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                                  DISCLAIMER

    This report  Is  an external  draft  for  review purposes only  and  does  not
constitute  Agency  policy.   Mention of  trade  names  or  commercial  products
does not constitute endorsement or recommendation for use.
                                      11

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                                   PREFACE
    Health and  Environmental  Effects  Documents  (HEEDs) are prepared  for «the
Office of Solid Waste  and  Emergency Response (OSWER).  This document  series
1s Intended to support listings under the Resource Conservation  and  Recovery
Act (RCRA) as  well  as to  provide  health-related  limits and goals for  emer-
gency and  remedial  actions under  the Comprehensive  Environmental Response,
Compensation   and  Liability  Act  (CERCLA).    Both  published  literature and
Information obtained for Agency Program Office files  are evaluated  as  they
pertain to potential human health, aquatic life and environmental  effects  of
hazardous waste constituents.   The  literature searched for 1n this  document
and  the  dates  searched  are  Included 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,  1s  an  estimate of  an
exposure  level  that would not  be expected  to cause  adverse effects  when
exposure  occurs during a  limited  time  Interval  I.e.,  for an Interval  that
does  not  constitute a  significant portion  of  the 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 1s  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-|*  (U.S.  EPA,  1980)  1s provided.   These
potency estimates are  derived  for both  oral  and  Inhalation exposures  where
possible.  In  addition,  unit  risk estimates  for  air  and  drinking water are
presented based on Inhalation  and  oral data,  respectively.

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

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                               EXECUTIVE  SUMMARY

    Chloroacetaldehyde  (107-20-0)   1s  a  colorless   liquid  with  an  acrid,
penetrating odor  (Hawley,  1981;  Wlndholz, 1983).  This compound  Is  prepared
Industrially by carefully  controlled chlorlnatlon  of  acetaldehyde (Wlndholz,
1983).   Chloroacetaldehyde  1s no  longer manufactured  1n  the United  States
(HSOB, 1987),  although  H  Is probably Imported.   Chloroacetaldehyde  1s  used
as a  fungicide,  1n the manufacture  of  2-am1noth1azole, 1n  facilitating  the
removal of bark from  trees and 1n  dentistry  (Lawrence and  Autlan, 1972;  U.S.
EPA/NIH,  1987;  Wlndholz, 1983).
    In  the  atmosphere,  Chloroacetaldehyde  Is   expected   to  exist  almost
entirely  In  the  vapor  phase.    Reaction  with  photochemlcally  generated
hydroxyl   radicals  (t,,- =  1«7 days) and  physical  removal  by wet deposition
would  probably  be the  dominant  fate processes.   Chloroacetaldehyde  removed
from  the  atmosphere  by wet  deposition,  however,  may reenter the atmosphere
by volatilization.   In  water, volatilization  Is expected  to be  a  signifi-
cant,  If  not  the  dominant, removal mechanism.   The  volatilization half-life
from a river 1 m  deep,  flowing 1 m/sec  with  a  wind velocity of  3 m/sec  has
been estimated to be  -2 days.  Chloroacetaldehyde  Is  not expected to undergo
chemical   oxidation,   bloaccumulate  significantly   In  aquatic  organisms  or
adsorb significantly  to suspended  solid or  sediments In  water.  In  moist
soil, Chloroacetaldehyde 1s  expected to  be highly mobile and susceptible to
significant leaching.  The relatively high  vapor  pressure  of chloroacetalde-
                 \
hyde suggests that H would volatilize  fairly rapidly from  dry soil surfaces.
    No monitoring data  are  available  to  Indicate   ambient  air  or  water
levels, drinking  water  or  food contamination or dermal exposure.  Potential
sources  of  Chloroacetaldehyde  entering   the   environment   are   losses   at
                                      1v

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processing sites,  losses  during transport, disposal  processes  and use as  a
fungicide.   Ando and  Sayato  (1984)  suggested  that  VCM  can  migrate  Into
drinking water from water  pipes made of polyvlnyl chloride and  subsequently
react with  chlorine  present  In  the  drinking water,  forming  chloroacetalde-
hyde.  The  detection  of chloroacetaldehyde  as  a  result  of  chlorlnatlon  of
VCM  1n   drinking  water,   however,  required  the  presence  of  much   higher
concentrations of  both  VCM and  chlorine than  are  expected  to be  present
under typical conditions.   Therefore, the  formation  of  chloroacetaldehyde  1n
potable  water by this  process  Is  questionable.   Another  possible  source  of
chloroacetaldehyde  1n   the  atmosphere   1s  - formation  from   reaction   of
1,3-d1chloropropene  with  ozone  and  OH   radicals   (Tuazon  et  al.,   1984).
1,3-D1chloropropene  1s   a  highly   volatile  component  of   widely   used
Insectlddal fumlgants  (Tuazon et al., 1984).
    Little  Information  1s   available  regarding  the  toxlclty  of  chloroacet-
aldehyde  to  aquatic  organisms.   A 96-hour  LC_n of  1.5  mg  chloroacetalde-
hyde/B.  was  reported  for   the  copepod,   Nltocra  splnlpes   (Bengtsson  and
Tarkpea,  1983).   Sea lampreys,  however,  were unaffected by exposure  to 5  mg
chloroacetaldehyde/a,  for 24 hours (Applegate  et  al.,  1957).
    No pertinent  data  regarding  the  absorption  and distribution  of  chloro-
acetaldehyde were  located  1n the literature.  Metabolism and  excretion ^ata
were limited  to  one  study  (Green and Hathway, 1977),  In which  three  urinary
metabolites    [N-acetyl-S-(2-hydroxyethyl)    cystelne,   S-(carboxymethyl)
cystelne and  th1;od1glycol1c add] were  found following oral  administration
of chloroacetaldehyde to rats.
    Few  studies  regarding   the  systemic  toxldty  of   chloroacetaldehyde
following administration of  the compound  by  relevant routes  (I.e., oral  and
Inhalation)  were located  In  the  available   literature.   Exposure of  rats,

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guinea pigs,  rabbits  and mice  to  chloroacetaldehyde (5.1 mg/m3)  by  Inhala-
tion 7 hours/day,  5  days/week for 6 months  had  no  adverse health effects  on
any of the  animal  species tested (Dow Chemical  Company,  1962).   Weekly oral
administration  of  chloroacetaldehyde  to mice  (0.25 mg  chloroacetaldehyde/
mouse/week) over an entire lifetime was  without  effect  on the mortality rate
(Van  Duuren  et  al.,  1979).   The  oral  LD5Q  of  chloroacetaldehyde  was
reported to be  between  -82 mg/kg 1n mice and  89-103 mg/kg In rats (Lawrence
et al., 1972).
    Intraperltoneal doses  of chloroacetaldehyde  of  0.0016 and  0.0032  ml/kg
given  to  rats  were  associated with  the production  of  a   focal,  chronic,
bronchopneumonla,  Increases  1n  segmented neutrophlls  and decreases  1n both
erythrocytes  and  lymphocytes (Lawrence  et  al.,  1972).    No  hematologlcal  or
pulmonary effects  were  associated with  a dose of 0.0008  mi  chloroacetalde-
hyde/kg.   Chloroacetaldehyde Injected IntraperHoneally  In   rats  (0.0016  or
0.0032 ml/kg)  3 times/week  for 12  weeks was reported to  produce changes. 1n
the respiratory epithelium,  suggestive of a  premallgnant  condition (Lawrence
et al., 1972).
    Chloroacetaldehyde has been  shown to Increase  the  pentobarb1tal-1nduced
sleeping time of mice (Lawrence et al.,  1972) and  to cause  J_n vitro  hemoly-
s1s  1n  rabbit  erythrocyte  preparations  and  cytotoxldty  1n murlne  L-cell
preparations.
    Oral  weekly administration  of chloroacetaldehyde to  mice  (0.25 mg/mouse/
week) for the  Hfespan  did not  Increase the  Incidence  of forestomach tumors
over that  observed In untreated  controls  (Van Duuren et  al.,  1979).
    Chloroacetaldehyde was   negative  as  a  whole carcinogen  or  as  a  tumor
Initiator  when  tested on  the skin of mice (Van  Duuren  et al., 1979;  Zajdela
et al., 1980).
                                      vl

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    Cardnogenldty data resulting from human occupational exposure were not
located  1n  the  available  literature;  also  there  were  no  ep1dem1olog1cal
studies regarding  possible  carcinogenic  effects  associated with exposure to
chloroacetaldehyde.
    Chloroacetaldehyde has been demonstrated to be mutagenlc  1n a variety of
assays  using  both  prokaryotes and  eukaryotes  with  and  without  metabolic
activation (B1gnam1 et al.,  1980;  Rannug  et al., 1976; McCann et al., 1975;
Malavellle et  al.,  1975; Phillips  et  al., 1980; Garro  and  Phillips, 1980;
Hussaln and  Osterman-Golkar,  1984;  Perrard,  1985;  lorprleno  et  al., 1977;
Huberman et  al.,  1975; Rosenkranz,  1977).
    Pertinent   data   regarding  the  teratogenldty  or  other  reproductive
effects associated  with  exposure  to chloroacetaldehyde  were  not  located In
the available  literature dted 1n  Appendix A.
    RfDs for chloroacetaldehyde are not presented as the available date were
regarded as Inadequate.   Data are Insufficient  for determining  an  RQ based
on  chronic   toxldty  or  on  carc1nogen1dty.    Since   data   regarding  the
carcinogenic potential  of chloroacetaldehyde are  Inadequate,  this  chemical
Is placed 1n EPA  Group D --  not classifiable as to human  carclnogenldty.

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                              TABLE  OF  CONTENTS
                                                                       Page
1.  INTRODUCTION	,	     1

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

2.  ENVIRONMENTAL FATE AND TRANSPORT	     4

    2.1.   AIR	     4

           2.1.1.   Reaction with Hydroxyl  Radicals 	     4
           2.1.2.   Reaction with Ozone 	     4
           2.1.3.   Physical Removal Processes	     4

    2.2.   WATER. . "	........     4

           2.2.1.   Oxidation	     4
           2.2.2.   Photolysis	     5
           2.2.3.   Mlcroblal Degradation 	     5
           2.2.4.   Volatilization	     5
           2.2.5.   Adsorption	     5
           2.2.6.   B1oaccumulat1on .  ....  	     5

    2.3.   SOIL .		     6

           2.3.1.   Mlcroblal Degradation ...'.'	     6
           2.3.2.   Adsorption		     6
           2.3.3.   Volatilization	     6

    2.4.   SUMMARY	     6

3.  EXPOSURE	     8

4.  AQUATIC TOXICITY	     9

    4.1.   ACUTE TOXICITY 	     9
    4.2.   CHRONIC EFFECTS	     9
    4.3.   PLANT EFFECTS	 . .	     9
    4.4.   SUMMARY		     9

5.  PHARMACOKINETCS	    10

    5.1.   ABSORPTION	    10
    5.2.   DISTRIBUTION	    10
    5.3,   METABOLISM	  .    10
    5.4.   EXCRETION	    11
    5.5.   SUMMARY	 .    13

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                          TABLE OF CONTENTS  (cont.)

                                                                        Page
 6.  EFFECTS	    14

     6.1.   SYSTEMIC TOXICITY	    14

            6.1.1.   Inhalation Exposures	    14
            6.1.2.   Oral  Exposures	    14
            6.1.3.   Other Relevant Information	    14

     6.2.   CARCINOGENICITY.  .  .	    16

            6.2.1.   Inhalation	4  •	    16
            6.2.2.   Oral.	    16
            6.2.3.   Other Relevant Information.  ...  	    17

     6.3.   MUTAGENICITY	    20
     6.4.   TERATOGENICITY .	    23
     6.5.   OTHER REPRODUCTIVE  EFFECTS 	    23
     6.6.   SUMMARY	    23

 7.  EXISTING GUIDELINES AND  STANDARDS 	    25

     7.1.   HUMAN	    25
     7.2.   AQUATIC	    25

 8.  RISK ASSESSMENT ..;.........	    26

     8.1.   CARCINOGENICITY		    26

            8.1.1.   Inhalation	    26
            8.1.2.   Oral	    26
            8.1.3.   Other Routes	    26
            8.1.4.   Weight of  Evidence	    26
            8.1.5.   Quantitative Risk Estimates  .  .	    27

     8.2.   SYSTEMIC TOXICITY		    27

            8.2.1.   Inhalation Exposures	    27
            8.2.2.   Oral  Exposures	    28

 9.  REPORTABLE QUANTITIES	    29

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

10.  REFERENCES	    32

APPENDIX A: LITERATURE SEARCHED	    40
APPENDIX B: SUMMARY TABLE  FOR CHLOROACETALDEHYDE  	    43
                                      1x

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                               LIST OF TABLES

No.                               Title                                Page

6-1     Weekly Intragastrlc Administration of an Aqueous Solution
        of Chloroacetaldehyde to Ha:ICR Mice: Incidence of Fore-
        stomach Tumors	    18

6-2     Mutagenldty Testing of Chloroacetaldehyde	    21

9-1     Chloroacetaldehyde: Minimum Effective Dose (MED) and
        Reportable Quantity (RQ)	    30

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                             LIST  OF ABBREVIATIONS

BCF                     B1oconcentrat1on factor
CAS                     Chemical Abstract Service
DNA                     Oeoxyr1bonude1c acid
GC                      Gas chromatography
Koc                     Soil sorptlon  coefficient
Kow                     Octanol/water  partition coefficient
LCso                    Concentration  lethal to 50% of recipients
1050                    Dose lethal to 50% of recipients
MED                     Minimum effective dose
MS                      Mass spectrometry
NOEL                    No-observed-effect level
ppm                     Parts per million
ppth                    Parts per thousand
RfD                     Reference dose
RQ                      Reportable quantity
VCM                     Vinyl chloride monomer
                                      x1

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                               1.  INTRODUCTION
1.1.   STRUCTURE AND CAS NUMBER
    Chloroacetaldehyde  Is  also  known  as  2-chloro-l-ethanal  and  2-chloro-
acetaldehyde (HSDB, 1987).  The  structure,  CAS  number,  empirical  formula  and
molecular weight are as follows:
                                      H   0
                                      I   //
                                   Cl-C-C
                                      I   \
                                      H   H
Molecular weight:  78.50
Empirical formula:  C.H.CIO
CAS Registry number:  107-20-0
1.2.   PHYSICAL AND CHEMICAL PROPERTIES
    At  room temperature,  Chloroacetaldehyde  1s  a  clear,  colorless  liquid
possessing an acrid, penetrating odor  (Hawley,  1981;  Wlndholz,  1983).   It 1s
soluble  1n  water  at concentrations  <50%, but  It .forms  Insoluble  hemlhydrate
at concentrations >50%  (U.S.  EPA/NIH,  1987).   Selected  physical  and chemical
properties are as follows:
       Melting point
       (40% aqueous d1l.):
       Boiling point:
       (40% aqueous d1l.):
       Vapor pressure at 20°C:
       Log Kow:  ;
       Water solubility at 20°C
       Flashpoint:
       Density
       (40% aqueous d1l,):
       Refractive. Index
       (40% aqueous dll., 25°C)
-16.3°C

85°C
100 mm Hg
0.39
~5xl O5 mg/9.
87.7°C
1
'•
    25
1.397
Hawley, 1981

Hawley, 1981
ACGIH, 1981
U.S. EPA, 1987a
U.S. EPA/NIH, 1987
Hawley, 1981

Hawley, 1981
Hawley, 1981
0086cl
-1-
                 01/21/88

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1.3.   PRODUCTION DATA
    Chloroacetaldehyde  1s  prepared  Industrially  by  carefully  controlled
chlorlnatlon of acetaldehyde (Wlndholz, 1983).  The  following  Information  on
chlororoacetaldehyde  was  obtained  from  the  U.S.  EPA  TSCA Production  File
(U.S. EPA, 1977):

    	Company/Location	     Production/Import Volume
    Texas Eastman Co.                              1-10 million  pounds
      Longvlew, TX
    International  Flavors  & Fragrances  Inc.        <1000 pounds
      Union Beach, NO   (Importer)
    Henley and Co., Inc.                           confidential
      New York, NY  (Importer)

According  to  HSDB (1987), Chloroacetaldehyde  1s  no longer produced  commer-
cially  In  the  United  States;  however,  CMR  (1986)  lists   five  domestic
suppliers  for  this   compound,  which  suggests  that  Chloroacetaldehyde  1s
probably Imported Into the United States.  Import data  for  recent years  were
not located 1n the available literature cited 1n Appendix  A.
1.4.   USE DATA
    Chloroacetaldehyde  1s  used  as  a  fungicide,   In  the manufacture  of
2-am1noth1azole,  1n   facilitating  the  removal  of  bark  from  trees  and  1n
dentistry (Lawrence and  Autlan, 1972;  U.S.  EPA/NIH,  1987;  Wlndholz, 1983).
1.5.   SUMMARY
    Chloroacetaldehyde  (107-20-0)   1s  a  colorless   liquid  with  an  acrid,
penetrating odor\(Hawley,  1981;  Wlndholz,  1983).  This compound  1s  prepared
Industrially by carefully  controlled chlorlnatlon of acetaldehyde (Wlndholz,
1983).   Chloroacetaldehyde  1s  no  longer  manufactured  1n the  United  States
0086d                               -2-                              01/21/88

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 (HSDB,  1987),  although It  1s  probably  Imported.   Chloroacetaldehyde 1s used
 as  a fungicide,  1n  the  manufacture of  2-am1noth1azole,  1n  facilitating the
 removal  of  bark from trees and 1n dentistry (Lawrence and Autlan, 1972; U.S.
 EPA/MIH,  1987;  Wlndholz, 1983).
0086d                               -3-                              01/21/88

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                     2.  ENVIRONMENTAL FATE AND TRANSPORT

    Limited  data  regarding the  environmental  fate and  transport  of  chloro-
acetaldehyde  were  located  In  the   available  literature.   When  possible,
predictions  regarding  environmental  fate  and  transport  were  derived  from
physical properties or molecular structure.                     <:"
2.1.   AIR                                                             >
    Based  on  a vapor  pressure of 100 mm Hg at  20°C,  chloroacetaldehyde  1s
expected  to  exist  almost  entirely   1n  the  vapor  phase  1n the  atmosphere
(ACGIH, 1981; Elsenrelch et al., 1981).  .
2.1.1.   Reaction  with Hydroxyl  Radicals.   Using the  method  of  Atkinson
(1985), the rate constant  for  the  reaction of  chloroacetaldehyde  with photo-
chemlcally  generated  hydroxyl  radicals In  the  atmosphere  has  been estimated
to  be 9.4xlO~12  cm3/molecule-sec  at 25°C.   Assuming  an  average  hydroxyl
radical   concentration  of   5xl05   molecules/cm3   (Atkinson,   1985),   the
hydroxyl reaction half-life was estimated to be 1.7 days.
2.1.2.   Reaction with  Ozone.   Reaction  of chloroacetaldehyde with ozone  1n
the atmosphere  1s  not  expected  to be an  Important fate  process  (U.S.  EPA,
1987b).
2.1.3.   Physical  Removal  Processes.   Based on  Its   relatively   high  water
solubility  1t appears  that chloroacetaldehyde would be highly susceptible  to
removal from  the  atmosphere  by wet deposition; however,  any chloroacetalde-
hyde  removed  from  the atmosphere  by this mechanism  has  the potential  to
reenter the atmosphere by volatilization.
2.2.   WATER
2.2.1.   Oxidation.  Chloroacetaldehyde  Is  expected to be Inert to  chemical
                                                       @»      '
oxidation In aqueous solution (Jaber  et al., 1984).

0086d                                -4-                              01/21/88

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2.2.2.   Photolysis.'   Data  regarding  the photolysis  of  chloroacetaldehyde
1n water were not located 1n the available literature cited 1n Appendix A.
2.2.3.   Mlcroblal Degradation.   Stuckl  and  Le1s1nger et  al. (1983)  deter-
mined  that  Pseudomonas  CElr  degraded  2-chloroethanol  to  glycollc  add
through  chloroacetaldehyde  and  2-chloroacetate  (Intermediary  compounds).
This  Information  Indicates  that  biological degradation  of  chloroacetaldehyde
Is  likely  to  occur;  however,   the  significance  of this   Information  with
regard  to  the  blodegradatlon  of  chloroacetaldehyde   under  environmental
conditions 1s uncertain.
2.2.4.   Volatilization.   Henry's  Law  constant  for  chloroacetaldehyde was
estimated  to  be 2xlO~s  m3-atm/mol  at  25°C  using the  bond  contribution
method of  H1ne and  Mookerjee  (1975).   This  value suggests  that  volatiliza-
tion  of  chloroacetaldehyde  from all bodies  of water would  be  a  significant
fate  process   (Lyman  et al.,  1982).   Based  on  this value  of  Henry's  Law
constant,  the  volatilization half-life  of chloroacetaldehyde  from a  river
1 m deep.,  flowing 1  m/sec  with a wind  speed  of  3 m/sec was  estimated  to  be
~2 days using the method of Lyman et al. (1982).
2.2.5.   Adsorption.   Experimental data  regarding  the adsorption of chloro-
acetaldehyde to  suspended  solids  and sediments In water were not located  In
the available  literature  cited 1n Appendix  A; however, the  relatively high
water  solubility and  low  K    suggest  that  adsorption  to  suspended  solids
and sediments 1n water Is probably not a significant  fate process.
2.2.6.   B1oaccumalat1on.  A  BCF  of 1  was  estimated for  chloroacetaldehyde
using  a  linear  regression  equation based  on a  log K    of 0.39  (Lyman  et
al.,  1982;  U.S.  EPA, 1987a).   This  BCF value and the  relatively high water
solubility  of  this   compound  suggest  that  chloroacetaldehyde  would  not
bloaccumulate significantly 1n aquatic organisms.
0086d                               -5-                              01/21/88

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2.3.   SOIL
2.3.1.   Mlcroblal  Degradation.   As  has  been  discussed  In  Section  2.2.3.,
blodegradatlon of chloroacetaldehyde  1s  likely  to  occur,  but no experimental
data  are  available  that would allow  estimations of blodegradatlon  rates  In
soil under environmental conditions.
2.3.2.   Adsorption.   A  K    of  39  was  estimated  for   chloroacetaldehyde
using a  linear regression  equation based on  a log K    of  0.39  (U.S.  EPA,
1987a; Lyman  et  al.,  1982).   This  KQC  value  and  the relatively  high  water
solubility of  chloroacetaldehyde suggest  that  this  compound would  be  very
highly mobile  In soil  and susceptible  to  significant  leaching (Swann et al.,
1983). .
2.3.3.   Volatilization.  Based  on  a  vapor  pressure of  100 mm  Hg  at  20°C
(ACGIH,   1981)  chloroacetaldehyde 1s  expected  to  volatilize fairly  rapidly
from dry soil surfaces.
2.4.   SUMMARY
    In  the  atmosphere,  chloroacetaldehyde  1s  expected  to  exist  almost
entirely  1n  the  vapor  phase.    Reaction  with  photochemically  generated
hydroxyl   radicals  (t,/? = 1.7 days) and  physical  removal  by wet  deposition
would probably  be the  dominant  fate  processes.   Chloroacetaldehyde removed
from  the  atmosphere  by wet deposition,  however, may reenter the  atmosphere
by  volatilization.   In water, volatilization  Is-expected  to be  a  signifi-
cant, 1f  not  the  dominant,  removal  mechanism.   The  volatilization half-life
from a river  1 m'deep, flowing 1 m/sec with  a  wind velocity of 3 m/sec  has
been estimated to be ~2  days.  Chloroacetaldehyde  1s  not  expected  to undergo
chemical   oxidation,   bloaccumulate   significantly   In  aquatic  organisms  or
adsorb significantly  to  suspended  solid  or  sediments  1n  water.    In  moist
0086d                               -6-                              01/21/88

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 soil,  chloroacetaldehyde 1s expected to  be  highly  mobile and susceptible  to
 significant  leaching.   The relatively high vapor pressure of chloroacetalde-
 hyde  suggests  that  It would  volatilize fairly rapidly from dry soil surfaces.
0086d                               _7_                              01/21/88

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                                  3.   EXPOSURE

     No monitoring  data  are  available  to  Indicate  ambient  air  or  water
 levels,  drinking water or  food  contamination  or dermal exposure.   Potential
 sources   of  chloroacetaldehyde  entering  the  environment  are   losses   at
 processing sites, losses .during  transport,  disposal processes  and use as  a
 fungicide.  Ando  and  Sayato (1984)  suggested  that  VCH  can  migrate  Into
 drinking  water from water  pipes  made  of polyvlnyl  chloride and  subsequently.
 react  with chlorine  present 1n  the  drinking  water, forming chloroacetalde-
 hyde:.   The detection of chloroacetalde as a result  of chlorlnatlon of VCM  In
-drinking  water,  however,  required the presence of much higher  concentrations
 of  both  VCM   and  chlorine  than  are  expected to  be  present  under  typical
 conditions.   Therefore, the formation of chloroacetaldehyde 1n  potable  water
 by  this  process  1s questionable.  Another possible  source  of chloroacetalde-
 hyde   1n  the   atmosphere  1s  formation  from reaction  of  1,3-d1chloropropene
 with  ozone and OH radicals  (Tuazon  et  al.,  1984).. 1,3-D1chloropropene  Is  a
 highly volatile  component  of widely used  Insectlddal  fumlgants  (Tuazon  et
 al.,  1984).
 0086d                                -8-                              01/21/88

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                             4.   AQUATIC  TOXICITY
4.1.   ACUTE TOXICITY
    Only  two studies  were  found  In  the  literature  concerning  the acute
aquatic   toxlclty   of    chloroacetaldehyde.   The   96-hour   1C    for   the
harpaetlcold  copepod,   NUocra  splnlpes.  was  reported  to   be  1.5  mg/8.
(Bengtsson and Tarkpea, 1983).  Exposure took place  In brackish water with a
salinity of  7 ppth.  No  signs of distress were observed In the sea  lamprey,
Petromyzon  marlnus. exposed to  5  mg  chloroacetaldehyde/a  for  24 hours
(Applegate et al.f  1957).
4.2.   CHRONIC EFFECTS
    Pertinent data   regarding  the effects  of  chronic exposure  of  aquatic
biota  to  chloroacetaldehyde  were  not  located  1n  the available  literature
cited 1n Appendix A.
4.3.   PLANT EFFECTS
    Pertinent' data  regarding the effects  resulting  from  exposure of  plants
to chlorbacetaldehyde were  not  located  1n the available literature  cited  1n
Appendix A.
4.4.   SUMHARY
    Little  Information  1s  available  regarding  the  toxldty  of  chloroacet-
aldehyde  to  aquatic organisms.   A  96-hour  LC,Q  of  1.5  mg  chloroacetalde-
hyde/si  was   reported  for  the   copepod,  NUocra   splnlpes   (Bengtsson   and
Tarkpea, 1983).   Sea lampreys,  however,  were unaffected by exposure  to 5  mg
chloroacetaldehyd«/l for  24 hours (Applegate et  al.,  1957).
0086d                               -9-                              01/21/88

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                             5.  PHARMACOKINETICS
5.1.   ABSORPTION
    Pertinent data  regarding  the absorption of  chloroacetaldehyde  following
either oral or  Inhalation exposure were not  located  1n  the  available  litera-
ture cited 1n Appendix A.
5.2.   DISTRIBUTION
    Pertinent data  regarding  the  distribution  of  chloroacetaldehyde were  not
located 1n the available literature dted  1n Appendix A.
5.3.   METABOLISM
    The metabolism  of chloroacetaldehyde has  not been studied  extensively.
Chloroacetaldehyde  has  been  found to be  a  metabolite of  a variety of  halo-
genated organic  compounds  (GuengeMch et  al.,  1980;  Gwlnner  et al.,  1983),
but only one study  (Green and  Hathway, 1977) was  found  regarding the  metabo-
lism of  chloroacetaldehyde  Itself.   An aqueous solution of  chloroacetalde-
hyde was  administered, by gavage  to  four  adult  AlderTy-Park  male  rats at  a
dose level of  50 mg/kg  (Green  and Hathway,  1977).  An unspecified number  of
control  animals was  also  used.   Urine  was  collected  and  separated  Into
fractions by anlon-exchange chromatography.  The 3N  acetic  add  fraction  was
analyzed by  GC-MS  and  mass  fragmentography for  N-acetyl-S-(2-hydroxyethyl)
cystelne.   The  3N HC1  fraction was analyzed by GC-MS for thlodlglycoUc  and
chloroacetlc   acids.  N-acetyl-S-(2-hydroxyethyl)  cystelne  and S-(carboxy-
methyl) cystelne were found  1n the urine of chloroacetaldehyde-treated  rats
and presumably  not  1n the  urine of control animals.  ThlodlglycoUc  add,  a
derivative of  S-(carboxymethyl)  cystelne, was  the  major  urinary metabolite
and accounted for 9.2X of the  administered chloroacetaldehyde  dose.
    A metabolic  scheme  proposed  by Green  and Hathaway (1977) Indicates  that
the first step  In  the metabolism  of  chloroacetaldehyde  1s  conjugation with
0086d                               -10-                              01/21/88

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glutathlone to yield  S-formylmethylglutath1one  (Figure 5-1).  Metabolism of
S-formylmethylglutath1one  can  then  proceed  along  two  alternate pathways.
One pathway Involving  further  degradation  and cleavage of the glutamate and
glyclne residues  from glutathlone results  1n  the  appearance'of  N-acetyl-S-
(2-hydroxy-ethyl) cystelne.  The  other  pathway Involving dehydrogenatlon of
S-formyl-methylglutath1one and  further  glutathlone cleavage  results  1n the
formation  of  S-(carboxymethyl)  cystelne.   Transam1nat1on followed by oxlda-
tlve decarboxylatlon of S-(carboxymethyl) cystelne leads to  formation of the
major  urinary  metabolite, thlodlglycoUc  add.
    Evidence  for  the  existence of two  separate pathways of  S-formylmethyl-
glutathlone metabolism comes from an experiment In which S-(2-hydroxyethyl)
cystelne  was  administered orally to a  separate  group  of  rats  (Green and
Hathway, 1977).  In this  group of rats,  the urinary yield of thlodlglycoUc
acid was 0.5% of the administered dose, whereas the urinary  yield of  thlodl-
glycoUc  acid was  9.2%  of  the  administered  dose  1n  chloroacetaldehyde-
treated   rats.    This    Indicates   that,    following   chloroacetaldehyde
administration,  the   formation   of   S-(carboxymethyl)  cystelne  (and  the
subsequent  formation  of   th1od1glyco!1c  acid) proceeds  by  a route  that 1s
Independent of the formation  of N-acetyl-S-(2-hydroxyethyl) cystelne.
5.4.   EXCRETION
    The only  Information  located regarding  excretion  of chloroacetaldehyde
and Its metabolites was that of Green and  Hathway  (1977).  The  three  urinary
metabolites observed   following   oral  administration  of chloroacetaldehyde
were  thlodlglycoUc  add,  S-(carboxymethyl)  cystelne   and N-acetyl-S-(2-
hydroxyethyl)   cystelne.   Information regarding other  routes of  elimination
was not located 1n the available literature.
0086d                               -11-                             03/30/88

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                        C1CHZ  -  C  - H
                           Ch1 oro*cetaldehyde
                                 •» Glutathione
C = 0
I
CHCHjS

NH
                        C  =  0
                        I
                        CH -  CHpSCHpCHO
                        I
                        NH
                        I
                      S-foriy)«
              OH
                                                 C  =  0
                                                 I
                                                 CHCHZ  S  CH2  C02H
                                                 NH
    COeH

    CHCH, SCH,CH,
    I          I
    NH(Qc)    OH
                                                 C0H
                                                       C0H
                                             S-Ccarbo>y«*thyl> cyctaiiw
                                                 COeH
                                                    -  CH2SCH2C02H
                                             C
                                             II
                                             0
                                                S(CHeC02H)2
                                               Thiodislycolic acid

                                 FIGURE  5-1
           Proposed Scheme for the Metabolism of Chloroacetaldehyde
                      Source:  Green and Hathway, 1977
0086d
                              •-12-
01/21/88

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5.5.   SUMMARY
    No pertinent  data  regarding the  absorption  and distribution of  chloro-
acetaldehyde were  located  In  the literature.  Metabolism and  excretion  data
were limited  to  one  study  (Green and Hathway, 1977),  1n which three  urinary
metabolites    (N-acetyl-S-(2-hydroxyethyl)     cystelne,     S-(carboxymethyl)
cystelne and  th1od1glyco!1c  add)  were  found following oral  administration
of chloroacetaldehyde to rats.
0086d                               -13-                             01/21/88

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                                  6.   EFFECTS
6.1.   SYSTEMIC TOXICITY
6.1.1.   Inhalation Exposures.
    6.1.1.1.   SUBCHRONIC — Rats  (20/sex),  guinea  pigs  (8/sex),  rabbits
(2/sex) and mice  (10  females) were exposed to  chloroacetaldehyde  at  1.6 ppm
(5.1  mg/m3)  7  hours/day,  5  days/week  for 6  months  (Dow  Chemical  Company,
1962).  There was  a   similar  number  of  air-exposed  and  unexposed  control
animals for  each  species.   Gross and  microscopic  examination and  observa-
tions  of   growth,-  mortality,  hematology   and  organ  weights   Indicated  that
chloroacetaldehyde exposure produced no adverse effects  on  the health  ,of any
of the species tested.
    6.1.1.2.   CHRONIC ~ Pertinent  data  regarding the  toxldty   of  chloro-
acetaldehyde  following  chronic  Inhalation  exposure were not  located  1n the
available  literature cited In Appendix A.
6.1.2.   Oral  Exposures.
    6.1.2.1,   SUBCHRONIC — Pertinent  data   regarding   the  toxldty   of
chloroacetaldehyde  following  subchronlc  oral  exposure  were  not   located  1n
the available literature dted 1n Appendix A.
    6.1.2.2.   CHRONIC — One  study  of  the toxldty  of  chloroacetaldehyde
following  chronic oral administration was  found  1n  the  available  literature.
In  this  study  (Van  Duuren  et  al.,  1979),   HarlCR  Swiss  mice  were  given
chloroacetaldehyde  In  water  by gavage  at  a dose of  0.25 mg chloroacetalde-
hyde/mouse/week. •" The study  was  conducted  over  the lifetime of the  mice
                 '.
(<636 days).   The  mortality rate of the  chloroacetaldehyde-treated mice did
not differ  from that of untreated controls.  No other  details were provided.
6.1.3.   Other Relevant  Information.   Rats (5/sex),  guinea pigs   (5/sex), 5
female mice  and  1  female  rabbit were  exposed by  Inhalation to  5   ppm  of


0086d                               -14-                             01/21/88

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chloroacetaldehyde 7 hours/day,  5 days/week, for a  total  of 8 exposures  1n
10  days  (Dow  Chemical  Company,  1962).   There  were  similar   numbers   of
unexposed controls.  Exposed  animals  exhibited  slight eye and nasal  Irrita-
tion.   The  growth of  the  male  rats  was slightly depressed  and  the  female
rabbit  exhibited  central lobular  fatty  degeneration  of the liver.  No  other
adverse  effects  related  to chloroacetaldehyde  exposure  were observed.   The
growth  of  the other exposed  animal  groups was  the  same  as controls,  organ
weight  and gross  pathology  data  were  negative,  and  there was no  microscopic
evidence of adverse effects  In tissues.
    A subchronlc  toxldty  study  of chloroacetaldehyde was conducted  In male
Sprague-Dawley rats by administering a 0.5% aqueous  solution of the compound
Intraperltoneally  3  times/week  for 12  weeks  (Lawrence et  a!.,   1972).   The
dose  levels  used  (calculated  as pure  chloroacetaldehyde)  were   0, 0.00032,
0.0008,  0.0016  and 0.0032  mi chloroacetaldehyde/kg.   There  were  12  rats  In
all groups except for  the  highest dose  group,  which had 8.  Liver  function
tests  (I.e.,  sulfobromophthaleln  excretion),   organ weight  determinations,
and hlstologlcal  and hematologlcal examinations  were performed.   .The  highest
dose  level  (0.0032 ml/kg)  caused death  In  5/8  rats during  the course  of
the  study.   The  two highest  dose levels  (0.0016  and 0.0032 ml  chloroacet-
aldehyde/kg)   were  associated  with   the  production  of   a   focal,   chronic
bronchopneumonla,  Increases  In  segmented  neutrophlls  and  decreases  1n  both
erythrocytes   and  lymphocytes.   There  was  also  a  significant   decrease  1n
hemoglobin at  the 0.0032 ml/kg  dose  level.  No hematologlcal  or  pulmonary
                 '.
effects  were  associated  with  a  dose  of 0.0008  ml  chloroacetaldehyde/kg.
The results of liver function  tests were unremarkable.
    The  acute toxldty of chloroacetaldehyde was also Investigated  following
oral  administration  of  the  compound to  rats   and  mice  (Lawrence  et  al.,


0086d                               -15-                             01/21/88

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 1972).   The  oral  LD50  value  1n  mice was  0.0692  mi  chloroacetaldehyde/kg
 (or  82.3  mg/kg,  assuming a specific  gravity  of  1.19 for chloroacetaldehyde)
 and  1n  rats,  the oral L05Q was  0.0751 ml/kg (or 89.3 mg/kg).
     Chloroacetaldehyde  administration,  either  by  Intraperlto'neal  Injection
 or by  Inhalation  exposure,  Increased  the  pentobarbltal  sleeping time In mice
 (Lawrence  et  al.,  1972).   Inhalation of chloroacetaldehyde  at  a concentra-
 tion  of  0.042  mg/m3  for  31  seconds on  3  consecutive  days  before  pento-
.barbUal  administration  resulted 1n a significant  Increase  1n sleeping time
 as measured by the  duration  of loss of the  righting  reflex.  Similarly,  an
 Increase  In pentobarbltal-lnduced  sleeping  time  was noted  1n mlee Injected
 IntrapeMtoneally  with  0.00061  ml  chloroacetaldehyde/kg  for 3  days  before
 pentobarbltal  administration.   These results were  subsequently  shown  not  to
 be an artifact of chloroacetaldehyde-lnduced hepatic necrosis.
     In  in  vitro  experimentation,   chloroacetaldehyde   was   found  to  cause
 hemolysls   1n  rabbit erythrocyte   preparations  and  cytotoxldty  In  murlne
 L-cell  preparations  (Lawrence et al., 1972).
 6.2.    CARCINOGENICITY
 6.2.1.    Inhalation.   Pertinent   data   regarding   the   cardnogenlcHy   of
 chloroacetaldehyde  following  Inhalation  exposure  were   not  located  1n it he
 available literature cited 1n Appendix A.
 6.2.2.   Oral.   One  study was located  1n  the  literature  regarding the
 carclnogenlclty  of   chloroacetaldehyde following  oral  administration  of  the
 compound  with ml.ce.  Ha:ICR  Swiss  mice  (30  males and  30  females) received
 weekly  oral doses  of  chloroacetaldehyde (0.25 mg chloroacetaldehyde/mouse/
 week)  in  water  (Van  Duuren  et  al.,  1979).  The mice  were  treated  with
 chloroacetaldehyde  until   they  were  moribund  or  found   dead.   The time  of
0086d                               -16-                             03/30/88

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death of  the  last mouse was  636  days.   Control  animals (100 females  and  60
males)  received  no  chloroacetaldehyde.   In  addition,  a  positive  control
group received B-prop1olactone.
    Following  treatment,  the stomach,  liver and  kidneys  were  analyzed  for
tumors.   The  results  Indicated  that  the  Incidence of forestomach  tumors  1n
chloroacetaldehyde-treated  mice   were   not  significantly  different   from
untreated controls  (Table 6-1).   In  addition,  none  of  the tumors  found  In
the chloroacetaldehyde-treated  mice  were squamous carcinomas.  Mice treated
with  3-prop1olactone,   however,   had  significantly   (p<0.0005)   Increased
Incidences  of  both   total   forestomach   tumors   and  squamous   carcinomas.
B-Prop1olactone-treated mice  also experienced  decreased longevity,  whereas
the  rate of   mortality  was  not   adversely affected by  chloroacetaldehyde
treatment.
6.2.3.   Other  Relevant  Information.   Several  studies  have  been  performed
to determine  whether  chloroacetaldehyde  produces   tumors 1n  the skin follow-
ing topical or subcutaneous application;   Chloroacetaldehyde  (T.O mg/mouse)
dissolved 1n  0.1  ma acetone was  applied  to the shaved  dorsal surface  of  30
female  Ha:ICR  Swiss  mice  3  times/week  for  83  weeks  (Van  Duuren  et  al.,
1979).   Control  groups  consisted  of  untreated   and acetone-treated  mice.
Following treatment,  skin,  liver,  stomach and kidney  tissue were observed
for pathology.  No  skin  paplllomas were  observed  1n  the chloroacetaldehyde-
treated   mice   and the  Incidence  of  remote  tumors   was  not  significantly
different from controls.
    Van   Duuren  et al.  (1979) also  studied the possible skin  tumor1gen1dty
of chloroacetaldehyde  by  administering the compound  1n  water  subcutaneously
and subchronlcally  to  30 female  Ha:ICR  Swiss  mice (0.25 mg chloroacetalde-
hyde/mouse/week for 90 weeks).  As a  positive  control, 30  mice  received 0.30


0086d                               -17-                             01/21/88

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                                   TABLE  6-1

          Weekly  Intragastrlc Administration  of an Aqueous  Solution
                  of  Chloroacetaldehyde to  Ha:ICR  Swiss Mice:
                       Incidence of Forestomach Tumors3
Sex
M
F
M
F
H
F
M
F
Ooseb
(mg/mouse)
0
0
0.25
0.25
0
0
0.25
0.25
Duration of
Treatment0**1
(days)
636
649
636
630
636
649
636
630
Tumor Type
all
all
all
all
squamous cell
carcinoma
squamous cell
carcinoma
squamous cell
carcinoma
. squamous cell •
Tumor
Incidence
8/60
5/100
1/30,
3/30
1/60
0/100
0/30
0/30
Strengths of Study:
Weakness of Study:
                                               carcinoma
         QUALITY  OF  EVIDENCE

Lifetime exposure  by relevant  route;  large numbers  of
control animals;  positive controls used.

Only one,  nontoxlc  dose  given;  weekly  administration;
limited number of endpolnts explored.
Overall Adequacy:    Inadequate
aSource: Van Duuren et al., 1979

^Compound administered once a week

cM1ce treated until moribund or found dead

^Duration of study equal to duration of treatment
0086d
               -18-
01/21/88

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mg B-proplolactone on the same  treatment  schedule.   Other  (negative)  control
groups  received  nothing  (100  mice),  water  (30  mice)  or  trloctanoln  (30
mice).   There  were  no  observed  differences   between   chloroacetaldehyde-
treated  mice and  negative  control  groups  with  respect  to  local  sarcoma
Incidence.   The  positive   control,   B-proplolactone-treated  mice,   had   a
statistically significant (p<0.0005)  Increase In tumor  Incidence.
    Several  studies  also   Indicate  that  chloroacetaldehyde  1s  unable  to
function as  an  Initiator of skin paplllomas  1n  Initiation-promotion  tumorl-
genesls  experiments.   Chloroacetaldehyde  (1.0 ml/mouse)  was  applied  1n  0.1
ml acetone  to  the  shaved backs of 30  female Swiss mice (Van Duuren  et  al.,
1979).   Chloroacetaldehyde Initiation was followed 14  days later  by applica-
tion  of  2.5  yg  of  the tumor  promoter   PMA  In 0.1  ml  acetone.   Promotion
with  PMA was continued 3 times/week for  ~60 weeks.   Positive controls  were
given  0.020  mg  DMBA as  an  Initiator,  whereas negative  controls  received
repeated  exposure  to the  promoter  at  dose  levels of 0.0025  (120 mice)  or
0.0050 (90  mice) mg  PMA/mouse.   Paplllomas  were  found  .1n 3/30  chloroacet-
aldehyde-lnltlated   mice, which  was  not  significantly  different  from  the
papHloma Incidence observed In the PMA-treated  controls  (9/120  and 6/90 for
the  respective  PMA  doses).  The  papllloma  Incidence  1n  DMBA-1n1t1ated  mice
(29/30)  was  significantly higher  (p<0.0005)  than the  tumor Incidence  In PMA
controls.
    Initiation of  skin  tumoMgenesIs  1n mice  using  chloroacetaldehyde  was
also  studied by  Zajdela  et al.  (1980).   Male XVIInc/Z  mice (groups of 20-28)
received  single  applications  of  chloroacetaldehyde  dissolved  In  80  yl
acetone  on  their shaved backs  at dose  levels  of 0.05,  0.1,  1.0  or  2.5  mg
chloroacetaldehyde/mouse.   Chloroacetaldehyde  Initiation  was   followed  by
promotion with TPA  3 times/week for  42 weeks.   The  occurrence  of paplllomas

0086d                               -19-                             03/30/88

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and carcinomas was observed  1n  the  mice  for  ~84 weeks.   The positive control
group  consisted  of  45  mice Initiated with  50  yg  DMBA,  followed  by  promo-
tion with croton oil  3  times/week  for  12 weeks.  Negative controls consisted
of 28 mice  receiving  TPA  (3  times/week  for  42 weeks) without chloroacetalde-
hyde  Initiation.   Survival  was not affected  by chloroacetaldehyde treatment
and was similar  to the  survival  rate  of  TPA-treated negative controls  (22/28
TPA controls  lived  for 84 weeks).   In  contrast, only  7/45  positive control
(DMBA-treated) mice   survived  the   average  observation period  of  50  weeks.
The  Incidence of  paplllomas  1n  the  chloroacetaldehyde-1n1t1ated mice  was
neither dose-related  nor  statistically different from the negative controls,
and  none  of  the  chloroacetaldehyde-1n1t1ated  mice   had  skin  carcinomas.
Persistent  paplllomas  and skin carcinomas  were observed, however,  1n  37/45
mice treated with DHBA-croton oil.
    Lawrence  et  al.  (1972)   Injected chloroacetaldehyde IntraperUoneally In
Sprague-Dawley  rats   (0.0016 or 0.0032  ma  chloroacetaldehyde/kg)  3  times/
week  for  12  weeks.    The authors  reported  "These  changes  Included  focal
chronic  bronchopneumonla  and  certain  changes  of  respiratory  epithelium
suggesslve  of a  premallgnant  condition",  but  this  1s  not supported  by  any
data.
    No carclnogenldty  data  from human occupational  exposure  were located 1n
the available literature  nor were  ep1dem1olog1cal  studies  located regarding
possible carcinogenic effects related to chloroacetaldehyde exposure.
6.3.   MUTAGENICJTY
    Chloroacetaldehyde  has  been  tested  for mutagenlclty  In  both prokaryotes
and eukaryotes using a variety of  assays  (Table 6-2).   Forward and reverse
mutation  assays  1n  prokaryotes  have  been  positive both  with  and  without
metabolic activation  of chloroacetaldehyde (B1gnam1 et al.,  1980;  Rannug et
al..  1976;  McCann  et  al.,  1975;  Malavellle  et al., 1975; Phillips et  al.,

0086d                                -20-                             07/05/88

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                                                              Hutagentclty Testing of Chloracetaldehyde
o
CO
IV

I
o
C*
Assay
Reverse
nutation
Reverse
nutation
Reverse
nutation
Reverse
•utatton
Reverse
mutation
Reverse
nutation
Forward
mutation
DMA repair
Indicator/
Organism
Salmonella
typhlmurlum
TA98. TA100
TA1535. TA1537. .
TA1S38
S. typhlimirlum
TA98. TA100
TA1S3S. TA1S37,
TA1538
S. tvphlmurlum
TA100. TA1535
S. typhlnurlum
TA1S35
S. typhlnurlum
TA1530
Bacillus
subtllts
llv 82.
lev A169
markers
B. subtllls
$105
strains G68
Gb7075
Escherlchla
coll pol A*
pol A*
Compound
and/or
Purity
NR
45X aqueous
solution
45X aqueous
solution
aqueous
solution
SOX aqueous
solution
SOX aqueous
solution
SOX aqueous
solution
NR
Application Concentration Activating
or Dose System
plate -2-28 yg/plate -S-9
Incorporation
plate 3-60xlO~» ±S-9
Incorporation pi/plate
spot test 3-30 rag/plate »S-9
plate 0.1-1. 5, nN -S-9
Incorporation
plate 0.4-40 *S-9
Incorporation iinol/njt
plate Incorpo- 0.2S-S oH NR
ration (DNA
transformation
mixture)
plate 1-4 a* NR
Incorporation
NR 10 »t NR
Response Comment
<• Highly mutagenlc to
TA100, weakly muta-
genlc to TA1S3S
»A Positive In TA100;
addition of S-9
decreased response.
*/» Positive In TA100;
addition of S-9
decreased response.
*• Dose-dependent In-
creases In revertants
at doses which were
originally cytotoxlc
f/f Highly cytotoxlc at
the highest concen-
tration
* Dose -dependent In-
crease In mutation
activity with base
pair, but not with
frameshlft, mutation
strain
t Mutagenlc to both
normal and repair-
deficient host cell
reactivation strains
t Preferential Inhibi-
tion of pol A*
growth
Reference
HcCann et al. .
1975
Blgnaml
et al.. 1980
Blgnaml
et al.. 1980
Rannug et al..
1976
Nalavetlle
et al.. 197S
Phillips
et al.. 1980
Garro and
Phillips. 1980
Rosenkranz.
1977
CO
00

-------
o
0
CO
c*
a.
Assay
Forward
mutation
Reverse
mutation
Reverse
mutation
£J Forward
i mutation
Forward
mutation
Gene
conversion
Polycls-
tronlc
mutation
Single
point
mutation
ON Forward
J^ mutation

Indicator/
Organism
E. coll
Sd-4
E. coll
K12 All
K12 A23
K12 A46
Streptomyces
coellcolor
A3(2) strain
his Al
S. coellcolor
A3(2) strain
his Al
Schlzosac-
charomyccs
pombe PI
Saccharomyces
cerevlslae D4
Asperqlllus
nldulans 35
A. nldulans 35
CHO V79 cells

Compound
and/or
Purity
dissolved
" In '0.2 M
EtOH
aqueous
solution
45X aqueous
solution
45X aqueous
solution
SOX aqueous
solution
SOX aqueous
solution
45X aqueous
solution
45X aqueous
solution
SOX aqueous
solution
TABLE 6-2 (cont
Application Concentration
or Dose
liquid -0.1-4 mM
suspension
liquid 10-200 mM
suspension
plate Incorpo- 0.25-1.0 wt
ration and
spot test
plate Incorpo- 0.25-10 ut
ration and
spot test
liquid 0.78-6.25 mM
suspension
liquid 3.1-12.5 mM
suspension
plate 20-40 pt
Incorporation
spot test 5-20 pt
liquid 1.6-12.8 pM
cultures
''
Activating Response Comment
System
NR * Dose-dependent muta-
tion to streptomycin
nondependence
none * Dose-response;
Reversion frequency
greatest near 100X
cytotoxlclty
none «• Strongly mutagenlc
only In spot test
none * Mutagenlc only In
spot test
^S-9 *A Dose-response
±S-9 i Weak Increase In
mutation frequency
at cytolethal con-
centrations
none <• Nutagenlclty not
replicated In spot
test
none «• ' Stronger Induction of
8-azoguanlne resis-
tance In liquid test
NR *

Reference
Hussaln and
Osterraan-
Golkar. 1984
Perrard. 1985
Blgnaml
et al.. 1980
Blgnaml
et al.. 1980
Lorprleno
et al.. 1977
Lorprleno
et al.. 1977
Blgnaml
et al.. 1980
Blgnaml
et al.. 1980
Huberman
et al.. 1975
GO
00
NR = Not reported

-------
1980; Garro  and  Phillips,  1980;  Hussaln and Osterman-Golkar,  1984;  Perrard,
1985).   In  eukaryotes   (yeast),  chloroacetaldehyde  has  been  demonstrated
overall  to  be mutagenlc  1n  a number of mutation  assays (LorpMeno et  al.,
1977;  B1gnam1  et  al.,   1980).   Chloroacetaldehyde  has  also  proven  to  be
mutagenlc In mammalian cells  (Huberman et al.,  1975).
6.4.   TERATOGENICITY
    Pertinent  data  regarding the  teratogenldty  of chloroacetaldehyde  were
not located 1n the available  literature dted 1n Appendix A.
6.5.   OTHER REPRODUCTIVE EFFECTS
    Pertinent  data  regarding other  reproductive  effects of  chloroacetalde-
hyde were not located 1n the  available literature dted  1n Appendix A.
6.6.   SUMMARY
    Few  studies  regarding   the   systemic   toxldty  of  chloroacetaldehyde
following administration of  the  compound by relevant routes  (I.e.,  oral  and
Inhalation)  were located  In the  available literature.   Exposure of  rats,
guinea pigs,  rabbits  and mice to  chloroacetaldehyde  (5.1 mg/m3)  by  Inhala-
tion  7 hours/day, 5  days/week for  6 months  had no  adverse  health  effects  on
any of the  animal  species  tested (Dow Chemical Company,  1962).  Weekly oral
administration of  chloroacetaldehyde  to  mice  (0.25 mg  chloroacetaldehyde/
mouse/week) over an entire lifetime was without  effect  on the  mortality rate
(Van  Duuren  et  al.,  1979).   The  oral   LD5Q  of  chloroacetaldehyde  was
reported to  be -82  mg/kg In  mice and 89-103 mg/kg  1n rats  (Lawrence  et al.,
1972).           f
    Intraperltoneal  doses  of chloroacetaldehyde of  0.0016 and  0.0032  ma/kg
given  to  rats  were  associated  with  the   production  of  a  focal,  chronic,
bronchopneumonla, Increases  In  segmented neutrophlls and decreases  1n both
erythrocytes and  lymphocytes (Lawrence et  al.,  1972).    No  hematologlcal  or

0086d                               -23-                             06/24/88

-------
pulmonary effects  were  associated with a  dose of 0.0008  ml  chloroacetalde-
hyde/kg.  Chloroacetaldehyde  Injected IntraperHoneally  1n  rats  (0.0016  or
0.0032  ml/kg)  3 times/week for  12  weeks  was reported to  produce  changes  In
the  respiratory  epithelium, suggestive of  a  premallgnant  condition (Lawrence
et al.. 1972).
    Chloroacetaldehyde has  been  shown to  Increase the  pentobarbHal-lnduced
sleeping time  of  mice (Lawrence  et al.,  1972) and to cause In  vitro  hemoly-
s1s  In rabbit  erythrocyte preparations  and  cytotoxlclty  1n  murlne  L-cell
preparations.
    Oral weekly  administration of  Chloroacetaldehyde  to mice  (0.25 mg/mouse/
week)  for the  llfespan  did not Increase  the  Incidence of  forestomach tumors
over that observed In untreated controls  (Van Duuren  et  al.,  1979).
    Chloroacetaldehyde was  negative  as  a  whole carcinogen  or as  a  tumor
Initiator when  tested on  the  skin of mice (Van  Duuren et  al.,  1979;  Zajdela
et al., 1980).
    Cardnogenldty data resulting  from human  occupational exposure were  not
located  1n   the  available  literature;  also  there  were  no  ep1dem1olog1cal
studies regarding  possible  carcinogenic  effects associated with exposure  to
Chloroacetaldehyde.
    Chloroacetaldehyde has been demonstrated to  be mutagenlc 1n  a  variety  of
assays  using  both  prokaryotes  and  eukaryotes  with and  without  metabolic
activation (B1gnam1 et al., 1980;  Rannug  et al., 1976; McCann  et  al.,  1975;
Malavellle et  al..,  1975;  Phillips  et al.,  1980;  Garro  and Phillips,  1980;
Hussaln and  Osterman-Golkar,  1984;  Perrard, 1985;  LorpMeno  et  al.,  1977;
Huberman et  al., 1975; Rosenkranz,  1977).
    Pertinent  data   regarding   the   teratogenlcHy   or   other   reproductive
effects associated  with  exposure  to  Chloroacetaldehyde  were  not  located  1n
the available literature dted In Appendix  A.

0086d                               -24-                             06/24/88

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                     7.   EXISTING  GUIDELINES  AND  STANDARDS
7.1.   HUMAN
    Because  of  chloroacetaldehyde's  severely Irritating  nature, a  celling
limit  of  1  ppm  (~3  mg/m3)  has  been  recommended  for  human  occupational
exposure  (ACGIH,  1986).   Continuous  exposure to  this  level  of  chloroacet-
aldehyde  was  discouraged, however,  because  of  the  compound's  demonstrated
mutagenlc activity (ACGIH, 1986).  The celling limit  of  1  ppm was adopted by
the ACGIH  (1987).  The  OSHA  (1985) permissible  exposure limit  1s  also  1  ppm
for chloroacetaldehyde.
7.2.   AQUATIC
    Guidelines  and  standards   for  the  protection   of  aquatic  biota  from
chloroacetaldehyde were not  located 1n  the available  literature cited  1n
Appendix A.
0086d                               -25-                             06/24/88

-------
                              8.   RISK  ASSESSMENT
8.1.   CARCINOGENICITY
8.1.1.   Inhalation.   Pertinent   data  regarding  the  cardnogenldty   of
chloroacetaldehyde  following  Inhalation  exposure were  not  located  1n  the
available literature cited 1n Appendix A.
8.1.2.   Oral..  The only  study found  In the available  literature  concerning
the carclnogenldty of  chloroacetaldehyde  following oral  administration  was
that  of  Van  Duuren  et al.  (1979),  1n which  30  male  and 30 female Ha:ICR
Swiss mice  receiving  0.25  mg chloroacetaldehyde/mouse  once a week  for  up to
636 days did  not  exhibit  an  Increased  Incidence  of  forestomach  total tumors
or squamous carcinomas compared with that of negative  controls.   Thirty mice
of each  sex receiving a  positive control  substance,  B-prop1olactone,  on  a
weekly  basis  had   statistically  significant  (p<0.0005)   Increases  In   both
total forestomach  tumors  and squamous  carcinomas.  Because of an  Inadequate
number of mice  1n  each  group and the use of only one  dose level,  this  study
was  judged  Inadequate  for   assessment  of  the  carcinogenic  potential  of
chloroacetaldehyde.                               ;
8.1.3.   Other  Routes.  Several  studies (Van  Duuren et  al.,  1979;  Zajdela
et al.,  1980)  have demonstrated  that  chloroacetaldehyde   1s not  tumorlgenlc
to the  skin following repeated  exposure  either  by  the topical  or  subcuta-
neous routes.   These  same studies also demonstrated that  chloroacetaldehyde
does  not  function  as  an   Initiator  when  used  1n Initiation-promotion   skin
tumor1genes1s  experiments.
8.1.4.   Weight   of Evidence.   Because  there  are   no data  regarding   the
carclnogenldty  of  chloroacetaldehyde  1n humans  and  because the only  study
on the carclnogenldty of  chloroacetaldehyde 1n mice following oral  exposure
0086d                               -26-                             06/24/88

-------
(Van Duuren  et  al.,  1979)  was  judged  Inadequate  for  assessment of  chloro-
acetaldehyde carcinogenic potential, this  compound  1s  placed 1n EPA  Group  0
(U.S. EPA, 1986b) - not classifiable as  to human  carclnogenlcHy.
8.1.5.    Quantitative Risk  Estimates.   The lack  of adequate studies on  the
carclnogenlcHy of  chloroacetaldehyde  following  exposure either by  the  oral
or Inhalation route precludes  the  derivation  of quantitative  risk estimates.
8.2.   SYSTEMIC TOXICITY
8.2.1.    Inhalation Exposures.
    8.2.1.1.   LESS  THAN  LIFETIME  EXPOSURES  (SUBCHRONIC) -- Rats,   rabbits,
guinea   pigs  and  mice  were  .exposed  to  1.6  ppm  chloroacetaldehyde   (5.1
mg/m3)  by  Inhalation 7  hours/day,   5  days/week  for 6  months  (Dow  Chemical
Company,   1962).   There  were   no  adverse  effects on  growth,  mortality,
hematology or organ weights.  H1stolog1cal analyses  were also unremarkable.
    The  study  by  Dow  Chemical  Company  (1962)  was   the  only Inhalation
toxldty study  of chloroacetaldehyde that was of  sufficient duration to be
classified as either  subchronlc or  chronic.  A number of  animal  species  were
used 1n  this  study but the numbers of animals  In  each group were  low.  In
addition,   there   was   only    one   exposure   level    In   this   study   of
chloroacetaldehyde  toxldty  and  this  exposure  level   proved  to be  a  NOEL
(I.e.,  no dose  response  data  are  available).  Even though RfDs  were derived
using  this  study  (U.S.  EPA,  1986c,  1987c),  revaluation of  the  data  base
under  the  present  RfD  guidelines  has  determined  1t   to  be Inadequate  for
derivation of RfQs.
    8.2.1.2.   CHRONIC EXPOSURES  — Data  regarding the  toxldty of  chloro-
acetaldehyde  following  chronic  Inhalation exposure were  not located 1n  the
available literature.
0086d                               -27-                             07/05/88

-------
8.2.2.   Oral Exposures.
    8.2.2.1.   LESS  THAN LIFETIME  EXPOSURES  (SUBCHRONIC)  — There  were  no
data  located  1n  the literature regarding  the  toxldty  of chloroacetaldehyde
following subchronlc oral exposure.
    8.2.2.2.   CHRONIC  EXPOSURES — A  chronic  oral  study of  chloroacetalde-
hyde  toxldty  Indicated that  the longevity of 30 male  and 30  female Ha:ICR
Swiss mice  was unaffected  by  exposure to 0.25 mg  chloroacetaldehyde/mouse/
week  over  an entire   lifetime   (Van  Duuren  et  al.,   1979).   This  dosing
schedule  (I.e., one  dose/week)  was suggestive of repeated  acute  rather  than
chronic exposure and-thls  study was therefore deemed Inadequate  for  chronic
toxldty risk assessment.
0086d                               -28-                             07/05/88

-------
                          9.  REPORTABLE QUANTITIES
9.1.   BASED ON SYSTEMIC TOXICITY
    The systemic toxldty of chloroacetaldehyde  was  discussed  In  Section  6.1.
    Because  the chloroacetaldehyde  exposure  level  used  In  the  subchronlc
Inhalation  toxldty  study  by  Dow Chemical Company (1962) did  not  produce
observable  toxldty,  the  data   are  Insufficient  for  derivation  of  an  RQ
(Table 9-1).
9.2.   BASED ON CARCINOGENICITY
    Studies   regarding   the  carclnogenldty   of   chloroacetaldehyde   were
reviewed 1n Section 6.2. and summarized  In Table 6-1.  The only  study of the
carcinogenic  effects of  chloroacetaldehyde  following exposure by  a  relevant
route  (I.e.,  oral  or  Inhalation) was  that  by Van  Duuren  et  al.  (1979),  1n
which  30  male and  30  female mice given an oral  dose of  chloroacetaldehyde
(0.25 mg chloroacetaldehyde/mouse/week) over the course of  a  lifetime had  an
Incidence of  forestomach  tumors  and  squamous  carcinomas  that did  not exceed
that of negative controls.  Because of the small number  of mice  used and the
use of only one chloroacetaldehyde dose  level,  this  study  was  not  considered
adequate to assess  the  carclnogenldty  of chloroacetaldehyde.
    Van Duuren  et  al.   (1979) and Zajdela  et al.  (1980)  also reported  that
chloroacetaldehyde  was  unable to  function as a  skin  tumoMgen  either follow-
ing repeated  exposure to  the compound  Itself  or by  using  chloroacetaldehyde
as  an  Initiator   followed   by   treatment   with  several   promoting  agents.
Lawrence et al. (1972),  however,  reported  changes  suggestive of a premallg-
nant condition  1n  the  respiratory epithelium  of  rats Injected  1ntraper1to-
neally  with  chloroacetaldehyde  (0.0016  or 0.0032  mi/kg)  3  times/week  for
12 weeks.
0086d                               -29-                             07/05/88

-------
                                   TABLE  9-1
                              Chloroacetaldehyde
           Minimum Effective  Dose  (MED) and  Reportable  Quantity  (RQ)


Route:
Dose:
Effect:
Reference:
RVd:
RVe:                                               :    ^
Composite Score:
RQ:                     Data are not sufficient for deriving an RQ.
0086d                               -30-                             07/05/88

-------
    Structurally related  compounds,  such  as  formaldehyde and  acetaldehyde,
are known  to  be  carcinogenic.   Unlike these related compounds,  there  are  no
data available to  show  carcinogenic  activity  of  chloroacetaldehyde.   Chloro-
acetaldehyde  1s  mutagenlc  and  a  presumed  Intermediate In*  the  metabolic
pathway  of   ethylenedlchlorlde.    Because  Information  on   the   potential
cardnogen1c1ty  of  chloroacetaldehyde   1s   Inadequate,   there   being  only
positive short term data  Indicating  potential  the  overall evidence Indicates
that chloroacetaldehyde  should be classified  1n we1ght-of-ev1dence Group  D
because  of   Inadequate   data   (U.S.   EPA,   1986b).    Accordingly,  Group   D
compounds cannot be ranked on the CERCLA hazard ranking scheme.
0086d                               -31-                             07/05/88

-------
                                10.   REFERENCES


ACGIH  (American  Conference  of Governmental  Industrial  Hyg1en1sts).   1981.
Documentation of  the  Threshold Limit Values, 4th  ed.  Supplemental  Documen-
tation.  Cincinnati, OH.  p. 82.


ACGIH  (American  Conference  of Governmental  Industrial  Hyg1en1sts).   1986.
Documentation of the Threshold  Limit  Values  and  Biological  Exposure  Indices,
5th ed.  Cincinnati, OH.  p. 120.


ACGIH  (American  Conference  of Governmental  Industrial  Hyg1en1sts).   1987.
TLVs - Threshold limit  values  and biological  exposure  Indices  for  1987-1988.
Cincinnati, OH.   p. 14.


Ando,  M.  and Y.  Sayato.   1984.   Studies on  vinyl  chloride migrating  Into
drinking  water  from  pbly(v1nyl chloride)  pipe and  reaction  between  vinyl
chloride and chlorine.   Water Res.   18(3): 315-318.


Applegate,  V.C.,   J.H.  Howell,  A.E.  Hall,  Jr.   and  M.A.   Smith.    1957.
Toxldty of  4346  Chemicals to  Larval  Lampreys  and Fishes.  Spec. Sd.  Rep.
F1sh.  No.  207,  F1sh  and  Wildlife  Service,   USDI,  Washington,  DC.   p.  157.
(Cited 1n U.S. EPA, 1986c)

                ;
Atkinson, R.  1985.   Kinetics  and mechanisms  of the gas phase reactions  of
the  hydroxyl  radical   with  organic   compounds  under atmospheric  conditions.
Chem. Rev.  85:  69-201.
0086d                               -32-                             07/05/88

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Bengstsson,  B.E. and M.  Tarkpea.   1983.   The acute aquatic toxlclty of some
substances carried by ships.   Mar.  Pollut.  Bull.   14(6): 213-214.

B1gnam1, M., G. Contl,  L.  Contl,  et al.   1980.  MutagenlcHy of halogenated
aliphatic hydrocarbons  In  Salmonella  typhlmuMum.  Streptomyces  coellcolor
and Asper1q1l1us nldulans.   Chem.  B1ol. Interact.   30: 9-23.

CMR  (Chemical  Marketing Reporter).  1986.   OPD  Chemical  Buyers  Directory,
74th annual  ed., H.  Van, Ed.   Schnell Publishing Co., New York, NY.

Dow  Chemical  Company.   1962.   Toxldty  of  chloroacetaldehyde determined  on
experimental animals (unpublished report).   Biochemical Research Laboratory,
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E1senre1ch,  S.J.,  B.B.  Looney  and  J.D.  Thornton.   1981.   Airborne organic
contaminants of  the Gireat; Lakes ecosystem.   Environ.  Sd. Techno!.  15(1):
30-38.

Garro, A.J.  and  R.A.  Phillips.   1980.   Detection  of mutagen-lnduced lesions
1n  Isolated  DNA by marker  rescue  of Bacillus  subtnils  phase  105.  Mutat.
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Green,  T.  and  U.E. Hathway.    1977.   The  chemistry  and  biogenesis  of  the
S-conta1n1ng metabolites  of  vinyl  chloride  In  rats.   Chem. B1ol.  Interact.
17(2): 137-150.
0086d                               -33-                            07/05/88

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Guengerlch,  P.P.,  W.M.  Crawford,  J.Y. Domoradzkl,  T.L.  MacDonald and  P.G.
Watanabe.   1980.   Iri  vitro  activation of  1,2-d1chloroethane by  mlcrosomal
and  cytosollc  enzymes.  Toxlcol. Appl.  Pharmacol.   55:  303-317.   (CHed  In
U.S. EPA, 1986c)

Gwlnner,  L.M.,  R.J.  La1b,  J.G. Fllser  and H.M.  Bolt.   1983.  Evidence  of
chloroethylene oxide  being  the reactive metabolite of vinyl  chloride  toward
DNA:  Comparative  studies  with  2,2-d1chlorod1ethyl  ether.   Cardnogen1s1s.
4(11): 1483-1486.   (CHed 1n U.S. EPA, 1986c)

Hawley,  G.G.   1981.   The  Condensed  Chemical   Dictionary.   Van Nostrand
Relnhold Co., New York.  p.  232.

Mine, J.  and  P.K.  Mookerjee.   1975.   The Intrinsic hydrophlllc  character  of
organic  compounds.   Correlations 1n  terms  of  structural  contributions.   J.
Org. Chem.  40(3);:  292-298.

HSDB  (Hazardous  Substance  Data).  1987.  Report  No.  2521.   On-Llne  October
19, 1987.  CAS No.  302-17-0.

Huberman, E., H. Bartsch and L.  Sachs.  1975.  Mutation  Induction  In  Chinese
hamster  V79  cells   by  two  vinyl chloride  metabolites,  chloroethylene  oxide
and  2-chloroacetaldehyde.   Int. 0.  Cancer.   16:  639-644.   (CHed 1n  U.S.
EPA, 1986c)
0086d                               -34-                             07/05/88

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Hussaln, S. and  S.  Osterman-Golkar.   1984.  Dose-response relationships for
mutations  Induced  1n E_.  coll  by some  model compounds.  WHh  an addendum:
Reaction kinetics 1n  water  of  chloroethylene oxide, chloroacetaldehyde, and
chloroacetone.   HeredHas.   101(1): 57-68.

Jaber,  H.M.,  W.R.  Mabey,   A.T.  Lu1, et  al.   1984.   Data  Acquisition for
Environmental  Transport  and Fate Screening.  SRI Intl., Menlo Park, CA.  EPA
600/6-84/009.   NTIS  PB84-243906.   p.  46.

Lawrence, W.H.  and J. Autlan.  1972.   Possible toxic effects from  Inhalation
of dental  Ingredients  by alteration  of  drug biologic  half-life.   J.   Dent.
Res.   51: 878.

Lawrence, W.H., E.O. DllUngham, J.E. Turner and J. Autlan.  1972.  Toxldty
profile of chloroacetaldehyde.   J. Pharm.  Sd.   61:  19-25.

LorpMeno, N.,  R.  Barale,   S.  BaroncelH,  et al.   1977.   Induction  of gene
mutations  and   gene  conversions  by   vinyl   chloride  metabolites  In  yeast.
Cancer Res.  3(1):  253-257.

Lyman,  W.J., W.F.  Reehl and D.H.  Rosenblatt.  1982.   Handbook  of Chemical
Property Estimation  Methods.   McGraw-Hill  Book  Co., New York.   p. 4-9, 5-5,
15-13 to 15-34. f

Malavellle, C., H.  Bartsch, A. Barbln et  al.   1975.   Mutagenldty of  vinyl
chloride,   chloroethyleneoxlde,   chloroacetaldehyde,   and   chloroethanol.
Blochem. Blophys.  Res.  Commun.   63: 363-370.   (CHed In  U.S.  EPA,  1986c)


0086d                              -35-                             07/05/88

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McCann,  J.,  V.  Simmon,  D. Stre1tw1eser  and  B.N.  Ames.  1975.   MutagenlcHy
of  chloroacetaldehyde,  a  possible  metabolic  product  of  1,2-d1chloroethane
(ethylene dlchlorlde), chloroethanol  (ethylene chlorohydrln), vinyl chloride
and cyclophosphamlde.  Proc.  Natl. Acad. Sc1. USA  72(8):  3190-3193.   (CHed
1n U.S. EPA, 1986c)

OSHA  (Occupational  Safety and  Health Administration).  1985.   OSHA   Safety
and Health  Standards.   Code  of  Federal Regulations.   29:  1910-1000.   (Cited
In U.S. EPA, 1986c)

Perrard, M.H.   1985.  MutagenlcHy  and toxlclty  of chloroethylene oxide and
chloroacetaldehyde.  Exper1ent1a.   41: 676-677.

Phillips, R.A.,  S.A.  Zahler  and  A.J. Garro.  1980.   Detection  of mutagen-
Induced  lesions  1n Isolated  ONA  using a  new  Bacillus subtnis  transforma-
tion-based assay.  Mutat.  Res.   74(4): 267-281.   (CHed  1n  U.S. EPA, 1986c)

Rannug,  U.,  R.   Goethe  and C.A.  Wachtmelster.   1976.   The  mutagenlclty of
chloroethylene  oxide,  chloroacetaldehyde,  2-chloroethanol  and   chloroacetlc
add,  conceivable metabolites of vinyl chloride.   Chem. Blol. Interact.  12:
251-263.  (CHed 1n U.S.  EPA,  1986c)

Rosenkranz,   H.S.   1977.   MutagenlcHy  of  halogenated  alkanes  and  their
derivatives.  Environ. Health  Perspect.   21:  79-84.

Stuckl,  G.  and  T.  Le1s1nger.   1983.   Bacterial  degradation  of 2-chloro-
ethanol  proceeds  via   2-chloroacet1c add.   FEMS  M1crob1ol.   Lett.   16:
123-126.  (Taken from CA98:120827v)
0086d                                -36-                             07/05/88

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Swann, R.L., D.A. laskowskl, P.J. HeCall, 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.

Tuazon, E.G., R. Atkinson, A.M.  Winer and J.N.  Pitts,  Jr.   1984.   A study of
the  atmospheric  reaction of l,3-d1chloropropene  and other  selected  organo-
chlorlne compounds.   Arch. Environ.  Contain.  Toxlcol.   13: 691-700.

U.S.  EPA.    1977.   Computer Print-out  of  Non-confidential  Production  Data
from TSCA Inventory.  OPTS, CID,  U.S.  EPA,  Washington,  DC.

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

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

U.S.  EPA.   1986a.   Methodology  for Evaluating Carclnogenldty  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.


0086d                               -37-                             07/18/88

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U.S.  EPA.   19865.    Guidelines   for  Carcinogen  Risk  Assessment.   Federal
Register.  51(185):  33992-34003.

U.S. EPA.   1986c.   Health and Environmental Effects Profile  for  Chloroacet-
aldehyde.   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.   1987a.    Graphical  Exposure  Modeling  System  (GEMS).    CLOGP3
computer program.  PC version.  Office  of Toxic Substances, Washington,  DC.

U.S.  EPA.   1987b.   Graphical  Exposure  Modeling System  (GEMS).   Fate  of
Atmospheric  Pollutants  (FAP).    PC  version.   Office  of  Toxic  Substances,
Washington. DC.

U.S. EPA.   1987c.   Interim Methods  for  Development  of  Inhalation  Reference
Doses.    Prepared by   the  Office  of  Health  and  Environmental  Assessment,
Environmental Criteria  and  Assessment  Office,  Cincinnati, OH for  the  Office
of A1r  Quality Planning and Standards,  Research Triangle  Park,  NC.

U.S. EPA/NIH (National   Institute  of  Health).    1987.    OHM-TADS  (Oil  and
Hazardous  Materials  Technical  Assistance  Data   System).   On-Hne  computer
data base.

Van Duuren,  B.L.,  B.M. Goldschmldt, G.  Loewengart,  et al.  1979.   Cardno-
genldty  of  halogenated  oleflnlc and  aliphatic  hydrocarbons  1n  mice.   J.
Natl.  Cancer Inst.   63(6): 1433-1439.
0086d                               -38-                             07/18/88

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Hlndholz, M.,  Ed.   1983.  The  Merck  Index, 10th ed.   Merck  and Co.,  Inc.,
Rahway. NO.   p. 296.

Zajdela, P., A. Crolsy. A. Barbln, C. Malavellle, L.  Tomatlc  and H.  Bartsch.
1980.  Carclnogenlclty of chloroethylene oxide, an  ultimate reactive metabo-
lite of  vinyl  chloride, and  b1s(chloromethyl)ether  after  subcutaneous  admin-
istration and  1n  Initiation-promotion  experiments  1n mice.   Cancer  Res.
40(2): 352-356.
0086d                               -39-                             07/18/88

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                                  APPENDIX A

                              LITERATURE SEARCHED



    This  HEED  1s  based  on  data  Identified  by  computerized  literature

searches of the following:

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


These  searches  were  conducted In  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  Hyglenlsts).
    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.  2ff78 p.

    Clayton,  G.D.  and  F.E.  Clayton,  Ed.    1981.   Patty's  Industrial
    Hygiene  and  Toxicology,  3rd  rev.  ed..  Vol.  2B.   John  WHey  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  Wiley  and
    Sons, NY.  p. 3817-5112.
0086d                               -40-                             07/05/88

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    Grayson,  M.  and  D. Eckroth,  Ed.   1978-1984.  K1rk-0thmer  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.  L1eu,  T.W.   Chou  and H.L.  Johnson.
    1984.   Data  acquisition   for  environmental  transport   and   fate
    screening for compounds  of Interest  to  the Office  of Solid Waste.
    EPA  600/6-84-010.    NTIS  PB84-243906.    SRI  International,   Menlo
    Park, CA.

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

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

    Sax, I.N.   1984.   Dangerous  Properties of  Industrial  Materials,  6th
    ed.  Van Nostrand Relrihold 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.
    1392, 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.
0086d                               -41-                             07/05/88

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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  Toxldty
    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, 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.
0086d                               -42-                             07/05/88

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o
o
CD
             APPENDIX B


Sunnary Table for Chloroacetaldehyde

Inhalation Exposure
Subchronlc
Chronic
9
Species
	 !
guinea pig
guinea pig
Exposure

5.1 mg/m*. 7 hours/day,
5 days/week (0.51 mg/kg/day)
5.1 mg/m*. 7 hours/day.
5 days/week (0.51 mg/kg/day)
Effect RfD or qj*

NOEL 0.4 rag/day or
0.02 rag/m»
NOEL 0.04 rag/day or
0.002 mg/raa
Reference

Dow Chemical
Company. 1962
Dow Chemical
Company. 1962
            Carclnogenlclty
                                                 NO
Oral Exposure.
Subchronlc
Chrpnlc
CarclnogenlcHy

guinea pig 5.1 og/m*. 7 hours/day.
5 days/week (0.51 mg/kg/day)
guinea pig 5.1 aq/m*. 7 hours/day.
5 days/week (0.51 mg/kg/day)


NOEL 0.003 mg/kg/day '
or 0.2 rog/day .V
NOEL 0.0003 mg/kg/day
or 0.02 rag/day
NO

Dow Chemical
Company. 1962
Dow Chemical
Company. 1962

            REPORTABLE QUANTITIES


            Based on Chronic Toxlclty:   NO


            Based on Carclnogenlclty:    NO
            ND = Not determined
 O
 Ifl

 oo

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