EPA-540/1-86-032
                                                          Off'ce of Research and Development
                                                          Office of Health and Environmental
                                                          Assessment
                                                          Environmental Criteria and
                                                          Assessment Office
                                                          Cincinnati OH 45268
                    Superfund
vvEPA
                    HEALTH EFFECTS  ASSESSMENT

                    FOR 1,1,2,2-TETRACHLOROETHANE

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                                           EPA/540/1-86-032
                                           September  1984
       HEALTH EFFECTS  ASSESSMENT
     FOR  1.1.2.2-TETRACHLOROETHANE
    U.S. Environmental  Protection Agency
     Office of Research and Development
Office of  Health and Environmental  Assessment
Environmental Criteria  and Assessment Office
            Cincinnati, OH  45268
    U.S. Environmental  Protection Agency
  Office of  Emergency and Remedial  Response
Office of Solid Waste and Emergency Response
            Washington, DC  20460

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                                  DISCLAIMER

    This  report  has  been  funded  wholly  or  In  part by  the  United  States
Environmental  Protection  Agency under  Contract  No.  68-03-3112  to  Syracuse
Research Corporation.  It has been  subject  to  the Agency's peer and adminis-
trative review, and  It has  been  approved  for  publication as an EPA document.
Mention of  trade  names or  commercial  products  does  not  constitute  endorse-
ment or recommendation for use.
                                      11

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                                    PREFACE
    This report  summarizes  and evaluates Information relevant  to  a prelimi-
nary  Interim  assessment of adverse  health  effects assocVated  with 1,1,2,2-
tetrachloroethane.   All estimates  of  acceptable  Intakes  and  carcinogenic
potency presented  1n  this  document  should  be considered as  preliminary  and
reflect limited  resources  allocated to  this  project.   Pertinent toxlcologlc
and environmental  data were  located  through  on-Hne literature  searches  of
the Chemical  Abstracts, TOXLINE,  CANCERLINE  and  the  CHEMFATE/DATALOG  data
bases.  The basic  literature  searched  supporting  this document  1s  current  up
to September, 1984.   Secondary sources of Information  have also been  relied
upon  1n the  preparation of  this  report  and  represent large-scale  health
assessment efforts  that entail extensive peer  and Agency review.   The  fol-
lowing  Office of  Health and  Environmental  Assessment  (OHEA)   sources  have
been extensively utilized:


    U.S. EPA.   1980a.  Ambient Water  Quality Criteria  for  Chlorinated
    Ethanes.   Environmental Criteria and Assessment Office,  Cincinnati,
    OH.  EPA 440/5-80-029.   NTIS PB 81-117400.

    U.S.  EPA.   1982a.   Revision  and  update  of  Hazard   profile  on
    1,1,2,2-tetrachloroethane.  Prepared  by  the  Environmental  Criteria
    and Assessment Office, Cincinnati, OH,  OHEA  for  the Office  of  Solid
    Waste and Emergency Response,  Washington,  DC.

    U.S. EPA.  1982b.   Review  of  Toxlcologlc  Data  1n  Support  of Evalua-
    tion for  Carcinogenic Potential  of 1,1,2,2-Tetrachloroethane.   Pre-
    pared by  the Carcinogen Assessment Group, OHEA, Washington,  DC for
    the Office of Solid Waste and  Emergency  Response,  Washington, DC.

    U.S.  EPA.   1983b.   Health and  Environmental  Effects  Profile  for
    1,1,2,2-Tetrachloroethane.  Prepared  by  the  Envlornmental  Criteria
    and Assessment Office, Cincinnati, OH,  OHEA  for  the Office  of  Solid
    Waste and Emergency Response,  Washington,  DC.


    The Intent 1n  these assessments  1s to suggest  acceptable  exposure  levels
whenever sufficient data were available.  Values were  not derived  or  larger
uncertainty  factors  were employed  when  the  variable  data  were limited  In
scope  tending to  generate conservative (I.e., protective) estimates.  Never-
theless, the  Interim  values  presented  reflect the relative degree  of  hazard
associated with  exposure or  risk to the chemlcal(s) addressed.

    Whenever  possible,  two categories  of values  have been estimated for  sys-
temic   toxicants  (toxicants for which cancer is  not the  endpolnt of  concern).
The first,  the  AIS  or acceptable  intake  subchronic,   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 lifespan).  This type  of
exposure estimate  has not  been  extensively  used  or  rigorously defined,  as
previous  risk  assessment   efforts  have  been  primarily  directed  towards
                                      111

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exposures from  toxicants  1n  ambient  air or water  where  lifetime exposure 1s
assumed.  Animal  data  used  for  AIS estimates  generally  Include  exposures
with durations  of  30-90 days.  Subchronlc  human data are  rarely available.
Reported exposures are  usually  from  chronic  occupational  exposure situations
or from reports of acute accidental exposure.

    The  AIC,  acceptable  Intake  chronic,  1s  similar  1n  concept to  the  ADI
(acceptable  dally  Intake).   It 1s  an   estimate  of an  exposure level  that
would  not  be expected  to  cause adverse effects  when  exposure  occurs  for  a
significant portion  of  the Hfespan  [see  U.S.  EPA  (1980b)  for  a discussion
of  this  concept].   The  AIC  1s   route specific  and  estimates  acceptable
exposure  for  a given  route  with  the  Implicit  assumption  that  exposure  by
other routes 1s Insignificant.

    Composite  scores  (CSs)  for  noncardnogens  have  also been  calculated
where data  permitted.   These  values  are used for  ranking  reportable  quanti-
ties; the methodology for their  development 1s explained  1n U.S.  EPA (1983).

    For compounds for which  there  1s  sufficient  evidence  of cardnogenldty,
AIS  and AIC values  are not derived.   For a  discussion  of risk  assessment
methodology for  carcinogens  refer to  U.S. EPA  (1980b).   Since cancer 1s  a
process  that  1s  not  characterized by a threshold,  any exposure contributes
an Increment of risk.   Consequently,  derivation of  AIS and AIC  values  would
be Inappropriate.   For  carcinogens,   q-j*s  have been computed  based  on oral
and Inhalation data 1f available.
                                      1v

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                                   ABSTRACT
    In  order  to  place the  risk assessment  evaluation  1n  proper  context,
refer  to  the preface  of   this  document.   The  preface outlines  limitations
applicable to all documents of  this  series as  well  as  the appropriate Inter-
pretation and use of the quantitative estimates presented.

    The Issue of  primary  concern 1s  the  carcinogenic  potential  of  1,1,2,2-
tetrachloroethane.   Human   data addressing  this  Issue  are  not  available.
Limited in  vitro  mutagenldty  data  are positive.   Only  one cancer  bloassay
has  been  conducted.   In  this  study  1,1,2,2-tetrachloroethane  was  not  car-
cinogenic 1n rats,  but was carcinogenic 1n mice by  oral  exposure.   Exposure
resulted  1n  an  Increased  Incidence  of  hepatocellular  carcinoma.  Using  the
mouse  data, a  human  q-|*  of  0.20  (mg/kg/day)"1  was computed.    Data  are
not  available that  would  allow  assessment of  the carcinogenic  potential  of
this compound by Inhalation exposure.

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                               ACKNOWLEDGEMENTS
    The  Initial  draft  of  this  report  was  prepared  by  Syracuse  Research
Corporation under  Contract No.  68-03-3112  for EPA's  Environmental  Criteria
and  Assessment  Office,  Cincinnati,  OH.   Dr. Christopher  DeRosa and  Karen
Blackburn were the Technical Project Honltors  and  Helen Ball  was»the Project
Officer.  The final documents  1n  this  series  were  prepared  for the Office of
Emergency and Remedial Response, Washington, DC.

    Scientists from  the  following U.S. EPA offices  provided  review  comments
for this document series:

         Environmental Criteria and Assessment Office, Cincinnati, OH
         Carcinogen Assessment  Group
         Office of A1r Quality  Planning and Standards
         Office of Solid Waste
         Office of Toxic Substances
         Office of Drinking Water

Editorial review for the document series was provided by:

    Judith Olsen and Erma Durden
    Environmental Criteria and  Assessment Office
    Cincinnati, OH

Technical support services for  the document series  was provided by:

    Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
    Environmental Criteria and  Assessment Office
    Cincinnati, OH
                                      v1

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                             TABLE  OF  CONTENTS

                                                                       Page

1.   ENVIRONMENTAL CHEMISTRY AND FATE	    1

2.   ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS 	    3

    2.1.   ORAL	    3
    2.2.   INHALATION	    3

3.   TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 	    4

    3.1.   SUBCHRONIC	    4

           3.1.1.   Oral	    4
           3.1.2.   Inhalation	    4

    3.2.   CHRONIC	    5
           3.2.1.   Oral	    5
           3.2.2.   Inhalation	    5

    3.3.   TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS	    5



4.








5.


3.4.
3.3.1. Oral 	
3.3.2. Inhalation 	
TOXICANT INTERACTIONS 	
CARCINOGENICITY 	
4.1.


4.2.


4.3.
4.4.
HUMAN DATA 	
4.1.1. Oral 	
4.1.2. Inhalation 	
BIOASSAYS 	
4.2.1. Oral 	
4.2.2. Inhalation 	
OTHER RELEVANT DATA 	
WEIGHT OF EVIDENCE 	
REGULATORY STANDARDS AND CRITERIA 	
	 	 5
	 7
	 7
	 8
	 8
	 8
	 8
, 	 8
	 	 8
	 8
, 	 8
	 	 10
	 11
                                     V11

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                          TABLE  OF CONTENTS  (cont.)

                                                                        Page

 6.  RISK ASSESSMENT	    12

     6.1.   ACCEPTABLE INTAKE SUBCHRONIC (AIS) 	    12
     6.2.   ACCEPTABLE INTAKE CHRONIC (AIC)	    12
     6.3.   CARCINOGENIC POTENCY (q^)	    12

            6.3.1.   Oral	    12
            6.3.2.   Inhalation	    12

 7.  REFERENCES	    13

APPENDIX A: Summary Table for 1,1,2,2-Tetrachloroethane	    18

APPENDIX B: Cancer Data Sheet for Derivation  of q-|*	    19

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                               LIST OF TABLES

No.                               Title                                -Page

1-1     Selected Physical and Chemical Properties and Half-Lives
        for 1,1,2,2-Tetrachloroethane 	    2
3-1     Percentage of Individuals with Hand Tremors with Respect
        to 1,1,2,2-Tetrachloroethane Exposure 1n Four Different
        Factories 	

4-1     Incidence of Tumors 1n Mice Exposed to >90% Pure
        1,1,2,2-Tetrachloroethane (in corn oil) by Gavage .  .  .  ,
                                     1x

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                             LIST OF ABBREVIATIONS

ACTH                    Adrenocort1cotrop1c hormone
ADI                     Acceptable  dally Intake
AIC                     Acceptable  Intake chronic
AIS                     Acceptable  Intake subchronlc
bw                      Body weight
CAS                     Chemical Abstract Service
CS                      Composite score
DNA                     Oeoxyr1bonucle1c add
ppm                     Parts per million
rpm                     Revolutions per minute
STEL                    Short-term  exposure limit
TLV                     Threshold limit value
TWA                     Time-weighted  average

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                     1.   ENVIRONMENTAL CHEMISTRY AND FATE

    The relevant physical  and  chemical properties and environmental  fate  of
1,1,2,2-tetrachloroethane (CAS  No.  79-34-5)  are given 1n  Table 1-1.
    The  half-life  for  1,1,2,2-tetrachloroethane  In the  atmosphere  (Table
1-1) 1s based  on  Us  Interaction with OH radicals.   Although  no  estimate  of
half-life 1s  available,  the removal  of  this  compound  by wet  precipitation
may play  an Important role  In removing the  compound from air  (Callahan  et
al.,  1979).   The  estimate  of  half-life   for  1,1,2,2-tetrachloroethane  1n
aquatic media  Is  based  on  the  estimated   half-life  of  evaporation  of  this
compound when  stirred  at 200  rpm  1n still  air  at  25°C  (D1ll1ng,  1977)  and
the  consideration  that,   In  natural  aquatic  media  containing  partlculate
matter and sediments,  an  Increase 1n evaporation half-life 1s  expected.
    The  half-life  of  this  compound  1n  soil  could  not  be  located In  the
available literature.  However,  by  analogy with aquatic media,  evaporation
1s expected  to  be  the  predominant  loss mechanism from the  soil  surface.   In
subsurface  soil, 1n the  absence  of significant blodegradatlon  (on  the  basis
of  lack  of  blodegradatlon 1n  aquatic  media)  (Tabak et al.,  1981),  the  com-
pound Is likely to leach  from soil  to groundwater (Page,  1981).
                                      -1-

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                                  TABLE  1-1

         Selected Physical and Chemical Properties and Half-Lives for
                          1,1,2,2,-Tetrachloroethane
    Properties
     Values
       Reference
Chemical class:


Molecular weight:

Vapor pressure:

Water solubility:

Octanol/water partition
coefficient:

BCF:


Half-lives 1n

  A1r:

  Water:
halogenated aliphatic
hydrocarbon

167.86

5 mm Hg at 20°C

2900 rng/8. at 20°C


245

8 for blueglll
(Lepomls macrochlrus)



1.6 years

>1  hour (estimated)
NA


Verschueren, 1983

Verschueren, 1983

Verschueren, 1983


Banerjee et a!., 1980

U.S. EPA, 1980a




Singh et al., 1981

NA
NA = Not applicable
                                      -2-

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           2.  ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1.    ORAL
    Pertinent data regarding  the  absorption of orally  administered  1,1,2,2-
tetrachloroethane could not be located 1n the available literature.
2.2.    INHALATION
    Lehmann  and  Hasegawa   (1910)  administered   9.1   mg/m3   1,1,2,2-tetra-
chloroethane by  Inhalation to  one  rabbit for a  period of 3  hours.   During
this  period, 258.3 mg of the 883.3  mg  administered was  absorbed.
    Human volunteers absorbed  97%  of  a single 2.5 mg  dose of  1,1,2,2-tetra-
chloroethane vapor (Morgan et  al., 1970,  1972).   One hour  later,  3-6% of the
administered dose was exhaled.
                                      -3-

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               3.  TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.   SUBCHRONIC
3.1.1.    Oral.    Pertinent  data  regarding  the  toxldty   of  orally  admin-
istered  1,1,2,2-tetrachloroethane  could  not  be  located  1n  the  available
literature.
3.1.2.    Inhalation.   Schmidt  et  al. (1972)  exposed  105  male  rats to  1.94
ppm  (13.32  mg/m3)  1,1,2,2-tetrachloroethane vapors for  4  hours/day for  265
days.  Multiplying 13.32  mg/m3 by  the  product of  4/24  hours,  7/7 days  and
the  average  Inhalation  rate for  a  rat  (0.26  mVday),  and then  dividing  by
the  average  weight of  a rat (0.35 kg), the  exposure  level 1s adjusted  to  a
dose of  1.65 mg/kg bw/day.   Control  rats  were exposed only to  air.   Effects
associated  with   exposure  to  1,1,2,2-tetrachloroethane  Included  Increased
white  blood  cell  count, pituitary ACTH and  total  fat content of  the  liver,
and decreased body weight.
    Navrotskly et al.  (1971)  exposed   unspecified  numbers  of  rabbits  to
either  0.3,  1.46  or  14.6 ppm  (2.06,  10.03 and  100.25 mg/m3)  1,1,2,2-tetra-
chloroethane  for  3-4  hours/day  for  7-11  months.   At  14.6  ppm, liver  and
kidney  degeneration,  "altered" blood chemistry  and  suppressed  hemaglutlnin
production  were  observed.   Decreased hematocrU,  decreased hemoglobin  con-
tent of  red cells,  and suppressed  hemaglutlnin  production were  observed  at
1.46 ppm, while no effects  were seen at  0.3 ppm.
    Hor1uch1  et   al.  (1962)   exposed  a   single  monkey  to   1000-4000  ppm
(13,734-27,468 mg/m3)   1,1,2,2-tetrachloroethane  for  2  hours/day,  6  days/
week for  a  total of 190  days.  Multiplying 27,468 mg/m3  by  the  product  of
2/24 hours, 6/7  days   and  the average  Inhalation  rate   for  a monkey  (1.4
mVday),   and  then  dividing by the  average  weight  of  a monkey  (3.5 kg),  the
4000 ppm  exposure  level  1s  equivalent to a dose of 756  mg/kg  bw/day.   These
                                      -4-

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Investigators reported  signs  of'weakness  after  the seventh  exposure,  diar-
rhea  and  anorexia  after  the   twelfth  exposure,  and   anesthesia  after  the
fifteenth exposure.  Other symptoms  reported  Include marked  vacuollzatlon of
the  liver  and  fluctuations  In  hematocrlt,  white blood  cell count  and  red
cell hemoglobin content.
3.2.   CHRONIC
3.2.1.   Oral.   Pertinent  data  regarding  the   chronic  toxldty  of  orally
administered 1,1,2,2-tetrachloroethane could  not  be  located  1n the available
literature.
3.2.2.   Inhalation.  The  effects  associated with  occupational  exposure  to
1,1,2,2-tetrachloroethane  by  Inhalation  or  dermal   routes  are  primarily
neurological.  Grimm et al. (1914) reported  that  workers  who were exposed to
1,1,2,2-tetrachloroethane  In   a  German  aircraft  factory  experienced  pain,
tremors, headaches,  numbness,   excessive  perspiration   and  the  sensation  of
"pins  and   needles"  1n  the  extremities.   Women  exposed to  1,1,2,2-tetra-
chloroethane  1n  a  factory   that  produced  artificial  pearls   experienced
paralysis of  the Interosseous  muscles of  the hands and  feet, and paralysis
of muscles  of  the  eye  and jaw  (Ler1  and  Breltel,  1922).   Workers  1n India's
bangle  Industry  were exposed  to 9-98 ppm 1,1,2,2-tetrachloroethane  and  had
tremors (35%), vertigo  (30.5%),  headache  (26.6%),  abdominal  pain (23.7%)  and
anorexia  (22.6%)  (Lobo-Mendonca,  1963).   As  summarized  1n  Table  3-1,  the
percentage of Individuals having hand  tremors was  correlated to  the level of
exposure to 1,1,2,2-tetrachloroethane 1n four different plants.
3.3.   TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1.   Oral.   Pertinent  data  regarding   the   teratogenldty   of  orally
administered 1,1,2,2-tetrachloroethane could  not  be  located  1n the available
literature.
                                      -5-

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                                    TABLE  3-1
             Percentage of Individuals with Hand Tremors with Respect
        to 1,1,2,2-Tetrachloroethane Exposure 1n Four Different Factories3
          Percent                     1,1,2,2-Tetrachloroethaneb (ppm)

            50                                  65 and 98
            40                                  50 and 61
            33 '                                 40 and 74
            14                                   9 and 17

aSource: Lobo-Mendonca, 1963
^Values are averages of unspecified numbers of samples
                                      -6-

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3.3.2.   Inhalation.    Pertinent   data  regarding   the  teratogenldty   of
Inhaled  1,1,2,2-tetrachloroethane  could  not  be  located   1n  the  available
literature.
3.4.   TOXICANT INTERACTIONS
    Pertinent  data  regarding the  Interactions of  1,1,2,2-tetrachloroethane
with other toxicants  could not be located 1n the available  literature.
                                     -7-

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                             4.  CARCINOGENICITY
4.1.   HUMAN DATA
4.1.1.   Oral.    Pertinent  data  regarding  the  cardnogenldty  of  Ingested
1,1,2,2-tetrachloroethane could not be located 1n  the available literature.
4.1.2.   Inhalation.    Pertinent   data   regarding  the  cardnogenldty  of
Inhaled  1,1,2,2-tetrachloroethane   could  not  be   located  1n  the  available
literature.
4.2.   BIOASSAYS
4.2.1.   Oral.    An  NCI  (1978)  bloassay  reported  that  1,1,2,2-tetrachloro-
ethane  was carcinogenic  In B6C3F,  mice  but  not   1n  Osborne-Mendel  rats.
Groups  of  50  males  and  50  females  of  each  species were exposed  to  1,1,2,2-
tetrachloroethane 1n  corn  oil   by  gavage for 5 days/week  for  78 weeks,  and
then  observed  for  12  weeks.   No significant Increase  1n  any  tumor  type or
total tumors was observed  1n  rats  exposed by gavage  to 1,1,2,2-tetrachloro-
ethane  at  TWA  doses  of 0,  62 and  108  mg/kg  or  0, 43 and  76 mg/kg/males  and
females, respectively.  The results 1n mice  are  summarized  1n Table  4-1.
4.2.2.   Inhalation.    Pertinent   data   regarding  the  cardnogenldty  of
Inhaled  1,1,2,2-tetrachloroethane   could  not  be   located  In  the  available
literature.
4.3.   OTHER RELEVANT DATA
    Brem et al.  (1974) reported  that  1,1,2,2-tetrachloroethane was  mutagenlc
to  h1st1d1ne-requ1r1ng strains  of  Salmonella typhlmurlum  and  preferentially
Inhibited  the  growth  of a  DNA polymerase-def 1dent  strain   of  Escher1ch1a
coll.   Callahan  et al.  (1979)  observed mltotlc  gene conversion  1n  Saccharo-
myces cerevlslae strain D7.
                                     -8-

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                                                 TABLE 4-1



     Incidence of Tumors 1n Mice Exposed to >90% Pure 1,1,2,2-Tetrachloroethane (In corn oil) by Gavage3
Sex
H
M
M
Y* F
F
F
Doseb
(mg/kg/day)
203
101
0
203
101
0
Duration
of Treatment
78 weeks
78 weeks
78 weeks
78 weeks
78 weeks
78 weeks
Duration
of Study
90 weeks
90 weeks
91 weeks
90 weeks
90 weeks
91 weeks
Tumor Type
hepatocellular carcinoma
hepatocellular carcinoma
hepatocellular carcinoma
hepatocellular carcinoma
hepatocellular carcinoma
hepatocellular carcinoma
Tumor Incidence
(p Value)c
44/49 (p<0.001)
13/50 (NR)d
1/18 (p<0.001)
43/47 (p<0.001)
30/48 (p<0.001)
0/20 (p<0.001)
^Source:  NCI, 1978



bTWA dose reflecting 5/7 days per  week  treatment



cp levels for the Fisher Exact test  and Cochran-Armltage tests  are given  when <0.05



dp = 0.033 when compared with pooled vehicle controls

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4.4.   WEIGHT OF EVIDENCE
    Pertinent  data   regarding  the  cardnogenlcHy  of  1,1,2,2-tetrachloro-
ethane 1n  humans  could  not be located  1n  the available literature.  In  the
NCI  (1978)  bloassay,  the  chemical  was  found  to  be associated with  hepato-
cellular  carcinoma  1n mice,  but  the validity  of  liver  tumors  In mice as an
Indicator  of  the  potential  of  a  chemical   to  cause  human  cancer  Is   not
universally  accepted.   The  evidence,   therefore,  that  1,1,2,2-tetrachloro-
ethane 1s  an  animal carcinogen 1s  best  considered to be limited.  Applying
the  criteria  proposed  by  the  Carcinogen  Assessment  Group  of  the  U.S.   EPA
(Federal  Register,  1984)  for  the overall  weight  of evidence  for human car-
dnogenlcHy, 1,1,2,2-tetrachloroethane  1s most  appropriately  classified In
Group C - Possible Human  Carcinogen.
                                     -10-

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                     5.   REGULATORY STANDARDS AND CRITERIA

    The OSHA  standard for  1,1,2,2-tetrachloroethane 1n  the  workplace  Is  5
ppm (35 mg/m3)  with the designation  that  dermal  exposure may  be  a signifi-
cant  route  of  absorption  (Code of  Federal  Regulations,  1981).   However,
NIOSH  (1976)  and  AC6IH  (1983)  recommend  a  TWA   of  1  ppm  (7  mg/m3)  for
occupational  exposure   to  1,1,2,2-tetrachloroethane.    ACGIH  (1983)  also
recommends  a  STEL  of  5  ppm (35 mg/m3).   The  ACGIH values were  established
to prevent  "serious  intoxication and nervous,  hepatic,  and  gastrointestinal
effects" (ACGIH, 1980).
    Hygenlc standards  for  permissible  levels  of 1,1,2,2-tetrachloroethane in
the working environment  of various  countries are 7 mg/m3  in the  Federal
Republic  of Germany,  10 mg/m3  1n  the  Democratic  Republic  of  Germany  and  5
mg/m3 (maximum permissible concentration) in the USSR (U.S.  EPA, 1983b).
    For ingestlon  of 1,1,2,2-tetrachloroethane, the U.S. EPA  (1980a)  recom-
mends  a  criterion  of  1.7  yg/8.  for  drinking  water.  This  value   was  based
on the NCI  (1978)  cancer data,  using  the linear multistage  model  to estimate
the  level  of   1,1,2,2-tetrachloroethane  associated with  a   10~5  risk  of
cancer.
                                     -11-

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                             6.  RISK ASSESSMENT
6.1.    ACCEPTABLE  INTAKE  SUBCHRONIC  (AIS)
    1,1,2,2-Tetrachloroethane 1s a  chemical  for  which there 1s limited  evi-
dence  for  cardnogenldty  In animals but  for  which data are  sufficient  for
computing a  q,*.   It  1s,  therefore, Inappropriate  to  calculate  an oral  or
Inhalation AIS for 1,1,2,2-tetrachloroethane.
6.2.    ACCEPTABLE  INTAKE  CHRONIC (AIC)
    1,1,2,2-Tetrachloroethane Is a  chemical  for  which there 1s limited  evi-
dence  for  cardnogenldty  1n animals but  for  which data are  sufficient  for
computing a  q *.   It  Is,  therefore, Inappropriate  to  calculate  an oral  or
Inhalation AIC for 1,1,2,2-tetrachloroethane.
6.3.    CARCINOGENIC POTENCY (q^)
6.3.1.   Oral.  Using the data on female mice  from the  NCI  (1978) bloassay,
U.S.   EPA  (1980a)  derived   a  carcinogenic  potency  factor,   q *   of   0.20
(mg/kg/day)"1.   The  data  base  used  1n  the  computation  of  this  q  *  1s
presented 1n Appendix B.
6.3.2.   Inhalation.   The  lack  of   data  regarding  the  cardnogenldty  of
Inhaled 1,1,2,2-tetrachloroethane  precludes  assessment of  carcinogenic risk.
                                     -12-

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                                8.   REFERENCES

ACGIH  (American  Conference  of  Governmental  Industrial  Hyg1en1sts).   1980.
Documentation of  the  Threshold  Limit Values, 4th ed.  (Includes  Supplemental
Documentation, 1981,  1982,  1983).   Cincinnati, OH.   p.  390.

ACGIH  (American  Conference  of  Governmental  Industrial  Hyglenlsts).   1983.
Threshold Limit  Values  for Chemical Substances  and Physical  Agencts  1n  the
Workroom  Environment  with  Intended. Changes  for  1983-84.   Cincinnati,  OH.
p. 32.

Banerjee, S.,  S.H.  Yalkowsky and  S.C.  Valvan.   1980.   Water  solubility  and
octanol/water partition  coefficients  of organlcs.   Limitations  of  the solu-
bility  partition  coefficient  correlation.   Environ.  Sc1.   Technol.   14:
1227-1229.

Brem, H., et  al.   1974.   The mutagenlcHy  and  DNA-mod1fy1ng  effect of halo-
alkanes.  Cancer Res.   34:  2576.  (Cited 1n U.S. EPA,  1982a)

Callahan, M.A.,  M.W.  SUmak,  N.W.  Gabel, et  al.   1979.  Water-Related Envi-
ronmental Fate of  129 Priority  Pollutants.  Vol. II.  Office  of Water Plan-
ning  and  Standards,   Office  of  Water and  Waste Management, U.S.  EPA,  Wash-
ington, DC.   EPA-440/4-79-029b.   (Cited 1n U.S. EPA, 1982a)

Code  of  Federal  Regulations.   1981.  OSHA  Safety and  Health  Standards.   (29
CFR 1910.1000).
                                     -13-

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Dining, W.L.   1977.   Interphase  transfer processes.  II.  Evaporation  rates



of chloromethanes, ethanes,  ethylenes,  propanes, and propylenes  from  dilute



aqueous solutions.  Comparison  with  theoretical predictions.   Environ.  Scl.



Techno!.  11: 405-409.







Federal   Register.    1984.    Environmental    Protection   Agency.   Proposed



guidelines    for    carcinogenic   risk    assessment.     Federal    Register



49:46294-46299.







Grimm, V., A.  Heffter and  G.  Joachimoglu.  1914.   Industrial  Intoxication 1n



airplane  manufacturing.    Vierteljahresschr   Gerichtl.   Med.   Oeff.   Sani-



taetswes.  48: 161-204.  (Ger.)  (Cited 1n NIOSH, 1976)







Horiuchi, K.,  S.  Horiguchi,  K.  Hashimoto, K.  Kadowakl,  K.  Aratake.   1962.



Studies on  the Industrial  tetrachloroethane  poisoning (2).   Osaka  City Med.



J.  8: 29-38.   (Cited in NIOSH, 1976)







Lehmann,  K.B.  and Hasegawa.   1910.    Absorption  on chlorinated  hydrocarbon



compounds  from air  in  animals and  man.   Chloroform, carbon tetrachloride,



tetrachloroethane.  Arch. Hyg.  72: 327-342.   (Cited 1n NIOSH, 1976)







Ler1,  A.  and  Breltel.   1922.   Chronic  polyneurltls.    Tetrachloroethane



induced  polyneurltls  in pearl  workers.   Bull.  Mem.  Soc. Med.  Hosp.  Paris.



46: 1406-1412.  (Cited  in NIOSH, 1976)







Lobo-Mendonca,  R.  1963.   Tetrachloroethane  -  A survey.    Br.  J.  Ind.  Med.



20: 50-56.   (Cited in NIOSH,  1976)
                                     -14-

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Morgan, A.,  et  al.   1970.  The  excretion  1n breath of some aliphatic  halo-
genated  hydrocarbons  following  administration  by  Inhalation.   Ann.  Occup.
Hyg.  13: 219.  (CHed In U.S.  EPA,  1980a)

Morgan, A.,  et  al.   1972.   Absorption of halogenated hydrocarbons  and  their
excretion  1n  breath  using chlor1ne-38  tracer  techniques.   Ann. Occup.  Hyg.
15: 273.  (Cited 1n U.S. EPA,  1980a)

Navrotskly,  V.K.,  L.M.  Kashln,  I.L.  Kullnskaya,  et al.   1971.   Comparative
assessment of the toxldty of  a  number  of  Industrial  poisons  when  Inhaled 1n
low  concentrations  for  prolonged periods.   Trudy  S'ezda  Glgenlstov  Ukranl-
so1.  8: 224-226.  (Rus.)  (CHed 1n NIOSH, 1976)

NCI  (National  Cancer  Institute).    1978.   Bloassay of  1,1,2,2-tetrachloro-
ethane  for  possible  cardnogenlclty.   NCI  Cardnogenesls  Tech.   Rep.  Ser.
No. 27.  p.  45.  [Also'publ. as  DHHS (NIH)  PB-277-453].   (CHed In U.S. EPA,
1982b)

NIOSH  (National  Institute for  Occupational  Safety  and  Health).   1976.   Cri-
teria  for  a  Recommended  Standard...Occupational  Exposure  to  1,1,2,2-Tetra-
chloroethane.   U.S. DHEW, PHS,  CDC,   Rockvllle, MD.  Publ.  No. 77-121.

Page,  G.W.   1981.   Comparison  of groundwater and surface  water  for patterns
and  levels  of  contamination  by toxic  substances.  Environ.   Sc1.  Techno!.
15:  1475-1480.
                                     -15-

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Schmidt, P.,  S.  B1nnew1es,  R. Gohlke  and  R. Rothe.   1972.   Subacute  action



of low  concentrations  of  chlorinated  ethanes on rats  with  and  without addi-



tional  ethanol  treatment.   I. Biochemical  and  toxlcometrlc  aspects,  especi-



ally  results  1n  subacute  and chronic  toxldty studies with  1,1,2,2-tetra-



chloroethane.    Int.   Arch.   Arbeltsmed.    30:   283-298.   (Ger.)   (Cited  1n



NIOSH, 1976)







Singh,  H.B.,  L.J.  Salas,  A.J. Smith  and H.  Sh1ge1sh1.  1981.   Measurements



of  some  potentially  hazardous   organic  chemicals  1n  urban  environments.



Atmos. Environ.  15:  601-612.







Tabak,  H.H.,  S.A.  Quare,  C.J. Mashnl  and  E.F.  Baoth.   1981.   B1odegradab1l-



1ty  studies with  organic  priority  pollutant  compounds.   J.  Water  Pollut.



Control Fed.  53: 1513-1518.







U.S.  EPA.   1980a.  Ambient  Water  Quality  Criteria  for  Chlorinated  Ethanes.



Environmental    Criteria   and   Assessment    Office,   Cincinnati,  OH.    EPA



440/5-80-029.   NTIS PB 81-117400.







U.S.  EPA.   1980b.   Guidelines  and Methodology Used  In  the Preparation  of



Health  Effects  Assessment  Chapters  of the Consent Decree Water Quality Cri-



teria.  Federal Register.   45:79347-79357.







U.S.  EPA.   1982a.  Revision  and  update  of hazard profile  on 1,1,2,2-tetra-



chloroethane.    Prepared by  the  Environmental  Criteria  and  Assessment Office,



Cincinnati, OH,  OHEA for  the Office  of Solid  Waste and  Emergency  Response,



Washington, DC.
                                     -16-

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U.S. EPA.   1982b.   Review of Toxlcologlc  Data In Support  of  Evaluation for
Carcinogenic  Potential  of 1,1,2,2-Tetrachloroethane.   Prepared by  the  Car-
cinogen Assessment Group, OHEA, Washington,  DC  for  the  Office  of Solid Waste
and Emergency Response, Washlngon, DC.

U.S. EPA.   1983a.  Methodology and  Guidelines  for  Reportable Quantity Deter-
minations  Based  on  Chronic  Toxldty  Data.   Prepared  by  the  Environmental
Criteria and Assessment Office, Cincinnati,  OH, OHEA  for  the Office of Solid
Waste and Emergency Response, Washington, DC.

U.S.  EPA.   1983b.   Health   and  Environmental   Effects  Profile  for  1,1,2,2-
Tetrachloroethane.   Prepared by  the Environmental  Criteria and  Assessment
Office,  Cincinnati,  OH,  OHEA  for  the  Office   of  Solid Waste  and  Emergency
Response, Washington, DC.

Verschueren, K.   1983.  Handbook  of  Environmental  Data  on Organic  Chemistry,
2nd ed.  Van Nostrand Relnhold Co.,  New York.  p.  1310.
                                     -17-

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I
CO
                                                         APPENDIX A
                                         Summary  Table  for  1,1,2,2-Tetrachloroethane
Carcinogenic
Potency
Inhalation
Oral
Species

female
B6C3F-| mice
Experimental
Dose/Exposure

1 vg/mVday
Effect

hepatocellular
carcinoma
qi*
ND
0.20
(mg/kg/day) a
Reference

NCI, 1978;
U.S. EPA, 1980a
        ND = Not derived

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                                  APPENDIX B
                             Cancer  Data Sheet for
                               Derivation of  q-|*
Compound:  1,1,2,2-Tetrachloroethane
Reference:  NCI, 1978
Species, Strain, Sex:  Mice, B6C3F-|, F
Body weight:  0.030 kg (measured)
Length of exposure (le) = 546 days
Length of experiment {Le) = 637 days
Llfespan of animal (L) = 637 days
Tumor site and type:  Hver, hepatocellular carcinoma
Route, vehicle:  oral, gavage
Experimental Doses
or Exposures
(mg/kg/day)
0
101
203
Transformed Dose
(mg/kg/day )t
0
86.571
174.000
Incidence
No. Responding/No.
or Examined
0/20
30/48
43/47

Tested

"•"Adjusted  to reflect  treatment  on  5  days/week and  exposure for  546  days
 of 637 day experimental period.
Unadjusted q-|* from study = 1.5181003xlO~2 (mg/kg/day)~l
Human q-j* = 0.20 (mg/kg/day)'1
                                     -19-

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