Environmental Protection
       Agency                                       March, 1988
        Research and
        Development
       HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
       FOR CHLORINATED CYCLOPENTADIENES
       Prepared for
       OFFICE OF SOLID HASTE AND
       EMERGENCY RESPONSE
       Prepared by

       Environmental Criteria and  Assessment Office
       Office of Health and Environmental Assessment
       U.S. Environmental Protection  Agency
       Cincinnati,  OH  45268
                  DRAFT: 00 NOT CITE OR QUOTE


                         NOTICE

   This document Is a preliminary draft.  It has not been formally released
by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency policy.  It Is being circulated for comments
on Us technical accuracy and policy Implications.

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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
Offlice 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 In this document
and the  dates  searched  are  Included 1n  "Appendix: Literature  Searched.*
Literature search  material  1s current up to 8 months previous  to  the  final
draft date  listed  on  the front  cover.   Final  draft document  dates  (front
cover) reflect the date the document 1s sent to the Program Officer (OSWER).

    Several quantitative  estimates are  presented  provided  sufficient  data
are  available.   For   systemic  toxicants,   these  Include:  Reference  doses
(RfDs) for chronic  and subchronlc exposures  for  both the  Inhalation and oral
exposures.  The  subchronlc or  partial lifetime  RfD, Is  an  estimate of an
exposure  level   that would not  be expected  to  cause  adverse  effects  when
exposure occurs  during a  limited time Interval  I.e.,  for an Interval  that
does  not  constitute a  significant portion  of the  llfespan.  This  type of
exposure estimate  has  not been extensively used,  or rigorously  defined as
previous risk assessment efforts  have  focused  primarily on lifetime exposure
scenarios.  Animal data  used  for  subchronlc  estimates  generally  reflect
exposure durations of  30-90  days.   The  general  methodology  for  estimating
subchronlc RfDs  Is  the same as  traditionally employed for  chronic estimates,
except that subchronlc  data are utilized when available.

   ' In the case  of suspected  carcinogens, RfDs are  not estimated.   Instead,
a  carcinogenic  potency   factor,  or   q-j*   (U.S.  EPA,  1980a)  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 toxlclty  and carcino-
gen IcHy  are   derived.   The  RQ  1s  used  to  determine  the   quantity  of  a
hazardous  substance for  which  notification  Is  required   In  the event of  a
release  as   specified  under  the  Comprehensive   Environmental   Response,
Compensation and Liability Act  (CERCLA).  These two RQs  (chronic toxlclty
and carc1nogen1c1ty)  represent two  of six  scores  developed  (the  remaining
four  reflect 1gn1tab1l1ty, reactivity, aquatic toxlclty,  and  acute mammalian
toxlclty).  Chemical-specific  RQs reflect  the lowest  of  these  six  primary
criteria.  The methodology for  chronic  toxlclty and cancer  based  RQs  are
defined 1n U.S. EPA, 1983a and 1986a,  respectively.
                                      111

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                              EXECUTIVE SUMMARY

    No  Information  on the physical  and chemical  properties  of any  chlori-
nated cyclopentadlenes other than the hexa-lsomer was  located  In  the  litera-
ture cited 1n Appendix A.  Hexachlorocyclopentadlene Is a  light  lemon yellow
liquid with a pungent odor  (Stevens, 1979).  It 1s not soluble  In  water  but
Is soluble  In  acetone, carbon tetrachlorlde, ethanol  and hexane (U.S.  EPA,
1978).  Chemically,  It 1s highly reactive towards addition and  substitution
reactions (Stevens, 1979).
    Velslcol  Chemical  Corporation  1s  currently  the   only   company  that
produces hexachlorocyclopentadlene  1n  the United  States   (SRI, 1987;  USITC,
1986).  The current United States production volume for this chemical 1s  not
available.   According to U.S. EPA (1984a), an estimated 18 million  pounds of
hexachlorocyclopentadlene was produced In  the United  States In  1983.
    Hexachlorocyclopentadlene Is  used primarily  as  an  Intermediate   1n  the
production  of  pesticides and  flame  retardants (Stevens,  1979).   With  the
exception of  endosulfan  and  pentac, the  use of  hexachlorocyclopentadlene-
based  pesticides   Is  banned, suspended  or  severely  restricted  (U.S.  EPA,
1980a).
    The  atmospheric  half-life  of  hexachlorocyclopentadlene,  which   Is  due
primarily to  Its  reaction with  HO* and 0~,  was estimated  to be  3.5 hours
(Cupltt,  1980).   Based  on  Its   atmospheric   half-life  and  Henry's  Law
constant,  the compound  may not significantly  transport  from air   to  the
hydrosphere  or  geosphere;   however, the  compound  may  undergo  1ntramed1a
transport  from  Its  source  to  other points  In the  atmosphere.    In  water,
hexachlorocyclopentadlene  will   be   degraded  primarily  by  photolysis  and
                                      1v

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hydrolysis.  In  clear  and shallow water,  the half-life of  hexachlorocyclo-
pentadlene may  be as  low  as <1  hour  because of  photolysis (Wolfe et  al.,
1982),  but the  effect  of photolysis  may  be  less Important  In  deeper  and
turbid  water,   and  hydrolysis  may   assume   a  more   Important   role.    The
half-life  of hexachlorocyclopentadlene In  these waters  may be several  days
(Wolfe    et     al.,    1982).     The    rate     of     volatilization     of
hexachlorocyclopentadlene from distilled water can be as high as  4.7-8.8X of
the  applied  dose  1n the  first hour  (Kllzer et  al.,  1979).  The rate  of
volatilization   from  natural  water bodies  will depend on  the turbulence  of
the water  and  the wind speed.   Adsorption to sediments will greatly  reduce
the rate of evaporation from natural  waters (U.S. EPA,  1984a).
    Significant  loss  of   hexachlorocyclopentadlene  from  soil  surface  may
occur  due to  photolysis.   But the  Importance of  photolysis will  not  be
significant below  the  surface  layers, due to  light  attenuation.  In  moist
soils,  hydrolysis  may  account for significant loss of  hexachlorocyclopenta-
dlene;  however,  the .hydrolysis, rate  In  soils  with  high  organic  carbon
content may  be  greatly reduced due  to  strong sorptlon of  hexachlorocyclo-
pentadlene 1n such soils.  Due to strong sorptlon, hexachlorocyclopentadlene
will  remain  Immobile In most  soils,  although the mobility may be  higher  1n
sandy soils containing low organic carbon (Chou et al.,  1981).
    The volatilization  of  hexachlorocyclopentadlene  from soils will be much
less  than from  water, and  this rate will   be  even  slower  as   the organic
carbon  content  of soils  Increases (Kllzer et al., 1979).   Hexachlorocyclo-
pentadlene will  not  bloaccumulate significantly 1n edible  aquatic  organisms
as Is Indicated  by a BCF  of  11-29 1n the fathead minnow, Plroeohales promelas
(Velth  et al.,  1979; Spehar  et al.,  1979)  and 100-323  1n goldfish,  Carasslus
auratus (Podowskl and Khan, 1984).

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    Limited data on the  level  of  hexachlorocyclopentadlene  1n  the atmosphere
are available.   Hexachlorocyclopentadlene  was  detected at a maximum concen-
tration  of 0.10  vg/m3  1n  homes  near  a  hazardous  waste  site  In  Hardeman
County,  Tennessee,  and  at  a  maximum concentration  of  39  jig/m3  In  area
air samples from a  wastewater treatment plant 1n Memphis. TN,  which handled
wastewater  from a  nearby  pesticide manufacturing  plant (S.  Clark et  al.,
1982;  EUa et  al.,  1983).  Hexachlorocyclopentadlene  has  been  detected  In
ambient  surface  water  (Fielding  et  al.,  1981).   1n  Industrial  effluents
(McMahon,  1983)  and In drinking water  (Benolt and Williams, 1981;  Thruston,
1978; Suffet et  al., 1980; K1m and  Stone,  n.d.).  The maximum  concentrations
of  hexachlorocyclopentadlene  detected  1n  water  were  100 ng/l  In  ambient
surface water  from  Wheeling,  WV (Ohio  River Valley  Water Sanitation Commis-
sion,  1980) and 650 ng/l  in  drinking  water from Niagara Falls,  NY  (K1m and
Stone,  n.d.).   Hexachlorocyclopentadlene  has  been   qualitatively  Identified
In  fish samples  taken from water  near a  pesticide manufacturing  plant  1n
Michigan  (Spehar et  al.,  1977)  and  from major watersheds near the  Great
Lakes  (Kuetil  et al.,   1983),   No  information regarding the contamination  of
foods   with   hexachlorocyclopentadlene  or  cases   of  dermal  exposure  to
hexachlorocyclopentadlene was  located  1n  the  available literature  cited  1n
Appendix A.
    Aquatic toxIcUy  data  for  the  chlorinated cyclopentadlenes  are limited
to  studies   of  hexachlorocyclopentadlene.   Hexachlorocyclopentadlene  Is
highly  toxic   to freshwater  organisms,  with  the   LC5Q  for  Daphnla  roaqna
reported   to   range   from   39-180   yg/l  (Buccafusco  and  LeBlanc,   1977;
Vllkas, 1977).  A 30-day study  with  fathead  minnows  found  that  mortality was
only slightly  higher  than  at 96 hours at  the  same  concentration. Indicating
that  hexachlorocyclopentadlene Is  not a  cumulative toxin  (Spehar et  al..
                                      v1

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1977, 1979).   The only data  for  a freshwater algae was  a 96-hour  EC5Q  for
Selenastrum caprlcornutus of 0.19 mg/i (Shell 011  Company, 1982).
    The  data  for saltwater  species  are  more   limited.   LC5Q  values  for
three Invertebrates and three fish species  were reported  to  range from 32-48
wg/l  for  all  species  except   the  polycheate   for  which  the  LC5Q  value
was  371  vg/l  (U.S.   EPA,  1980c).   In  four species  of  saltwater  algae.
7-day  EC--  values were  reported  1n  the  range of  3.5-100  pg/1  (Walsh,
1981).
    Comparative   pharmacoklnetlc   studies   of  l4C-hexach1orocyc1opentad1ene
have shown higher  levels of fecal  excretion following  oral exposure than for
Intravenous  or  Inhalation  exposure,  (El  Dareer   et  al.,  1983; Lawrence  and
Oorough,  1982).   Increased  elimination  of  radioactivity  following  oral
exposure  1s  consistent with  toxlclty data which Indicate  that  hexachloro-
cyclopentadlene  1s  more  toxic  following  Inhalation  exposure   than  oral
exposure.
    Following  .  Inhalation    exposure   to   **C-hexach1orocyclopentad1ene,
considerable  radlolabel  remained  In  the lung and trachea.  Indicating that
hexachlorocyclopentadlene reacts  with  biological material   (Oorough,  1980;
Lawrence and Oorough,  1981, 1982;  El  Dareer et al..  1983).  The low level of
extractable  radioactivity from tissues exposed to hexachlorocyclopentadlene
both ht vivo and  jlrt vitro provide  further  evidence of  the high reactivity of
hexachlorocyclopentadlene and/or  Us  metabolites  (El  Career et  al.,  1983).
Following oral exposure, the  highest  levels of hexachlorocyclopentadlene are
associated with the kidney and liver.
    The metabolites of hexachlorocyclopentadlene have not been characterized.
It  has  been  proposed, however,  that tetra- and pentachlorocyclopentadlene
are metabolized  to the reactive tetrachlorocyclopentadlenone (Gdggelmann et

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al.,  1978).  The  additional  chlorine atom  may hinder  the formation  of  the
pentadlenone from hexachlorocyclopentadlene.
    Following  oral  exposure  to  l4C-hexachlorocyc1opentad1ene,  the  radio-
activity Is excreted predominantly In the feces.  Biliary excretion accounted
for **18% of an  oral  dose (Lawrence and  Dorough,  1982). When  compared  with
oral  exposure,  higher  levels of  radioactivity are  excreted  In the  urine
following Inhalation exposure.
    Except for mutagenlclty  assays  of  penta- and  tetrachlorocyclopentadlene,
toxlclty  data  are  limited  to studies  concerning  hexachlorocyclopentadlene.
Subchronlc  Inhalation  studies of   hexachlorocyclopentadlene   have  shown  a
steep dose-response curve.   In a 6- to  30-week  study  by Treon  et al. (1955),
rabbits,  mice  and  rats  exposed  to 0.34  ppm hexachlorocyclopentadlene  by
Inhalation  7 hours/day,  5  days/week  at 0.34  ppm died,  while  guinea  pigs
survived.  At 0.15  ppm,  only the mice  died.  Renal and hepatic degeneration
was observed In  all species, and lung  lesions  were noted 1n mice,  rats  and
guinea pigs.
    0. Clark et  al. (1982)  reported that rats exposed  by Inhalation  to  0.5
ppm hexachlorocyclopentadlene died;  no  significant treatment-related effects
were  observed  at 0.1  ppm.   The rats were  exposed 6 hours/day,  5  days/week
for 30 weeks followed by a  14-week recovery period.   In a 13-week  study by
Rand  et  al.  (1982a,b), no effects were observed In monkeys exposed  by Inha-
lation to hexachlorocyclopentadlene  at  0.01,  0.05  or  0.2 ppm,  6 hours/day, 5
days/week.  In rats exposed  at  the  same hexachlorocyclopentadlene concentra-
tion,  the  only  consistent  treatment-related  effect  was   ultrastructural
changes In the Clara cells of the lungs.
    A 13-week  study sponsored by the  NTP  (Battelle  Northwest  Laboratories,
1984;    Abdo   et   al.,    1986)    found    no   effects    In   mice    at

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0.04 ppm and 1n rats at 0.15  ppm.   Mice  exposed  to hexachlorocyclopentadlene
at  >0.15  ppm  developed  lung  lesions,  with  deaths occurring  at >0.4  ppm.
Lung lesions were  observed  In rats at >0.4 ppm, with deaths at >1  ppm.   The
animals were exposed  6 hours/day,  5  days/week.   A chronic  Inhalation  study
using rats and mice Is In  progress (NTP,  1987).
    A 13-week gavage  study  (SRI,  1981a;  Abdo et al., 1984)  found ulceratlon
of  the stomach In mice treated 5  days/week  at >38  mg/kg,  and at >19 mg/kg In
rats.  No effects  were observed  1n mice at 19 mg/kg or In rats at  10  mg/kg.
No  effects  were  reported  1n  rats  fed hexachlorocyclopentadlene  In  the  diet
at up to 300 ppm for 90 days (IBT, 1975).
    The  lowest  oral   LD5Q   1s  315 mg/kg  1n  female  weanling  rats   (SRI,
1981a).   The lowest  Inhalation  LC_Q reported  1s 1.6  ppm  In  young  adult
male rats  (Rand  et al.,  1982a).   A  short-term  Inhalation  study  In rats  at
0.5 ppm (Rand et al.,  1982a)  found that  lung  lesions  observed when rats were
exposed  for  five   6-hour  periods  were  not present  after  14-21  days  of
recovery.
    The  odor  recognition   concentration  for  hexachlorocyclopentadlene  was
reported  to be  0.0017 mg/m3 (Levin,  1980).   Questionnaires  completed  by
workers at  the  Morris Forman Uastewater  Treatment Plant In Louisville,  KY,
where  an   acute  exposure   Incident  occurred.  Indicated  that  95%  of  the
respondents  detected  the odor  of hexachlorocyclopentadlene before  symptoms
of  Irritation occurred (Norse et al., 1978,  1979).
    Mortality studies  of  hexachlorocyclopentadlene  production workers  have
not.  shown  Increased cancer  death  rates.  No  animal studies of the carcino-
genic 1ty of hexachlorocyclopentadlene were available.
                                      1x

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    Results of  mutagenldty  assays of penta- and  tetrachlorocyclopentadlene
1n  bacteria have  been  positive   (Gdggelroann  et  al.(  1978;  Grelm  et al..
1977);  however,  hexachlorocyclopentadlene has  consistently  tested  negative
In mutagenldty assays.
    Oral  teratogenlclty  studies   of   hexachlorocyclopentadlene   using rats
(IRDC, 1978), mice and rabbits  (Murray et a!., 1980) have reported  negative
results,  although  an  Increase In skeletal  anomalies  was  observed  at   75
mg/kg/day, a dose that also  resulted  1n maternal toxldty.  Hexachlorocyclo-
pentadlene  has  also  tested  negative  for dominant  lethal  effects  In mice
(Litton B1onet1cs,  Inc., 1978a).
    Using   the  13-week   NTP-sponsored   rat   study   (Battene  Northwest
laboratories, 1984),  human  subchronlc and chronic RfDs for hexachlorocyclo-
pentadlene  of   0.01   mg/day  (0.0007  mg/m»)   and  0.001  mg/day   (0.00007
rag/raa),  respectively,  were  calculated.   Confidence  In the  Inhalation RfDs
Is  medium.   Subchronlc and  chronic  oral  RfDs  for hexachlorocyclopentadlene
of  5 mg/day (0.07 mg/kg/day) and 0.5  mg/day  (0.007. mg/kg/day), respectively.
were calculated  from the 13-week  gavage  study using  rats  sponsored  by  the
NTP (SRI, 1981a; Abdo  et al., 1984).   Because  of the lack of additional oral
studies,  confidence  In  the  oral   RfDs  Is low.  A chronic toxldty RQ  for
hexachlorocyclopentadlene of 10 pounds was calculated from the NTP-sponsored
13-week  Inhalation  study using mice  (Abdo  et al.,  1986).   Because of  the
lack of data an RQ  based on care1nogen1city could not be calculated.
    The  lack  of  toxlclty  data for  chlorocyclopentadlene,  trlchlorocyclo-
pentadlene,    tetrachlorocyclopentadlene    and    pentachlorocyclopentadlene
precludes the calculation of  risk  assessment  estimates.

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                              TABLE  OF  CONTENTS
1.  INTRODUCTION	    1

    1.1.   STRUCTURE AND CAS NUMBER	    1
    1.2.   PHYSICAL AND CHEMICAL PROPERTIES 	    1
    1.3.   PRODUCTION DATA	    4
    1.4.   USE DATA	    4
    1.5.   SUMMARY	    5

2.  ENVIRONMENTAL FATE AND TRANSPORT	    6

    2.1.   AIR	    6
    2.2.   HATER	    7
    2.3.   SOIL	   11
    2.4.   SUMMARY	   13

3.  EXPOSURE	   15

    3.1.   INHALATION	   15
    3.2.   HATER	   16
    3.3.   FOOD	   17
    3.4.   DERMAL	   17
    3.5.   SUMMARY	   17

4.  AQUATIC TOXICITY	   19

    4.1.   ACUTE TOXICITY	   19
    4.2.   CHRONIC EFFECTS	   21
    4.3.   PLANT. EFFECTS. . . .	   21
    4.4.   SUMMARY	   25

5.  PHARMACOKINETCS	   26

    5.1.   ABSORPTION	   26
    5.2.   DISTRIBUTION	   27
    5.3.   METABOLISM	   30
    5.4.   EXCRETION	   32
    5.5.   SUMMARY	   33

6.  EFFECTS	   36

    6.1.   SYSTEMIC TOXICITY	   36

           6.1.1.   Inhalation Exposures	   36
           6.1.2.   Oral Exposures	   39
           6.1.3.   Other Relevant Information	   41
                                     x1

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                          TABLE  OF CONTENTS  (cont.)

                                                                        Page
     6.2.   CARCINOGENICITY	   46

            6.2.1.   Inhalation	   46
            6.2.2.   Oral	   46
            6.2.3.   Other Relevant Information	   46

     6.3.   MUTAGENICITY	   46
     6.4.   TERATOGENICITY	   49
     6.5.   OTHER REPRODUCTIVE EFFECTS 	   51
     6.6.   SUMMARY	   51

 7.  EXISTING GUIDELINES AND STANDARDS 	   54

     7.1.   HUMAN	   54
     7.2.   AQUATIC	   54

 8.  RISK ASSESSMENT	   56

     8.1.   CARCINOGENICITY	   56

            8.1.1.   Inhalation	   56
            8.1.2.   Oral	   56
            8.1.3.   Other Routes	   56
            8.1.4.   Weight of Evidence	   56
            8.1.5.   Quantitative Risk Estimates 	   56

     8,2. .  SYSJEMC TOXICITY.	   56

            8.2.1.   Inhalation Exposures	   56
            8.2.2.   Oral Exposures	   62

 9.  REPORTABLE QUANTITIES 	   64

     9.1.   BASED ON SYSTEMIC TOXICITY 	   64
     9.2.   BASED ON CARCINOGENICITY	   64

10.  REFERENCES	   70

APPENDIX A:  LITERATURE SEARCHED	   91
APPENDIX B:  SUMMARY TABLE FOR HEXACHLOROCYCLOPENTADIENE	   94
                                      xll

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                               LIST OF  TABLES
No.                               Title                                Page
1-1     Identities of Selected Chlorinated Cyclopentadlenes 	     2
1-2     Selected Physical Properties of Hexachlorocyclopentadlene .  .     3
4-1     Acute Toxlclty Data for Freshwater Species Exposed to
        Hexachlorocyclopentadlene 	    20
4-2     Acute Toxic1ty Data on Marine Organisms Exposed to
        Hexachlorocyclopentadlene 	    22
4-3     Effects of 28 Days Exposure of Mysld Shrimp, Mvsldopsls
        bahla. to Hexachlorocyclopentadlene 	    24
5-1     Distribution of Hexachlorocyclopentadlene Equivalents In
        Tissues and Excreta of Rats 72 Hours After Oral, Inhalation
        and Intravenous Exposure to 14C-Hexachlorocyclopentad1ene . .    29
5-2     Distribution of Radioactivity Expressed as Percentage
        of Administered Dose from l4C-Hexachlorocyclopentad1ene
        In Rats Dosed by Various Routes	    34
6-1     Acute Toxlclty of Hexachlorocyclopentadlene 	    42
6-2     MutagenlcUy Testing of Chlorinated Cyclopentadlenes	    47
9-'l     Toxlclty Summary for Hexachlorocyclopentadlene	    65
9-2     Composite Scores for Hexachlorocyclopentadlene	    67
9-3     Hexachlorocyclopentadlene: Minimum Effective Dose (MED)
        and Report able Quantity (RQ)	    68
9-4     Chlorocyclopentadlene, TMchlorocyclopentadlene,
        Tetrachlorocyclopentadlene and Pentachlorocyclopentadlene:
        Minimum Effective Dose (MED) and Reportable Quantity (RQ) . .    69

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                             LIST  OF ABBREVIATIONS

ATP                     Adenoslne tMphosphate
BCF                     Bloconcentratlon factor
CS                      Composite score
DMA                     DeoxyMbonuclelc acid
DUEL                    Drinking water exposure level
EC5Q                    Concentration  effective to  50% of  recipients
                        (and all other subscripted  concentration levels)
HA                      Health advisory
K                       Soil sorptlon  coefficient
K                       Octanol/water  partition coefficient
                        Concentration  lethal to 50% of recipients
                        (and all other subscripted  concentration levels)
LD50                    Dose lethal to 50% of recipients
LOAEL                   Lowest-observed-adverse-effect level
NED                     Minimum effective dose
NOAEL                   No-observed-adverse-effect  level
ppb                     Parts per billion
ppm                     Parts per million
RBC                     Red blood cell
RQ                      Reportable quantity
RV                      Effect-rating  value
  Q
RfD                     Reference dose
RVd                     Dose-rating value
SO                      Standard deviation
SGOT                    Serum glutamlc oxaloacetlc  transamlnase
TLC                     Thin layer chromatography
TLV                     Threshold limit value
TWA                     Time-weighted  average
v/v                     Volume per volume
w/v                     Height per volume
                                     xlv

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                               1.   INTRODUCTION
1.1.   STRUCTURE AND CAS NUMBER
    The  five  chlorinated eye1opentadlenes selected  for examination  1n  this
document   are  chlorocyclopentadlene, trlchlorocyclopentadlene,  tetrachloro-
cyclopentadlene,  pentachlorocyclopentadlene  and  hexachlorocyclopentadlene.
Of  the  five chlorinated  cyclopentadlenes  listed above,  the  first four  can
exist  1n more  than one  Isomerlc  form,  depending  on  the  position  of  the
chlorine  substitution  on the  cyclopentadlene ring.  No  Information on  the
physical  and  chemical  properties of any other  chlorinated  cyclopentadlenes
(other  than the  hexa-lsomer)  could  be  found  In  the  available  literature
cited  1n the Appendix;  however,  the formation  of  lower chlorinated  cyclo-
pentadlenes during  the chlorlnatlon  of  cyclopentadlene (Stevens,  1979)  and
the  photolysis  of  hexachlorocyclopentadlene  (Section  2.2.)  are  mentioned
frequently  1n  the  literature.   Table   1-1  gives  the  molecular  formula,
molecular  weight  and  CAS numbers  for  the  selected chlorinated cyclopenta-
dlenes and the synonyms and structure for hexachlorocyclopentadlene.
1.2..   PHYSICAL AND CHEMICAL PROPERTIES
    In  the  absence of  data  on  other   chlorinated  cyclopentadlenes,  only
hexachlorocyclopentadlene will be discussed.   Hexachlorocyclopentadlene  Is a
nonflammable liquid  at room temperature  (Stevens,  1979).  Selected physical
properties  of hexachlorocyclopentadlene are given  In Table 1-2.   Hexachloro-
cyclopentadlene  Is   stable  towards  storage  In  moisture-free  and  Iron-free
environments.   Chemically,  hexachlorocyclopentadlene  1s a  highly  reactive
dlene  that  readily undergoes addition  and  substitution  reactions.   The
products of the addition  reactions  are generally 1:1 endo adducts containing
a  hexach1orob1cyclo-[2,2,1]heptene  structure  (Stevens, 1979).   Hexachloro-
cyclopentadlene  Is  also  susceptible to hydrolysis and  photolysis,  and  these
reactions are discussed In Chapter 2.

0077d                               -1-                              04/05/88

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                                                    TABLE  1-1

                                Identities  of  Selected Chlorinated  Cyclopentadlenes
            Conpounds
      Synonyms3
Molecular
 Formula
Holecular
 Weight
Structure      CAS No.
   Chlorocyclopentadlene0
IS)
I
   Hexachlorocyclopentadlene
NA
 C5H5C1
   Tr1chlorocyc1opentad1eneb      NA
   Tetrach1orocyclopentad1eneb    NA
   Pentachlorocyclopentadlene0    NA
C56; HRS 1655
graphlox; perchloro-
cyclopentadlene;
hexachloro-1,3-cyclo-
pentadlene; 1.2,3,4,5.5-
hexachloro-1,3-cyclo-
pentadlene; hexachloro-
cyclopentadlene
 C5H2C14
                          C5HC15
 C5C16
 100.55
                                        169.44
                                        203.88
               238.33
 272.77
                                                                                       ci
                                                                                               ci
              Cl
                                                                                               Cl
              41851-50-7
                                         77323-84-3
        ci    77323-85-4
                            25329-35-5
              77-47-4
S  *U.S. EPA. 1987a

3   These compounds can exist  In several Isoroerlc forms

   NA a Not available

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                                  TABLE 1-2

           Selected  Physical Properties of Hexachlorocyclopentadlene
        Property
    Value/Description
                                                              Reference
Physical form at ambient
temperatures:

Color:
Odor:

A1r odor threshold:


Water odor threshold:


Melting point, °C:


Boiling point, °C:


Density, g/cm»:

Vapor pressure, mm Hg
at 25°C:

Water solubility:



Organic solvents:
Log octanol/water parti-
tion coefficient (Kou):
Henry's Law constant
(atmos-m'/mol):

Soil partition co-
efficient (Koc):

Wavelength at maximum
absorption (50% aceto-
nltrlle In water):
liquid


light lemon yellow (pure)
greenish tinge (Impure)

pungent

0.03 ppm (v/v)


0.0077 ppm (w/v)


9.5-11.35


239


1.7019

0.06-0.08
2.10 rag/1 at 25°C
1.8 rog/j. at 28°C
3.4 mg/i at 20°C

soluble In acetone,
CC14, ethanol and hexane

5.04 at 28*C
3.99
5.51

2.7xlO~a
1.64x10'*

12,000 (estimated)
322 nm
                                                         Stevens,  1979
                                                         Stevens,  1979
                                                         Stevens.  1979

                                                         Amoore'and  Hautala,
                                                         1983

                                                         Amoore and  Hautala,
                                                         1983

                                                         U.S. EPA, 1978;
                                                         Stevens,  1979

                                                         U.S. EPA, 1978;
                                                         Stevens,  1979

                                                         Horvath,  1982

                                                         U.S. EPA, 1978
                                                         U.S.  EPA,  1978
                                                         Wolfe et al., 1982
                                                         Horvath, 1982

                                                         U.S.  EPA,  1978
                                                         Wolfe et al.,  1982
                                                         Yoshlda et  al..  1983
                                                         Mackay. 1982

                                                         Wolfe et al.,  1982
                                                         Shen. 1982

                                                         Wolfe et al..  1982
                                                         Wolfe et al..  1982
0077d
        -3-
                                                                     12/23/87

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1.3.   PRODUCTION DATA
    Hexachlorocyclopentadlene  Is  produced   for   commercial   use  only  by
Velslcol Chemical  Corporation at  Us Memphis, TN site  (SRI,  1987;  USITC,
1986).  Hexachlorocyclopentadlene  produced  by Velslcol Chemical  Corporation
at  Us  Marshall,  IL site  Is  used  captlvely for the production of  chlordane
(U.S. EPA,  1984a).   Because there Is  only  one producer of hexachlorocyclo-
pentadlene, current  production data  are not  available.   According to U.S.
EPA  (1984a), an estimated  18 million  pounds  of hexachlorocyclopentadlene was
produced 1n 1983.
    The three  primary processes commonly  used for the  production of  hexa-
chlorocyclopentadlene are  chloMnatlon of cyclopentadlene, dechlorlnatlon of
octachlorocyclopentene  and  the  dehydrochlor1nation  of  hexachlorocyclopen-
tane.  In  the  first  process,  freshly prepared cyclopentadlene Is mixed with
alkaline hypochlorlte  solution  at  -40°C.  The  hexachlorocyclopentadlene  Is
recovered  from lower  chlorinated  products  by  fractional  distillation.  In
the  dechlorlnatlon  process,  octachlorocyclopentene  Is  thermally  dechlorl-
nated at  470-480'C to produce hexachlorocyclopentadlene.  Hexachlorocyclo-
pentadlene  can  be   dehydrochloMnated  at   elevated   temperatures  1n  the
presence of a catalyst to produce hexachlorocyclopentadlene (Stevens, 1979).
1.4.   USE DATA
    Although  hexachlorocyclopentadlene has  essentially no  end  use  of Us
own.  It has  been  used as  a  chemical  Intermediate  In  the  production of
several   Insecticides  Including   aldrln,    dleldrln,   endrln,   chlordane,
heptachlor, endosulfan, pentac,  mlrex and others  (Stevens,  1979) and as an
Intermediate In  the  manufacture of flame retardants  Including wet acid and
anhydride,  chlorendlc  acid  and   anhydride  and  dechlorane  plus  (Stevens,
0077d                               .4-                             04/05/88

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1979).  As a  flame  retardant,  U 1s used In a number of plastics  and  epoxy-
reslns (U.S. EPA, 1980b).  With  the exception of  endosulfan  and  pentac,  both
of  which  are  currently  used,  the use  of  hexachlorocyclopentadlene-based
pesticides 1s banned, suspended or severely  restricted.
1.5.   SUMMARY
    No Information  on the physical  and chemical  properties of any chlori-
nated  cyclopentadlenes  other   than  the hexa-1somer   was   located  1n   the
literature cited  In Appendix A.  Hexachlorocyclopentadlene  Is a light  lemon
yellow liquid  with a  pungent  odor (Stevens,  1979).   It  1s not  soluble  1n
water but  Is soluble  1n  acetone, carbon tetrachloMde,  ethanol  and  hexane
(U.S. EPA,  1978).  Chemically,  It  Is  highly reactive  towards addition  and
substitution reactions (Stevens, 1979).
    Velslcol  Chemical  Corporation  1s  currently  the  only   company   that
produces  hexachlorocyclopentadlene  1n  the  United  States  (SRI,  1987;  USITC.
1986).   The  current  U.S.  production  volume   for  this   chemical  Is   not
available.  According to U.S. EPA (1984a),  an estimated 18  million pounds of
hexachlorocyclopentadlene was  produced  1n the United States  1n  1983.
    Hexachlorocyclopentadlene  1s  used  primarily  as an  Intermediate In  the
production  of  pesticides  and   flame  retardants   (Stevens,  1979).   With  the
exception  of  endosulfan and  pentac,   the use of  hexachlorocyclopentadlene-
based  pesticides  1s  banned,  suspended or  severely restricted  (U.S.  EPA,
1980b).
0077d                               -5-                              04/05/88

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                     2.  ENVIRONMENTAL FATE AND TRANSPORT
2.1.   AIR
    Available data on  the fate and  transport  of hexachlorocyclopentadlene  1n
the atmosphere are  limited.   Cupltt (1980) estimated the rate constants  for
HO* and ozone  reactions  with  vapor phase  hexachlorocyclopentadlene to  be
5.9x10""  and  8xlO~ia  cma/molecule~sec,  respectively.   Based   on atmo-
spheric  HO*   and  0.  concentrations   of   10*  and   10"   molecules/cm3,
respectively, the  half-life of  hexachlorocyclopentadlene  1n  the  atmosphere
can be estimated as  3.5 hours.   Cupltt  (1980)  reported  phosgene,  dlacyl-
chlorldes,  ketones and Cl radicals  as anticipated reaction products, all  of
which  are  likely  to  react  with  other  species  In  the  atmosphere.    The
photolysis of  hexachlorocyclopentadlene sorbed  to silica  gel  with light  of
wavelengths  >290  nra   (wavelengths  available   1n  sunlight) was  reported  by
FreHag et  al.  (1982, 1985).   Korte (1978)  reported  46X mineralization  of
hexachlorocyclopentadlene 1n  17  hours  of  Irradiation  with the  formation  of
Cl"  (44.9X).  C02  (48.3X),   C^  (5.4%)   and  CO  (1.2X).   According   to
E1senre1ch et  al. (1981),  organlcs with vapor  pressure >10~* mm  Hg should
exist  almost entirely 1n  the  vapor  phase  1n the  atmosphere.  Therefore,
hexachlorocyclopentadlene,   with  a  vapor  pressure  of  0.06-0.08  mm  Hg,  Is
expected to  exist primarily  In  the  vapor phase  and  not  1n  the  partlcle-
sorbed  state as  reported by Freltag  et al.  (1982, 1985).  Nonetheless,  the
experiments  of  Freltag et  al.  (1982,  1985)  Indicate  the susceptibility  of
hexachlorocyclopentadlene to  degradation under natural  sunlight  conditions.
Hexachlorocyclopentadlene may  also undergo  hydrolysis  1n moist  air  (U.S.
EPA, 1984a).
    Pertinent  data  regarding  the  1ntra-  and Intermedia  tranport of hexa-
chlorocyclopentadlene  present  1n  the  atmosphere  were  not located  In  the

0077d                               -6-                              04/06/88

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 literature  cited  1n  Appendix A.   Given that the transport characteristics of
 a  chemical  In  the  atmosphere  are  likely  to  be  controlled  by   Us  air
 residence time and  air/water  partition coefficient,  this  property  may be
 predicted as  follows:  since the  atmospheric  residence  time  of hexachloro-
 cyclopentadlene Is likely to be short, and the Henry's Law constant predicts
 higher  concentrations  1n  the  vapor  phase,   significant transfer  of hexa-
 chlorocyclopentadlene  from the  atmosphere to water and soil  1s not expected,
 and  the  chemical may  not  travel  long distances 1n  the  atmosphere  from Us
 source.
 2.2,.    HATER
    A detailed discussion of the fate and transport  of hexachlorocyclopenta-
 dlene 1n aquatic  media Is  available  In  U.S.  EPA (1984a).  The photolysis of
 hexachlorocyclopentadlene 1n water  was  reported by  Zepp et  al.  (1984)  and
 Wolfe et al. (1982).  Neither huralc materials  nor algae  In natural water was
 found  to  photosensitize   the  process.   The  rate constant  for near-surface
.photolysis  of  hexachlorocyclopentadlene at 40°M  latitude on  a clear day was
 estimated as  3.9 hour'1.  This corresponds  to a half-life  of -11  minutes.
 Although no product was   Identified,  Zepp et  al. (1984)  and Wolfe  et  al.
 (1982)  speculated that the primary phototransformatlon product was hydrated
 tetrachlorocyclopentadlenone,  which   dlmerlzed  or  reacted  to  form  higher
 molecular weight  products.  The dlmerlzatlon of  hexachlorocyclopentadlene to
 form  higher molecular weight products represented  a  minor pathway according
 to Butz et al. (1982) and Yu and Atallah (1977a).  According to Chou  et al.
 (1987), the photolysis half-life of  hexachlorocyclopentadlene  1n water was
 <4 minutes  when  exposed  to sunlight.   These  authors positively  or  tenta-
 tively  Identified  at  least eight  photoproducts:   2,3,4.4,5-pentachloro-2-
 cyclopentenone;    hexachloro-2-cyclopentenone;   hexachloro-3-cyclopentenone


 0077d                               -7-                               04/05/88

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(primary  product);  pentach1oro-c1s-2,4-pentad1eno1c  add;  Z- and  E-penta-
chloro-butadlene,  tetrachlorobutyne  (secondary  products)  and  hexachloro-
Indenone (minor product).
    Studies of the hydrolysis of  hexachlorocyclopentadlene Indicate  that  Us
hydrolytlc half-life 1s 3-11 days at 25-30°C and  a  pH  range of 5-9 (Wolfe et
al., 1982; Yu  and Atallah, 19775).  In  both studies,  the  authors  concluded
that the  hydrolysis  rate was  higher  as  temperatures  Increased,  and  that
sorptlon to sediments would not significantly affect the rate  of  hydrolysis.
Although the hydrolysis products  were  not Identified,  high  molecular  weight
polyhydroxy compounds appeared to be the  major  products.
    The rate constants  for the  oxidation of hexachlorocyclopentadlene  with
singlet  oxygen  (^O.)  and  peroxy  radicals  In  water  were   estimated  as
<10»  and  12  NT*  hour'1,  respectively  (Mabey  et   al.,  1982).   If   the
concentrations   of  ML  and  R0_  radicals  In   water   are assumed  to  be
10'"  and 10~*  N,  respectively  (Mill  and Nabey,  1985),  It  1s  probable
that under ordinary  environmental conditions,  oxidation of hexachlorocyclo-
pentadlene will not be significant.
    Tabak et al.  (1981) conducted a  static-culture  flask-screening procedure
with  settled  domestic   wastewater  as   mlcroblal   Inoculum   to   test   the
b1odegradab111ty  of  several  compounds.  Including hexachlorocyclopentadlene.
Hexachlorocyclopentadlene   at  original  concentrations  of  5   and  10  rag/l
degraded completely  with  rapid adaptation  1n  7  days  Incubation  time.   The
authors  reported  that   volatilization   of  hexachlorocyclopentadlene  from
aquatic solution  was  not  significant  but  failed  to account for the loss of
hexachlorocyclopentadlene   that   was   due  to  hydrolysis.    Based   on   the
hydrolytlc half-life  data  for  hexachlorocyclopentadlene, hydrolysis alone
0077d                               -8-                              04/05/88

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cannot  account  for  the  100X  observed loss  of  hexachlorocyclopentadlene.
Therefore,  U  can  be  assumed  that some  of the  observed loss  was due  to
blodegradatlon.
    The  blodegradabHUy  of  radlolabelled  hexachlorocyclopentadlene   with
acclimated  mixed microorganisms  and several  pure  cultures  of  Pseudomonas
putIda was  studied  by  Atallah et  al.  (1980).   Only a small  percent (<2.5X)
of  added  hexachlorocyclopentadlene completely  mineralized  to  CO. In  2-3
weeks.   Wolfe  et  al.   (1982)  observed  no  detectable  difference  In  the
degradation rate when sterile and  nonsterlle natural  sediments  were added to
hexachlorocyclopentadlene  solutions.   Hence,  these  Investigators  concluded
that aerobic blodegradatlon  may  not be significant  1n water.   The  anaerobic
blodegradatlon  of  hexachlorocyclopentadlene  1n  water  was  reportedly  very
slow  or  not  significant,  and  at  higher  concentrations  (100  mg/l),  hexa-
chlorocyclopentadlene was  Inhibitory  to  anaerobic microorganisms  (Johnson
and Young, 1983)..
    The  Intermedia'  transport  of .hexachlorocyclopentadlene  from water  may
occur through  volatilization  Into  air,  adsorption onto  suspended partlculate
matters  and subsequent  sedimentation  and  uptake  by plants  and animals  In
water.   The   Intramedla  transport  of  hexachlorocyclopentadlene   may  be
responsible for  transporting the pollutant from Us source to  other points
1n  the  water.   The significance  of  hexachlorocyclopentadlene  sorptlon  In
water  was  predicted  by Wolfe  et  al.  (1982)  on  the  basis of a  computer
simulated  Exposure  Analysis  Modeling  System (EXAMS).   The distribution  of
hexachlorocyclopentadlene 1n  the sediments of  a river,  pond,  eutrophlc and
ollgotrophlc lake was estimated  to be 98.8, 86,  87 and  97.1%,  respectively,
of total  hexachlorocyclopentadlene 1n  the system,  and the residual  portions
were suspected to be 1n the water column.


0077d                               -9-                              04/05/88

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    From an  experimental  anaerobic blodegradatlon  study,  Johnson and  Young
(1983) observed that adsorption plays an  Important  role  In  reducing  the con-
centration of hexachlorocyclopentadlene In aqueous  solutions.   The predicted
strong  sorptlon  of hexachlorocyclopentadlene  In sediments  Is  supported  by
the experimental  sorptlon data In soils  (discussed 1n Section 2.3).
    The volatility  of  hexachlorocyclopentadlene  from  water was reported  by
Weber  (1979).   When an  unstoppered,  half  full, glass  bottle  containing  a
0.41  mg/l   aqueous   solution  of  hexachlorocyclopentadlene  was   left   at
ambient temperature, -45-47X of hexachlorocyclopentadlene was lost 1n a day,
presumably   from   volatilization.   Kllzer   et  al.   (1979)  reported   that
volatility  of hexachlorocyclopentadlene  ranged  from 4.7-8.8%/hour  from  a
static  aquatic  solution  of  concentration   50 yg/l.   In their   aqueous
blodegradabHUy  test,  Atallah   et  al.  (1980)  observed  a  high  rate  of
volatilization of  (>80%  1n  1 day)  hexachlorocyclopentadlene from  unlnocu-
lated  media  containing .45  rag/l  hexachlorocyclopentadlene.  Tabak  et  al.
(1981),. on. the   other   hand,  observed  Insignificant  volatilization   of
hexachlorocyclopentadlene  from  aqueous   solutions   (5 and  10  mg/l)  In  a
blodegradablllty test.   The  studies of  Atallah et  al.  (1980)  and  Tabak  et
al. (1981) were not designed  to  test the  volatility of hexachlorocyclopenta-
dlene from  aqueous  solutions  and both studies  used  substrate concentrations
that exceeded the solubility of the compound.   Wolfe et  al. (1982) predicted
the volatility of  hexachlorocyclopentadlene from aqueous solution using  the
mathematical EXAMS model.  The model  predicted  that volatilization  of  hexa-
chlorocyclopentadlene  from a  river, pond,  eutrophlc  lake  and  oHogotrophlc
lake would account for only 0.69,  1.33, 1.56  and 1.08% loss of  water.   These
values  are  much lower than   values  obtained  from  laboratory studies.   The
EXAMS  model  assumes  that  a  large  percent  of  hexachlorocyclopentadlene
(86-99X) will  remain adsorbed to  sediment;  whereas,  the laboratory studies

0077d                               -10-                             04/05/88

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were  performed  using distilled  water without  any sediments  In them.   The
EXAMS model  also predicted 72%  loss  of hexachlorocyclopentadlene  by  Intra-
medla transport  from a  typical  river  and  Insignificant loss of hexachloro-
cyclopentadlene from pond water, eutrophlc  lake water  and  ollogotrophlc lake
water.
    The uptake  and  bloconcentratlon of hexachlorocyclopentadlene  1n  aquatic
plants and  animals  was  studied  In  a  laboratory model  aquatic  ecosystem (Lu
et  al.,  1975).   The BCFs  for  hexachlorocyclopentadlene In  alga,  Edoqonlum.
snail, Phvsa. mosquito,  Culex. and fish,  Gambusla.  were 340,  929,  1634 and
448,  respectively.   In green alga,  Chlorella fusca. the BCF  for hexachloro-
cyclopentadlene  was  1090  (Geyer  et  al.,  1981).   The  BCFs  for hexachloro-
cyclopentadlene  In   several  species  of fish  were as  follows:  <11   1n  the
fathead minnow, Plmeohales promelas (Spehar  et al., 1979);  29 1n the fathead
minnow, Plmephales  promelas  (Velth et al.. 1979)  and 100-323  1n  goldfish,
Carasslus auratus (Podowskl and Khan,  1984).
2.3.   SOIL            ,   ..,    . .  .    .
    Although  experimental  data  on  photolysis  and  hydrolysis,  Important
abiotic processes that may be  responsible for some loss  of hexachlorocyclo-
pentadlene  from  soils,   were  not  available  In  the  literature  cited  In
Appendix  A,  U   Is  likely that  significant  loss  will  occur as a  result of
photolysis  of  hexachlorocyclopentadlene  from  soil  surfaces  (see  Sections
2.1,.  and  2.2.).  Below  the  surface  layer,  the photodegradatlon  losses  may
not be significant because of  light attenuation and strong sorptlon of hexa-
chlorocyclopentadlene 1n   soil.   Hydrolytlc losses of hexachlorocyclopenta-
dlene  1n  moist  soils may  also be significant, but the significance  of this
process  will be reduced  greatly  by  strong   sorptlon of  hexachlorocyclo-
pentadlene 1n soils.

0077d                               -11-                             04/05/88

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    Pertinent data  regarding  the  loss  of hexachlorocyclopentadlene by blotlc
processes were  located 1n the available  literature.   R1eck  (1977a) provided
Indirect  evidence  of  the blodegradatlon  of  hexachlorocyclopentadlene  In
soils  under both  aerobic and  anaerobic conditions.   Thuma  et  al.  (1978)
Isolated seven pure cultures  of microorganisms  that  could blodegrade >33% of
hexachlorocyclopentadlene In soils 1n 14 days.
    The  estimated  K   value  for  hexachlorocyclopentadlene  1s  12,000 (Wolfe
et  al.,  1982).   According   to  Kenaga  (1980).  compounds   with  K    values
>1000  remain tightly  bound  and  Immobile In soils.   Therefore,  hexachloro-
cyclopentadlene 1s expected to remain  strongly  sorbed  to  soils.  The experi-
mental  results  of  Weber  (1979),  with  flooded soil confirm  this  hypothesis.
Weber  (1979) reported  that  an average  of 68% of applied  hexachlorocyclo-
pentadlene  In aqueous  solution was adsorbed  to  a  loam soil  In 24 hours.  The
adsorption  of  hexachlorocyclopentadlene In  different  kinds  of   soils  was
studied  by  Chou et al,  (1981).   These authors reported  that the adsorption
of  hexachlorocyclopentadlene  can be  represented  by Freundllch's  adsorption
equation.   From both  soil TIC  and soil  column experiments,  they concluded
that  the mobility  of hexachlorocyclopentadlene was proportional  to the soil
organic  carbon  content,  and  that  hexachlorocyclopentadlene  was significantly
more mobile  In  low organic sandy soil than 1n  high  organic  muck  soil.   When
leached  with tap  water or landfill  leachate,  however, hexachlorocyclopenta-
dlene  remained  Immobile In all soils.   Hexachlorocyclopentadlene  was highly
mobile  when  leached with acetone/water,  acetone  and methanol.  Chou et  al.
(1981)  also concluded  that  polar degradation  products  of  hexachlorocyclo-
pentadlene  may  have  a  tendency  to  migrate  through  soils  rather   than
hexachlorocyclopentadlene Itself.
0077d                               -12-                             12/23/87

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    The volatilization of hexachlorocyclopentadlene from silt loam  soils was
examined by  Rleck  (1977b),  who reported evaporation  of 9.3% of  hexachloro-
cyclopentadlene  and  Us  nonpolar  metabolites  from  the  soil  In  1  day.
Following the  first  day.  the evaporation rate  was  slow,  as Indicated by  an
additional  2% evaporation  In  14  days.   These  results  suggest  that  the
evaporation that occurred during  the  first  day was probably associated with
the surface soil only.  KHzer et al.  (1979) also  studied  the evaporation  of
hexachlorocyclopentadlene  from soil and  concluded  that the evaporation rate
was related to the soil organic carbon content, with  the  evaporation slowest
for  humus  soils  and  highest for  sandy  soil.   Only 0.7-1.2%  of  applied
hexachlorocyclopentadlene  evaporated  from a  sandy soil  1n  the  first hour,
and the evaporation  rate  was  
-------
al., 1982), but the effect of  photolysis may  be less Important In deeper and
turbid  water,  and  hydrolysis  may  assume  a  more  Important  role.    The
half-life  of  hexachlorocyclopentadlene In  these  waters  may be  several  days
(Wolfe     et    al.,    1982).      The    rate    of    volatilization     of
hexachlorocyclopentadlene from distilled water can be as  high  as 4.7-8.8% of
the  applied  dose  In  the  first hour  (Kllzer et  al.,  1979).   The rate  of
volatilization from natural  water  bodies  will depend on the  turbulence  of
the water  and the wind speed.   Adsorption to sediments  will  greatly  reduce
the rate of evaporation from natural waters (U.S. EPA,  1984a).
    Significant  loss   of   hexachlorocyclopentadlene  from soil  surface  may
occur  due to  photolysis.   But the  Importance  of  photolysis  will  not  be
significant  below the  surface  layers,  because  of light  attenuation.   In
moist   soils,    hydrolysis    may   account   for   significant   loss    of
hexachlorocyclopentadlene; however,  the  hydrolysis  rate  In soils  with  high
organic  carbon content  may  be  greatly reduced  due to  strong  sorptlon  of
hexachlorocyclopentadlene   In    such   soils.    Due  to   strong   sorptlon.
hexachlorocyclopentadlene will  remain Immobile  1n  most   soils,  although the
mobility may be higher 1n  sandy  soils  containing low organic  carbon (Chou et
al., 1981).
    The volatilization of hexachlorocyclopentadlene from soils  will be  much
less  than from  water,  and  this rate will  be  even slower  as  the  organic
carbon content  of soils  Increases  (Kllzer et al.,  1979).   Hexachlorocyclo-
pentadlene will  not bloaccumulate significantly  1n  edible  aquatic organisms
as Is Indicated by a BCF  of  11-29  1n  the fathead minnow, Plmephales promelas
(Velth et  al., 1979; Spehar  et  al., 1979)  and 100-323  1n goldfish, Carasslus
auratus (Podowskl and  Khan, 1984).
0077d                               -14-                             04/05/88

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                                 3.  EXPOSURE
3.1.   INHALATION
    Release of  hexachlorocyclopentadlene  to the atmosphere can  occur  during
the production,  use and disposal  of the  chemical.   Limited data  regarding
the level  of  hexachlorocyclopentadlene In  the  atmosphere were  available  In
the literature  cited  1n Appendix A.  Hexachlorocyclopentadlene  was  detected
1n  three out  of five  homes near a hazardous waste disposal  site In  Hardeman
County 1n  Tennessee,  1n 1978 (S.  Clark et al., 1982; Harris et  al.,  1984).
In  the  monitored  homes,  concentrations   ranged  .from  0.006-0.10  pg/ma.
Hauser and Bromberg (1982) reported  the qualitative  detection of hexachloro-
cyclopentadlene  In Love  Canal  (Niagara  Falls) air samples  collected  1n
1980.   Area air  samples collected  at  a Memphis  wastewater treatment  plant 1n
Tennessee  that  handled wastewater   from  a  pesticide  manufacturer  showed
hexachlorocyclopentadlene  concentrations   In  the  range  of  0.03-39  jig/m9
(Ellia  et  al.,  1983).   The average  hexachlorocyclopentadlene emission  rate
from  an  abandoned. waste-  site  In  Michigan was  reported  to  be  0.26  g/hour
(U.S.   EPA, 1984a).   An Inventory  of atmospheric  hexachlorocyclopentadlene
emissions  In  the  United  States  was reported  by Anderson   (1983a,b).   The
total  emission was estimated  to be 59.500 pounds/year, and an estimated 1.38
million people  In  the  United States were exposed  to  hexachlorocyclopenta-
dlene; however,  this  estimate,  made  with the  1978  production  Inventory,  Is
no  longer  valid  since two of  the  three production companies  used to estimate
the total  emission of hexachlorocyclopentadlene do  not  produce  the  compound
currently.  Inhalation  exposure  to hexachlorocyclopentadlene for the general
population  1n  the  United  States  cannot be  estimated   because of  limited
monitoring data.
0077d                               -15-                             04/06/88

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3.2.   WATER
    BenoU and  Williams  (1981) monitored both  raw and drinking waters  from
an  Ottawa  water  treatment  plant for  the presence of  hexachlorocyclopenta-
dlene.   Although  hexachlorocyclopentadlene  was   not  detected  In  the  raw
waters,  1t was  found  In  the concentration  range of  57-110  pg/l  In  the
drinking  water.   The  source  of  hexachlorocyclopentadlene  In  the  drinking
water  was  possibly the  chloMnatlon  step of  the  treatment process.   Hexa-
chlorocyclopentadlene at  a  concentration  range of 20-80  ng/i was  detected
1n drinking water  from  Athens, 6A,  collected In 1976  (Thruston,  1978).   The
Great  Lakes  Water  Quality  Board (1983)  qualitatively detected  hexachloro-
cyclopentadlene In water from  Lake Ontario but  not from waters  of Lake Erie,
Lake  Michigan and  Lake  Superior.   The  concentrations  of  hexachlorocyclo-
pentadlene In the drinking  water  from  Niagara  Falls monitored  In 1979 by the
NY  State Department of  Health were  In  the  range of  <0.01-0.65 jig/l  (Kim
and  Stone,  n.d.).  The  results  of  monitoring hexachlorocyclopentadlene  In
the  Ohio  River  were  as  follows:    0.1  yg/l In  T  of  12  samples  from
Wheeling.  UV;  <0.1  »g/l   1n  2  of  21  samples  from Hunting ton,  WV;  <0.1
wg/l  1n  2 of  11  samples  from Louisville,   KY;  and <0.1 yg/l In  1  of
11 samples  from Evansvllle, IN  (Ohio  River  Valley Hater Sanitation  Commis-
sion,  1980).  No  hexachlorocyclopentadlene was detected (detection  limit  of
0.04  pg/l)  In   51  other   samples  collected  from different  sites  of  the
river.   Hexachlorocyclopentadlene was  qualitatively  Identified  In water  as
follows: In Philadelphia drinking water  (Suffet et al., 1980);  In  wastewater
from a  gas  diffusion  plant  at Oak Ridge, TN (HcMahon, 1983); In  Rhine River
water  (Haberer and  Normann, 1979) and  1n surface  water In  England (Fielding
et al.,  1981).  Using data  from  U.S. EPA's STORET  data base, which reflected
good  quality assurance  practices.  Staples  et   al.   (1985)  reported  that


0077d                               -16-                             04/05/88

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hexachlorocyclopentadlene was detectable 1n 0.9X of 1228 effluent  samples  at
a  median  concentration   of  <10  vg/i  and  1n 0.1%  of  854  ambient  water
samples at a median concentration  of <10 vg/l.
3.3,.   FOOD
    Hexachlorocyclopentadlene was  qualitatively Identified  In fish  samples
taken from water near a  pesticide manufacturing plant  In Michigan  (Spehar  et
a!., 1977) and  from water of the Great Miami River In Hamilton, OH  and Mill
Creek  In  Cincinnati,  OH  (Kuehl   et  al.,   1983).    No   other   Information
regarding hexachlorocyclopentadlene contamination 1n food was  located  In the
literature cited 1n the Appendix A.
3.4.   DENIAL
    No  Information  regarding  dermal  exposure to  hexachlorocyclopentadlene
was available 1n the literature dted 1n Appendix  A.
3.5.   SUMMARY
    Limited data on  the  level  of hexachlorocyclopentadlene  1n  the  atmosphere
are available.   Hexachlorocyclopentadlene  was  detected at a maximum concen-
tration  of  0.10  jig/m*  In  homes  near  a-  hazardous  waste  site  In  Hardeman
County  1n Tennessee  and at  a maximum concentration of  39  yg/m8  1n  area
air samples  from a  wastewater  treatment plant In  Memphis, TN that  handled
wastewater  from a  nearby pesticide manufacturing  plant  (S.  Clark  et  al..
1982;  EUa  et  al.,  1983).  Hexachlorocyclopentadlene has  been detected  1n
ambient  surface  water   (Fielding  et  al.,  1981),  In  Industrial effluents
(McNahon, 1983)  and  In drinking water  (Benolt and Williams, 1981; Thruston,
1978; Suffet et  al.,  1980; Kim and  Stone,  n.d.).  The  maximum  concentrations
of  hexachlorocyclopentadlene detected  In water  were  100  ng/i   1n  ambient
surface water from Wheeling,  WV (Ohio  River Valley Water  Sanitation Commis-
sion,  1980)  and 650  ng/ft  In  drinking water  from Niagara Falls, NY  (Kim and


0077d                               -17-                             04/05/88

-------
Stone,  n.d.).   Hexachlorocyclopentadlene has  been qualitatively  Identified
In  fish samples  taken  from water  near a  pesticide  manufacturing  plant  In
Michigan  (Spehar  et  al.t  1977)  and  from  major watersheds  near the  Great
Lakes  (Kuehl  et a!., 1983).  No  Information regarding the contamination  of
foods   with   hexachlorocyclopentadlene  or   cases  of  dermal   exposure  to
hexachlorocyclopentadlene was  located In the  available literature  cited  In
Appendix A.
0077d                               -18-                             12/23/87

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                             4.   AQUATIC TOXICITY
4.1.   ACUTE TOXICITY
    Data  concerning  the  acute  toxldty  of   hexachlorocyclopentadlene   to
freshwater species  are  presented 1n Table  4-1.   In studies completed  under
static  conditions   (Buccafusco  and  LeBlanc,  1977;  Vllkas,  1977),  48-hour
LC50  values   for   Daohnla  maqna   ranged   from   39-52   yg/l,   while   the
48-hour no effect level  ranged  from 18-32 yg/l.
    Spehar  et  al.  (1977,  1979)  reported  a  96-hour LC5Q  value  of  7 yg/l
for  fathead minnow larvae  In  a  flowthrough  test with  measured  toxicant
concentrations.  Acute toxldty  tests  In several  species of fish  have  found
96-hour   LC_Q   values   ranging   from  59-180   yg/l   (Henderson,    1956;
Buccafusco and  LeBlanc,  1977;  Podowskl  and  Khan,  1979;  Khan et al.,  1981).
The  results  reported by  Davis  and  Hardcastle (1957)  for  blueglll  (25,000
yg/ft)   and   largemouth   bass   (20,000   yg/l)   are  abnormally  high,  with
values  well  above  the  solubility  limit  of  800-2100  yg/l.   These  values
may be  high  as a result of  failure  to properly disperse the toxicant  or  to
volatilization of the compound  (or both), since the water was  aerated during
the study.
    Slnhasenl  et al.  (1982)  exposed  rainbow trout,  Salmo  qalrdnerl.   to
hexachlorocyclopentadlene  at 130  yg/l  In a  nonredrculatlng flowthrough
chamber.  Oxygen consumption, measured polarographlcally.   Increased  by 195X
within  80 minutes,  followed by  a  gradual  decrease until death at  -5  hours.
ID.  vitro studies   In which hexachlorocyclopentadlene  was added  to  normal
trout  mitochondria  resulted  1n  Increased  basal  oxygen consumption.  In  a
similar  study  (Slnhasenl   et   al.,  1983),  acclimated  rainbow  trout were
exposed  to   hexachlorocyclopentadlene   at  130  yg/l  1n  a  flowthrough well
water circuit designed to  permit  measurements  of  oxygen  consumption In fish.

0077d                               -19-                             04/05/88

-------
                                                                                TABLE 4-1
                                             Acute Toilclty Data  for Freshwater Species Eiposed  to Hexachlorocyclopentadlene*
g
~J
•J
o.



1
o




1
_«
»v
£
00
Species
Cladoceran
Oaphnta imani

Fathead Minnow
(larvae. <0.1 g)
PlMephales proielas
Fathead Minnow (1-1.5 g)
PlMephales proMelas
Fathead Minnow (0.72 g)
PlMephales, proMelas
Goldfish
Carasslus auratus
Channel catfish (2.1 g)
Ictalurus punctatuf
Blueglll (0.45 g)
LeppMls Macrochlrus
Bluegtll (8-13 CM)
LepoMls Macrochlrus
LargeMouth bass (0-13 CM)
Hlcfopterut sa IMP Ides
•Source: U.S. EPA. 1984a
DNiMbers In parentheses are
NR . Not reported; NO • not


Method
s.u
s.u
FT.N
S.U
s.u
NR
S.U
S.U
s.u
s.u

the 95X

24-Hour
93.0
(78.9-109.6)
130
(68-260)
NR
115
93
75
240
(170-320)
NR
190
(140-250)
170
(140-210)
>500.000
>500.000

LC$o (vg/l)D
48-Hour
52. 2
(44.3-60.9)
39
(30-52)
NR
110
78
59
210
(180-250)
NR
ISO
(130-180)
150
(120-180)
30.000
35.000

Acute No-Effect
Concentration CoM»ents
96-Hour (wg/t)
NO
NO
7.0
104
78
59
180
(160-220)
70
97
(81-120)
130
(110-127)
25.000
20.000
•
32
18
3.7
NR
NR
NR
07
NR
56
65
NR
NR

17*C. soft water
22*C. soft water
25*C. soft water
hard water, acetone soln.
soft water, acetone soln.
i hard water, ewlston
(no acetone)
22*C. soft water
no details given
22*C. soft water
22*C. soft water
water aerated during test
water aerated during test

Reference
Vllkas. 1977
Buccafusco and LeBlanc


. 1977
Spehar et al.. 1977. 1979
Henderson. 1956
Buccafusco and LeBlanc

. 1977
Podowskt and Khan. 1979
Buccafusco and LeBlanc
Buccafusco and LeBlanc
Davis and Hardcastle.
Davis and Hardcastle.

. 1977
. 1977
1957
1957

confidence Intervals.
deteralned; S • static;




FT • flowthrough; U • umeasured




concentrations; N • Measured concentrations









-------
Oxygen consumption rates  Increased  186% In -84 minutes with  decreases  until
death at  -6.5 hours.   Slnhasenl  et a "I.  (1983)  postulated that  hexachloro-
cyclopentadlene  Intoxication  1n  the Intact  fish may  be  due to  Increased
oxygen consumption  and  Impaired  oxldatlve ATP  synthesis, a  result of  the
mitochondria! uncoupling action of hexachlorocyclopentadlene.
    In a  study by Applegate  et al. (1957),  sea  lamprey, rainbow  trout  and
blueglll  were  exposed  to  hexachlorocyclopentadlene at concentrations of 1000
or 5000 ug/l.  Death or distress was observed In 0.5-1.0 hours.
    Acute  toxlclty  data  for  hexachlorocyclopentadlene  to  saltwater species
are presented  In Table  4-2.   The  least  sensitive  species was  the sediment
dwelling  polycheate,  Neanthes  arenaceodentata.  with a  96-hour  LC5Q of  371
pg/l. The most  sensitive species  was   the  mysld  shrimp, Hysldopls  bahla.
with a 96-hour LC5Q of & yg/t In a flowthrough test.
    Acute  toxlclty data  In aquatic  species for  other chlorinated cyclopenta-
dlenes are limited  to one  study  of  tetrachlorocylcopentadlene.   Loeb  and
Kelly (1963)  reported that  carp force  fed tetrachlorocyclopentadlene at  174
and 279 rag/kg  showed  no  effects In  95 minutes.   Carp fed a dose of 257  rag/kg
died 1n 4.5 hours.
4.2.   CHRONIC EFFECTS
    Spehar et  al. (1977,  1979)  conducted 30-day early life stage flowthrough
toxlclty  tests with  fathead  minnows beginning with 1-day-old  larvae.   The
96-hour  mortality  data  Indicated   a   sharp  toxlclty  threshold,  with  94%
survival    at   3.7  »g/l,  70%  at   7.3  ug/l  and  2%   at   9.1   wg/l.   At
the end  of the  30-day exposure period,  mortality  was  only  slightly higher
with  90%  survival   at  3.7   wg/l.  55%  at  7.3   vg/t  and   0%  at  9.1
tig/i.   From   these  results  and  the  determination  of  a  BCF  value  <11
(Spehar et al.,  1979), the authors  concluded that  hexachlorocyclopentadlene

0077d                                -21-                             12/23/87

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                                  TABLE 4-2
                    Acute Toxlclty Data on Marine Organisms
                     Exposed  to Hexachlorocyc1opentad1enea
Species
Polychaete
Neanthes arenaceodentata
Grass shrimp
Palaemonetes puqlo
Nysld shrimp
Nysldopls bah la
Nysld shrimp
Nvsldopls bah la
Nysld shrimp
Nvsldopls bahla
Plnflsh
Laqodon rhomboldes
Spot
Lelostorous xanthurus
Sheepshead minnow
Cyprlnodon varleqatus
Nethod
S.U
S.U
S.U
FT.U
FT.N
S.U
S.U
S.U
96~?8Jj?l7C5°b
371
(297-484)
42
(36-50)
32
(27-37)
12
(10-13)
7
(6-8)
48
(41-58)
37
(30-42)
45
(34-61)
aSource: U.S. EPA. 1980c. 1984a
b95X confidence Interval
N «  Neasured concentrations;  S
 concentrations
static; FT •  flowthrough;  U »  unmeasured
0077d
 -22-
04/05/88

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does not bloaccumulate  In  fish as a result of  continuous  low-level  exposure
to  hexachlorocyclopentadlene.    The body   length  and  weight  of  surviving
larvae did  not  differ from controls at  any concentration tested.   Based  on
these  data,  Spehar  et  al.  (1977, 1979)  concluded  that  3.7  yg/l was  the
highest concentration of  hexachlorocyclopentadlene that produced  no adverse
effects on fathead minnow l.arvae.
    In a  study by  U.S.  EPA (1981),  groups of  40 mysld  shrimp  (saltwater)
were exposed  to  hexachlorocyclopentadlene  at  measured, flowthrough  concen-
trations for  28 days.  The  results are presented In Table  4-3.   Mortality
occurred  at  all  concentrations  except  the  control,  but  there  was  no
consistent  dose-response  relationship.    A  dose-related  decrease  1n  the
number of offspring per  female  was observed.
    Pertinent  data  regarding   the chronic  toxldty  of  other  chlorinated
cyclopentadlenes  In  aquatic   species  were  not   located  In  the  available
literature cited In Appendix A.
4.3.   PLANT EFFECTS
    The  Shell   011  Company  (1982) reported  a  96-hour  EC5Q  for  the  green
algae,  Selenastrum  caprlcornutus. of   0.19  mg/i.   Walsh  (1981)  reported
unpublished data on  the effects  of hexachlorocyclopentadlene on four species
of  marine  algae.   The 7-day  ECSQ  was  calculated  as  the  concentration
causing a  SOX  decrease  In blomass  compared with the control.   Isochrvsls
galbana and Skeletoneroa costatum were the most  sensitive  species,  with 7-day
EC5Q   values   of   3.5   and   6.6   yg/t,   respectively.    The  7-day   EC5Q
values for Dunallella tertlolecta  and  Porphyrldlum cruentum were  100  and  30
wg/l,  respectively.   Walsh  (1983) found  that  after  48  hours of  exposure
to  hexachlorocyclopentadlene  at  25  yg/l,  mortality  of  S.  costatum  was
only 4%,  Indicating that  the  alglcldal  effect  of hexachlorocyclopentadlene
was less pronounced then Us effect on growth.

0077d                               -23-                             12/23/87

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                                  TABLE 4-3
                 Effects rf 28 Days  Exposure of Mysld Shrimp.
               Hvsldops  L  bahla.  to Hexachlorocyclopentad1enea
Concentration
Nominal
Control
0.75
1.5
3.0
6.0
12.0
(ug/t)
Heasured
NO
0.30
0.70
3.0
2.9
6.2
Mortality
(X)
0
18.9
43. 6b
18. 4C
23.1
97. 5b
Total
Offspring
195
167
67
79
72
0
Offspring
per Female
15.7
11.6
5.0b
5.4"
5.5b
Ob
aSource: U.S. EPA. 1981  1984a
Significantly dlffereni  Prom the control (p<0.05)
cNo explanation  was g1  n  1n original text as  to this value  In comparison
 with the next measured  ilue of 2.9
NO - Not detected
0077d                               .24-                             04/05/88

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    No studies concerning  the effects of other chlorinated  cyclopentadlenes
on aquatic plants were located.
4.4.   SUMMARY
    Aquatic toxldty  data  for  the  chlorinated cyclopentadlenes are  limited
to  studies   of   hexachlorocyclopentadlene.   Hexachlorocyclopentadlene   1s
highly  toxic   to freshwater  organisms,  with the  LC5Q  for  Daphnla  maqna
reported   to   range  from  39-180   yg/l   (Buccafusco  and  LeBlanc,   1977;
Vllkas, 1977).  A 30-day study  with  fathead minnows found  that  mortality was
only slightly  higher  than  at  96 hours at the  same  concentration.  Indicating
that  hexachlorocyclopentadlene  1s  not  a  cumulative  toxin  (Spehar  et  al.,
1977,   1979).   The only data  for  a  freshwater algae  was  a 96-hour EC.Q  for
Selenastrum capMcornutus of 0.19 mg/i (Shell  011  Company,  1982).
    The  data   for  saltwater  species  are  more   limited.   LCSQ  values  for
three  Invertebrates and three fish  species were reported  to  range  from 32-48
yg/9,  for  all  species  except   the  polycheate   for  which  the  LC5Q  value
was  371   ug/l  (U.S.   EPA,  1980c).   In  four species  of  saltwater  algae,
7-day  ECfQ  values  were   reported  In  the range  of  3.5-100  i*g/l  (Walsh,
1981).
0077d                               -25-                             04/05/88

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                             5.  PHARMACOKINETICS
5.1.   ABSORPTION
    In a  comparative study  of the pharmacoklnetlcs  of  14C-hexachlorocyc1o-
pentadlene In rats  after  intravenous  and oral dosing, Yu  and  Atallah (1981)
found  results  Indicating  that  only  a  fraction  of  an  oral dose  may  be
absorbed.   After  rats  were  given  an  Intravenous   Injection of  14C-hexa-
chlorocyclopentadlene at 0.25 mg, 20% of  the  dose  was  excreted In the feces;
however,  after   a  3-6  mg  oral  dose  of l4C-hexach1orocydopentad1ene,  72%
was excreted In the feces.
    Lawrence and  Oorough  (1982)  examined the uptake,  disposition and elimi-
nation  of hexachlorocyclopentadlene after  Intravenous,  Inhalation and  oral
routes of exposure.  The Investigators  noted  that  1n  order to  obtain  measur-
able  levels  of  radioactivity  1n the  tissues,  oral  doses  (6  mg/kg  In  corn
oil)  250  times  larger than  Inhalation  doses  (24   yg/kg)   and  600  times
larger than  Intravenous doses  (10  yg/kg  1n DMSO  or  10:4:1  sallne-.propylene
glycolrethanol)  were required.   The  authors attributed  this  to the  poor
bloavallablllty  of  hexachlorocyclopentadlene when administered by the  oral
route.   In  the Inhalation  studies,   rats  were  exposed  to  14C-hexachloro-
cyclopentadlene  for  30-120 minutes  using respirators, so  that they received
doses  that  ranged from 1.4-37.4 yg/kg.  Immediately  following exposure,  1t
was  found  that  the rats  retained  76.8-95.2%  of   the  dose,  with  higher
retention at the longer exposure periods.
    In a  similar comparative study  by  El  Dareer  et al. (1983). radioactivity
In  the  tissues of  rats   72 hours  after  dosing  with  l4C-hexachlorocyclo-
pentadlene was  39,  11.5 and 2.4X by  Intravenous, Inhalation  or  oral routes
of exposure,  respectively.   From these  results  1t 1s clear that relatively
0077d                               -26-                             04/05/88

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low  levels  of  hexachlorocyclopentadlene or  metabolites  are  available  for
tissue distribution following oral  exposure.   This result may be  due  to low
gastrointestinal absorption of  hexachlorocyclopentadlene  and metabolites,  or
to rapid hepatic metabolism and biliary excretion.
5.2.   DISTRIBUTION
    Seven  days   after  rats  were  given  single  oral  doses  of  14C-labeled
hexachlorocyclopentadlene  by  gavage  (5  ymol),  -0.5X  of the  radioactivity
was retained  In  the  kidney with <0.5X  In the  liver  (Mehendale,  1977).   Fat.
lung, muscle and blood had smaller traces, of radioactivity.
    Yu  and  Atallah  (1981) administered single  oral  doses  of  3  or   6  mg
(8.S-25.6  mg/kg)   l4C-hexachlorocyclopentad1ene   to   Sprague-Daw!ey   rats.
The l*C-act1v1ty was  found 1n  the  blood shortly  after dosing and reached a
maximum  1n  -4  hours.   Tissues  were analyzed  for *4C-act1v1ty  8.  24.  48,
72, 96  and 120  hours  after dosing.  At 24 hours after-dosing,  the highest
levels of activity  were found  In  the  kidneys  and liver  with 0.96 and  0.75%
of the dose, respectively.
    Rats and  mice were  treated by  gavage  with  a  single dose  of  14C-hexa-
chlorocyclopentadlene  at  2.5  or  24  mg/kg  (Dorough,  1979;   Dorough  and
Ran1er1, 1984).  The animals  were  killed at 1,  3  and 7  days after dosing,
and samples of  muscle,  brain,  liver, kidney, fat  and  ovaries or testes were
analyzed for  l*C-act1v1ty.   The results  Indicated that the  liver,  kidney
and  fat  were the most  significant  sites  of deposition  for 14C-res1dues  In
both  rats and mice, with  levels  In the  kidneys  of  rats and livers of mice
being the highest.
    Dorough  (1979)  also examined  the  distribution of  radioactivity In rats
and  mice fed l4C-hexachlorocyclopentad1ene  1n the  diet  at 1,  5 or 25 ppm
0077d                               -27-                             04/06/88

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for  30 days.   Feed was  replaced every  12 hours  to minimize  the loss  of
14C-hexach1orocyclopentad1ene.  During  the treatment  period,  rats and  mice
were killed at  1,  3, 7, 12, IS and 30 days.  The  remaining  animals were fed
a normal diet and  were sacrificed at 1,  3, 7,  15  or 30 days  after the  last
day  of treatment.    In  all  cases, the  liver,  kidney  and  fat contained  the
highest levels  of  14C-label,  and  steady-state  for these levels  appeared  to
be  reached after   15  days of feeding.   A  good  correlation  was  observed
between  the  level  of  hexachlorocyclopentadlene  1n  the  diet  and   the
14C-leve1s found In all of the tissues examined.
    In  a  comparative   study   (Dorough,  1980;   Lawrence  and Dorough,  1981,
1982),  rats  were  exposed  to  single  doses of  l4C-hexachlorocyclopentad1ene
by  oral,  Inhalation and Intravenous  routes.  Data regarding distribution  of
l4C-act1v1ty following  the  three  routes  of exposure are presented 1n Table
5-1.   The  results  showed  that  72   hours following oral  and  Intravenous
exposure,  the highest  level of l4C-act1v1ty was 1n  the kidneys.  Following
Inhalation  exposure, l4C-act1v1ty was  highest In  the trachea and  lungs.
The kidneys were also a site of accumulation following Inhalation exposure.
    In  the comparative  study  by El Dareer et al.  (1983),  the highest  levels
of  radioactivity were  found 1n the kidneys and  liver  of rats following  oral
and  Intravenous  dosing  with  14C-hexachlorocyclopentad1ene,  while  radio-
activity levels  were highest  In  the kidneys and  lung following  Inhalation
exposure.   The  majority  of  the  radioactivity  (>99X) associated with  the
tissues could not be extracted with organic solvents.
    In.  vitro  studies Indicate that  hexachlorocyclopentadlene readily binds
to  biological   material.    El  Dareer  et  al.  (1983)  found  that  within  60
minutes  61.8,   30.2 and  58.6X  of  the  radioactivity from  14C-hexachloro-
cyclopentad1ene could  not  be extracted  from  rat  liver  tissue, plasma  and
whole blood, respectively.

0077d                               -28-                             04/05/88

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                                  TABLE 5-1

       Distribution of Hexachlorocyclopentadlene Equivalents  1n Tissues
      and  Excreta of Rats 72 Hours After Oral, Inhalation and Intravenous
                Exposure to ^C-Hexachlorocyclopentadlene3^*0
Sample
Oral Dose
(6 rag/kg )d
Inhaled Dose
(-24 ,,g/kg}
Intravenous Dose
(10 ,,9/kg)
Trachea
Lungs
Liver
Kidneys
Fat
Remaining carcass
                                           nq/q of Tissue
292 + 170
420 + 250
539 * 72
3272 7 84
311 * 12
63 7 40
107.0 + 65.0
71.5 7 55.2
3.6 7 1.9
29.5 7 20.2
2.8 7 0.4
1.3 7 0.6
3.3 + 1.7
14.9 7 1.1
9.6 7 1.1
22.3 7 0.6
2.3 7 0.2
0.5 + 0.1
                                           Percent of Dose
Whole body
Urine
Feces
Total Recovery
2.8 + 1.1
15.3 + 3.3
63.6 * 8.5
81.7 * 6.7
12.9 * 4.7
33.1 * 4.5
23.1 + 5.7
69.1 + 9.6
31.0 * 7.8
22.1 + 5.7
31.4 * 1.9
84.6 + 4.6
aSources: Dorough, 1980; Lawrence and Dorough, 1982; U.S.  EPA, 19865

bOne  hexachlorocyclopentadlene  equivalent  Is  defined  as  the  amount  of
 radlolabel equivalent  to one  nanograro  of  hexachlorocyclopentadlene based on
 the specific activity of the dosing solution.

CA11 values are the mean+SD of three replicates.

dNote  that  the oral  dose was  250 and  600  times  that of  the Inhaled  and
 Intravenous  doses,  respectively.  That  was  necessary  since  residues  were
 not detected In  Individual  tissues  of animals  treated  orally at  doses of
 5-25
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5.3.   METABOLISM
    Autoradlographs  of  urine  extracts   from  rats  given  single  doses  of
14C-labe1ed  hexachlorocyclopentadlene  revealed  at  least  four  metabolites
(Mehendale, 1977).  These metabolites were not  Identified or characterized.
    Yu and  Atallah (1981)  found  no unchanged  hexachlorocyclopenta  dlene  In
the  urine  or  feces  of  rats  given  single oral  doses  of  "C-hexachloro-
cyclopentadlene.    Both  the  urinary  and  fecal  metabolites  were  charac-
terized as  polar, with  11X of the  14C-content  soluble In organic  solvents
and 32% rendered organo-soluble after acid-catalyzed  hydrolysis,  suggesting
the formation of metabolic ester-conjugates.
    In an  in vitro study of  the  ability of rat liver  and  fecal  homogenates
and  gut  contents  to  metabolize  hexachlorocyclopentadlene,  Yu and  Atallah
(1981) found  that hexachlorocyclopentadlene was metabolized  with  half-lives
of  14.2,   1.6 and  10.6 hours,  respectively.   The  addition  of  mercuric
chloride to  the  gut  contents  and fecal  homogenate as  a bacteMdde resulted
In an Increase 1n  half-lives  to 17.2  and 6.2 hours,  respectively.   Denatura-
tlon  of   the liver  homogenate  had  virtually  no  effect  on  the  .in  vitro
metabolic  rate.  These  results  Indicate that gut and  fecal flora may have a
major role In the  metabolism  of hexachlorocyclopentadlene,  while  the role  of
enzyme dependent processes may be limited.
    Given  the positive  results  for  tetra- and  pentachlorocyclopentadlene and
negative results for hexachlorocyclopentadlene  1n  mutagenldty assays  with
metabolic  activation,  Gdggelmann   et  al.  (1978)  proposed   the   metabolic
pathway shown  In  Figure  5-1.   In this  pathway, tetra- and pentachloroyclo-
pentadlene can be transformed  to the  reactive tetrachlorocyclopentadlenone.
The additional chlorine atom may hinder the  formation  of  tetrachlorocyclo-
pentadlenone from hexachlorocyclopentadlene.


0077d                               -30-                             04/07/88

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       Cl       Cl
       HtiachUr*-
       c jc lop*ntaifl«n«
                                                                     NuclMphilc
                              Tetr«hlor»-
                            cyclepcntadicntne
                                 FIGURE 5-1

                   Proposed Metabolic Formation of Reactive
        Tetrachlorocyclopentadlenone from Chlorinated Cyclopentadlenes

                       Source:  Gdggelmann et al., 1978
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5.4.   EXCRETION
    Rats  given  single  oral  doses  of 14C-labeled  hexachlorocyclopentadlene
(5 ymol)  excreted  33% of the  dose In the  urine  and  10% of the dose  1n  the
feces 1n  7  days  (Nehendale,  1977).  About 87% of the  dose  eliminated  In  the
urine and 60% of the dose eliminated  1n  the feces were excreted In the first
24  hours.   Nehendale  (1977)  suggested  that  the remaining  hexachlorocyclo-
pentadlene  was  excreted  through  the  lungs.   This  was  later  disproved  by
Dorough  (1979)  who found that  <1% of an oral  dose of  14C-hexachlorocyclo-
pentadlene  given  to rats  was excreted  In the  lungs.  The  level of  fecal
excretion reported  In  the Nehendale  (1977) study  was probably low  because
the feces were  dried and powdered  before analysis.  Whltacre  (1978)  and  El
Oareer  et  al.  (1983)   reported   that   hexachlorocyclopentadlene  and  Us
volatile metabolites can be lost during this kind of preparation.
    Yu and  Atallah  (1981)  found  that during 120 hours following a  3 or 6  mg
oral  dose  of  l4C-hexachlorocyclopentad1ene,   rats  excreted  -72%  of  the
radioactivity 1n the feces and -17% 1n the urine.
    In a  single-dose  study,  Dorough  (1979)  found that 73-96%  of  the  radio-
label of  l4C-hexachlorocyclopentad1ene was excreted  In  the urine  and feces
of rats and mice given a gavage dose  of 2.5  or  25 mg/kg.   In  rats and mice
fed diets containing  1,  5 or  25  ppm l4C-hexachlorocyclopentad1ene  for  30
days 63-79% of  the radioactivity was excreted In the  urine  and feces.   In a
separate  experiment  with male rats.  In  which the  bile duct was  cannulated
and a  single  dose of  25 mg/kg 14C-hexachlorocyclopentad1ene was  adminis-
tered orally,  only  16% of the dose was excreted  1n the bile.
    In  a  comparative  study,  Lawrence and Dorough  (1982)  found  that  rats
orally  dosed  with l4C-hexachlorocyclopentad1ene  at  6  mg/kg  excreted  2-3
0077d                               -32-                             04/05/88

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tiroes more  of  the dose 1n  the  feces than rats  dosed  by the  Intravenous  or
Inhalation  routes.   Biliary excretion  was  greater  following  oral  exposure
and accounted for 18% of the dose.
    Data  regarding  excretion of  radioactivity  following oral.  Intravenous
and  Inhalation   exposure   of   rats  to  *4C-hexach1orocyc1opentad1ene   are
presented 1n  Table  5-2 (El  Dareer  et al., 1983).   This study supports  the
observation  that little  hexachlorocyclopentadlene  or  Its  metabolites  Is
excreted  1n the  respiratory  tract.   Following oral and  Intravenous  exposure,
fecal excretion  predominates, while  a larger percentage  of  the radioactivity
Is excreted 1n the urine following Inhalation  exposure.
5.5.   SUMMARY
    Comparative  pharmacoklnetlc  studies  of   l4C-hexachlorocyclopentad1ene
have shown higher levels of  fecal excretion following oral  exposure than for
Intravenous or  Inhalation exposure  (El Dareer  et al.,  1983; Lawrence  and
Dorough,  1982).   Increased elimination  of radioactivity  following oral  expo-
sure 1s  consistent  with toxldty data  which  Indicate that  hexachlorocyclo-
pentadlene Is more toxic following Inhalation  exposure  than  oral exposure.
    Following    Inhalation    exposure   to    l4C-hexachlorocyc!opentad1ene,
considerable  radlolabel  remained In the lung  and trachea. Indicating  that
hexachlorocyclopentadlene reacts  with  biological material  (Dorough,  1980;
Lawrence and Dorough, 1981,  1982; El Dareer et  al.,  1983).   The low level of
extractable radioactivity from  tissues exposed  to hexachlorocyclopentadlene
both in vivo and  Ui  vitro provide further evidence of  the high reactivity of
hexachlorocyclopentadlene and  Us  metabolites  or  both  (El  Dareer et  al.,
1983).   Following  oral  exposure,   the  highest  levels  of  hexachlorocyclo-
pentadlene are associated with the kidney and  liver.
00774                               -33-                             04/05/88

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§
—j
•4
O.
                                TABLE 5-2

   Distribution of Radioactivity Expressed as Percentage of Administered
Dose from *4C-Hexachlorocyclopentad1ene  In  Rats  Dosed by  Various Routes*»D

Feces
Urine
Tissues
C02
Other volatile
TOTAL RECOVERY
Oral Dose
Low Dosec
(4.1 mg/kg)
79.4 * 2.9
35.5 * 2.5
2.4 ± 0.6
0.8 ±0.0
0.2 i 0.0
118.3 * 3. 0^
M
High Dosec
(61 mg/kg)
65.3 i 6.9
28.7 * 4.2
2.4 ± 0.1
0.6 i 0.0
0.3 ± 0.0
97.3 * 7.0
. Intravenous Dose (X)c
(0.59 mg/kg)
34.0 f 1.0e
15.8 ± 1.4
39.0 * 1.0
0.1 ± 0.0
0.1 ± 0.0
89.0 i 2.0
Inhalation
Group Ad
(1.0 mg/kg)
28.7 i 4.3
41.0 ± 4.8
28.9 ± 1.6
1.4 ± 0.3
NR
(100)
Dose (X)
Group Bc
(1.4 mg/kg)
47.5 » 6.4
40.0 ± 6.6
11.5 i 0.8
1.0 ± 0.5
NR
(100)
          aSource: El Dareer et al.. 1983;  U.S.  EPA.  1986b

          ^The values represent the mean % of dose ± SO for  three rats.

          cAt 72 hours after dosing or exposure

          dAt 6 hours after exposure

          ePlus Intestinal contents
                an unexplained  reason,  the  total  recovery  for  this  dose  was higher  than  theoretical.   If  the
           percent recoveries for  this  dose  are •normalized* to 100X. differences  In disposition for  the  two  doses
           are minimal, an Indication that no saturable process  Is operative In this dose range.

          NR * Not reported

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    The  metabolites  of  hexachlorocyclopentadlene  have  not been  character-
ized.   It  has  been  proposed,  however,  that  tetra- and  pentachlorocyclo-
pentadlene  are  metabolized  to  the  reactive  tetrachlorocyclopentadlenone
(Goggelmann  et  al..  1978).   The  additional  chlorine  atom may  hinder  the
formation of the tetrachlorocyclopentadlenone  from hexachlorocyclopentadlene.
    Following  oral  exposure  to  l4C-hexachlorocyclopentad1ene,  the  radio-
activity  1s  excreted   predominantly  1n  the  feces.    Biliary   excretion
accounted  for  -18X  of  an oral  dose  (Lawrence  and Dorough,  1982).   When
compared with oral exposure,  higher  levels  of radioactivity are excreted In
the urine following Inhalation exposure.
0077d                               -35-                             04/06/88

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                                  6.   EFFECTS
6.1.   SYSTEMIC TOXICITY
6.1.1.  • Inhalation Exposures.
    6.1.1.1.   SUBCHRONIC — Treon et  al.  (1955)  exposed two  guinea pigs,
six  rabbits,  five  mice and  four rats  to hexachlorocyclopentadlene  (89.5%
pure) at  0.34  ppm  (3.7 mg/raa),  7 hours/day,  5 days/week  for  up  to  25-30
exposures.  Both  guinea pigs survived 30  exposures,  while only  two rabbits
survived 30 exposures  and  no rats or mice survived  5  exposures.  Degenera-
tive  changes  were observed  In  the brain,  heart,  liver, adrenal  glands  and
kidneys with  severe  pulmonary  edema and  hyperemla and acute  necrotlzlng
bronchitis.  The  study did  not  discuss  the  severity or Incidence  of  these
effects 1n  the  various species.   Using  a lower concentration  (0.15 ppm,  or
1.7  mg/ma,  hexachlorocyclopentadlene),   2/2  guinea  pigs,   4/4  rats,   3/3
rabbits and only  1/5 mice  survived  up to 150 seven-hour exposure periods  5
days/week.  Slight  renal and hepatic  degeneration was noted  In  all  species.
Nice, rats an.d  guinea  pigs also developed  lung  lesions.  This  study differs
from  more recent  studies   (Battelle  Northwest  Laboratories.  1984; Abdo  et
al.,  1986),  which  found  no deaths  1n  mice  exposed  to 0.15  ppm, and  no
effects 1n rats exposed to 0.15 ppm.
    In a NTP sponsored  study  (Battelle Northwest Laboratories,  1984; Abdo et
al.,  1986), groups  of   10  F344  rats/sex  and 10  B6C3F1 mice/sex  were exposed
to hexachlorocyclopentadlene  (99.42%)  at 0, 0.04, 0.15,  0.4, 1  or 2 ppm (0,
0.45,  1.67,  4.46.  11.1  or  22.3 mg/m*)  6  hours/day,  5 days/week for  13
weeks.  Information concerning  the  mouse  study was  available  only In  an
abstract  (Abdo  et al.,  1986).   All   rats  and mice exposed  to  >1  ppm  died,
with  5/10  male  and 2/10 female  mice dying at  0.4 ppm [the  abstract  Incor-
rectly stated that mice died  at  0.04  ppm rather  than 0.4 ppm (Abdo, 1987)].

0077d                               -36-                              04/06/88

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Exposure-related changes  In hematology and  clinical chemistry  changes  were
not  observed  In either  rats or  mice.  Body  weight gain was  significantly
(p<0.05) reduced 1n  male rats at 0.4  ppm;  a similar but  less  severe effect
was observed 1n female rats  (Battelle  Northwest  Laboratories,  1984).   At 0.4
ppm, relative lung weights  were higher 1n females and  significantly  (p<0.5)
higher  In  males.   Relative weights of  heart,  kidney and  testes  In 0.04 ppm
males  were also Increased.   Dose-related hlstopathologlcal  changes   In  the
respiratory tract epithelium were observed 1n  rats at >0.4 ppm.   The  changes
observed Included necrosis and acute Inflammation.   No  effects  were observed
In rats at 0.15 ppm.
    In  mice  (Abdo  et al.,  1986),  body weight gains were 10% lower  In  both
sexes  at  0.4  ppm.   The only  change   1n  organ weight  was  an  Increase  In
relative lung weights of males exposed  to  0.4  ppm.   Dose-related hlstopatho-
loglcal alterations  In the  respiratory  epithelium.  Including hyperplasla and
metaplasia, were observed In mice at >0.15 ppm.  No  effects  were observed 1n
mice at 0.04 ppm*
    In  a  study  by D.  Clark et  al.  (1982), groups  of  eight male and eight
female  Wlstar  rats were exposed  to  hexachlorocyclopentadlene  (96X pure)  at
nominal  concentrations  of  0,  0.05,  0.1  or  0.5 ppm  (0, 0.56,  1.1   or  5.6
rog/ra8),  6  hours/day, 5 days/week  for  30 weeks,  followed  by  a  14-week
recovery  period without hexachlorocyclopentadlene  exposure.   At  0.5  ppm,
four male  and  two  female rats died.   In males  exposed  to 0.5 ppm,  depressed
body weight  gain relative  to  controls was  observed at 7 weeks  of  exposure
and persisted through  the  remainder  of the  study.   In  females, body  weights
1n  the 0.5 and 0.1   ppm groups were  significantly  Increased  compared  with
controls during the  first half  of  the  exposure period;  however, body weights
were significantly (p<0.01)  decreased  1n  these groups  compared with  controls


0077d                               -37-                             04/05/88

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at  the end  of  the recovery  period.  At  0.5  ppm,  pulmonary  degenerative
changes were  noted  In  both  sexes,  with males affected more  severely.   N11d
degenerative  changes  In the  liver  and kidney  were also  observed In a  few
rats  at  0.5  ppm,  with kidney  weights significantly  Increased  1n  females.
Changes In  organ  weights  or hlstopathologlcal  changes  were not  observed  In
rats exposed to 0.05 or 0.1  ppm hexachlorocyclopentadlene.
    Rand  et  al.  (1982a)  exposed groups of  40 male  and  40  female  Sprague-
Dawley  rats   (160-226  g),  and   groups  of  6 male  and 6  female  cynomolgus
monkeys  (1.5-2.5  kg,  average  2.0  kg)  to  hexachlorocyclopentadlene at  0,
0.01, 0.05  or 0.2 ppm (0, 0.1,  0.6 or 2.2 mg/m3), 6 hours/day,  5 days/week
for up  to 14 weeks.  No effects were observed In monkeys at  any concentra-
tion.  Evaluation Included mortality,  clinical  signs,  body weight, pulmonary
function, eye examinations, hematology,  clinical  chemistry  and  hlstopatho-
loglc examinations.  Male  rats   In  this  study had a  transient appearance  of
dark-red eyes at  0.05  and  0.2 ppm  hexachlorocyclopentadlene.   There  were  no
treatment-related changes 1n body wetght  gain or food  or  water consumption.
At  12  weeks,  there  were  marginal,  but  not  statistically  significant.
Increases  1n hemoglobin  concentration  and  erythrocyte  count  In 0.01  ppm
males,  0.05  ppm  females  and  0.2  ppm rats  of both  sexes.    No  treatment-
related abnormalities In gross pathology or hlstopathology were observed.
    Rand et  al.  (1982b) examined the  Clara cells of the  lungs  from exposed
monkeys and  rats  from  the  study described above, using electron microscopy.
No ultrastructural  changes were  observed  In monkeys.   In  rats,  the examina-
tions  showed a  dose-related Increase  In  the  Incidence   of  electron-lucent
Inclusions  In  the bronchlolar Clara  cells.   These Increases  were statisti-
cally significant (p<0.01) compared with controls at  all  exposure concentra-
tions.  According to  Evans  et al.  (1978),  Clara cells respond  to Injury  by

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regression to  a more  primitive  cell  type.  Rand  et  al. (1982b) noted  that
some  of the  ultrastructural  changes  1n  the  exposed rats  were similar  to
changes  described  In  the  Evans et  al.  (1978)   study.   The  toxlcologlcal
significance  of these  changes   Is  not  known.   The  Clara  cell  contributes
Important materials  to the extracellular  lining  of the  peripheral  airways,
and If  this  effect from hexachlorocyclopentadlene vapors causes  the content
of the  contributed material to be changed,  then the extracellular lining may
be altered and breathing may be Impaired (Rand  et  al., 1982b).
    Pertinent  data  regarding  the toxlclty of  other  chlorinated  cyclopenta-
dlenes  following  subchronlc  Inhalation  exposure were  not  located 1n  the
available literature cited In Appendix A.
    6.1.1.2.   CHROMIC — Wang  and  MacMahon   (1979)  found  a  statistically
significant (p<0.05) Increase 1n deaths  from cerebrovascular  disease among a
group  of  1403  males   employed  at  plants  producing  hexachlorocyclopenta-
dlene.   Because the deaths  showed  no  consistent  pattern  with  duration  of
employment  or- with  duration-  of  follow-up,   the- authors  suggested   that
cerebrovascular disease was not related to exposure.
    The  NTP  Is  sponsoring a  chronic  Inhalation  study  of  hexachlorocyclo-
pentadlene In rats and mice (NTP, 1987).
    Pertinent  data  regarding  the toxlclty of  other  chlorinated  cyclopenta-
dlenes were not located In the available literature cited In Appendix A.
6.1.2.   Oral Exposures.
    6.1.2.1.   SUBCHRONIC — IBT (1975)  fed groups of IS male and  15  female
albino  rats  hexachlorocyclopentadlene  1n  the  diet  at concentrations of  0.
10V 100 or  300 ppm for 90 days. Treatment began  when the rats were 28  days
old.    No  treatment-related  effects   on  survival,   behavior,  hematology.
0077d                               -39-                             04/05/88

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clinical  chemistry  or  urlnalysls  were  noted.   Gross  and  hlstopathologlc
examinations  of  tissues   revealed  no  lesions   that  could  be  considered
treatment-related.
    In  a study  by  SRI  (1981a),  which  was  also reported  by  Abdo  et  al.
(1984),  groups  of 10 male and  10  female B6C3F1  mice were treated  by  gavage
with hexachlorocyclopentadlene  (94.3-97.4%  pure)  In corn  oil  at 0. 19,  38.
75, 150  or 300 mg/kg, 5 days/week  for  13 weeks.   At  300 mg/kg, all  male mice
died  by  day  8  and  three  female mice died  by day   14.   A  dose-related
depression 1n mean body weight gain was observed, with mice  In the 150  and
300 mg/kg  groups gaining  significantly  (p<0.05)  less weight  than  controls.
A significant (p<0.05)  Increase  In k1dney-to-bra1n and  llver-to-braln  weight
ratios was observed  In females at  all  doses,  with Increases  In Iung-to-bra1n
weight also observed  In females at 300  mg/kg.  Toxic nephrosls  was observed
In female mice  at doses >75 mg/kg.  This  effect  was not  observed  In  males.
Treatment at >38  mg/kg resulted  1n forestomach lesions.  Including  alteration
and Inflammatory  changes In  the epHhella 1n both male'and  female  mice.   No
effects were noted at 19 mg/kg In either  male or  female  mice.
    In a similar study (SRI,  1981b; Abdo et al.. 1984).  groups of 10 F344
rats/sex were dosed  by  gavage  with hexachlorocyclopentadlene  In corn  oil  at
0, 10,  19.  38.  75 or 150 mg/kg.  5 days/week for  13 weeks.  Mortality  was
Increased at 150  and 300  mg/kg, with  toxic  nephrosls observed 1n  both sexes
at doses >38 mg/kg.   A dose-related depression of body  weight gain relative
to controls was noted, with  significant (p<0.05) depressions compared with
controls 1n males  at 38,  75  and 150 mg/kg  and  females  at 75  and  150  mg/kg.
The 11ver-to-bra1n weight ratios  were  significantly  (p<0.05)  Increased  1n
females  at >38 mg/kg, and  k1dney-to-bra1n ratios  were significantly (p<0.05)
Increased 1n females  at >75  mg/kg.  A dose-related  Incidence  of forestomach

0077d                               -40-                              04/05/88

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les'ions (ulceratlon and  Inflammation) was  observed  beginning at 19 mg/kg  1n
femiile  rats  and  at  38  mg/kg 1n  male  rats.   No effects  were observed  In
either sex at 10 mg/kg.
    Pertinent data regarding the  toxldty  of other chlorinated  cyclopenta-
dlenes following  subchronlc  oral  exposure  were not  located  1n  the  available
literature cited In Appendix A.
    6.1.2.2.   CHRONIC — Pertinent  data  regarding  the  toxlclty  of  the
chlorinated  cyclopentadlenes  following  chronic  oral   exposure   were   not
located In the available literature cited 1n Appendix  A.
6.1.3.   Other  Relevant  Information.   Acute  toxldty data  for hexachloro-
cyclopentadlene are  presented 1n  Table 6-1.   Reported  oral  LD5Qs 1n  rats
range from 315 and 425 mg/kg In weanling female and male rats (SRI, 1980)  to
926 mg/kg  In young adult  male  and female  rats  (IRDC,  1968).   Rand et  al.
(19B2a) reported  4-hour Inhalation  LC5Qs   of  1.6 and  3.5  ppm  In  male  and
female  rats,  respectively.   The  acute  data  Indicate that  hexachlorocyclo-
pentadlerie  Is  Irritating  to the  eyes and  skin  (IRDC,  1972;  Treon et  al.,
1955).  No acute data were available for other chlorinated cyclopentadlenes.
    In a  range-finding  study, Litton B1onet1cs (1978a)  determined  the  oral
LD50  of  hexachlorocyclopentadlene  In CD-I  mice  to  be  76 mg/kg.  When  the
dose was administered to 24 mice for 5 consecutive days,  all the mice died.
    SRI (1980)  conducted  a  range-finding   study  1n  groups  of five  Fischer
rats/sex.   The rats were treated  by gavage  with hexachlorocyclopentadlene  at
25, 50, 100,  200  or  400 mg/kg for  12 doses In 16 days.   No deaths occurred
at  doses  <100 mg/kg.   At  both  200 and 400 mg/kg, all  male and 4/5  female
rats died.  In a  similar gavage study,  using  groups of five B6C3F1  mice/sex.
mice  treated  at  400  and  800 mg/kg died.   Nice  treated  at  50,  100 or  200
mg/kg  survived.   Pathologic  changes  of the  stomach  wall  were observed  In
both rats and mice at all doses  except 25 mg/kg.

0077d                               -41-                             12/23/87

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                                   TABLE  6-1

                 Acute Toxlclty of Hexachlorocyclopentadlene*
   Species, Age
             Results
                                         Reference
Rat, young adult


Rabbit, adult


Rat. young adult


Rat. young adult


Mouse, young adult


Rat. weanling


Mouse, weanling


Rabbit, adult


Rabbit, adult


Rat, young adult


Rat, young adult


Rabbit, adult
oral
         : males - 510 mg/kg
           females - 690 mg/kg
oral 1050: females - 640 mg/kg
oral LD.5Q: males and females -
926 mg/kg

oral 1050: males and females -
651 mg/kg
oral LDsg: males and females -
600 mg/kg

oral 1050: males - 425 mg/kg
           females - 315 mg/kg
oral LDSQ: males and females -
680 mg/kg

dermal 1059: females - 780 mg/kg
dermal LD-so,: males - 200 mg/kg
             females - 340 mg/kg

3.5-hour Inhalation 1059: males
          and females - 3.1 ppra
4-hour Inhalation LCsg: males -
         1.6 ppra, females - 3.5 ppm

3.5-hour Inhalation 1053:
females - 5.2 ppm
Treon et al..
1955

Treon et al.,
1955

IROC, 1968


Dorough, 1979


Dorough, 1979


SRI, 1980


SRI, 1980
                                        Treon et al.,
                                        1955

                                        IROC, 1972
                                        Treon et al.,
                                        1955

                                        Rand et al.,
                                        1982a

                                        Treon et al.,
                                        1955
Guinea pig,
young adult
Mouse, adult
3.5-hour Inhalation LCs(
and females - 7.1 ppm
3.5-hour Inhalation LC$(
and females - 2.1 ppm
j: males
j: males
Treon et al.,
1955
Treon et al.,
1955
0077d
            -42-
                                             12/23/87

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                              TABLE 6-1 (cont.)
   Species, Age                      Results                      Reference


Rabbit, adult           severe eye Irritant  (0.1  ml  for          IRDC,  1972
                        5 minutes  or  24 hours)  all dead  by
                        day 9 of study (primary eye
                        Irritation study)

Rabbit, adult           moderate skin Irritant  (250  mg/kg),      Treon  et  al..
                        one application (primary dermal          1955
                        Irritation study)

Rabbit, adult           severe skin Irritant  (200 mg/kg);        IROC.  1972
                        all males  died 1n  study (primary
                        dermal Irritation  study)

Monkey, adult           mild skin  discoloration (0.05 ml        Treon  et  al.,
                        of 10X hexachlorocyclopentadlene        1955
                        solution)  (primary dermal Irritation
                        study)


*Source: U.S. EPA, 1986b
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    In an  Inhalation  range finding study (Rand et  al.,  1982a),  groups  of 10
male and 10  female  Sprague-Dawley  rats  were exposed to hexachlorocyclopenta-
dlene  (97.7X pure)  at  0, 0.022,  0.11  or 0.5  ppm  (0,  0.25,  1.2 or  5.6
rag/m»), 6  hours/day,  5 days/week  for  10 exposures.  Four additional  groups
of 5  rats/sex were exposed for  5  dally periods and were allowed  to recover
for 14 or  21  days  following the  exposure.   Nine male rats and one female rat
exposed to 0.5  ppm were moribund  after 5-7 exposures.  All  females  and two
males  1n   the recovery  group   survived  5 exposures  and  the  21-day  recovery
period.  At  0.5 ppm,  dark red eyes, labored  breathing  and  paleness of the
extremities  were  observed.  A significant  (p<0.05) decrease  1n  body weight
was observed  In males at 0.022 and 0.11 ppm. Body weights were significantly
reduced at  day  1   after  the   exposure  at  0.5  ppm  In  both  sexes  (p<0.001,
males; p<0.01,  females).   The  packed cell volume,  hemoglobin  and  RBC counts
of rats at 0.5  ppm were significantly  higher  than  controls.   The hematology
changes  showed   some  recovery after  exposure  was ended.    No  significant
macroscopic  or  hlstopathologlc changes  were observed 1n tissues at  0.022 or
0.11  ppm.   At  0.5  ppm, pale  areas of consolidation were  observed In  the
lungs and  hlstopathologlc  lesions  were  observed 1n  the bronchioles and  nasal
passages.   These changes were  not observed after 14-21  days of recovery.
    In humans exposed to  hexachlorocyclopentadlene by  Inhalation,  the most
noticeable  effect  1s  the  pungent.  Irritating  odor.  Levin  (1980)  reported
that  the   odor  recognition for  100% of the  Individuals  on  the panel  was
0.0017  mg/ma   (0.00015  ppm).   Other   than  stating  that   the  study  was
completed  1n a dynamic chamber, details of the study design were not stated.
    In 1977,  an acute exposure Incident occurred  at the  Morris Forman Waste-
water Treatment Plant  1n  Louisville. KY (Wilson  et  al.. 1978; Norse et al.,
0077d                               -44-                             04/05/88

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1979; Komlnsky at al., 1980; U.S. EPA,  1984a,  1986b).   The Louisville treat-
ment  facility  was contaminated with  large amounts of  hexachlorocyclopenta-
dlene  and  lower  levels  of octachlorocyclopentene,  a waste  by-product  of
hexachlorocyclopentadlene manufacture  (Morse  et al.,  1979).   Concentrations
of hexachlorocyclopentadlene detected  In  the  sewage water at  the  plant  were
as high  as  1000  ppm. Airborne  levels of  hexachlorocyclopentadlene 1n  the
primary treatment areas  (screen and grit  chamber) measured 4  days after the
plant closed ranged  between 270  and 970 ppb.   During  the  clean-up,  when the
workers  used steam  to  remove  the contamination,  hexachlorocyclopentadlene
concentrations were reported to be 19.2 ppm (Komlnsky et al..  1980).
    Employees of  the  plant  were  given questionnaires regarding the  type and
duration  of  symptoms  (Norse et al..  1979;  Komlnsky et al., 1980).   A  total
of 193  employees  were Identified as  potentially  exposed  for  >2 days during
the 2  weeks before the  plant was  closed  (Norse et al., 1979).  The results
of the questionnaire,  completed by 145 (75X) of  the  workers.  Indicated  that
the most  common  symptoms  were  eye  Irritation (59X).  headaches   (45X)  and
throat Irritation  (27X).  In 9SX  of the workers  responding to the question-
naire, the  odor of  hexachlorocyclopentadlene  was detected before  the  onset
of symptoms.   Of  the 41 workers  physically examined,  6 had signs of  eye
Irritation and 5  had  signs  of  skin  Irritation.  Laboratory analyses of blood
and urine specimens  from workers  given physical exams  revealed elevation of
lactic dehydrogenase  1n  27% and  protelnurla 1n 15X.   No  clinical  abnormali-
ties were reported 3 weeks later (Norse et al.. 1978, 1979).
    During  the cleanup,  the clinical  chemistry   parameters  of the workers
were  monitored.   The only  abnormalities  noted were  several  minimal-to-mild
abnormalities  In  liver  function  tests (SGOT, serum  alkaline  phosphatase,
serum  total blllrubln,  serum lactate  dehydrogenase).   All persons showing
these  changes  also  had physical  signs   of   mucous  membrane  Irritation.

0077d                               -45-                             04/05/88

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Because  these workers  used  protective  equipment  during  the  cleanup  and
because of possible prior  exposure,  exposure levels could not be  accurately
estimated (Norse et al., 1979).
6.2.   CARCINOGENICITY
6.2.1.   Inhalation.    A   number   of  mortality   studies   (Shlndell   and
Associates, 1980,  1981; Wang  and  MacHahon,  1979; Buncher et al.,  1980)  have
not shown  Increased  cancer death rates 1n   workers Involved In the  produc-
tion  of  hexachlorocyclopentadlene.  These  studies  are  reviewed  In U.S.  EPA
(1984a. 19865).
    An NTP  Inhalation care1nogen1city bloassay  of  hexachlorocyclopentadlene
1n rats and mice Is 1n progress  (NTP, 1987).
    Pertinent  data regarding the  cardnogenlclty  of  the other chlorinated
cyclopentadlenes  following  Inhalation exposure were  not  located  1n  the
available literature cited In Appendix A.
6.2.2.   Oral.  Pertinent  data  regarding  the cardnogenlclty of the  chlori-
nated  cylcopentadlenes  following oral  exposure  were  not  located  In  the.
available literaturedted 1n Appendix A.  A chronic oral toxlclty  study of
hexachlorocyclopentadlene  being conducted  by SRI for the NTP was  terminated
1n  April,  1982 because Inhalation was  determined to  be the more  relevant
route of exposure  (U.S.  EPA, 1986b).
6.2.3.   Other Relevant Information.   Pertinent  data  regarding  the carcino-
gen 1c1ty  of  the  chlorinated  cyclopentadlenes  following  other  routes  of
exposure were not  located In the available literature cited  In Appendix A.
6.3.   MUTAGENICITY
    In vitro  and  jn, vivo  mutagen1c1ty data  for the  chlorinated cyclopenta-
dlenes are  presented In  Table  6-2.   Negative  results  for  hexachlorocyclo-
pentadlene have been  reported 1n  mutagenlclty assays  1n bacteria  (Goggelmann

0077d                               -46-                             04/05/88

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                                                                                 TABLE 6-2
                                                           Hutagentclty  Testing of  Chlorinated  Cyclopentadlenes
I
fj
fO
ro
Assay
Reverse
autatlon
Reverse
autatlon
Reverse
autatlon
Reverse
autatlon
Reverse
autatlon
Reverse
autatlon
Reverse
autatlon
Indicator/
Organlsa
Escherlchla
coll k12
i. coll k12
I. colt k!2
Salaonella
typhlaurlua
TA1535.
TA1538
J. typhlaurlua
TA1535. TA1538
§. typhlaurlua
TA100
f. typhtaurlua,
A98. TA100.
1A1S35, TA1S37
Coapound
and/or
Purity
hexacnloro-
cyclopenta-
dtene/gas-
chroaato-
graphlcally
pure
pentachloro-
cyclopenta-
dlene/gas-
chroaato-
graphlcally
pure
tetrachloro-
cyclopenta-
dlene/gas-
chroaato-
graphlcally
pure
hexachloro-
cyclopenta-
dlene
tetracbloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
dtene/9BX
Application
prelncuba-
batlon
prelncuba-
batlon
pretncuba-
batlon
MR
MR
vapor
prelncuba-
tlon
Concentration Activating
or Dose Systea
2. 7x10" * - i aouse liver
2.7xlO~* H alcrosoaal
protein
2.4xlO"» - » aouse liver
2.4xlO~* N atcrosoaal
protein
1.0x10"" - i aouse liver
1.0x10~» N atcrosoaal
protein
MR » aouse liver
alcrosoaal
protein
MR • » aouse liver
alcrosoaal
protein
MR »S-9
3.3 pg/plate -S-9
100 |ig/plate »S-9
Response Coanent
• 70X survival at 72 hours.
cytotoxtc at higher
concentrations
i Positive results with.
but not without aeta-
bollc activation
i Positive results with.
but not without aeta-
bollc activation
NC
» NC
• Exposure tlaes of 30. 60
and 120 atnutes were used
which Bay not have been
long enough to observe
a autagenlc effect.
Higher levels could not
be tested due to cyto-
toxtctty.
Reference
Gfiggelaann
et al.. 1978
Gflggelaann
et al.. 1978
GOggelaann
et al.. 1978
Greta
et al.. 1977
Greta
et al.. 1977
IBT. 1977
Haworth
et al.. 1983

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                                                                   TABLE 6-2 (cont.)
1
a.



h
Assay
forward
mutation
OKA repair
Cell trans-
formation
Sex-linked
recessive
lethal
Dominant
lethal
Indicator/
Organism
mouse lymphoma
U178Y cells
rat primary
hepatocytes
IALI/3T3
cells
Drosophlla
melanooaster
CD-I mice
Compound
and/or
Purity
hexachloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
dlene
Application
added to
cultures
added to
cultures
added to
cultures
feeding
Injection
gavage.
S days
Concentration Activating
or Dose System
1.25xlO~* »S-9
t>9/tt
10~« - NA
10'« N
0-0. 156 nt/iil
40 ppm NA
200 ppm
i
0.1. 0.3 or NA
l.Omg/kg/day
Response Comment
Cytotoxlclty was ob-
served at higher con-
centrations.
NC
Doses selected allowed
80-100X survival.
NC
Nice were mated for
7 weeks.
Reference
Litton
Blonetlcs.
Inc.. 1978b
Brat. 1983
Litton
Blonetlcs.
Inc.. 1977
Juodelka,
1983
Litton
Blonetlcs.
lnc.,1978a
NA . Not applicable; NC . no conwnt; NR - not reported

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et al.. 1978;  Greta et  al.. 1977; IBT. 1977; Haworth et al.. 1983) and  1n  a
mutation  assay 1n  mouse  lymphoma  cells  (Litton B1onet1cs,  Inc.,  1978b).
Hexachlorocyclopentadlene  also  tested  negative  for  cell  transformation  1n
BALB/3T3  cells  (LHton   B1onet1cs,  Inc.,  1977).  DNA repair  In  rat  primary
hepatocytes  (Brat,  1983),  sex-1Inked  recessive  lethal  mutations  1n  Droso-
phlla melanoqaster  (Juodelka, 1983) and a dominant lethal mutation study  1n
mice (LHton Blonetlcs,  Inc.. 1978b).
    Studies of penta- and  tetrachlorocyclopentadlene  In  bacteria  (Gdggelmann
et al.. 1978; Grelra et al..  1977) have reported  positive results  for  reverse
mutation  In  the  presence of metabolic  activation.  Gdggelmann et al.  (1978)
suggested  that  penta- and  tetrachlorocyclopentadlene  can  be metabolized  to
tetrachlorocyclopentadlenone, which can react with nucleophlles.   The addi-
tional  chlorine  atom on  hexachlorocyclopentadlene  may hinder the  formation
of the dlenone, preventing mutagenlc activity.
6.4.   TERATOGENICITY
   •* *              *  •      •»                   ,
    In  a  teratogenlclty  study,  pregnant  Charles  River  CO rats were  treated
by gavage  with hexachlorocyclopentadlene  (98.25% pure) In corn oil at 3,  10
or  30 rag/kg  on   gestation  days  6-15  (IROC. 1978;  Root et  al.,  1983).   A
control group  was  treated  with corn  oil  at  a volume of 10  mi/kg/day.   All
rats  survived, with no  differences  1n maternal  body weight gain  observed.
Persistent anogenltal staining was observed  1n dams  at  the  highest  dose.  No
differences  1n the number  of  Implantations, corpora  lutea, live  fetuses,
mean  fetal body  weight  or male/female sex  ratios  were observed.   Examina-
tions  of   fetuses  revealed no statistically  significant differences  In the
number of  external, soft tissue or skeletal  abnormalities.
    In  an  Yn vivo teratology screening study of  hexachlorocyclopentadlene In
pregnant  CD-I  mice,  no  effects  were noted on maternal  weight  gain,  pup


0077d                               -49-                             04/05/88

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survival or  average pup weight  (Chernoff  and Kavlock. 1982).  The  pregnant
mice were  treated by  gavage  with hexachlorocyclopentadlene  at  45 rag/kg  on
gestation  days  8-12.    Gray   and Kavlock  (1984)  studied  these  offspring
further  and  found no  effects  on growth,  morphology,  locomotor function  or
reproductive  function.   Gray  et  al.  (1986)  observed no  effect  on  figure-
eight maze activity In these offspring.
    Hurray et  al. (1980)  treated pregnant CF-1  mice  and New Zealand  WhHe
rabbits  by gavage with hexachlorocyclopentadlene In cottonseed oil at  0,  5,
25 or 75 rag/kg/day.  Nice  were treated on  gestation days  6-15 and  sacrificed
on day  18, while rabbits were treated on  gestation days  6-18 and  sacrificed
on  day   29.   The  fetuses  (23-33 litters/group,  rats; 12-24  Utters/group,
rabbits)  were  weighed, measured and examined  for  external alterations.
One-third of  the fetuses were  examined  for  soft tissue  abnormalities,  with
all the  fetuses  cleaned and stained  for skeletal examinations.  No  signs  of
maternal toxldty were observed  In  mice.   Rabbits  treated  at 75  mg/kg/day
had diarrhea  and  significant  weight  loss and  several (number unspecified)
died.   No  significant  effects on the  average number of  Implantations,  live
fetuses, resorptlons,  or  mean fetal  body weight  and  length were noted  In
either  species.   No Increases In gross  or   soft  tissue  abnormalities  were
observed.  The proportion  of rabbit  fetuses with  13 ribs  was  Increased  at  75
mg/kg/day.    No  other   significant   Increases   In   skeletal  variations   were
observed In either species.
    Pertinent  data  regarding  teratogenlc  effects  for   other   chlorinated
cyclopentadlenes  were   not located  In  the   available literature  cited  1n
Appendix A.
0077d                               -50-                             12/23/87

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6.5.   OTHER REPRODUCTIVE EFFECTS
    No evidence  of  a dominant lethal  effect  was  observed In male CD-I mice
given  hexachlorocyclopentadlene  by gavage  at 0.1,  0.3  or 1.0  mg/kg for  5
days  (LUton  B1onet1cs(  Inc.,  1978a).   The  mice  were  mated  throughout
spermatogenesls (7 weeks).
    Pertinent  data  regarding other  reproductive  effects  for  other  chlori-
nated cyclopentadlenes were not located In the available  literature cited  1n
Appendix A.
6.6.   SUMMARY
    Except for mutagenldty assays  of  penta-  and  tetrachlorocyclopentadlene,
toxldty  data  are  limited  to studies concerning  hexachlorocyclopentadlene.
Subchronlc  Inhalation  studies   of  hexachlorocyclopentadlene  have  shown   a
steep dose-response curve.  In a 6- to 30-week study  by Treon  et al.  (1955),
rabbits,  mice and  rats  exposed to  0.34  ppm  hexachlorocyclopentadlene  by
Inhalation  7 hours/day,  5 days/week  at  0.34 ppm died,  while  guinea pigs
survived.  At  0.15  ppm,  only  the mice died.  Renal  and hepatic  degeneration
was observed  In  all species, and  lung lesions were noted In mice, rats and
guinea pigs.
    0. Clark  et  al. (1982) reported  that  rats  exposed by Inhalation  to 0.5
ppm hexachlorocyclopentadlene died; no significant  treatment-related  effects
were  observed  at 0.1 ppm.   The  rats were  exposed  6 hours/day,   5  days/week
for 30  weeks followed by a 14-week  recovery  period.   In  a 13-week study  by
Rand  et  al.   (1982a,b),  no  effects  were  observed  1n  monkeys  exposed   by
Inhalation  to  hexachlorocyclopentadlene   at  0.01,  0.05,  or  0.2  ppm,   6
hours/day,  5  days/week.   In  rats  exposed  at  the same hexachlorocyclopenta-
dlene concentration, the only consistent treatment-related effect  was ultra-
structural changes In the Clara cells of  the lungs.


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    A  13-week study  using  rats  and  mice sponsored  by  the  NTP  (Battelle
North- west Laboratories,  1984; Abdo et al.,  1986) found  no effects  In  mice
at   0.04   ppro    and    1n   rats   at   0.15   ppm.    Nice    exposed    to
hexachlorocyclopentadlene  at  >0.15  ppm developed  lung lesions, with  deaths
occurring at >0.4  ppm.  Lung  lesions were  observed  1n  rats at  >0.4 ppro,  with
deaths at  >1  ppm.   The animals  were  exposed 6 hours/day,  5  days/week.   A
chronic Inhalation study using rats  and mice Is  In  progress (NTP, 1987).
    A  13-week  gavage study  using rats and mice (SRI,  1981a;  Abdo et  al..
1984)  found  ulceratlon of  the stomach 1n  mice treated 5 days/week at  >38
rag/kg, and  at >19 mg/kg  In  rats.   No effects  were observed  In mice at  19
mg/kg  or  In  rats  at  10  mg/kg.   No effects  were  reported  1n  rats  fed
hexachlorocyclo- pentadlene  1n  the  diet at up  to  300  ppm for  90  days  (IBT,
1975).
    The  lowest  oral  LD5Q  Is  315  mg/kg  1n  female  weanling  rats  (SRI,
1981a).  The  lowest  Inhalation  LC.Q  reported  Is 1.6  ppm In  young  adult
male rats (Rand et al., I982a).   A  short-term Inhalation study using rats at
0.5 ppm  (Rand et al., 1982a)  found  that lung  lesions observed  when rats  were
exposed  for  five 6-hour  periods  were  not  present  after  14-21  days  of
recovery.
    The  odor   recognition  concentration  for  hexachlorocyclopentadlene  was
reported to be  0.0017 rag/m*  (Levin,  1980).   Questionnaires  completed  by
workers  at  the  Morris  Forman Wastewater  Treatment  Plant  In Louisville,  KY,
where  an  acute   exposure  Incident  occurred.  Indicated  that  95X  of  the
respondents detected  the  odor  of hexachlorocyclopentadlene before  symptoms
of Irritation  occurred (Norse et al., 1978, 1979).
    NortalHy studies  of  hexachlorocyclopentadlene  production workers  have
not shown  Increased  cancer death rates.   No  animal studies of  the  carcino-
gen 1c1ty of hexachlorocyclopentadlene were available.

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    Results of mutagenldty  assays  of penta- and tetrachlorocyclopentadlene
1n  bacteria  have  been positive  (Goggelmann et  a1.(  1978;  Grelm et  al.,
1977); however,  hexachlorocyclopentadlene  has consistently  tested  negative
1n mutagenlcUy assays.
    Oral   teratogenldty   studies  of  hexachlorocyclopentadlene  using  rats
(IROC, 1978), mice and rabbits  (Murray  et  al.,  1980)  have reported negative
results,   although  an  Increase  In  skeletal   anomalies  was  observed  at  75
mg/kg/day, a dose that also resulted 1n maternal toxldty.  Hexachlorocyclo-
pentadlene has  also  tested  negative for  dominant lethal  effects In  mice
(Litton Blonetlcs,  Inc.,  1978a).
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                     7.   EXISTING GUIDELINES AND  STANDARDS
7.1.   HUNAN
    Hexachlorocyclopentadlene  1s the  only chlorinated cyclopentadlene  for
which  guidelines  and  standards have  been  developed.   ACGIH  (1986)  has
recommended  a  TLV-TWA  of  0.01  ppra  (0.1  mg/ma)  for persons  occupatlonally
exposed  to  hexachlorocyclopentadlene.   NIOSH  (1978)  has  classified  hexa-
chlorocylopentadlene as  a  Group II  pesticide.   Standards based  on  engineer-
Ing  controls,  work  practices and  medical  surveillance  programs have  been
recommended to protect workers (NIOSH, 1978).
    An RQ of 10  pounds  has  been  proposed  for  hexachlorocyclopentadlene (U.S.
EPA,  1987b).   The  ambient  water   quality  criteria  for   hexachlorocyclo-
pentadlene  to  protect  human  health  Is  206  vg/l.   Using organoleptlc  data
for  controlling  undesirable  taste   and  odor,  the  estimated  level  1s  1
tig/ft  (U.S.  EPA.  198Gb).   U.S.  EPA  (1988a)  has  recommended  the  following
HAs  for  hexachlorocyclopentadlene:   1-day HA for  a child.  1.5  mg/l;  10-day
HA  for  a  child,  0.179  rag/l;  longer-term  health  advisory  0.25  mg/l  and
the   lifetime    DUEL.   0.25   mg/l.    An   RfO   of  0.007   mg/kg/day   for
hexachlorocyclopentadlene has  been  verified  and 1s available on  IRIS (U.S.
EPA, 1988b).
7.2.   AQUATIC
    U.S.  EPA  (1980b) stated  that acute and  chronic toxlclty to  freshwater
aquatic  life occur at hexachlorocyclopentadlene  concentrations as  low as 7.0
and  5.2  yg/l,  respectively,   and   would  occur   at  lower  concentrations
among more  sensitive species.   The  limited data  for acute  hexachlorocyclo-
pentadlene  toxlclty   to saltwater  species  Indicate  that effects  occur  at
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                             8.  RISK ASSESSMENT
8.1.   CARCINOGENICITY
8.1.1.   Inhalation.   Pertinent  data  regarding  the  cardnogenldty of  the
chlorinated cyclopentadlenes following  Inhalation  exposure  were not located
In the available  literature cited  1n  Appendix A.  An Inhalation carclnogen-
Iclty bloassay of hexachlorocyclopentadlene  1s  In progress (NTP, 1987).
8.1.2.   Oral.   A number  of  mortality  studies  (Shlndell  and  Associates,
1980, 1981;  Wang and MacMahon,  1979;  Buncher et al.,  1980)  have  not shown
Increased  cancer death  rates  1n  workers  Involved  In  the   production  of
hexachlorocyclopentadlene.  Animal  studies  regarding  the  cardnogenlclty of
chlorinated cyclopentadlenes following oral  exposure were not located In the
available literature  cited  In  Appendix  A.
8.1.3.   Other Routes.  Pertinent data  regarding the  cardnogenlclty of the
chlorinated  cyclopentadlenes  following other  routes of  exposure  were not
located In the available literature cited  In Appendix  A.
8.T..4.   Weight of Evidence.  No reports  of  cardnogenlclty  of hexachloro-
cyclopentadlene  or  the other chlorinated  cyclopentadlenes  were  located 1n
the  available  literature.   Applying the criteria  of  the Carcinogen Assess-
ment  Group  (U.S. EPA,  1986b).  the  chlorinated   cyclopentadlenes can  be
considered Group D -  not classified compounds.
8.1.5.   Quantitative Risk Estimates.   The  lack  of  cardnogenlclty data for
the chlorinated cyclopentadlenes  precludes the derivation of potency factors.
8.2.   SYSTEMIC TOXICITY
8.2.1.   Inhalation Exposures.
    8.2.1.1.   LESS   THAN   LIFETIME   EXPOSURES   (SUBCHRONIC) —  Inhalation
exposure  to hexachlorocyclopentadlene  1s very  Irritating and  the  compound
has  a pungent 'odor.   ACGIH (1986) stated  that "once  hexachlorocyclopenta-
dlene has been smelled the odor  Is  unmistakable  and Us  lacrlmatory activity

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Is  not  conducive  to  prolonged  Inhalation."   To  prevent  Irritation,  any
recommended  Inhalation   RfO   should  be  below   the  dose   resulting  from
continuous exposure at  the  odor  threshold.  Levins  (1980) reported  that  the
hexachlorocyclopentadlene odor recognition for  100X of the  Individuals on  a
panel  was  0.0017  mg/ma   (0.00015   ppm).   Multiplying   the   0.0017  mg/ma
concentration  by  20  mVday,  the  human breathing rate,  and  dividing by  a
human body weight of 70 kg,  a dose of 0.0005 mg/kg/day Is  calculated.
    During an acute exposure  Incident at the  Morris  Forman Wastewater Treat-
ment Plant  In  Louisville, KY  (Morse et al.. 1978.  1979) It was  found  that
the  majority  of  workers   detected   the   odor  of  hexachlorocyclopentadlene
before the onset  of symptoms  of  Irritation,  providing  support  that a dose at
or below  the hexachlorocyclopentadlene  odor  threshold  should prevent Irrita-
tion.  Human data do not  Indicate  1f exposure at or  below the odor threshold
will prevent subchronlc or chronic effects.
    Treon et al.  (1955) exposed  guinea  pigs,  rabbits,  mice and rats to hexa-
chlorocyclopentadlene at  0.15 or 0.34  ppm,  7 hours/day,  5  days/week  for up
to 150 exposure periods.  At  0.34  ppm,  deaths occurred In all  species except
guinea pigs, with degenerative changes.In  major  organs.   At  0.15 ppm, deaths
occurred  only  In  mice.  Slight  renal  and  hepatic degeneration  was  observed
1n all  species,  with  lung  lesions  also  reported In  mice,  rats  and  guinea
pigs.  Because  only 2-6  animals per species were studied at  each  exposure
concentration,  this  study 1s not  considered adequate for  risk assessment.
    In a  study  by Rand et al. (1982a), groups of  40 rats/sex  and 6 cynomol-
gus monkeys/sex were exposed  to  hexachlorocyclopentadlene at 0,  0.1,  0.6 or
2.2 mg/ra3 (0.  0.01, 0.05  or 0.2  ppm), 6 hours/day,  5  days/week for up to
14 weeks.  No  effects  were  observed In monkeys.   In rats, transient appear-
ance of  dark-red  eyes  was  observed  In  males at  0.6 and  2.2 mg/m»  (Rand et


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al.,, 1982a).   At  12 weeks, marginal  changes  In hemoglobin were  observed  In
males  at  0.1  mg/m8 and  1n females  at 0.6  and 2.2  mg/ma.   No  treatment-
related changes  1n body weight,  food and  water consumption, and  gross  and
hlstopathology were  observed.   Electron microscopy  revealed  ultrastructural
changes In  the Clara cells In  rats  at all exposure concentrations,  with  no
effects 1n monkeys  (Rand  et al.,  1982b).  The  lexicological  significance  of
this effect 1s not known.
    U.S.  EPA  (1984b)  considered   the 2.2  mg/ma exposure  concentration  In
the  Rand  et al.  (1982a)  study to be a NOAEL  In both rats and  monkeys  and
calculated a  subchronlc  Inhalation RfO  based  on monkeys.  U.S.  EPA  (1984b)
did  not  state why the rat  data were  not,  used for   RfD  derivation.   Because
subsequent  subchronlc  studies  have   reported  effects   In  rats and mice  at
lower concentrations, a new subchronlc Inhalation RfO will be derived.
    0. Clark  et  al. (1982) exposed  groups of  eight rats/sex  to  hexachloro-
cyclopentadlene at  0,  0.56, 1.1 or  5.6 mg/m3  (0,  0.05,  0.1  or  0.5  ppm), 6
hours/day, 5  days/week  for 30  weeks,  followed by a 14-week  recovery period
without  hexachlorocyclopentadlene  exposure.   At 5.6  mg/m8,  four male  and
two  female  rats  died, weight gain  was  depressed  1n  males and  pulmonary
degenerative changes were noted In both  sexes.   H1ld degenerative changes  1n
the  liver and kidney  were also  observed   In  a few rats at  5.6 mg/m8  and
kidney weights Increased  significantly  In females.   In  female rats  at  5.6
and  1.1  mg/m8, significantly  Increased  body weights  were  noted  during  the
first half of  the exposure period, followed by significantly decreased body
weights compared  with  controls at the end of  the  recovery  period.   Because
these  body weight  gains  were  transient,   they are not  clearly  related  to
hexachlorocyclopentadlene treatment.   The  LOAEL Identified  1n this study was
0077d                               -58-                             04/05/88

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5.6  rog/ma,  a  concentration  associated  with  death.   Nultlplylng  the  5.6
mg/m8  concentration by  6/24  hours  and  5/7 days  to  expand  to  continuous
exposure,  and multiplying  by a  reference  rat  breathing  rate  of  0.223
m'/day and  dividing by the reference  rat  body  weight of 0.35 kg  (U.S.  EPA.
1985), results 1n  a LOAEL dose of 0.64 mg/kg/day.  Although the  D.  Clark et
al.  (1982)  Is  study Is the longest duration  Inhalation  study  of  hexachloro-
cyclopentadlene available,  the NTP-sponsored  13-week study  using rats  and
mice  (Battelle  Northwest  Laboratories,  1984; Abdo et  al., 1986)  described
below.  Identified  lower  Inhalation  LOAELs;  therefore,  the NTP  study  Is  a
better basis for  a subchronlc Inhalation RfO.
    In the  NTP-sponsored  study (Battelle  Northwest  Laboratories,  1984; Abdo,
et al.,  1986),  groups  of  10  rats/sex  and 10 mice/sex were exposed  to hexa-
chlorocyclopentadlene at  0,  0.45,  1.67, 4.46,  11.1  or 22.3 mg/m3  (0. 0.04,
0.15, 0.4,  1  or  2 ppm), 6 hours/day,  5 days/week for  13  weeks.   Information
concerning  the mouse study was available  only  In an abstract (Abdo  et  al.,
1986).   All  rats  and  mice exposed to >11.1  mg/m8  died.  In  rats  (Battelle
Northwest  Laboratories.  1984), body weight gain was  significantly  (p<0.05)
reduced  1n  males   at  4.46  mg/m3;  a  similar  but  less  severe  effect  was
observed  1n females.   At  0.4 ppm,  relative  lung  weights were higher  In
females  and significantly  (p<0.5)  higher  1n  males.   Relative  weights  of
heart,  kidney  and  testes  In  4.46  rog/ra8 males  were  also  Increased.   Dose-
related  hlstopathologlcal  changes  In  the  respiratory tract epithelium  were
observed  In rats  at >4.46 mg/m8.   The changes  observed  Included  necrosis
and  acute Inflammation.   No  effects  were  observed 1n  rats  at  1.67  mg/m8.
Multiplying  the  LOAEL  (4.46  mg/m8)  and NOAEL  (1.67 mg/m8)  concentrations
by 6/24  hours and  5/7  days  to expand  to  continuous  exposure,  and  multiplying
by the  Inhalation rate  of 0.16 mVday  calculated  by methodology  described

0077d                               -59-                             04/05/88

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1n  U.S.  EPA (1985)  from  the rat body  weight  estimated from growth  curves,
and  dividing  by the estimated  rat  body weight of  0.22 kg, LOAEL and  NOAEL
doses of 0.6 and 0.2 mg/kg/day,  respectively,  are  derived.
    In mice  (Abdo et al.,  1986),  5/10  male  and  2/10  females  died  at  4.46
mg/ma,  and  body  weight   gains  were  10%  lower  In  both  sexes   at   this
concentration.  The  only  change In  organ weight was an  Increase  In  relative
lung   weights    of   males    exposed    to   4.46   mg/ma.     Dose-related
h1stopatho1og1ca1  alterations  1n   the   respiratory  epithelium.   Including
hyperplasla  and  metaplasia,  were  observed  1n  mice  at  >1.67  mg/ma.   No
effects were  observed  In mice  at 0.45  mg/m».  Multiplying the LOAEL  (1.67
mg/m3) and NOAEL  (0.45  mg/m3)  concentrations by  6/24 hours  and  5/7  days
to  expand  to  continuous  exposure,  multiplying  by  the  reference  mouse
Inhalation  rate  (0.039 mVday) and  dividing  by  the  reference  mouse  body
weight (0.03  kg)  (U.S.  EPA, 1985) yields  LOAEL and NOAEL doses of  0.39  and
0.2 mg/kg/day, respectively.
    The  lowest  LOAEL   1n  the  NTP-sponsored  subchronic   studies   1s   0.39
mg/kg/day,  a  dose  at  which hyperplasla  and metaplasia  of the  respiratory
epithelium were  observed  In mice.   The  highest NOAEL below the mouse  LOAEL
1s  the rat  NOAEL  of 0.2 mg/kg/day.   Application  of an  uncertainty  factor of
100  (10  for  Interspedes  extrapolation and  10  to  protect sensitive  Indi-
viduals) and a modifying  factor of 10  results  1n  a  subchronic  Inhalation RfD
of  0.0002 mg/kg/day  or 0.014 mg/day  for  a  70  kg human.   The modifying factor
1s  used  because of  the steep  dose-response curve Indicated 1n the  0.  Clark
et  al.  (1982)  and the  NTP-sponsored study  (Battelle  Northwest  Laboratories,
1984;  Abdo et al.,  1986).   The modifying  factor also  brings the RfD  below
the  dose  that  may  be  associated with  Irritation  at  the odor  threshold.
0077d                               -60-                             04/05/88

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Multiplying the  0.0002  rag/kg/day RfD by  70  kg body weight, and dividing  by
20  mVday human  breathing  rate,  the  subchronlc  RfD  for  hexachlorocyclo-
pentadlene corresponds to a air concentration of 0.0007  mg/m8.
    Confidence  In  the  RfD  Is medium.   Several studies  Indicated  that  the
lungs are the  target  of  Inhalation  exposure  to  hexachlorocyclopentadlene.
These studies  also  Indicated  that the  dose-response curve  Is  very  steep.
Acute human  data and the  odor  threshold also Indicate that the subchronlc
Inhalation RfD should protect against  Irritation.
    A lack of pertinent data regarding the subchronlc Inhalation toxldty  of
the  other chlorinated  cyclopentadlenes  precludes  the derivation  of  sub-
chronic  Inhalation RfDs.
    8.2.1.2.    CHRONIC  EXPOSURES — There are  no  chronic Inhalation  studies
of  hexachlorocyclopentadlene.  An  NTP chronic bloassay  Is  In progress  (NTP.
1987).  U.S.  EPA (1984b) considered the 30-week D.  Clark  et al.  (1982)  study
(see  Section  8.2.1.1.)  to be  a  chronic  study.   The  0.1  ppm  (1.1  mg/m3)
concentration,  a  level  at  which  the only   effect  was  an  Increase   In  body
weight  1n  females  during  treatment followed by  a  decrease  during  the
recovery  period,  was considered  the  LOAEL.   A  chronic  Inhalation  RfD  of
0.00006  rag/kg/day  or   0.0046  mg/day  was calculated  from 0.05  ppm  (0.56
mg/m*),   the   lowest concentration  tested  (NOAEL).  using  a  rat  breathing
rate  of  0.26 raVday, a rat body  weight  of 0.35  kg, an uncertainty factor
of   100   (10   for  Interspecles  extrapolation,  10  to   protect  sensitive
Individuals)   and  a  modifying  factor  of  10  to  reflect  concern  about
discrepancies In the data base.  Because  the 0.1  ppm concentration should be
considered a  NOAEL rather  than  a  LOAEL  (weight  changes were transient  and
not clearly treatment-related), and because  the 13-week mouse study  (Abdo et
al., 1986) Identifies a lower  LOAEL,  the  mouse study 1s a better basis for a

0077d                               -61-                             04/05/88

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chronic Inhalation  RfD.   Application  of an additional uncertainty  factor  of
10  to  the  subchronlc  Inhalation RfD  results 1n  a chronic  RfD of  0.00002
rog/kg/day (0.0014 rag/day), or a concentration of  0.00007  mg/m».
    As  stated  for  the  subchronlc  Inhalation  RfD  for  hexachlorocyclopenta-
dlene, confidence 1n the  chronic Inhalation RfD Is medium.   The chronic RfD
should be reviewed when the  chronic NTP study 1s  available.   Because Irrita-
tion  and  lung lesions  are  the major  effects  of Inhalation  exposure  to
hexachlorocyclopentadlene, an  additional uncertainty  factor to  extrapolate
from subchronlc to chronic exposure may not be necessary.
    A  lack  of  pertinent  data  regarding the  chronic  Inhalation  toxlclty  of
the other  chlorinated  cyclopentadlenes  precludes  the derivation of  chronic
Inhalation RfDs.
8.2.2.   Oral Exposures.
    8.2.2.1.   LESS  THAN  LIFETIME  EXPOSURES — The  only  subchronlc  oral
study  available  Is the  gavage  study  using rats and  mice completed  by SRI
(1981a) and reported  1n  Abdo  et al.  (1984).  In  this  study,  groups  of  10
B6C3F1  mice/sex were  treated  by gavage  with hexachlorocyclopentadlene  In
corn oil at  0,  19.  38.  75.  150 or 300 mg/kg, and similar groups of  F344 rats
were treated at 0.  10,  19.  38. 75 or  150 mg/kg.   Both species were  treated 5
days/week  for  13 weeks.   Nice  treated  at  300 mg/kg  died,  and  body weight
gain was significantly depressed at 150 mg/kg.   Toxic  nephrosls was observed
In  female mice  at doses  >75  mg/kg,  but  this  effect  was  not  observed  1n
males.   Treatment  at >38 mg/kg  resulted  In forestomach  lesions.  Including
ulceratlon  In  both  male and  female  mice.  The NOAEL for  both male and female
mice was 19 mg/kg.
0077d                               -62-                             04/05/88

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    In  rats,  mortality  and  toxic  nephrosls  were observed  In  males  and
females at  doses  >38 rag/kg.  A  dose-related depression of  body  weight gain
relative  to  controls  was  noted,  with  significant   (p<0.05)   depressions
compared with  controls  In  male  rats at 38, 75  and  ISO  rag/kg and  female rats
at  75 and  ISO rag/kg.   At 19  rag/kg,  the LOAEL,  forestomach lesions  were
observed 1n  female  but  not male rats.  The  10  mg/kg dose level  was  a NOAEL
In both male and female rats.
    Because  stomach  lesions  were  observed  In  female  rats  at  19 mg/kg,  a
NOAEL dose  1n  mice,  the rat NOAEL of 10 mg/kg  Is  the most appropriate basis
for  a  subchronlc oral  RfO.   Expanding  this  dose to  dally  exposure  by
multiplying by 5/7 days results  In a  dose  of 7  mg/kg/day.  Application of an
uncertainty  factor  of 100,  10   to  protect sensitive  Individuals and  10  to
extrapolate from animals to humans, results  In  a  subchronlc  oral  RfD of 0.07
mg/kg/day  or  5 mg/day  for a  70  kg  human.   Confidence In  this  RfD  Is  low
because of the lack of additional oral studies.
    A lack  of  pertinent data regarding  the  subchronlc oral toxlclty of the
other  chlorinated cyclopentadlenes  precludes  the  derivation  of subchronlc
oral RfOs.
    8.2.2.2.   CHRONIC  EXPOSURES — There  are  no  chronic   oral  studies  of
hexachlorocyclopentadlene.   A chronic  oral   RfO  of 0.007 mg/kg/day  or  0.5
mg/day  for  a  70  kg  human may   be  derived by  dividing the subchronlc oral
NOAEL  by  an additional  uncertainty  factor  of  10  to  extrapolate  from sub-
chronic to  chronic  exposure.   This RfD  was  verified by the EPA  RfD Working
Group  on  October 9,  1986  and  1s   available  on  IRIS (U.S.  EPA,  1988b).
Because supporting  oral  data are  not available,  confidence 1n  this  RfD Is
low.
    A  lack  of  pertinent data regarding the  chronic oral  toxlclty  of other
chlorinated cyclopentadlenes precludes the derivation of chronic  oral RfDs.
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                          9.  REPORTABLE QUANTITIES
9.1,.   BASED ON SYSTEMIC TOXICITY
    The toxldty of hexachlorocyclopentadlene was discussed  In  Chapter  6  and
the  data  useful for  RQ derivation are  summarized  1n  Table 9-1.  The  data
clearly  Indicate  that   hexachlorocyclopentadlene  Is  more  toxic  following
Inhalation than oral exposure, with death occurring In  rats  at  a dose as  low
as 0.64 mg/kg/day  via  Inhalation (D.  Clark et al., 1982} and at 107.1  mg/kg
(SRI, 1981a; Abdo et al., 1984}  by oral  exposure.  Although  the Treon et  al.
(1955).study has been  used  for  the derivation of a CS  (U.S. EPA,  1984b),  It
Is not  presented 1n Table 9-1  and Is not  being  considered  for  the  deriva-
tion of  an RQ  because  only 2-6  animals of each  species were  exposed,  and
better studies are now available.
    The derivations  of  CSs  for  hexachlorocyclopentadlene are   presented  1n
Table  9-2.   Because effects  following  oral  exposure occur  at much  higher
doses  than following  Inhalation  exposure,  the  13-week oral   gavage  study
(SRI,  1981 a;  Abdo  et al., 1984)  1s not  considered  for the  derivation  of  an
RQ.   The  highest  CS  (59)  Is   calculated  from  the  NTP-sponsored  13-week
Inhalation study using  mice (Abdo et  al.,  1986)  1n which death occurred  at
0.4  ppm,  6  hours/day,  5  days/week  (a  transformed animal  dose  of  1.04
mg/kg/day). The  chronic human  NED of 0.56 nig/day corresponds  to an  RV.  of
5.9. while death corresponds to  an RVg of 10.
    A CS  of 59  corresponds  to an RQ  of  10  pounds.   This RQ Is  presented  In
Table 9-3.  Table 9-4 Indicates  that  data were  not available for the deriva-
tion of RQs for the other chlorinated cyclopentadlenes.
9.2.   BASED ON CARCINOGENICITY
    The lack of data precludes the derivation  of carclnogenlclty based RQs.
0077d                               -64-                             04/05/88

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                  TABU 9-1
Toxlctty Suiury for Hexachlorocyclopentadtene
Species/
Route Strain Sex
Inhalation rats/Ulstar N.F






Inhalation rats/F344 N.F





Inhalation rats/F344 N.F




Inhalation «lce/B6C3Fl H.F




Inhalation atce/B6C3F1 N.F




Oral Mtce/B6C3F1 N.F



Oral •1ce/B6C3F1 N.F



No. at Average
Start Height
(kg)
8/sex 0.350






10/sex 0.2211





10/sex 0.23d




10/sex 0.03*




10/sex 0.03°




10/sex 0.03°



10/sex 0.03°


'
Vehicle/ Purity • Transformed Equivalent
Physical (X) Exposure AnlMl Dose Hiwan Dose*
State (tig/kg/day) (og/kg/day)
air 96 0.5 pp* 0.64C 0.11
(5.6 •g/a'l.
, 6 hours/day,
S days/week.
for 30 weeks
plus 14 weeks
recovery
air 99.42 1 ppa (11.2 1.45e 0.21
•9/1'K
. 6 hours/day.
5 days/week.
for 13 weeks
i
air 99.42 0.4 ppa (4.5 0.58* 0.08
•g/B*),
6 hours/day.
5 days/week.
for. 13 weeks
air 99.42 0.4 ppa (4.5 1.04C 0.08
•g/B*),
6 hours/day.
5 days/week.
for 13 weeks
air 99.42 0.15 ppm 0.39C 0.03
11.67 •*/••).
6 hours/day.
5 days/week.
for 13 weeks
corn oil 94-97 300 ng/kg by 214. 3f 16.2
gavage, 5
days/week.
for 13 weeks
corn oil 94-97 150 og/kg by 107. 1* 8.1
gavage. 5
days/week.
for 13 weeks
Response
Death of 4/8 Mies and
2/8 feMles; kidney.
liver and pulmnary
degenerative changes



Death of all rats





Decreased body weights of
•ales, necrosis and acute
InflaaMtton of respira-
tory eplthella

Death of 5/10 Mies and
2/10 feMles



Hyperplasla and Meta-
plasia of respiratory
eplthella


Death of all Mies and
3/10 feMles


Toxic nephrosts In fe-
Mles. stoMch lesions.
depressed body weight
gain
Reference
Clark
et al.. 1982b





Battelle
Northwest
Laboratories,
1984


Battelle
Northwest
Laboratories.
1984

Abdo et al..
1986



Abdo et al..
1986



SRI. 19Bla;
Abdo et al..
1984

SRI. 1981a;
Abdo et al..
1984


-------
                                                                     TABLE 9-1 (cont.)
§
5 Route
o.
Oral
Oral
Species/
Strain
rats/F344
rats/F344
No. at Average
Sex Start Height
(kg)
N.F 10/sex 0.35b
N.F 10/sex 0.35b
Vehicle/
Physical
State
corn oil
corn oil
Purity
(X) Exposure
94-97 150 mg/kg by
gavage. 5
days/week,
for 13 weeks
94-97 19 mg/kg by
gavage. 5
days/week.
for 13 weeks
Transformed
Animal Dose
(mg/kg/day)
107. lf
13.6'
Equivalent
Human Dose4
(mg/kg/day)
18.3
2.3
Response
Death, toxic nephrosls
and stomach lesions
Stomach lesions In
females
Reference
SRI. 1981a;
Abdo et al..
1984
SRI. 1981a;
Abdo et al..
1984
'Calculated by multiplying  the animal transformed dose by the cube  root ratio of the animal body weight  to  the human body weight (70 kg)
Reference rat (0.35 kg) and mouse (0.03 kg) body weights (U.S.  EPA. 1985)
Calculated by  multiplying the concentration by the hours/day,  days/week,  by the animal  Inhalation rate (0.223  mVday rats;  0.039 mVday mice  (U.S.
 EPA (1985)) and by dividing by the animal body weight
^Estimated from growth curves In the study
'Calculated as described In c except the Inhalation rate of 0.16 mVday calculated from I - 0.105 (w/0.113)2'3 (U.S. EPA. 1985) was used
'Calculated by multiplying  the dose by 5 days/7 days

-------
g
                  TABLE 9-2
Composite Scores for Hexachlorocyclopentadlene
5
i
o
in
Chronic
Species Animal Dose Human NED* RVjj
(rag/kg/day) (mg/day)
Rat 0.64 0.77 5.7
Rat 1.45 1.47 5.2
Rat 0.58 0.56 5.9
Mouse 1.04 0.56 5.9
Nouse 0.39 0.21 6.5
*The dose was divided by an uncertainty factor
Effect RVe CS RQ
Death of 4/8 males, 10 57 10
2/8 females
Death 10 52 10
Decreased body weight. 4 23.6 100
necrosis and acute In-
flammation of respira-
tory epithelium
Death of 5/10 males. 10 59 10
2/10 females
Hyperplasla and met a- 6 39 100
plasla of respiratory
epithelium
of 10 to approximate chronic exposure.
Reference
Clark
et al.. 1982b
Battelle
Northwest
Laboratories,
1984
Battelle
Northwest
Laboratories,
1984
Abdo et al..
1986
Abdo et al..
1986


-------
                                  TABLE 9-3
                          Hexachlorocyclopentadlene
          Minimum Effective Dose  (MED) and Reportable Quantity (RQ)
Route:
Species:
Dose*:
Duration:
Effect:
Reference:
RVd:
RVe:
Composite Score:
RQ:
Inhalation
Mouse
0.56 rag/day
13 weeks
death
Abdo et al.. 1986; SRI, 1981a
5.9
10
59
10
'Equivalent human dose
0077d
            -68-
04/05/88

-------
                                  TABLE 9-4
               Chlorocyclopentadlene, Trlchlorocyclopentadlene,
          Tetrachlorocyclopentadlene and  Pentachlorocyclopentadlene
          Minimum Effective  Dose  (MED) and Reportable Quantity (RQ)
Route:
Oose:
Effect:
Reference:
RVd:
RVe:
Composite Score:
RQ:                     Data are not sufficient for  deriving  an  RQ for these
                        compounds.
0077d                               -69-                             12/23/87

-------
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0077d                               -77-                             04/05/88

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0077d                               -78-                             04/05/88

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chlorinated chemical  residues  In fish from major  watersheds near  the  Great
Lakes, 1979.  Environ. Int.   9: 293-299.

Lawrence,  L.J.  and  H.U. Oorough.   1981.   Retention  and  fate  of  Inhaled
hexachlorocyclopentadlene 1n the rat.   Bull. Environ.  Contain.  Toxlcol.   26:
663-668.

Lawrence,  L.J.  and H.U.  Dorough.  1982.   Fate of  Inhaled  hexachlorocyclo-
pentadlene  1n  albino  rats   and   comparison to  the  oral  and  1v routes  of
administration.   Fund. Appl. Toxlcol.   2: 235-240.

Levin,  A.P.   1980.   Odor   thresholds  of  selected  chemicals  for  Hooker
chemical  - Eleven additional  samples  with  cover  letter.   Doc.  #878211178.
Microfiche #0780205956.

Litton  Blonetlcs,  Inc.1   1977.   Evaluation  of hexachlorocyclopentadlene  .In.
vitro malignant  transformation  In  BALB/313 Cells.   LBI  Project No.  29840.
Prepared  for  Velslcol Chemical  Corp.,  Chicago,  IL.   7 p.   (Cited In  U.S.
EPA, 1986b)

Litton  Blonetlcs,  Inc.  1978a.   Mutagenldty  evaluation  of hexachlorocylo-
pentadlene  1n  the  mouse domlnanat  lethal  assay.   LBI  Project  No.  20862.
March 1978,  Revised August  1978.  Kensington,  MD.   13 p.   (Cited 1n  U.S.
EPA, 1984a)
0077d                               -79-                             04/05/88

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Litton Blonetlcs, Inc.   1978b.   MutagenlcHy evaluation of hexachlorocyclo-
pentadlene In  the  mouse lymphoma  forward  mutation assay.  LBI  Project No.
20839.  Prepared for Velslcol Chemical Corp., Chicago* IL.  10 p.  (CHed 1n
U.S. EPA, 1984a)

Loeb, H.A. and M.H. Kelly.   1963.   Acute oral  toxlclty  of 1,496 chemicals
force-fed to  carp.   Special Scientific  Report—Fisheries  No.  471.  p. 6-7,
111.

Lu. P.Y.. R.L.  Metcalf,  A.P.  Hlrwe and J.W.  Williams.  1975.  Evaluation of
environmental  distribution  and  fate  of  hexachlorocyclopentadlene,  chloro-
dane, heptachlor and heptachlorepoxlde 1n  a  laboratory model ecosystem.  J.
Agrlc. Food Chem.  23:  967-973.

Mabey, U.R.,  J.H.  Smith, R.T.  Podoll, et al.   1982.   Aquatic fate process
data  for  organic priority  pollutants.  Monitoring  and  Data  Support  D1v.,
Office of  Mater Regulations and  Standards,  U.S.  EPA,  Washington, DC.  EPA
440/4-81-014, p. 174.

Mackay, D.   1982.   Correlation of  bloconcentratlon  factors.   Environ. Sc1.
Technol.   16: 274-278.

McNahon,   L.W.   1983.    Organic  priority  pollutants  1n  wastewater.   NTIS
OE83010817.  Gatlnburg, TN.   p.  220-250.

Mehendale. H.N.   1977.  Chemical  reactivity-absorption,  retention,  metabo-
lism   and  elimination   of  hexachlorocyclopentadlene.    Environ.    Health
Perspect.  21: 275-278.
0077d                               -80-                             12/23/87

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Mill,  T.  and  U.  Mabey.  1985.   Chapter 8.   Photochemical  transformations.
In: Environmental Exposure from Chemicals,  Vol.  1,  W.B.  Neely and G.E. Blau,
Ed.  CRC Press, Inc., Boca Raton,  FL.  p. 207.

Horse,  D.L.,   P.3.  Landrlgan and  3.H.  Flynt.   1978.   Internal  COC  report
concerning  hexachlorocyclopentadlene  contamination  of  a  municipal  sewage
treatment plant,  Louisville, KY.   Center  for Disease Control, Atlanta.  GA.
(Cited 1n U.S. EPA, 1984a)

Morse,  D.L.,   J.R.  Komlnsky  and  C.L.  Hlsseman,  III.   1979.   Occupational
exposure  to  hexachlorocyclopentadlene  (how safe 1s  sewage?).   3.  Am.  Med.
Soc.  241: 2177-2179.

Murray, F.3.,  B.A.  Schwetz,  M.F.  Balmer and  R.E.  Staples.  1980.   Terato-
genlc  potential  of  hexachlorocyclopentadlene 1n mice and  rabbits.   Toxlcol.
Appl. Pharmacol.  53:. 497-500.

NIOSH  (National  Institute  for  Occupational  Safety  and  Health).   1978.
Criteria  for   a  Recommended Standard...Occupational  Exposure  During   the
Manufacture and Formulation  of  Pesticides.  DHEU  (NIOSH)  Pub. No.  78-174.
Cincinnati, OH.  (Cited In U.S.  EPA,  1984a,b)

NTP (National  Toxicology  Program).   1987.  Management Status Report.   Dated
10/13/87.

Ohio  River  Valley Hater  Sanitation  Commission.   1980.   Assessment  of water
quality conditions.   Ohio  River  mainstream 1978-1979.   Ohio  River  Valley
Hater Sanlt. Comm., Cincinnati,  OH.   p. T-48.
0077d                               -81-                             12/23/87

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Podowskl, A.A. and N.A.Q. Khan.  1979.   Fate  of  hexachlorocyclopentadlene  In
goldfish  (Carasslus  auratus).   Paper  presented  at  the  Am.   Chem.   Soc.
Heetings, April, Honolulu. HI.  (Cited 1n U.S. EPA,  1984a)

Podowskl. A.A. and N.A.Q. Khan.  1984.   Fate  of  hexachlorocyclopentadlene  In
water and goldfish.  Arch. Environ. Contain.  Toxlcol.  13:  471-481.

Rand,  G.N.,  P.O.  Nees,  C.J.  Calo,  D.J. Alexander  and  G.C. Clark.   1982a.
Effects  of  Inhalation  exposure  to  hexachlorocyclopentadlene  on  rats  and
roomkeys.  J. Toxlcol. Environ. Health.  9: 743-760.

Rand,  G.N.,  P.O. Nees, C.J.  Calo, G.C.  Clarke  and H.A.  Edmondson.   1982b.
The  Clara  cell: An  electron  microscopy  examination of  the terminal  bron-
chioles  of  rats and  monkeys  following  Inhalation   of  hexachlorocyclopenta-
dlene.  J. Toxlcol. Environ. Health.  10: 59-72.

Rleck,  C.E.   1977a.   Soil   metabolism  of   **C-hexachlorocyclopentad1ene.
Univ.  Kentucky.   Unpublished  report  prepared for  Velslcol Chemical  Corp.,
Chicago, II.  (Cited In U.S. EPA. 1984a)

Rleck,  C.E.   1977b.   Volatile  products  of  14C-hexachlorocyclopentad1ene.
Univ.  Kentucky.   Unpublished  report  prepared for  Velslcol Chemical  Corp.,
Chicago, IL.  (Cited In U.S. EPA, 1984a)

Root,  M.S.,  D.E. Rodwe11  and  E.I.  Goldenthal.   1983.   Teratogenlc  potential
of hexachlorocyclopentadlene In rats.  Toxlcologlst.  3: 66.
0077d                               -82-                             12/23/87

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Shell  011  Company.   1982.   TSCA  8(0) Submission  Hexachlorocyclopentadlene
(HEX): Acute toxlclty to Selenastrum caprlcornutum.   H1chrof1che #205967.

Shen,  T.T.   1982.   A1r  quality  assessment for  land disposal  of  Industrial
wastes.  Environ. Management.  6: 297-305.

Shlndell  and  Associates.    1980.    Report  of  Epldemlologlc  Study  of  the
Employees of Velslcol Chemical Corporation  Plant  Marshall,  Illinois,  January
1946-December  1979.   Velslcol  Chemical Corp..  Chicago,  IL.  (Cited  In  U.S.
EPA, 1984a. 1986D)

Shlndell and  Associates.  1981.   Report  of the  Epldemlologlc  Study of  the
Employees of Velslcol Chemical Corporation  Plant  Memphis,  Tennessee,  January
1952-December  1979.   Velslcol  Chemical Corp.,  Chicago.  IL.  (Cited  In  U.S.
EPA, 1984a, 1986b)

Slnhasenl, P., L.G.  O'Alecy,  R.  Hartung and M. Shlater.   1982.  Hexachloro-
cyclopentadlene  Increases  oxygen  consumption  by Intact  rainbow trout  and
Isolated heart mitochondria.  Abstract  In Fed.  Proc.  March 1982.   (Cited In
U.S. EPA, 1984a)

Slnhasenl, P., L.G.  O'Alecy,  R.  Hartung and M. Shlater.   1983.  Respiratory
effects  of  hexachlorocylopentadlene on Intact rainbow  trout  (Salmo  qalrd-
nerD  and on oxldatlve  phosphorylatlon  of  Isolated  trout  heart  mitochondria.
Toxlcol. Appl. Pharmacol.  67: 215-223.
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Spehar,  R.L.,  G.O. Velth,  D.L.  DeFoe  and B.V.  Bergstedt.   1977.  A  rapid
assessment  of  the toxlclty  of  three  chlorinated  cyclodlene  Insecticide
Intermediates  to  fathead minnows.   Environmental  Research Laboratory,  U.S.
EPA, Duluth, MN.  EPA-600/3-77-099.   (Cited In U.S.  EPA,  1984a)

Spehar,  R.L.,  G.O. Velth,  D.L.  DeFoe and  B.V.  Bergstedt.  1979.   Toxlclty
and  bloaccumulatlon  of  hexachlorocyclopentadlene,  hexachloronorbornadlene
and  heptachloronorbornene  1n  larval  and  early juvenile fathead  minnows,
Plmephales promelas.  Bull.  Environ. Contam. Toxlcol.   21: 576-583.

SRI  (Southern  Research  Institute).   1980.  Acute  Toxlclty  Report  on  Hexa-
chlorocyclopentadlene   (C53607) In  F1scher-344 and  B6C3F1  Nice.   Unpublished
Report for NTP.  44 p.  (Cited In U.S. EPA, 19866)

SRI  (Southern  Research  Institute).   1981a.  Subchronlc  Toxlclty Report  on
Hexachlorocyclopentadlene  (C53607)   1n  B6C3F1  Mice.    Report  for   the  NTP.
Project No. 4419-XXXVIX.  Doc  #40-8349130.  Microfiche #OTS0507497.

SRI  (Southern  Research  Institute).   1981b.  Subchronlc  Toxlclty Report  on
Hexachlorocyclopentadlene (C53607)  In Fischer-344 Rats.   Report  for  the NTP.
Project No. 4419-XXXVIII.  Doc.  140-8349130.  Microfiche JOTS0507497.

SRI  (SRI International).   1987.   Directory  of  Chemical  Producers.  United
States of America,  p. 691.

Staples,  C.A., A.  Werner and T.  Hoogheem.  1985.   Assessment  of  priority
pollutant   concentrations   In  the   United  States  using  STORET  database.
Environ. Toxlcol. Chem.  4:  131-142.

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Stevens,  3.E.   1979.   Chlorinated  derivatives  of  cyclopentadlene.   Iru
K1rk-0thmer Encyclopedia of Chemical Technology. Vol.  5,  3rd  ed.,  N.  Grayson
and D. Eckroth. Ed.  John Wiley and Sons. Inc.. New York.   p.  791-797.

Suffet.  I.H.,  L.  Brenner  and  P.R. Cairo.   1980.  Gas  chromatography-mass
spectrometry  Identification   of  trace   organlcs   In   Philadelphia,  PA.  USA
drinking waters during a two  year period.  Hater Res.  14: 853-867.

Tabak, H.H., S.A.  Quave,  C.I. Mashnl and E.F.  Barth.   1981.   Blodegradabll-
1ty  studies  with  organic  priority  pollutant  compounds.   J. Mater  Pollut.
Control Fed.  53: 1503-1518.

Thruston, A.D.,  Jr.   1978.   High pressure liquid  chromatography  techniques
for  the  Isolation  and   Identification of   organlcs  In drinking   water.
Chromatogr. Scl.  16: 254-259.

Thuma, N.K..  P.E.  O'Neill. S.G.  Brown Tee and  R.S. Valentine.  1978.   Bio-
degradation  of  spilled  hazardous  materials.   In:  Control  of   Hazardous
Materials Spills.   Information Transfer,  Inc.. Rockv1lie, MD.  p. 217-220.
(Cited 1n U.S. EPA, 1984a)

Treon, J.F.,  F.P.  Cleveland  and  3.  Cappel.    1955.   The toxlclty of  hexa-
chlorocyclopentadlene.  Arch.  Ind. Health.  11: 459-472.

U.S. EPA.   1978.   Reviews  of the Environmental Effects of Pollutants:  XII.
Hexachlorocyclopentadlene.     EPA-600/1-78-047.   U.S.   EPA.   Columbus,   OH.
p. 8-38.


0077d                               -85-                             12/23/87

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U.S.  EPA.   198Qa.  Guidelines  and Methodology  Used 1n  the Preparation  of
Health  Effect  Assessment  Chapters  of  the  Consent Decree  Water  Criteria
Documents.  Federal Register.  45(31):  79347-79357.

U.S.  EPA.   1980b.   Ambient Water Quality Criteria  for  Hexachlorocyclopenta-
dlene.  Office  of Water Planning  and  Standards, U.S.  EPA, Washington,  DC.
EPA-440/5-80-055.  NTIS PB 81-117665.

U.S.  EPA.   1980c.  Summary  of UWF Co-op  Data  on  Hexachlorocyclopentadlene
and  Hexachlorocylopentadlene.   Unpublished  laboratory  data.   Environmental
Research Laboratory, U.S. EPA. Gulf Breeze,  FL.  (Cited  In U.S.  EPA, 1984a)

U.S.  EPA.   1981.  Effects of  Chronic  Hexachlorocyclopentadlene  Exposure  on
Mortality  and Fecundity of  Mys1dops1s  bahla.   Laboratory  report.   Environ-
mental  Research  Laboratory,  U.S.  EPA,  Gulf   Breeze,  FL.   (Unpublished)
(Cited in U.S. EPA, 1984a)

U.S.  EPA.    1983.    Methodology   and   Guidelines   for   Reportable  Quantity
Determinations  Based  on Chronic Tox1c1ty  Data.  Prepared  by  the  Office  of
Health  and Environmental  Assessment,  Environmental Criteria and Assessment
Office, Cincinnati, OH  for the  Office  of  Solid Waste and Emergency Response.
Washington, DC.

U.S.  EPA.   1984a.   Health  Assessment  Document for Hexachlorocyclopentadlene.
Office  of Health  and Environmental Assessment, Environmental Criteria  and
Assessment  Office.  Cincinnati,  OH.  Final  Report.   EPA-600/8-84-001F.  NTIS
PB  85-124915.   .

0077d                              -86-                             04/05/88

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U.S. EPA.   1984b.   Health Effects Assessment  for  Hexachlorocyclopentadlene.
Prepared by the Office of  Health  and  Environmental  Assessment,  Environmental
Criteria and  Assessment  Office,  Cincinnati, OH  for the Office of  Emergency
and  Remedial  Response.   Washington.   DC.    EPA/540/1-86-001.    NTIS   PB
86-134129/AS.

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

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

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

U.S.  EPA.    1987a.   SANSS   (Structure   and   Nomenclature   Search  System).
Database.  Online.

U.S. EPA.   1987b.   Hazardous substances;  reportable quantity  adjustments;
proposed  rules.   40  CFR  Parts   117  and  302.  Federal  Register.   52(50):
8140-8186.
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U.S.  EPA.   1988a.   Drinking Mater  Criteria  Document  for  Hexachlorocyclo-
pentadlene.  Prepared by  the Office of Health and  Environmental  Assessment,
Environmental  Criteria and  Assessment  Office,  Cincinnati, OH for  the  Office
of Drinking Water, Washington, DC.   External  Review Draft.

U.S. EPA.  1988b.  Integrated Risk  Information System  (IRIS): Reference  Dose
(RfD) for  oral  exposure  for hexachlorocyclopentadlene.   Online.   (Verifica-
tion  date  10/09/86).   Office  of  Health  and   Environmental   Assessment,
Environmental  Criteria and Assessment Office, Cincinnati,  OH.

USITC  (U.S.  International  Trade   Commission).    1986.    Synthetic  Organic
Chemicals.  United  States  Production  and  Sales,  1985.   USITC  Publ.  1892,
Washington, DC.   p. 41.

Velth, G.O., D.L. DeFoe and  B.V. Bergstedt.  1979.   Measuring and estimating
the  bloconcentratlon  factor  of chemicals In fish.   J. F1sh Res.  Board  Can.
36: 1040-T048.  '

Vllkas, A.G.  1977.   The  acute toxldty of  hexachlorocyclopentadlene  to the
water  flea,  Daphnla  maqna  straus.   Union  Carbide Environmental  Services.
Prepared  for  Velslcol Chemical  Corp.,  Chicago,   II.   (Cited In U.S.  EPA,
I984a)

Walsh, G.E.   1981.   Effects of chlordane,  heptachlor and  hexachlorocyclo-
pentadlene on growth  of  marine unicellular algae.   Laboratory report.   U.S.
EPA, Gulf Breeze, FL.  (Unpublished)  (Cited In U.S. EPA,  1984a)
0077d                               -88-                             04/05/88

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Walsh, G.E.  1983.  Cell death and  Inhibition of  population  growth  of  marine
unicellular algae  by pesticides.   Aquat. Toxlcol.   3:  209-214.   (Cited  In
U.S. EPA, 19865)

Hang,  H.H.  and B.  NacNahon.   1979.   Mortality of workers  employed  1n  the
manufacture  of chlordane  and  heptachlor.   J.  Occup.  Ned.   21:   745-748.
(Cited In U.S. EPA, 1984a.  1986b)

Weber,  J.B.   1979.   Adsorption of  Hex  by Cape Fear  Loam  Soil.   North
Carolina  State Univ.   Prepared  for  Velslcol   Chemical  Corp.,  Chicago,  IL.
(Cited 1n U.S. EPA, 1984a)

Whltacre, O.N.  1978.  Letter to R.A.  Ewlng,  Battelle Columbus  Laboratories,
dated August 9, 1978.  Comments  on  document: Review of Environmental Effects
of  Pollutants: XII.  Hexachlorocylopentadlene.    5 p.   (Cited  In  U.S.  EPA,
1984a)

Wilson, J.A.,  C.P. Bladwln  and  T.J. McBMde.   1978.   Case History:  Contami-
nation  of Louisville Kentucky  Morris Foreman  Treatment Plant,  Hexachloro-
cyclopentadlene: Control of  Hazardous Material  Spills,  p.  170-177.   (Cited
In U.S. EPA, 19843, 19865)

Wolfe, N.L.,  R.G.  Zepp,  P.  Schlotzhauer  and N. Sink.   1982.   Transformation
pathways  of hexachlorocyclopentadlene 1n the  aquatic environment.   Chemo-
sphere.  11: 91-101.
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YoxMda, K., T. Shlgeoka and F. Yaroauchl.  1983.  Relationship between molar
refraction  and  N-octanol/water   partition   coefficient.   Ecotox.  Environ.
Safety.  7: 558-565.

Yu, C.C. and Y.H. Atallah.  1977a.   Photolysis  of Hexachlorocyclopentadlene.
Laboratory  report.   Project  No.  482428.   Rep.  No.  4.   Velslcol Chemical
Corp.. Chicago. IL.   (Cited In U.S.  EPA,  1984a)

Yu,  C.C.  and  Y.H.  Atallah.   1977b.   Hex  hydrolysis  at  various  pH  and
temperature.  Laboratory report.  Project No. 482428.  Rep. No. 8.  Velslcol
Chemical Corp.. Chicago. IL.   (Cited 1n U.S.  EPA,  1984a)

Yu,  C.C.  and  Y.H.  Atallah.   1981.   Pharmacok1net1cs  and  metabolism  of
hexachlorocyclopentadlene  1n  rats.   Rep. No.  10,  Project 482428.  Velslcol
Chemical Corp., Chicago, IL.   (Cited In U.S.  EPA,  1986b)

Zepp, R.G., P.P.  Schlotzhauer, M.S.  Simmons, G.C. Miller, 6.L. Baughman and
N.L. Wolfe.  1984.  Dynamics of pollutant photoreactlons  In  the hydrosphere.
Fresenlus Z. Anal. Chem.  319: 119-125.
0077d                               -90-                             04/05/88

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                                  APPENDIX A

                             LITERATURE SEARCHED



    This  HEED  Is  based  on  data  Identified  by  computerized  literature

searches of the following:

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


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

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

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

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

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

    Clayton.   G.D.  and  F.E.  Clayton,  Ed.    1982.   Patty's  Industrial
    Hygiene  and  Toxicology,  3rd  rev.  ed..  Vol.  2C.   John  Wiley  and
    Sons, NY.  p. 3817-5112.
0077d                               -91-                             04/05/88

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

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

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

    Jaber, H.M., W.R.  Mabey,  A.T.  L1eu,  T.W.  Chou and H.L.  Johnson.
    1984.   Data  acquisition  for  environmental  transport  and   fate
    screening  for compounds  of Interest to  the Office  of Solid Waste.
    EPA  600/6-84-010.    NTIS  PB84-243906.    SRI   International.   Menlo
    Park, CA.

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

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

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

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

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

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

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

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

    Wlndholz,  M.. Ed.  1983.   The Merck  Index,  10th ed.   Merck  and Co.,
    Inc., Rahway,  NJ.
0077(1                               -92-                             04/05/88

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    In  addition,  approximately 30  compendia of  aquatic  tox1c1ty  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 N.T. Flnley.   1980.  Handbook of  Acute  Toxlclty
    of  Chemicals  to  F1sh and   Aquatic   Invertebrates.   Summaries  of
    Toxlclty  Tests  Conducted  at  Columbia  National Fisheries  Research
    Laboratory.   1965-1978.   U.S.  Dept.  Interior, Fish  and  Wildlife
    Serv. Res. Publ. 137, Washington, DC.

    NcKee, 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.
0077d                               -93-                             04/05/88

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                                                 APPENDIX  B

                                Summary Table for Hexachlorocyclopentadlene
                Species
                     Exposure
                                Effect
            RfD or
     Reference
Inhalation Exposure

Subchrontc      rat
           0.15 pp« (0.45 ng/n»)
           6 hours/day, 5 days/week
           for 13 weeks (0.2 rag/kg/day)
                                NOAEL     0.01  rag/day or
                                          0.0007 ng/m*
                             Battelle Northwest
                             Laboratories. 1984;
                             Abdo et al., 1986
Chronic
rat
0.15 ppra (0.45 rag/a8)
6 hours/day, 5 days/week
for 13 weeks (0.2 mg/kg/day)
NOAEL     0.001 og/day or
          0.00007 mg/n*
Battelle Northwest
Laboratories. 1984;
Abdo et al., 1986
Oral Exposure

Subchronlc      rat
10 ing/kg, by gavage 5 days/
week for 13 weeks
NOAEL     5 rag/day
                                                                       SRI.  198la;
                                                                       Abdo  et al..  1984
Chronic
rat
10 rog/kg, by gavage 5 days/     NOAEL      0.5 rag/day
week for 13 weeks
                             SRI.  1981a;
                             Abdo  et al..  1984
REPORTABLE QUANTITIES

Based on Chronic Toxlclty:

Based on Carclnogenlclty:
                    10 pounds

                    10
                                                             Abdo  et  al..  1986
10 = insufficient data

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