S. EPA,  1986b).   It  1s  used  as
an external germicide,  antiseptic and disinfectant and as a  preservative  for
glues,   gums,  paints,   Inks,  textile  and   leather   goods   (Hawley,   1981;
Wlndholz,  1983).
    The dominant  environmental  fate process  for p-chloro-m-cresol   In  the
atmosphere  Is  expected  to  be  vapor-phase photooxldatlon  with  hydroxyl
radicals.   In  a  typical  ambient  atmosphere, the p-chloro-m-cresol  hydroxyl
radical reaction  half-life  has  been  estimated  to  be 1.1  days   (U.S.  EPA,
1987).   If released  to water, photooxldatlon  and  blodegradatlon appear to  be
the  major  removal   processes.   Based  on an  estimated  rate  constant  and
natural water  radical   concentrations   (Jaber  et  al.,  1984;  Mabey  et  al..
1981),   the  half-life  of  p-chloro-m-cresol   with  respect  to  reaction  with
peroxy  radicals  In  sunlit natural  water has  been  estimated  as  0.8 days.
Various screening tests have demonstrated that  p-chloro-m-cresol  1s  signifi-
cantly  biodegradable under aerobic conditions,  but  resistant to  blodegrada-
tlon under  anaerobic conditions  (Tabak  et  al.,  1964,  1981; Voets  et  al.,
1976;  Chambers et  al.,   1963;  Paull and Franke, 1971;  Johnson   and  Young,
1983).   If released  to  soil,  leaching  1s  likely  to  occur along with aerobic
blodegradatlon.   Two  laboratory  studies have  concluded  that  p-chloro-m-
cresol  will   be  mobile  In  soil   systems  (Zullel,   1981;  Hudson-Baruth  and
                                      1v

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SeHz,  1986).   In  various  subsurface  soil  regions  or  groundwaters  where
aerobic  degradation  1s  not  viable  and other  degradation processes  cannot
occur, p-chloro-m-cresol may  be relatively  persistent.  :
    The greatest potential for human exposure  to  p-chloro-m-cresol  may occur
In occupational settings that  formulate products  (glues,  gums,  paints, Inks,
textile  or  leather goods)  or  use  products that  have been  formulated  with
p-chloro-m-cresol.    With   the  exception   of  effluent  monitoring   data,
published environmental monitoring data are very  limited.  p-Chloro-m-cresol
has been  detected  1n drinking well  water  1n  areas  of China that  are Irri-
gated with sewage effluents  (Tu et al., 1986)  and In an  unspecified finished
drinking  water  (Kool   et  al.,  1982).   Uastewater  effluents  from  various
Industries and  from municipal  sewage  treatment have  been found to  contain
p-chloro-m-cresol  (U.S.  EPA,  1981;  BourquVn  and Gibson,  1978;  Bulsson  et
al.,  1984;   Shackelford and  Keith,  1976;  Bursey  and  Pelllzzarl,  1982).
Halogenated organic compounds  (such as p-chloro-m-phenol)  can be  released  to
the environment  from  Inadvertent  formation In waters  (potable  water,  waste-
water,  cooling  water)  that have undergone  chlorlnatlon  procedures  (Bourquln
and Gibson,  1978).
    The  limited data  regarding the  aquatic  toxlclty of  p-chloro-m-cresol
Indicate  that  freshwater  plants may be  less  sensitive  to p-chloro-m-cresol
than  fish and  Invertebrate  species.   No   data  for  saltwater  species  were
found 1n the available literature.
    The toxldty data concerning p-chloro-m-cresol are limited.   In a  28-day
gavage  study,  decreased body  weight  was   observed  In rats  treated  at  400
mg/kg/day, with no effects noted at 200 mg/kg/day  (Madsen et  al., 1986).  In
a single  dose  study,  hlstopathologlcal effects were observed In the  livers

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of rats treated with p-chloro-m-cresol at 400 mg/kg by gavage or by subcuta-
neous  Injection  (Robenek  et  al.,  1980).   Subcutaneous  and IntraperUoneal
dosing of  rats  and rabbits  has resulted  In kidney and liver hlstopathology
(W1en, 1939).
    In humans,  sensUlzatlon  has  been  reported  In  Individuals  exposed to
chlorocresols  (Guy  and  Jacob, 1941;  Hancock  and  Naysmlth,  1975;  Alnley et
al., 1970).
    The only  mutagenldty study available  reported negative results  1n S.
typhlmurlum strains  TA100,  TA1535,  TA1537  and  TA98,  both  with  and without
metabolic   activation  (Madsen et al.,  1986).   Pertinent  data  regarding the
cardnogenlclty,   teratogenlcHy  and   the   toxldty   of   p-chloro-m-cresol
following   subchronlc  or  chronic   Inhalation  exposure,  and  chronic   oral
exposure were  not located  1n  the available literature  cited  1n Appendix A.
    The lack of Inhalation data precluded the derivation of  Inhalation RfDs.
Using  the  28-day  study  by Madsen  et al. (1986),  a human subchronlc RfD  of 2
mg/kg/day   or  140  mg/day  for  a 70  kg human was  calculated.  Confidence 1n
this  RfO  1s  very  low.  A chronic  oral RfD was not calculated,  because the
only  subchronlc  study available (Madsen  et al.,  1986)  was of  Insufficient
duration for the derivation of a chronic  RfO.  A  provisional RQ  for systemic
toxldty of 1000 pounds was calculated on the basis of decreased body weight
1n  rats 1n the  Madsen et  al. (1986) study.   Because of the  lack of data, an
RQ based on cardnogenlclty  could  not  be calculated.
    A  90-day  oral  study  1s available  1n  the  FIFRA CBI literature.  The RfD
and RQ calculations will be  reviewed when this  study Is available.
                                      v1

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                             TABLE OF CONTENTS
                                                                       Page
1.  INTRODUCTION	    1

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

2.  ENVIRONMENTAL FATE AND TRANSPORT	    5

    2.1.   AIR	'.	    5
    2.2.   WATER	    5

           2.2.1.   Hydrolysis	    5
           2.2.2.   Oxidation 	    5
           2.2.3.   Photolysis	    6
           2.2.4.   Mlcroblal Degradation 	    6
           2.2.5.   Volatilization	    7
           2.2.6.   Adsorption	    7
           2.2.7.   Bloconcentratlon	    7

    2.3.   SOIL	    7

           2.3.1.   Mlcroblal Degradation 	    7
           2.3.2.   Adsorption. ..... 	    8

    2.4.   SUMMARY	    8

3.  EXPOSURE	   10

    3.1.   WATER	   10
    3.2.   FOOD	   11
    3.3.   INHALATION	   12
    3.4.   DERMAL	   12
    3.5.   SUMMARY	   12

4.  AQUATIC TOXICITY	   13

    4.1.   ACUTE TOXICITY	   13
    4.2.   CHRONIC EFFECTS	   13
    4.3.   PLANT EFFECTS	   13
    4.4.   SUMMARY	   13

5.  PHARMACOKINETCS	   14

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                          TABLE OF CONTENTS (cont.)

                                                                        Page
 6.   EFFECTS	    15

     6.1.    SYSTEMIC TOXICITY	    15

            6.1.1.    Inhalation Exposures	    15
            6.1.2.    Oral  Exposures	    15
            6.1.3.    Other Relevant  Information	    15

     6.2.    CARCINOGENICITY	    17
     6.3.    MUTAGENICITY	    17
     6.4.    TERATOGENICITY	    17
     6.5.    OTHER REPRODUCTIVE  EFFECTS 	    17
     6.6.    SUMMARY	    17

 7.   EXISTING GUIDELINES AND STANDARDS 	    19

     7.1.    HUMAN	    19
     7.2.    AQUATIC	    19

 8.   RISK  ASSESSMENT	    20

     8.1.    CARCINOGENICITY	    20

            8.1.1.    Weight of  Evidence	    20
            8.1.2.    Quantltatlve'RIsk Estimates .  .  .	    20

     8.2.    SYSTEMIC TOXICITY	    20

            8.2.1.    Inhalation Exposure ... 	    20
            8.2.2.    Oral  Exposure	    20

 9.   REPORTABLE QUANTITIES 	    22

     9.1.    BASED ON SYSTEMIC TOXICITY 	    22
     9.2.    BASED ON CARCINOGENICITY	    22

10.   REFERENCES	    26

APPENDIX A: LITERATURE SEARCHED	    34
APPENDIX B: SUMMARY TABLE FOR p-CHLORO-m-CRESOL	    37
                                     V111

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                               LIST OF TABLES

No.                               Title                                Page

1-1     1977 U.S. Production Data for p-Chloro-m-cresol	    3

9-1     Oral Toxlclty Summary for p-Chloro-m-cresol Using the Rat . .   23

9-2     Oral Composite Scores for p-Chloro-m-cresol Using the Rat . .   24

9-3     p-Chloro-m-cresol: Minimum Effective Dose (MED) and
        Reportable Quantity (RQ)	   25
                                     1x

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                            LIST OF ABBREVIATIONS
BCF                     Bloconcentratlon factor
CS                      Composite score
Kow                     Octanol/water  partition coefficient
                        Concentration  lethal to 50% of recipients
                        Dose lethal to 50% of recipients
MED                     Minimum effective dose
NOAEL                   No-observed-adverse-effect level
ppb                     Parts  per billion
ppm                     Parts  per million
RfD                     Reference dose
RQ    *                  Reportable quantity
RVj                     Dose-rating value
RVe                     Effect-rating value
UV                      Ultraviolet
v/v                     Volume per volume
WS                      Water  solubility

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                               1.   INTRODUCTION
1.1.   STRUCTURE AND CAS NUMBER
    p-Chloro-m-cresol  Is  a common chemical  name  for the  compound  currently
referenced by Chemical Abstracts Service (CAS) as  phenol, 4-chloro-3-methyl-.
It  Is  also  known by  the chemical  synonyms  4-chloro-m-cresol,  4-chloro-3-
cresol,  2-chloro-5-hydroxytoluene,   4-chloro-5-methylphenol  and  4-chloro-3-
methylphenol (SANSS, 1987).  Tradename  products containing p-chloro-m-cresol
Include  Aptal,   Baktol,  Baktolan,  Candaseptlc,   Ottafact,  Parmetol,  Parol,
Perltonan,   Preventol,   Raschlt  and  Rasen-Anlcon   (SANSS,   1987).    The
structure, molecular  weight,  empirical formula and CAS Registry number  for
p-chloro-m-cresol are as follows:
                                   OH
Molecular weight:  142.59
Empirical formula:  C?H7C10
CAS Registry number:  59-50-7
1.2.   PHYSICAL AND CHEMICAL PROPERTIES
    p-Chloro-m-cresol  1s  a white  to  slightly  pinkish crystalline  compound
that Is  odorless  when  very pure, but  usually has  a  phenolic odor (Ulndholz,
1983; Hawley,  1981).   It  Is freely soluble In  alcohol, benzene,  chloroform,
ether, acetone,  petroleum ether,  fixed  oils,  terpenes and  aqueous  alkaline
solutions (Wlndholz, 1983).   Selected physical  properties are  listed below:
     Melting point:
     Boiling point:
66-68°C
235°C
Ueast, 1985
Ueast. 1985
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     Water solubility:
       at 20°C             3850 ppm                Wlndholz,  1983
       at 25°C             4000 ppm                Hawley,  1981
     Vapor pressure:
       at 25°C             0.0116 mm Hg            Jaber  et al., 1984
     Log Kow:              3.10                    Hansch and Leo,  1985
     Air conversion
     factors at 20°C:       1  mg/m3 = 0.166 ppm
                           1  ppm =6.04 mg/m3

    p-Chloro-m-cresol  1s volatile with  steam.  Aqueous solutions  turn  yellow
on exposure to light  and air  (Wlndholz, 1983).
1.3.   PRODUCTION DATA
    p-Chloro-m-cresol  1s not  currently manufactured In  the  United  States  on
an  Industrial  scale;  however,  It  1s  Imported (U.S.  EPA,  1986b).   Imports
through principal  United States  customs districts In recent  years  have  been
reported as follows (USITC, 1982, 1983, 1984):
                                           Imports
                    Year             (millions of  pounds)
                    1983                    0.293
                    1982                    0.260
                    1981                    0.274

Production  data  cited   In  the  U.S.  EPA  TSCA Production  File  for 1977  are
presented  In  Table 1-1.  p-Chloro-m-cresol  can be prepared  by  the chlorlna-
tlon of m-cresol (Wlndholz, 1983).
1.4.   USE DATA
    p-Chloro-m-cresol  1s  used  as   an  external   germicide,  antiseptic  and
disinfectant  and  as  a  preservative for  glues, gums,  paints,  Inks,  textile
and  leather goods (Hawley,  1981; Wlndholz,  1983).   It  has  been used  as  a
topical antiseptic for  both humans and animals (Wlndholz, 1983).
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                                  TABLE  1-1



               1977 U.S. Production Data for p-Chloro-m-cresol*
Producer
(Location)
Key Chemical Co.
(Greensboro, NC)
Gallard-Schleslnger Chemical
(Carle Place, NY)
Mobay Chemical Corp.
(Plttsburg, PA)
Aceto Chemical Co.
(Flushing, NY)
Agfa-Gevaett Inc.
(Teterboro, NJ)
Struktol Co.. of America
(Akron, OH)
3M Company
(St. Paul, MN)
Hercules Inc.
(Wilmington, DE)
The Frank Herzl Corp.
(New York, NY)
Cosan Chemical Corp.
(Clifton, NJ)
Type of Producer
Importer
Importer
Importer
Importer
Importer
Importer
Importer
Importer
Importer
Importer
Production Range
(pounds)
<1000
1-10 thousand
confidential
10-100 thousand
<1000
confidential
none
confidential
none
confidential
*Source:  U.S. EPA, 1977
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1.5.   SUMMARY
    p-Chloro-m-cresol  1s  a white  to slightly  pinkish  crystalline  compound
that 1s odorless when very pure,  but usually has a phenolic  odor  (Wlndholz,
1983; Hawley,  1981).   It  1s freely  soluble  1n  common organic  solvents,  but
only very  slightly soluble  (3850 ppm  at 2(TC)  In  water (Wlndholz,  1983).
p-Chloro-m-cresol Is not  currently manufactured  In the  United States on  an
Industrial  scale; however.  1t  1s  Imported (U.S. EPA, 1986b).   It  Is  used  as
an external germicide,  antiseptic and disinfectant and as  a  preservative  for
glues,   gums,  paints,   Inks,  textile  and   leather  goods   (Hawley,   1981;
Wlndholz,  1983).
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                     2.  ENVIRONMENTAL FATE  AND TRANSPORT
2.1.   AIR
    p-Chloro-m-cresol has a vapor pressure of  0.0116 mm  Hg  at  25°C {Jaber  et
al., 1984).  Organic compounds  having vapor  pressures of this  magnitude  are
expected  to  exist  almost  entirely   1n  the  vapor  phase  In  the  ambient
atmosphere (Elsenrelch  et al., 1981).
    The  dominant   environmental  fate   process  for  p-chloro-m-cresol  In  the
atmosphere Is probably  the vapor  phase reaction with hydroxyl  radicals  that
are photochemlcally formed by sunlight.  The half-life of this  reaction  1n a
typical  ambient  atmosphere has  been  estimated  to  be 1.1  days based on  an
estimated  reaction  rate  constant  of  9.1xlO~12  cmVmolecule-sec  at  25°C
and  an  atmospheric  hydroxyl radical  concentration  of  8xl05  molecules/cm3
(U.S.  EPA,  1987).   p-Chloro-m-cresol  absorbs  UV  light   >290  nm,  which
suggests a  potential  for direct photolysis; however,  kinetic   rate data  are
not available, to  assess the  relative  Importance of photolysis  (Callahan  et
al., 1979).
    The  relative   Importance  of  physical  removal   from the  atmosphere  by
processes such as  rainfall cannot be  predicted accurately from the available
data.
2.2.   WATER
2.2.1.   Hydrolysis.    p-Chloro-m-cresol   1s  not   expected   to   hydrolyze
significantly 1n environmental  waters  {Mabey et al., 1981;  Callahan  et  al.,
1979).
2.2.2.   Oxidation.  Rate  constants  for  the  reaction  of  p-chloro-m-cresol
with  peroxy  radicals  and  singlet  oxygen have  been estimated  to be  IxlO4
and  IxlOVM-sec,  respectively  (Jaber  et al.,  1984).   Assuming the  concen-
trations of  peroxy radicals and singlet  oxygen In sunlit  natural  water  are


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-TO"9  and  10"12 M  (Mabey  et a!.,  1981),  respectively,  the half-life  with
respect to peroxy  radicals  would  be 0.8 days and  the  half-life  with  respect
to singlet oxygen would be 80 days.
2.2.3.   Photolysis.   The   UV   absorption  spectrum  of   p-chloro-m-cresol
exhibits absorption  at >290 nm,  which  suggests potential  direct  photolysis
(Callahan  et  al.,  1979).   Similar  compounds (chlorophenol,  dlch'lorophenol)
have  been  shown  to photodegrade  In sunlight  or UV light (>290  nm),  but the
rate  at  which photolysis may  occur In the  environment  has not been deter-
mined (Callahan et al., 1979; U.S. EPA,  1980b).
2.2.4.   M1crob1al  Degradation.   Various   screening  tests  have  demonstrated
that   p-chloro-m-cresol   Is   significantly  biodegradable  under   aerobic
conditions, but  resistant to blodegradatlon  under anaerobic conditions.   A
static-culture  flask-screening  procedure   using settled   domestic  wastewater
as  the mlcroblal  Inoculum  found  p-chloro-m-cresol to degrade  significantly
with  rapid adaptation,  as   100%  of Initial  concentrations (5  and  10  ppm)
blodegraded within  14  days  (Tabak et al.,  1981).   Screening tests  similar to
detergent  blodegradabHlty  studies  determined   30-100%  p-chloro-m-cresol
degradation  under  aerobic   conditions  and  0%   degradation under  anaerobic
conditions  (Voets  et  al.,   1976).   Significant  degradation of  p-chloro-m-
cresol  has  been  observed   using  Warburg  resplrometer   tests  with  phenol-
adapted  bacteria  (Chambers  et  al.,  1963;  Tabak  et  al.,   1964).   Sapromat
apparatus  procedures  using  activated  sludge  Inocula have determined  85-100%
blodegradatlon  of  p-chloro-m-cresol with  Initial  concentrations as  high as
100   ppm   (Paull  and  Franke,  1971).    p-Chloro-m-cresol  has   been  found,
however,  to  have  small  Inhibitory effects  on   anaerobic digestion  of  test
chemicals  (Johnson and Young, 1983).
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2.2.5.   Volatilization.  Based  on  a vapor  pressure  of 0.0116  ram Hg  and  a
water  solubility  of 4000  ppm at 25°C  (see Section  1.2.}.  the  Henry's  Law
constant   for  p-chloro-m-cresol    can   be   estimated   to   be   5.44xlO~7
atm-m3/mol.   This  value  of  Henry's  Law constant  Indicates  that  volatili-
zation  from water  Is   very  slow (Lyman  et  a!.,  1982).   Using  the  method
outlined In Lyman et al.  (1982),  the volatilization  half-life of p-chloro-m-
cresol from a  model  river (1 m deep flowing 1 m/sec  with  a  wind velocity of
3 m/sec)  has  been estimated  to  be  80.5 days.   This  rate of  removal  Is  not
competitive with  rates of  removal  by photooxldatlon or,  perhaps,  blodegra-
datlon.
2.2.6.   Adsorption.   Based  on  the  soil  adsorption   data  presented   1n
Section 2.3.2., p-chloro-m-cresol Is  not  expected  to significantly partition
from the water column to sediment.
2.2.7.   B1oconcentrat1on.   Estimation  of  the  BCF  of  an organic  chemical
can  be made   from  the  following  recommended  regression-derived  equations
(Lyman et al., 1982):
                         log BCF  = 0.76 log  KQW - 0.23                  (2-1)
                    log BCF  = 2.791  - 0.564  log WS  (In ppm)             (2-2)
For p-chloro-m-cresol,  the  BCF  values calculated from Equations  2-1  and  2-2
are  134  and   6,  respectively,  based on  a  log K    of  3.10  and  a  water
solubility  of  3850  ppm  at  20°C  (see  Section  1.2.).   Bloconcentratlon does
not appear to be a major fate process based on these estimated BCF values.
2.3.   SOIL
2.3.1.   H1crob1al   Degradation.    Experimental   data   pertaining   to  the
mlcroblal   degradation  of  p-chloro-m-cresol In  soil were not  located.   As
noted  In   Section  2.2.4.,  various   screening  tests  have demonstrated that
p-chloro-m-cresol  blodegrades significantly  under  aerobic   conditions,  but


0076d                               -7-                              02/01/88

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resists   blodegradatlon   under  anaerobic   conditions.    It   Is   possible,
therefore, that blodegradatlon will occur under aerobic soil  conditions.
2.3.2.   Adsorption.  The results  of  two experimental  studies  Indicate that
p-chloro-_m-cresol  will  be  mobile  In  soil  and  susceptible to  significant
leaching.   Zullel   (1981)   found  p-chloro-m-cresol  to  have  significant
mobility  1n  an  activated carbon-sand  filter  system,  which was  considered
Indicative of a  low adsorption potential 1n  soil  systems. Hudson-Baruth and
Seltz  (1986)   determined  that  only  minor   adsorption  of  p-chloro-m-cresol
occurred  1n  dolomite  systems and  suggested  that  leaching  would occur  In
dolomite  groundwater  aquifers.  The  detection of p-chloro-m-cresol  1n well
water  In  China  (Section  3.1.) has demonstrated  that  leaching can  occur  In
the environment.
2.4.   SUMMARY
    The  dominant  environmental  fate  process  for  p-chloro-m-cresol   In  the
atmosphere  Is  expected  to  be  vapor-phase  photooxldatlon  with  hydroxyl
radicals.  In  a typical  ambient  atmosphere,  the  p-chloro-m-cresol  hydroxyl
radical  reaction  half-life  has   been  estimated  to  be 1.1  days  (U.S.  EPA,
1987).  If released  to water,  photooxldatlon and  blodegradatlon appear to be
the  major  removal  processes.   Based  on  an  estimated  rate  constant  and
natural  water   radical  concentrations  (Jaber  et  al.,  1984;  Mabey  et al.,
1981),  the half-life  of  p-chloro-m-cresol  with  respect  to  reaction with
peroxy  radicals  1n sunlit natural  water has been estimated  to be 0.8 days.
Various screening  tests  have demonstrated that p-chloro-m-cresol Is signifi-
cantly  biodegradable under  aerobic conditions, but  resistant to blodegrada-
tlon  under anaerobic  conditions   (Tabak  et al.,  1964,  1981;  Voets  et al.,
1976;  Chambers  et al.,   1963; Paull  and Franke,  1971;  Johnson  and Young,
1983).   If  released to soil,  leaching  1s likely  to occur along with aerobic


0076d                               -8-                              02/01/88

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blodegradatlon.   Two  laboratory  studies   have  concluded  that  p-chloro-m-
cresol  will  be  mobile  1n  soil  systems  (Zullel,  1981;  Hudson-Baruth  and
Seltz,  1986).    In  various  subsurface  soil  regions  or groundwaters  where
aerobic  degradation 1s  not viable  and other  degradation processes  cannot
occur, p-chloro-m-cresol may be relatively persistent.
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                                 3.   EXPOSURE

    Occupational exposure to p-chloro-m-cresol  through  Inhalation  and dermal
contact may be  possible  at  facilities that  formulate products  (glues,  gums,
paints,  Inks,   textile  or  leather  goods)  or  use  products  that  have  been
formulated  with  p-chloro-m-cresol.   Consumer   exposure   may   be  possible
through  use of  these  products;  however,  no  data regarding  actual  human
exposure  to  p-chloro-m-cresol  were  located  1n the  literature  cited  1n  the
Appendix.
    Exposure  of  p-chloro-m-cresol   to  the  general  population  may  occur
through  oral  consumption of  drinking water  that  has  been  contaminated  by
Inadvertent formation during chlorlnatlon  treatment  or  by  leaching Into well
water.
3.1.   WATER
    p-Chloro-m-cresol detection In a  finished  drinking  water  sample  has been
reported  (source  or concentration were  not reported)  (Kool  et al.,  1982).
Groundwater  from  11  drinking water wells  1n  areas  of  China  that  are
Irrigated with  sewage effluents have  been  found to  contain p-chloro-m-cresol
(Tu et al., 1986).   Monitoring of surface  waters  at various locations of the
Lake Erie or Lake Michigan  ecosystems  did  not  detect any positive concentra-
tions of p-chloro-m-cresol (Great Lakes Hater Quality Board, 1983).
    p-Chloro-m-cresol has been detected  1n a number of  wastewater  effluents.
Positive  detections  have  been  reported for  raw and  treated wastewaters from
the  following   Industries  (U.S.  EPA,  1981):  Iron  and  steel  manufacturing,
aluminum  forming,  foundries,  metal  finishing,  photographic equipment  and
supplies,   pharmaceutical   manufacturing,   organic   chemicals  and  plastics
manufacturing,  paint and Ink formulation,  soap and detergent manufacturing,


0076d                               -10-                             12/14/87

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textile mills,  and auto and  other  laundries.  Reported  mean  concentrations
1n the  raw wastewaters ranged  from  0.01  ppb  (organic  chemical  and plastics
manufacturing)  to  100 ppm  (metal  finishing).  Reported  mean  concentrations
1n  the  treated wastewaters  ranged  from  0.01   ppb  (organic  chemical  and
plastics  manufacturing)  to  36  ppb   (foundries).    Chlorinated  municipal
effluents  have  been  reported to contain  p-chloro-m-cresol  levels  of  ~2  ppb
(Bourquln  and  Gibson,  1978).   p-Chloro-m-cresol  levels  of  73  ng/l,  154
ng/i  and   0.22  mg/kg  (dry  wt)  were detected  1n a  final  effluent  from  a
treatment  works,   1n  a soil  leachate and  1n a  wastewater sludge,  respec-
tively,  from the  United  Kingdom  (Bulsson  et  al.,  1984).  Effluents  from
chlorinated  domestic  sewage (Shackelford  and Keith, 1976)  and  from mechani-
cal products  and transportation  equipment  Industries  (Bursey and PelUzzarl,
1982) have also been found to contain positive levels  of p-chloro-m-cresol.
    The gross  analysis of  the  water monitoring  data  contained  In  the  U.S.
EPA STORET  Data Base cites 7667  reporting stations with a minimum, maximum
and mean concentration of  0.0, 101,  331  and 78.5 ppb,  respectively.
    Halogenated  organic  compounds   (such  as   p-chloro-m-phenol)   can   be
released  to the environment  from Inadvertent  formation  In waters (potable
water,  wastewater,  cooling water)  that  have  undergone  chlorlnatlon  proce-
dures  (Bourquln and  Gibson, 1978).   p-Chloro-m-cresol  may  potentially occur
1n the environment as  a  metabolite  of  the  soil degradation of herbicides
such as 4-chloro-2-methylphenoxyacetate, although this  supposition  has never
been demonstrated  experimentally (U.S.  EPA, 1980b).
3.2.    FOOD
    Pertinent  food  monitoring  data  were  not  located   1n  the  available
literature cited In the Appendix.
0076d                               -11-                             02/03/88

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3.3.-   INHALATION
    p-Chloro-m-cresol  has  been  detected  In  the  stack  effluent  from  a
municipal waste Incinerator (James et al., 1985).
3.4.   DERMAL
    Pertinent  dermal monitoring  data  were  not   located  In  the  available
literature cited In the Appendix.
3.5.   SUMMARY
    The greatest potential for  human  exposure to  p-chloro-m-cresol  may occur
In occupational settings  that formulate products  (glues,  gums,  paints. Inks,
textile  or  leather  goods)  or  use  products  that  have been  formulated  with
p-chloro-m-cresol.   With  the   exception   of  effluent   monitoring   data,
published environmental monitoring  data are very  limited.  p-Chloro-m-cresol
has been  detected In drinking  well  water  1n  areas  of China that  are Irri-
gated with sewage  effluents  (Tu et  al., 1986) and In an unspecified finished
drinking  water  (Kool  et al.,  1982).   Wastewater   effluents  from  various
Industries and from municipal  sewage treatment  have  been found  to  contain
p-chloro-m-cresol  (U.S.   EPA,  1981;  Bourquln and Gibson,  1978;   Bulsson  et
al.,  1984;  Shackelford   and Keith,   1976;   Bursey  and  Pell1zzar1,  1982).
Halogenated organic  compounds (such  as  p-chloro-m-phenol) can be  released to
the environment  from Inadvertent  formation  In waters  (potable  water,  waste-
water, cooling water)  that  have  undergone  chlorlnatlon procedures (Bourquln
and Gibson, 1978).
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                             4.  AQUATIC TOXICITY
4.1.   ACUTE TOXICITY
    Gerslch  and  Hayes   (1986)  reported  a  48-hour  LC5Q  of  2.0  mg/a.  for
Daphnla magna exposed to  p-chloro-m-cresol .   The test was  conducted  at a pH
of 7.5-8 at 19.6-20.8°C  under static conditions.
    Hattula  et  al.  (1981)   reported  a  24-hour  LC5Q  of 1.3  ppm  In  trout,
Sal mo  trutta. exposed  to p-chloro-m-cresol.  The  test was conducted  at  5°C
under  static  conditions.   The  static  96-hour LC5_ for  p-chloro-m-cresol  1n
the  fathead minnow,  Plmephales  promelas.  was  reported  as  30  yg/i  (U.S.
EPA, 1972).
4.2.   CHRONIC EFFECTS
    Pertinent data  regarding  effects on aquatic organisms  following chronic
exposure were not located In the available literature cited 1n Appendix A.
4.3.   PLANT EFFECTS
    Blackman  et   al.   (1955)   reported  an   LC5Q  of   95,488  yg/l   for
duckweed, Lemna minor, exposed to p-chloro-m-cresol.
4.4.   SUMMARY
    The  limited data  regarding  the aquatic  toxldty  of  p-chloro-m-cresol
Indicate that  freshwater plants  may be less sensitive  to  p-chloro-m-cresol
than  fish  and  Invertebrate  species.   No data  for  saltwater species  were
found In the available literature.
0076d                               -13-                             12/14/87

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                             5.   PHARMACOKIMETICS

    The  only  data  regarding   the   pharmacoklnetlcs   of   p-chloro-m-cresol
located  1n  the  literature  concerns  excretion.   Zondek  and Shapiro  (1943)
recovered 15-20% of an  -1000  rag/kg dose 1n the  urine of rabbits  (wt.  ~1  kg)
given a  single subcutaneous Injection of p-chloro-m-cresol.   In  humans given
an  unspecified  dose  of p-chloro-m-cresol  by  Intramuscular Injection,  the
compound was  not  recovered  In the  urine  In appreciable amounts  (Zondek  and
Shapiro, 1943).
0076d                               -14-                             03/08/88

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                                  6.   EFFECTS
6.1.   SYSTEMIC TOXICITY
6.1.1.   Inhalation  Exposure.    Pertinent  data  regarding  the  toxlclty  of
p-chloro-m-cresol  following  subchronlc or  chronic  Inhalation  exposure  were
not located In the available literature cited In Appendix A.
6.1.2.   Oral Exposure.
    6.1.2.1.   SUBCHRONIC — Hadsen et al.  (1986)  treated groups of 10  male
and 10  female  rats by gavage with p-chloro-m-cresol  In  soybean oil  at doses
of  0,  50,  200  or  400  mg/kg/day.   Compared  with  controls,   a  significant
decrease 1n weight gain  (p<0.05 males, p<0.01  females)  was observed In rats
treated at  400 mg/kg/day during  the  last  week of treatment.   No  effects  on
hematology  or  clinical  chemistry were noted.   At  necropsy,  no  significant
alterations 1n  relative  organ  weights were observed.  Without providing any
details, the  authors stated that  no  pathological  changes  were noted  In the
kidneys, spleen,  brain,  .adrenals, liver,  testes,  stomach,  small  Intestine,
pancreas, lung, aorta, heart, thymus,  thyroid and parathyroid.
    6.1.2.2.   CHRONIC — Pertinent   data   regarding    the   toxlclty   of
p-chloro-m-cresol  following  chronic   oral  exposure were  not  located  1n the
available literature cited 1n Appendix A.
6.1.3.   Other  Relevant  Information.   Hlen  (1939)  reported  subcutaneous
LD5Qs of  400  and  360  mg/kg  for p-chloro-m-cresol  In rats  and mice, respec-
tively.   An  Intravenous  ID™  In mice  was   70  mg/kg.   p-Chloro-m-cresol
treatment resulted  1n  muscle tremors,  and  death occurred In a  few hours as a
result of respiratory  failure.   Damage to  renal tubules  was observed at high
doses.
    Robenek et al.  (1980)  found  alterations  1n the  livers of rats sacrificed
60 hours after being  given a single oral  or subcutaneous dose of p-chloro-m-
cresol  1n  peanut  oil  at 400 mg/kg.    Control  rats  were  treated  with  peanut

0076d                               -15-                             02/01/88

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oil.  The observed liver effects were  similar  following  both  oral  and subcu7
taneous  exposure.   Electron micrographs  showed a  considerable Increase  In
mitochondria,  and   freeze  fracturing   revealed   Irregularities    In   bile
canallcull.   Numerous vacuoles were  observed  In the cytoplasm  of  cells  that
are presumably hepatocytes  (Increase In mitochondria,  vacuoles  In  cytoplasm,
etc.).   Light  microscopy revealed dilation of the sinusoids and  activation
of Kupffer cells  In both groups of rats.
    In a 14-day  study  conducted  by  Wlen  (1939),  groups of five  young  rats
(sex  unspecified)  were  treated  by  subcutaneous  Injection with  p-chloro-m-
cresol at 0  or 80 mg/kg/day.  Growth was  not  affected,  and lesions  were not
observed In  the  kidney,  liver  or spleen.  H1ld  Inflammation  was  reported at
the  Injection  site.   W1en  (1939)  also treated  three  rabbits  with  subcuta-
neous  Injections  of  p-chloro-m-cresol  at 12.5  mg (5  ml  of  a 1/400  (v/v)
solution) dally  for  4  weeks.   No  changes  In  hematology, or  hlstologlcal
changes  In  the  liver or kidney  were noted.   Controls  were not used In  this
study.
    In an l£ vitro  study,  W1en  (1939)  found  that 1/1000 p-chloro-m-cresol
solution decreased  the  magnitude of the  heart beat of  Isolated hearts  from
rabbits.  Similar effects were observed with phenol.
    Guy  and  Jacob  (1941) reported that a  1.5% aqueous  solution of p-chloro-
m-cresol can cause  vesicular  dermatitis  1n sensitive humans.  The  symptoms
occur within 4 hours and regress within 1 week.
    Hancock  and Naysmlth (1975)  and  Alnley et  al.  (1970) reported  sensltlza-
tlon  reactions  In humans  treated  with heparln  preserved  with  chlorocresol.
Testing  with heparln without  chlorocresol Indicated  that chlorocresol  was
the  cause  of  the  reaction.  The   specific  chlorocresol  Involved  was  not
stated.


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6.2.   CARCINOGENICITY
    Pertinent  data   regarding  the  cardnogenldty   of   p-chloro-m-cresol
following any route of exposure were not  located  1n  the available literature
cited In Appendix A.
6.3.   MUTAGEMICITY
    p-Chloro-m-cresol   tested  negative  for  reverse  mutation  In  Salmonella
typhlmurlum  strains TA100,  TA1535, TA1537  and TA98  {Madsen  et  al.,  1986).
The  tests  were  conducted  both with  and without  metabolic activation  (rat
S-9) at concentrations of 1.28, 6.4, 32, 160 or 800 jig/plate.
6.4.   TERATOGENICITY
    Pertinent  data  regarding  the   teratogenlclty  of p-chloro-m-cresol  were
not located In the available literature In Appendix A.
6.5.   OTHER REPRODUCTIVE EFFECTS
    Pertinent data regarding  other  reproductive  effects of p-chloro-m-cresol
were not located In the available literature cited 1n Appendix  A.
6.6.   SUMMARY
    The toxldty data concerning p-chloro-m-cresol are  limited.   In  a  28-day
gavage  study,  decreased  body weight  was  observed  In  rats  treated at  400
mg/kg/day, with no effects noted at 200  mg/kg/day  (Madsen  et al., 1986).   In
a  single  dose  study,  hlstopathologlcal effects  were observed  In  the  livers
of rats treated with p-chloro-m-cresol at 400  mg/kg  by  gavage  or by  subcuta-
neous  Injection  (Robenek et  al.,   1980).   Subcutaneous and  Intraperltoneal
dosing of  rats  and rabbits  has  resulted 1n kidney  and liver  hlstopathology
(Wlen, 1939).
    In  humans,  sensltlzatlon  has  been  reported  In  Individuals exposed  to
chlorocresols  (Guy and  Jacob, 1941;  Hancock and  Naysmlth,  1975; Alnley  et
al., 1970).


0076d                               -17-                             03/10/88

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    The  only  mutagenlclty study  available reported negative  results In  S.
tvphlmuMum strains  TA100,  TA1535, TA1537  and TA98,  both  with and  without
metabolic activation  {Madsen et  al.,  1986).   Pertinent  data  regarding  the
carclnogenlclty,  teratogenlclty   and   the  toxlclty  of   p-chloro-m-cresol
following  subchronlc  or  chronic  Inhalation   exposure,   and   chronic  oral
exposure were not located 1n  the available literature cited 1n  Appendix A.
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                     7.   EXISTING GUIDELINES  AND  STANDARDS
7.1.   HUMAN
    U.S. EPA  (1980b)  recommended an ambient water quality  criterion  of 3000
yg/l,   which  was   based   on   an   odor   threshold   of   3000  vg/ft.   for
p-chloro-m-cresol 1n water {Deltz and Traud,  1978).  U.S.  EPA (1980b) stated
that  data  on human  health  effects  must  be  developed  as a  more substantial
basis for recommending a criteria to protect human health.
    The RQ for p-chloro-m-cresol 1s  5000 pounds (U.S. EPA,  1985a).
7.2.   AQUATIC
    Acute toxldty  1n aquatic  species  has been  shown  to occur at concentra-
tions as low as 30 yg/i, (U.S. EPA, 1980b).
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                             8.  RISK ASSESSMENT
8.1.   CARCINOGENICITY
    Pertinent data  regarding the  cardnogenlclty  of p-chloro-m-cresol  were
not located In the available literature  cited In Appendix A.
8.1.1.   Weight   of  Evidence.   The  lack  of  data  concerning  the   cardno-
genlclty of p-chloro-m-cresol 1n either humans  or animals  Indicates  that the
compound should be  classified as  an EPA Group  D chemical  {U.S.  EPA, 1986c),
not classifiable as  to human carclnogenlclty.
8.1.2.   Quantitative Risk Estimates.  The  lack of  carclnogenlclty  data  for
p-chloro-m-cresol precludes the  derivation  of a potency  factor.
8.2.   SYSTEMIC  TOXICITY
8.2.1.   Inhalation  Exposure.  The  lack  of  data  concerning  the  toxlclty  of
p-chloro-m-cresol following  Inhalation  exposure precludes the  derivation  of
subchronlc or chronic Inhalation RfDs.
8.2.2.   Oral Exposures.
    8.2.2.1.   LESS  THAN  LIFETIME  EXPOSURES — The  only  subchronlc  study
available  Is  the 28-day study  by  Madsen  et al.  (1986).   In this  study,  no
effects were  observed  1n  rats  treated  by  gavage  with  p-chloro-m-cresol  1n
soybean  oil  at  doses  of  50  or 200  mg/kg/day.  A  significant  decrease  1n
weight  gain  (p<0.05 males, p<0.01  females)  was observed  In  rats treated  at
400  mg/kg/day during  the  last  week of  treatment.   No  other   effects  were
noted.  The  parameters  examined Included hematology  and  clinical chemistry.
Detailed  descriptions  of  the experimental  protocol  were  not provided.   The
lowest  NOAEL  found  1n  this  study  (200 mg/kg/day)  can  be used  to  derive a
subchronlc RfD for  p-chloro-m-cresol.  A human  subchronlc  RfD of 2 mg/kg/day
or  140  mg/day for a 70  kg  human  Is calculated by dividing  the  rat  NOAEL  by
an  uncertainty  factor  of  100  (10  for  Interspecles  extrapolation and  10  to
protect sensitive Individuals).

0076d                               -20-                             03/08/88

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    Confidence 1n this RfD 1s very  low.   The  study  used for the basis of the
RfD 1s only  28  days 1n duration; there are no  supporting  subchronlc  studies
and a  single dose  study  (Robenek  et a!., 1380)  found  liver lesions  at 400
mg/kg, a  dose resulting  In  only decreased body  weight 1n the  28-day study
(Madsen  et  al.,   1986).    In   addition,  p-chloro-m-cresol  has   not  been
evaluated for teratogenldty or carclnogenlclty and no pharmacoklnetlc  data
were available.
    8.2.2.2.    CHRONIC EXPOSURES --  No  chronic  oral  studies of  p-chloro-m-
cresol are available.  The only subchronlc study available was  28  days  long
(Madsen  et   al.,  1986),   a   duration  Insufficient  for  the  derivation  of  a
chronic RfD.
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                          9.  REPORTABLE QUANTITIES
9.1.   BASED ON SYSTEMIC TOXICITY
    The tox1c1ty of  p-chloro-m-cresol  was  discussed  In Chapter 6.   The  only
study suitable  for  the derivation of  an RQ  1s summarized In Table  9-1.   In
the 28-day  rat  study (Madsen et  al.,  1986),  decreased body weight  gain  was
observed 1n rats treated  by  gavage at 400 mg/kg/day.  The derivation  of  the
RQ  1s presented  1n  Table  9-2.   A human MED of 478.8 mg/day  Is  calculated by
multiplying the  equivalent human  dose  of 68.4 mg/kg/day  by  70  kg  and  divid-
ing by  10  to  extrapolate  from subchronlc exposure.  This MED  corresponds to
an  RV   of  1.5.  The effect, decreased  body weight,  corresponds  to  an  RV,
of 4.  Multiplying  the RV& by the RVd,  a CS of 6  1s derived.
    The CS  of  6 derived from  the 28-day  rat study  (Madsen  et  al.,  1986)
corresponds to  an  RQ  of  1000 pounds.   This  RQ  1s  presented   1n  Table  9-3.
Because this  RQ  1s  based  on  a study only  28  days 1n duration.  It should be
considered provisional until  'longer-term studies  are  available.
9.2.   BASED ON CARCINOGENICITY
    The lack of data precludes the derivation of  a carclnogenldty based  RQ.
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-------
                                  TABLE 9-2

           Oral  Composite Score  for p-Chloro-m-cresol Using the Rata
                 Chronic
Animal Dose     Human MEDb     RVd         Effect         RVe     CS      RQ
(mg/kg/day)      (mg/day)


    400           478.8        1.5     decreased body      4      6      1000
                                       weight gain


aSource: Madsen et al.. 1986

bThe dose was divided by an uncertainty factor of 10 to approximate chronic
 exposure.
0076d                               -24-                             12/14/87

-------
                                  TABLE 9-3
                              p-Chloro-m-cresol
          Minimum  Effective Dose  (MED) and Reportable Quantity  (RQ)

Route:                  oral
Dose*:                  478.8  mg/day
Effect:                 decreased body weight gain
Reference:              Madsen et al., 1986
RVd:                    1.5
RVe:                    4
Composite Score:        6
RQ:                     1000
*Equ1va1ent human dose
0076d                               -25-                             12/14/87

-------
                               10.  REFERENCES

Alnley,  E.J..   et  al.   1970.   Adverse  reaction  to  chlorocresol-preserved
heparln. Lancet.  1803:  705.   (Cited In U.S.  EPA,  1980b)

Blackman,  G.E.,  et  al.   1955.   The  physiological  activity of  substituted
phenols.   I.   Relationships   between   chemical  structure  and  physiological
activity.  Arch. Blochem.  Blophys.  54: 45.   (Cited In U.S.  EPA,  1980b)

Bourquln, A.M. and D.T. Gibson.   1978.  Mlcroblal  Degradation of Halogenated
Hydrocarbons.    In:  Water  Chlorlnatlon   Environmental  Impacts   and  Health
Effects, Vol.  2.  Ann Arbor Science, Ann  Arbor,  MI.  p. 253-264.

Bulsson,  R.S.K,  P.W.W.   Kirk and  3.N.  Lester.   1984.   Determination  of
chlorinated phenols  1n  water, wastewater  and wastewater sludge  by  capillary
GC/ECD.  J. Chromat.  Sc1.   22: 339-342.

Bursey,  J.T.  and  E.O.  Pelllzzarl.  1982.  Analysis  of  Industrial  Wastewater
for  Organic  Pollutants  In Consent  Degree Survey.   U.S.  EPA, Environ.  Res.
Lab., Athens,  GA.   p. 79,  80.

Callahan,  M.A.,  SLImak,  M.W..   N.W.  Gabel,  et   al.   1979.   Water-Related
Environmental   Fate  of  129   Priority  Pollutants   -  Volume  II.   U.S.  EPA,
Washington, DC.  EPA 440-79-029B.

Chambers,  C.W., H.H.  Tabak  and P.W. Kabler.  1963.   Degradation of aromatic
compounds  by  phenol-adapted  bacteria.   3.  Water  Pollut.   Control  Fed.   35:
1517-1528.
0076d                               -26-                             02/01/88

-------
Deltz, F.  and  J.  Traud.  1978.   Odor  and taste  threshold  concentrations  of
phenol bodies.   Guf-wasser/abwasser.   119: 318.   (Cited In U.S.  EPA,  I980b)

Elsenrelch, S.J.,  B.B.  Looney  and O.J.  Thornton.   1981.  Airborne  organic
contaminants  1n  the  Great  Lakes ecosystem.   Environ.  Scl.  Techno!.   15:
30-38.

Gerslch,  P.M.  and  M.A. Hayes.   1986.   Acute  toxlclty  tests  with  Daphnla
magna  and Plmephales promelas  1n  support of  national  pollutant  discharge
elimination permit requirements.  Water Res.   29(7):  939-941.

Great Lakes Water Quality Board.   1983.   An Inventory  of  Chemical  Substances
Identified 1n the Great Lakes Ecosystem.   Report, Volume  1  -  Summary.   Great
Lakes Water Quality Board,  Windsor Ontario, Canada,   p. 59.

Guy,  W.H. and  P.M.  Jacob.   1341.   Occupational  dermatitis  due  to  para-
chloro-meta-cresol.   3.  Am.  Med.  Assoc.   116:  2258.   (Cited  In  U.S.  EPA,
1980b)

Hancock,  B.W.  and  A.  Naysmlth.   1975.   HypersensHlvlty  of  chlorocresol
preserved heparln.  Br.  Med.  3.   p. 746.  (Cited In  U.S. EPA,  1980b)

Hansch,  C.  and A.J.  Leo.    1985.   Hedchem Project.   Issue No.  26.   Pomona
College, Claremont, CA.

Hattula,  M.L., V.H.  Wasenlus,  H.  Reunanen and  A.U.  Arstlla.   1981.   Acute
toxlclty  of some  chlorinated phenols  catechols  and cresols to trout.   Bull.
Environ. Contam.  Toxlcol.   27(3):  295-298.

0076d                               -27-                             02/01/88

-------
Hawley,  6.G.    1981.    The  Condensed  Chemical  Dictionary,  10th  ed.    Van
Nostrand Relnhold Co., New York.   p.  238.

Hudson-Baruth,  B.A.   and  M.G. SeHz.   1986.   Adsorption  of  Select Phenol
Derivatives by Dolomite.  Environ. Pollut.  Ser.  B.   11(1):  15-28.

Jaber, H.M.,  W.R.  Mabey,  A.T.  L1u, T.W.  Chou and H.L.  Johnson.   1984.   Data
Acquisition  for  Environmental  Transport  and  Fate Screening.   SRI  Inter-
national,  p.  239.  EPA 600/6-84-009.   NTIS PB84-243906, PB84-243955.

James, R.H.,  R.E.  Adams,  J.H. Flnkel, H.C.  Miller  and L.D.  Johnson.   1985.
Evaluation of analytical methods  for the determination  of  POHC  In combustion
products.  J.  Air Pollut.  Control  Assoc.   35(9): 959-961.

Johnson,  L.O. and J.C. Young.  1983.  Inhibition  of anaerobic digestion  by
organic priority pollutants.  J.  Water  Pollut. Control  Fed.  55:  1441-1449.

Kool,  H.J., C.F.  Van  Kreljl and  B.C.J. Zoeteman.   1982.   Toxicology  assess-
ment  of  organic compounds  In  drinking water.   Cr1t.  Rev. Env.  Contr.   12:
345.

Lyman,  U.J.,  W.F. Reehl  and  D.H. Rosenblatt.   1982.   Handbook  of  Chemical
Property  Estimation Methods.  McGraw-Hill  Book  Co.,  New York.   p. 5-4,  5-10,
15-16  to  15-29.

Mabey,  W.R.,  J.H. Smith,  R.T.  Podoll, et  al.   1981.   Aquatic  Fate  Process
Data  for Organic  Priority  Pollutants.  U.S.  EPA,  Washington,  DC.   p. 273,
274.   EPA 440/4-81-014.

0076d                               -28-                             12/14/87

-------
Madsen  C.,  P.M.  Andersen,  0.  Meyer  and  G.  Wurtzen.   1986.   4-Chloro-3-
methylphenol:  Salmonell a/mamma 11 an-ml crosome mutagenldty  test and  subacute
toxIcHy test  1n rats.   Bull. Environ.  Contam.  Toxlcol.   37(5): 651-654.

Paull,  0.  and  G.  Franke.   1971.   Behavior  and  Degradation  of  Technical
Preservatives  1n the Biological Purification of Sewage.  In:  Proc.  2nd Symp.
Int. Blodeter. Mater,  p. 52-60.

Robenek, H., R. Melss, J. Gehllng and  H.  Themann.  1980.   Alterations In the
rat  liver  Induced  by  p-chloro-m-cresol  with  emphasis  on  the  Intercellular
junctions:  A  thin-section  and  freeze-fracture study.  0.  SubmTcrosc.  Cytol.
12(4): 635-646.

SANSS (Structure  and Nomenclature Search System).   1987.   Chemical  Informa-
tion System (CIS) computer data base.  Online.

Shackelford,  W.M.  and  L.H.  Keith.   1976.   Frequency  of   Organic  Compounds
Identified 1n  Water.  U.S. EPA, Athens, GA.   EPA 600-4-76-062.  p. 194.

Tabak, H.H.,  C.W.  Chambers  and P.M.  Kabler.  1964.  Mlcroblal  metabolism of
aromatic compounds.  I.  Decomposition of  phenolic  compounds and  aromatic
hydrocarbons by phenol-adapted  bacteria.   J. BacteMol.   87-910-919.

Tabak, H.H..  S.A.  Quave,  C.I.  Mashnl and E.F. Barth.   1981.   B1odegradab1l-
Ity  studies  with  organic  priority  pollutant  compounds.   J. Water  Pollut.
Control  Fed.  53: 1503-1518.
0076d                               -29-                             12/14/87

-------
Tu, J.,  D.  Chen,  X.  Shu and M. Heng.  1986.   Organic  pollutants  In  drinking
water wells  within an  area  Irrigated with  sewage  water.  Huanjlng  Huaxue.
5: 60-74.  (CA 106:22946x)

U.S. EPA.   1972.   The  effect  of chlorlnatlon on  selected  organic  chemicals.
Water Pollut. Control Res.  Series 12020.   (Cited In U.S.  EPA,  1980b)

U.S.  EPA.    1977.   Computer print-out  of  non-confidential  production  data
from the TSCA Production File for  1977.   U.S. EPA, Washington,  DC.

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

U.S.  EPA.   1980b.  Ambient Water  Quality Criteria Document for  Chlorinated
Phenols.   Prepared by  the Office  of Health  and  Environmental  Assessment,
Environmental Criteria  and Assessment Office, Cincinnati, OH  for  the Office
of Water  Regulations and  Standards,  Washington,  DC.  EPA-440-5-80-032.  NTIS
PB81-117434.

U.S. EPA.   1981.   Treatablllty Manual - Volume 1.  U.S. EPA,  Washington, DC.
EPA 600/2-82-OOla.  p.  1.8.12-1 to 1.8.12-4.
0076d                               -30-                             02/01/88

-------
U.S.  EPA.   1984.   Methodology  and   Guidelines   for   Reportable  Quantity
Determination 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.   1985a.   Notification  requirements;  reportable quantity  adjust-
ments;  final  rule and  proposed  rule.   40  CFR Parts  117 and  302.   Federal
Register.  50(65): 13456-13522.

U.S.  EPA.   1985b.  Reference  Values  for Risk  Assessment.   Prepared  by  the
Office  of  Health  and  Environmental Assessment,  Environmental Criteria  and
Assessment Office, Cincinnati, OH for  the Office  of  Solid Waste,  Washington,
DC.

U.S.  EPA.   1986a.  Methodology for  Evaluating  Carc1nogen1c1ty  1n  Support  of
Reportable  Quantity  Adjustment.   Pursuant  to  CERCLA Section  102.   Prepared
by  the  Office of Health and  Environmental  Assessment,  Carcinogen Assessment
Group, Washington, DC  for  the Office of Solid  Waste and Emergency Response,
Washington,  DC.

U.S.  EPA.  1986b.  The Verification of  the  Production  of 41  Chemicals.  Test
Rules Dev.  Branch, Existing  Chem.  Assess.  D1v.,  OTS, U.S. EPA,  Washington,
DC.  p. 1, 2, 4.

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


0076d                               -31-                             02/01/88

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U.S. EPA.  1987.   Graphical  Exposure  Modeling System (GEMS).  Fate  of  Atmo-
spheric Pollutants  (FAP)  computer  data systems.  PCGEMS Version April  1987.
U.S. EPA, Research Triangle Park,  NC.

USITC  (U.S.  International Trade  Commission).  1982.   Imports  of  Benzenold
Chemicals and Products 1981.   USITC Publ.  1272,  Washington,  DC,   p.  13.

USITC  (U.S.  International  Trade  Commission.   1983.   Imports  of  Benzenold
Chemicals and Products 1982.   USITC Publ.  1401,  Washington,  DC.   p.  12.

USITC  (U.S.  International  Trade  Commission.   1984.   Imports  of  Benzenold
Chemicals and Products 1983.   USITC Publ.  1548,  Washington,  DC.   p.  13.

Voets, 3.P., P. P1pyn, P.  Van  Lancker  and  W.  Verstraete.   1976.   Degradation
of   mlcroblcldes   under   different   environmental   conditions.     0.   Appl.
Bacterlol.  40(1): 67-72.

Weast,  R.C.,  Ed.   1985.   CRC  Handbook  of Chemistry  and  Physics,  66th  ed.
CRC Press, Boca Raton, FL.  p. C-219.

W1en,  R.   1939.   The toxlclty  of  parachlorometacresol  and  of phenylmercurlc
nitrate.  Quart. J. Yearbook Pharm.  12: 212.

Wlndholz, M.,  Ed.   1983.   The Merck Index, 10th  ed.   Merck and  Co., Rahway,
NJ.  p. 299.
 0076d                               -32-                             02/01/88

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Zondeck,  8.  and  8.  Shapiro.    1943.   Fate  of  halogenated  phenols   In  the
organism.  Blochem. J.  37: 592-595.

Zullel,  N.   1981.  Behavior of  disinfectants (chlorophenols)  during under-
ground passage.  Sc1. Total Environ.  21: 215-220.
0076d                               -33-                             02/01/88

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                         •         APPENDIX  A

                             LITERATURE SEARCHED



    This  HEED  1s  based  on  data  Identified   by   computerized   literature

searches of the following:

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


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

sources were reviewed:


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

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

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

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

    Clayton,  G.D.  and  F.E.  Clayton,  Ed.   1982.   Patty's  Industrial
    Hygiene  and Toxicology,  3rd  rev.  ed.. Vol.  2C.   John  WHey  and
    Sons, NY.  p. 3817-5112.
0076d                               -34-                             02/01/88

-------
    Grayson, N.  and 0.  Eckroth,  Ed.   1978-1984.   Klrk-Othmer  Encyclo-
    pedia of Chemical Technology, 3rd ed.   John  Wiley  and  Sons,  NY.   23
    Volumes.

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

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

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

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

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

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

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

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

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

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

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

    Wlndholz, M., Ed.  1983.  The Merck  Index,  10th ed.   Merck and Co.,
    Inc., Rahway, NJ.
0076d                               -35-                             02/01/88

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    In addition,  approximately 30  compendia of  aquatic toxlclty  data were

reviewed, Including the following:


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

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

    McKee. O.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.
                                      U.S. environmental Protection Agenqr
                                      Region 5, Library (PU-12J)
                                      77 West Jackson Boulevard, IZUi
                                      Ch»c»go,  It  60604-3S90
0076d                               -36-                              02/01/88

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