FINAL DRAFT
               United States                                     f CAD-C.lt! GO?<1
               Environmental Protection                               E   I  7lS!
               Agency                                        March. 1988
v>EPA       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                            DRAFT: DO NOT CITE OR QUOTE
                                    HUTICE

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

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                                  DISCLAIMER

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

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                                    PREFACE
    Health and  Environmental  Effects  Documents (HEEDs) are prepared  for  the
Office of Solid  Waste  and Emergency Response  (OSUER).  This  document series
Is Intended to support listings under  the  Resource  Conservation  and Recovery
Act (RCRA) as  well  as to  provide  health-related limits and  goals  for  emer-
gency and  remedial  actions under  the Comprehensive  Environmental  Response,
Compensation  and Liability  Act  (CERCLA).   Both  published  literature  and
Information obtained for  Agency Program Office  files are evaluated  as  they
pertain to potential human health, aquatic  life  and environmental  effects of
hazardous waste  constituents.   The  literature searched for In  this document
and the  dates  searched  are  Included 1n  "Appendix:  Literature  Searched.*
Literature search material  1s current up  to 8 months previous  to  the  final
draft date  listed  on  the front  cover.   Final  draft document  dates  (front
cover) reflect the date the document Is sent to the Program Officer (OSMER).

    Several quantitative  estimates are  presented  provided  sufficient  data
are  available.   For   systemic  toxicants,   these  Include:  Reference  doses
(RfOs) 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)  Is  provided.
These potency  estimates  are  derived  for  both oral  and Inhalation exposures
where possible.  In addition, unit  risk estimates for air  and drinking water
are presented  based on Inhalation  and  oral data, respectively.

    Reportable quantities  (RQs) based on both chronic tox1c1ty  and carclno-
genlclty  are   derived.   The  RQ  Is  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 carclnogenlclty)  represent two  of six  scores  developed  (the  remaining
four  reflect  1gn1tab111ty, reactivity, aquatic toxldty,  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 In 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-Uomer was located In the  litera-
ture cited 1n Appendix A.  Hexachlorocyclopentadlene 1s a light lemon yellow
liquid with a pungent  odor  (Stevens, 1979).  It 1s not soluble In water but
1s soluble  1n 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  1n  the United States  In 1983.
    Hexachlorocyclopentadlene Is  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   Is  banned, suspended  or  severely  restricted  (U.S.  EPA,
1980a).
    The  atmospheric half-life  of  hexachlorocyclopentadlene,  which  1s due
primarily to  Us  reaction with  HO* and  0.,  was estimated  to  be 3.5  hours
(CupUt,  1980).    Based  on  Us   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  Intramedla
transport  from  Us  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.t
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 1n 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,  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 In 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  In edible  aquatic  organisms
as Is Indicated  by a BCF  of  11-29  In the fathead minnow, Plmephales promelas
(VeHh et  al..  1979; Spehar  et  al.,  1979)  and 100-323  In goldfish,  Carasslus
auratus (Podowskl and Khan. 1984).

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    Limited data on  the  level  of  hexachlorocyclopentadlene  In  the atmosphere
are available.   Hexachlorocyclopentadlene  was  detected at a maximum  concen-
tration  of  0.10  vg/ma   In  homes  near  a  hazardous  waste  site  In Hardeman
County,  Tennessee,   and  at  a  maximum  concentration  of 39  yg/ma  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  1n
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; Kim and  Stone,  n.d.).  The maximum  concentrations
of  hexachlorocyclopentadlene  detected  In  water  were  100  ng/l  In  ambient
surface water  from  Wheeling,  WV (Ohio  River Valley Water Sanitation  Commis-
sion.  1980) and  650 ng/l  1n 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  (Kuehl  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 toxldty 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.,
                                      vl

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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  Oil  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
vg/l  for  all  species  except   the  polycheate  for  which  the  LC5Q  value
was  371  ug/i  (U.S.   EPA,  1980c).    In  four  species  of  saltwater   algae,
7-day  EC,,  values were  reported  In  the range of  3.5-100  vg/8.  (Walsh,
1981).
    Comparative  pharmacoklnetlc  studies   of   l4C-hexachlorocyclopentad1ene
have shown higher  levels of fecal excretion following  oral exposure than  for
Intravenous  or  Inhalation  exposure,  (El  Career  et  al..  1983; Lawrence  and
Oorough,  1982).   Increased  elimination  of   radioactivity   following oral
exposure  1s  consistent with  toxldty data which Indicate  that  hexachloro-
cyclopentadlene  1s  more  toxic  following  Inhalation  exposure   than oral
exposure.
    Following    Inhalation    exposure    to   l*C-hexach1orocyclopentad1ene,
considerable  radlolabel  remained 1n  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 J[n vivo and In vitro provide further  evidence  of  the high reactivity of
hexachlorocyclopentadlene and/or  Us  metabolites  (El  Dareer 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
                                      vll

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al.,  1978).  The additional  chlorine atom  may hinder  the  formation of  the
pentadlenone from hexachlorocyclopentadlene.
    Following  oral  exposure  to  l4C-hexachlorocyclopentad1ene.  the  radio-
activity Is excreted predominantly 1n 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  1n  the  urine
following Inhalation exposure.
    Except for mutagenldty  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 ppro 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.                      :
    D. 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 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    1n   mice    at

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0.04 ppm and In 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  In mice at 19 mg/kg or In rats at 10  mg/kg.
No effects  were  reported  In rats  fed hexachlorocyclopentadlene In  the  diet
at up to 300 ppm for 90 days (IBT, 1975).
    The  lowest  oral   LD5Q   1s  315   mg/kg  In  female  weanling  rats   (SRI,
1981a).   The lowest  Inhalation  LC5Q reported  is  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
recover yi     ,-  '.  .•..--•..•...'• -..-..   .      ......   -..  ;...  .  .
    The  odor  recognition   concentration  for  hexachlorocyclopentadlene  was
reported  to be  0.0017 mg/m3  (Levin,  1980).   Questionnaires  completed  by
workers at  the  Morris Forman Mastewater  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).
    Mortality studies  of  hexachlorocyclopentadlene  production workers  have
not  shown  Increased cancer  death  rates.  No  animal studies of the  cardno-
genlcUy of hexachlorocyclopentadlene were available.
                                      1x

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    Results of  mutagenldty  assays of penta- and  tetrachlorocyclopentadlene
In  bacteria  have  been  positive   (Gdggelmann et  a1.t  1978;  Grelm  et a1.t
1977); however,  hexachlorocyclopentadlene has  consistently  tested  negative
1n mutagenldty assays.
    Oral   teratogenldty  studies   of   hexachlorocyclopentadlene   using  rats
(IRDC, 1978), mice and  rabbits  (Murray et al.,  1980) have reported  negative
results,   although  an  Increase 1n 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  1n mice
(Litton Blonetlcs.  Inc., 1978a).
    Using   the  13-week   NTP-sponsored   rat   study   (Battelle  Northwest
laboratories,  1984),  human  subchronlc and chronic RfDs for hexachlorocyclo-
pentadlene  of   0.01   dig/day  (0.0007  mg/m»)   and  0.001  ing/day   (0.00007
rag/raa),  respectively,  were  calculated.   Confidence  1n  the  Inhalation RfDs
Is  medium.   Subchronlc and  chronic  oral  RfDs  for hexachlorocyclopentadlene
of  5 rag/day (0.07 mg/kg/day) and 0.5  rag/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   RfOs  1s low.   A chronic toxlclty 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 carclnogenlcUy 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.   WATER	     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.	    23
    4.4.   SUMMARY	    25

5.  PHARHACOKINETCS	    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.    Height of Evidence	    56
            8.1.5.    Quantitative  Risk Estimates	    56

     8.2.   SYSTEMIC.TOXICITY. .......  ...  ...........    56

            8.2.1.    Inhalation Exposures	    56
            8.2.2.    Oral Exposures	    62

 9.  REPORTABLE QUANTITIES 	    64

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

10.  REFERENCES	    70

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

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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 Toxlclty Data on Marine Organisms Exposed to
        Hexachlorocyclopentadlene 	   22
4-3     Effects of 28 Days Exposure of Hysld Shrimp, Mvs1dops1s
        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 l4C-Hexachlorocyclopentad1ene .  .   29
5-2     Distribution of Radioactivity Expressed as Percentage
        of Administered Dose from 14C-Hexach1orocyclopentad1ene
        1n Rats Dosed by Various Routes	   34
6-1     Acute Toxlclty of Hexachlorocyclopentadlene 	   42
6-2     Mutagenlclty Testing of Chlorinated Cyclopentadlenes	   47
9-1     Toxlclty Summary for Hexachlorocyclopentadlene	   65
9-2     Composite Scores for Hexachlorocyclopentadlene. .	   67
9-3     Hexachlorocyclopentadlene: Minimum Effective Dose (MED)
        and Reportable Quantity (RQ)	   68
9-4     Chlorocyclopentadlene, Tr1ch1orocyclopentad1ene.
        Tetrachlorocyclopentadlene and Pentachlorocyclopentadlene:
        Minimum Effective Dose (MED) and Reportable Quantity (RQ) .  .   69
                                    xlll

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                             LIST  OF  ABBREVIATIONS

ATP                     Adenoslne trlphosphate
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 SOX of recipients
                        (and all other subscripted concentration levels)
LD5Q                    Dose lethal to SOX of recipients
LOAEL                   Lowest-observed-adverse-effect level
MED                     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
RfD                     Reference dose
RV.                     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
                                      x1v

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                                1.   INTRODUCTION
 1.1.    STRUCTURE  AND  CAS  NUMBER
     The five chlorinated  cyclopentadlenes  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  1somer1c  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-1somer)  could be found  In the  available  literature
dted 1n  the  Appendix; however, the  formation  of  lower  chlorinated cyclo-
 pentadlenes  during the chloHnatlon 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  1n Table 1-2.   Hexachloro-
 cyclopentadlene  1s  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  hexachlorob1cyclo-[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 Cyclopentadtenes
            Conpounds
                                     Synonyms*
                                                       Molecular     Molecular    Structure      CAS No.
                                                        Formula       Height
Chlorocyclopentadlene0
                                  NA
                                                        C5H5C1        100.55       clx  .        41851-50-7
                                                                                      ITU
Tr1chlorocyclopentad1eneD      NA
Tetrachlorocyclopentadlene0    NA
Pentachlorocyclopentadlene0    NA
Hexachlorocyclopentadlene
                                  C56; MRS 16S5
                                  graphlox; perchloro-
                                  cyclopentadtene;
                                  hexachloro-1 ,3-cyclo-
                                  pentadlene; 1,2.3,4.5.5-
                                  hexachloro-1 ,3-cyclo-
                                  pentadlene; hexachloro-
                                  cyclopentadlene
                                                            C5H3C13
                                                            C5H2C14
                                                            C5HC15
                                                        C5C16
                                                                      169.44
                                                                      203.88
                                                                      238.33
                                                                      272.77
                                                                                              Cl
                                                                                         Cl  •
                                                                                    «,
                                                                                         Cl
            77323-84-3
       ci    77323-85-4
„     „     25329-35-5
  inf
      „     77-47-4
S  "U.S. EPA. 1987a
^  b
2   These compounds can exist In several Isoroerlc forms

   NA B 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:
Air odor threshold:

Water odor threshold:

Melting point. °C:

Boiling point, °C:
Density, g/cm3:
Vapor pressure, mm Hg
at 25°C:
Hater solubility:

Organic solvents:
Log octanol/water parti-
tion coefficient (Kow):
Henry's Law constant
(atmos-raVmol):
Soil partition co-
efficient (Koc):
Wavelength at maximum
absorption (SOX 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/l at 25°C
1.8 rag/l 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'2
1.64xlO~»
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
Nackay, 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  1s   produced   for  commercial  use   only   by
Velslcol Chemical  Corporation at  Its 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  1s  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  chlorlnatlon of cyclopentadlene.  dechlorlnatlon of
octachlorocyclopentene  and  the  dehydrochlorlnatlon  of  hexachlorocyclopen-
tane.  In  the  first  process,  freshly prepared cyclopentadlene 1s mixed with
alkaline hypochlorUe  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   dehydrochlorlnated  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  Its
own.  It has  been  used as  a  chemical  Intermediate  1n  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,  11 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 Is 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  In   the
literature cited  In  Appendix  A.  Hexachlorocyclopentadlene Is a light  lemon
yellow liquid  with  a  pungent  odor  (Stevens,  1979).   It  Is  not  soluble  In
water but  1s soluble  In  acetone, carbon tetrachlorlde,  ethanol  and  hexane
(U.S. EPA,  1978).  Chemically,  1t  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).   UUh  the
exception  of endosulfan and  pentac, the use of  hexachlorocyclopentadlene-
based  pesticides  Is  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 In
the atmosphere are limited.   CupUt  (1980)  estimated  the rate constants for
HO* and  ozone  reactions  with  vapor  phase  hexachlorocyclopentadlene  to be
5.9xlO~"  and  8xlO~18  cmVmolecule-sec,   respectively.   Based  on  atmo-
spheric  HO*   and  0«   concentrations   of  10*   and   1012  molecules/cm8,
respectively,  the  half-life of hexachlorocyclopentadlene  In  the atmosphere
can be  estimated as  3.5  hours.   CupUt  (1980)   reported  phosgene,  dlacyl-
chloMdes,  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  nm  (wavelengths available In  sunlight)  was  reported by
FreHag  et  al. (1982, 1985).   Korte  (1978) reported  46X mineralization of
hexachlorocyclopentadlene In  17  hours  of Irradiation  with  the formation of
CT"  (44,9%),  C02   (48.3X),   C>2  (5.4X)   and  CO  (1.2X).   According  to
E1senre1ch et  al.  (1981),   organlcs with  vapor pressure  >10~4  mm Hg should
exist   almost  entirely  In   the vapor  phase In  the  atmosphere.  Therefore.
hexachlorocyclopentadlene,   with  a  vapor  pressure  of  0.06-0.08  mm  Hg, Is
expected to  exist primarily  1n  the vapor  phase  and  not  1n  the partlcle-
sorbed state as  reported  by FreHag 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  In moist  air  (U.S.
EPA, 1984a).
    Pertinent  data  regarding  the 1ntra- and  Intermedia tranport  of hexa-
chlorocyclopentadlene present  In  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 1s 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  Is  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 in aquatic media  1s  available In U.S. EPA (1984a).   The  photolysis  of
hexachlorocyclopehtadlene 1n water  was reported by  Zepp  et al. (1984)  and
Wolfe et al. (1982).  Neither humlc materials  nor  algae  In natural  water  was
found  to photosensitize  the  process.   The rate  constant  for  near-surface
photolyils of  hexachlorocyclopentadlene at  40°N  latitude on $ 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  dlmeMzed  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   In 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);  pentachloro-ds-2,4-pentad1eno1c  acid;  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 Is 3-11 days at 25-30°C and  a  pH  range of 5-9 (Wolfe et
al., 1982; Yu  and Atallah, 1977b).  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  (10_)  and  peroxy  radicals  1n  water   were   estimated  as
<10»  and  12  H~l  hour"1,  respectively  (Habey  et   al.,  1982).   If   the
concentrations   of  X02  and  R0_   radicals  In   water   are assumed  to  be
10~"  and 10"»  N,  respectively  (Mill  and Mabey, 1985),  H  Is  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/i
degraded completely  with  rapid adaptation  In  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  100%  observed  loss  of  hexachlorocyclopentadlene.
Therefore,  U  can  be  assumed  that some  of the  observed loss  was due  to
blodegradatlon.
    The  b1odegradab1l1ty  of  radlolabelled  hexachlorocyclopentadlene  with
acclimated  mixed microorganisms  and  several  pure  cultures  of  Pseudomonas
put Ida was  studied  by  Atallah  et  al.  (1980).   Only a  small  percent (<2.5X)
of  added  hexachlorocyclopentadlene completely  mineralized  to  C0_ 1n  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  In  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  1n
water.   The   Intramedla  transport  of  hexachlorocyclopentadlene   may  be
responsible for  transporting the pollutant  from  Its source to  other  points
In  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.IX,  respectively.
of total  hexachlorocyclopentadlene In  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  1n reducing the con-
centration of hexachlorocyclopentadlene  In  aqueous  solutions.   The predicted
strong  sorptlon  of  hexachlorocyclopentadlene  1n sediments  1s 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, -45-47%  of hexachlorocyclopentadlene  was  lost In 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
b1odegradab1!1ty  test,  Atallah   et  al.  (1980)  observed  a   high  rate  of
volatilization of  (>80%  1n 1 day)  hexachlorocyclopentadlene  from unlnocu-
lated  media  containing; 45 mg/i  hexachlorocyclopentadlene.   fabak  et  al.
(19Q1),.  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 ollogotrophlc
lake would account for only 0.69,  1.33,  1.56 and 1.08X 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  1n 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  1n  a  laboratory model  aquatic  ecosystem (Lu
et al.,  1975).   The BCFs  for  hexachlorocyclopentadlene In  alga,  Edogonlum.
snail, Physa. 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  1n   several  species  of fish  were as  follows:  <11  In  the
fathead minnow, Plmephales promelas (Spehar  et al., 1979);  29 In the fathead
minnow, Plmephales  promelas  (Velth et  al., 1979)  and 100-323  1n  goldfish,
Carasslus auratus (Podpwskl.and Khan.  1984).
2.4. ..•.•VSOIL.
    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,  It  1s  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 In   soil.   Hydrolytlc losses of hexachlorocyclopenta-
dlene In 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 In 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  representedby  Freundllch's  adsorption
equation.  From both soil  TLC  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 In  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.  Kllzer 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  In  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 1n  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   .so1H.    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  In edible  aquatic organisms
as Is  Indicated by a  BCF  of  11-29  In 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  1n
the literature  dted  1n Appendix  A.  Hexachlorocyclopentadlene  was  detected
In  three out  of five  homes near a hazardous waste disposal  site 1n  Hardeman
County In  Tennessee.  1n 1978 (S.  Clark et  al., 1982; Harris et  al..  1984).
In  the  monitored  homes,  concentrations   ranged  .from  0.006-0.10  yg/m3.
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  In
Tennessee  that  handled  wastewater  from   a   pesticide  manufacturer  showed
hexachlorocyclopentadlene  concentrations   In  the  range  of  0.03-39  wg/m3
(Ella  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  1n  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  1n  the concentration  range of  57-110  yg/l 1n  the
drinking  water.  The  source  of  hexachlorocyclopentadlene  1n the  drinking
water  was  possibly the  chlorlnatlon  step of  the treatment  process.   Hexa-
chlorocyclopentadlene at a  concentration  range  of  20-80  ng/i was  detected
In  drinking water  from  Athens, GA,  collected 1n  1976  (Thruston,  1978).   The
Great  Lakes  Hater  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 1n 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 yg/i  (K1m
and  Stone,  n.d.).  The  results  of monitoring hexachlorocyclopentadlene  In
the  Ohio  River  were  as  follows:   O.T jig/a,  1n 1  of  12  samples  from
Wheeling,  WV;  <0.1  yg/l  in  2  of 21  samples  from Huntlngton,  UV;  <0.1
yg/l  In  2 of  11  samples  from Louisville.  KY;  and  <0.1  yg/l  In  1  of
11  samples  from Evansvllle. IN  (Ohio  River  Valley  Water  Sanitation Commis-
sion,  1980).  No  hexachlorocyclopentadlene was detected (detection  limit  of
0.04  tig/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 0.9% of 1228 effluent  samples at
a  median  concentration   of  <10  yg/l  and  In  0.1X  of  854  ambient water
samples at a median concentration  of <10 yg/4.
3.3.   FOOD
    Hexachlorocyclopentadlene was  qualitatively Identified  In fish  samples
taken from water near a  pesticide manufacturing plant  In Michigan  (Spehar et
al., 1977) and  from water of the Great Miami River 1n Hamilton, OH  and  mil
Creek  1n  Cincinnati,  OH  (Kuehl   et  al.,   1983).    No   other   Information
regarding hexachlorocyclopentadlene contamination 1n food was  located 1n the
literature dted 1n the Appendix A.
3.4.   DERMAL
    No  Information  regarding  dermal  exposure  to  hexachlorocyclopentadlene
was available In the literature cited In Appendix  A.
3.5.   SUMMARY
    Limited data on  the  level  of hexachlorocyclopentadlene  In  the  atmosphere
are available:   Hexachlorocyclopentadlene  was  detected at a maximum concen-
tration  of  0.10  jig/ma  In  homes  near a  hazardous  waste  site  1n  Hardeman
County  In Tennessee  and at  a maximum concentration of  39  yg/ma   1n  area
air samples  from a  wastewater  treatment plant 1n  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),  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  In water  were  100  ng/l  In  ambient
surface water  from Wheeling,  UV (Ohio  River Valley Water  Sanitation Commis-
sion,  1980)  and 650  ng/l  In  drinking  water  from Niagara Falls, NY  (Kim and


0077d                               -17-                             04/05/88

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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  (Kuehl  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  In
Appendix A.
0077d                               -18-                             12/23/87

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                             4.   AQUATIC  TOXICITY
4.1.   ACUTE TOXICITY
    Data  concerning  the  acute  tox1c1ty  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
LC5Q  values   for   Daphnla  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   LC5Q   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/l)  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, Sal mo  galrdneM.   to
hexachlorocyclopentadlene  at 130  yg/l   In a  nonredrculatlng  flowthrough
chamber.  Oxygen consumption, measured polarographlcally. Increased  by 195%
within 80 minutes,  followed by a  gradual  decrease until death at  ~5 hours.
|n  vitro studies   In which hexachlorocyclopentadlene was  added   to  normal
trout  mitochondria  resulted  In  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 1n  fish.

0077d                               -19-                             04/05/88

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                                                                               TABLE 4-1

                                            Acute Toilclty Data for  freshwater Species Exposed to Heiachlorocyclopentadlene'
,
>>
Species
Cladoceran
Daphnla Maana

fathead Minnow
(larvae. <0.1 g)
PlMeohales Dnwelaf
Fathead Minnow (1-1.5 g)
PlMeohales prooela,}

Fathead Minnow (0.72 g)
PlMeohales oroMelas
Goldfish
Carasslus auratus
Channel catfish (2.1 g)
Ictalurus punctatus
Bluegtll (0.45 g)
Lepoats Macrochlrin
Blueglll (8-13 CM)
Lepoals Macrochlrus
LargeMouth bass (8-13 CM)
Hlcropterus salMoldes,
Method
s.u
s,u
FT.N
S.U
s.u
NR
s.u
s.u
S.U
S.U
1
24-Hour
93.0
(78.9-109.6)
130
(68-260)
NR
115
93
75
240
(170-320)
HR
190
(140-250)
170
(140-210)
>500.000
>500.000
•Cso (nfl/M*
48-Hour
52.2
(44.3-60.9)
39
(30-52)
NR
110
78
59
210
(180-250)
NR
150
(130-180)
150
(120-180)
30.000
35.000

96-4tour
NO
NO
7.0
104
78
59
180
(160-220)
70
97
(81-120)
130
(110-127)
25,000
20.000
Acute No-Effect
Concentration
(vg/t)
32
18
3.7
NR
NR
NR
87
NR
56
65
NR
NR
CoMaents
17*C. soft water
22*C. soft water
25*C. soft water
hard water, acetone soln.
soft water, acetone soln.
hard water, eMUlslon
(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
Podowskl and Khan. 1979
Buccafusco and LeBlanc
Buccafusco and LeBlanc
Oavts and Hardcastle,
Davis and Hardcastle,
, 1977
, 1977
1957
1957
      •Source: U.S. EPA. 1984a

      DNiMbers In parentheses are the 95* confidence Intervals.
x,    HR  • Not reported; NO • not determined; S • static; FT - flowthrough;  U  • uranasured concentrations; N • Measured concentrations

-------
Oxygen consumption  rates  Increased  186% 1n -84 minutes with  decreases  until
death  at  -6.5 hours.   Slnhasenl  et al.  (1983)  postulated that  hexachloro-
cyclopentadlene  Intoxication  1n  the  Intact  fish may  be  due  to  Increased
oxygen consumption  and  Impaired  ox1dative ATP  synthesis, a  result of  the
mltochondrlal 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 yg/l.  Death or distress was observed  In 0.5-1.0 hours.
    Acute  toxldty  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
yg/i.   The  most  sensitive species  was  the  mysld shrimp, Hysldopls  bahla.
with a 96-hour LC,Q of & yg/i In a flowthrough test.
    Acute toxldty  data  1n 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 In 4.5 hours.
4.2.   CHRONIC EFFECTS
    Spehar et al. (1977,  1979)  conducted  30-day early life stage  flowthrough
toxldty tests  with fathead  minnows  beginning with 1-day-old larvae.   The
96-hour  mortality  data  Indicated   a   sharp  toxldty  threshold,  with  94%
survival   at   3.7  ug/i,  70%  at   7.3  yg/l  and   2%  at  9.1   yg/l.    At
the end  of   the  30-day exposure period,  mortality was  only  slightly  higher
with   90%   survival  at  3.7   vg/4,   55%  at  7.3   yg/l  and  0%  at   9.1
yg/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 Tox1c1ty Data on Marine Organisms
                    Exposed to Hexachlorocyclopentadlene3
Species
Polychaete
Neanthes arenaceodentata
Grass shrimp
Palaemonetes puqlo
Nysld shrimp
Mysldopls bahla
Nysld shrimp
Nvsldopls bahla
Nysld shrimp
Nvsldopls bahla
Plnflsh
Laqodon rhomboldes
Spot
Lelostomus xanthurus
Sheepshead minnow
Cyprlnodon varleqatus
Method
S.U
S.U
S.U
FT.U
FT.M
S.U
S.U
S.U
><-«5o>
371
(297-484)
42
(36-50)
32
(27-37)
12
(10-13)
7
(6-8)
48
(41-58)
37
(30-42)
45
(34-61)
^Source: U.S. EPA. 1980c. 1984a
b95X confidence Interval
N -  Measured 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 larvae.
    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 1n Appendix A.
4.3.   PLANT EFFECTS
    The  Shell   Oil  Company  (1982)  reported a 96-hour  EC™  for  the  green
algae,   Selenastruro  caprlcornutus.  of   0.19  mg/i.   Malsh  (1981)   reported
unpublished data on  the effects  of  hexachlorocyclopentadlene on four species
of  marine  algae.    The 7-day   EC.Q  was  calculated  as  the  concentration
causing a  SOX  decrease  1n blomass  compared  with  the control.   Isochrysls
galbana and Skeletonema costaturo were the most sensitive species, with  7-day
ECSQ   values   of    3.5   and  6.6   jig/I,  respectively.    The  7-day   EC™
values for Dunallella tertlolecta and  PorphyMdlum cruentum were 100 and  30
yg/t,  respectively.   Ualsh  (1983)  found  that after  48  hours of  exposure
to  hexachlorocyclopentadlene   at 25  yg/l,  mortality  of  S.  costatum  was
only 4%,  Indicating that  the  alglddal  effect of  hexachlorocyclopentadlene
was less pronounced then Us effect  on  growth.

0077d                               -23-                             12/23/87

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                                  TABLE 4-3
                 Effects of 28 Days  Exposure  of  Mysld  Shrimp,
               Mys1dops1s  bahla. to Hexachlorocyclopentadlene*
Concentration
Nominal
Control
0.75
1.5
3.0
6.0
12.0
(uq/i)
Measured
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
0°
aSource: U.S. EPA, 1981, 1984a
Significantly different from the control (p<0.05)
cNo explanation  was given  1n  original  text as  to  this value  In  comparison
 with the next measured value 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 toxlclty  data  for  the  chlorinated cyclopentadlenes  are  limited
to   studies   of  hexachlorocyclopentadlene.   Hexachlorocyclopentadlene   1s
highly  toxic   to freshwater  organisms,  with  the  LC5Q  for  Daphnla  magna
reported   to   range  from  39-180   vq/i  (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.t
1977,  1979).   The only data  for  a  freshwater algae was  a 96-hour EC5Q  for
Selenastrum caprlcornutus of 0.19 mg/l (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
ng/l  for  all  species   except  the  polycheate   for  which  the  LCrQ  value
was  371   iig/l  (U.S.  EPA,  1980c).   In  four species  of  saltwater  algae,
7-day  EC-,  values  were  reported  1n  the  range of 3.5-100  yg/i  (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-hexachlorocyclo-
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 14C-hexachlorocyclopentad1ene,  72%
was excreted In the feces.
    Lawrence and  Dorough  (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  1n  corn
oil)  250  times  larger  than  Inhalation  doses  (24   iig/kg)  and 600  times
larger than  Intravenous doses (10  wg/kg 1n DMSO  or  10:4:1  sa11ne:propy1ene
g1ycol:ethanol)  were required.   The  authors attributed  this  to the  poor
b1oava1lab111ty  of hexachlorocyclopentadlene when administered  by the  oral
route.   In  the Inhalation  studies,   rats  were  exposed  to  X4C-hexachloro-
cyclopentadlene  for  30-120 minutes using respirators, so  that  they received
doses  that  ranged from 1.4-37.4 ug/kg.  Immediately  following  exposure.  It
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 Oareer  et al. (1983), radioactivity
1n  the  tissues of  rats   72  hours  after  dosing  with  14C-hexachlorocyclo-
pentadlene was  39, 11.5 and  2.4% by  Intravenous, Inhalation  or  oral routes
of  exposure,  respectively.   From these  results  It is 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  "C-labeled
hexachlorocyclopentadlene  by  gavage  (5  ymol),  -0.5X  of the  radioactivity
was retained  In  the  kidney with <0.5%  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
(8.5-25.6  mg/kg)   l4C-hexachlorocyclopentad1ene   to   Sprague-Dawley   rats.
The l4C-act1v1ty was  found 1n  the  blood shortly  after dosing and  reached a
maximum  1n  -4  hours.   Tissues  were analyzed  for l4C-act1v1ty  8, 24,  48,
72, 96  and 120  hours  after dosing.  At 24 hours after-dosing,  the highest
levels of activity were found  1n  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  (Oorough.  1979;   Dorough  and
Ranlerl, 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  l4C-act1v1ty.   The  results  Indicated that the  liver,  kidney
and  fat  were the  most  significant  sites  of deposition  for l4C-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 1n rats
and  mice fed l4C-hexachlorocyclopentad1ene  In 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
l4C-hexach1orocyclopentad1ene.  During  the treatment  period,  rats and  mice
were killed at  1.  3.  7. 12. 15 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-levels found 1n all of the tissues examined.
    In  a   comparative   study  (Dorough,  1980;   Lawrence  and  Dorough.  1981.
1982).  rats  were  exposed  to  single  doses of  14C-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-act1vity was In  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 In  the kidneys and  liver  of rats following oral
and  Intravenous  dosing  with  14C-hexach1orocyclopentad1ene,  while   radio-
activity levels  were highest 1n  the kidneys and   lung  following  Inhalation
exposure.    The  majority  of  the radioactivity  (>99%)  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-
cyclopentadlene  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 14C-Hexachlorocyclopentad1enea'D»c
Sample
Oral Oose
(6 mg/kg)d
Inhaled Dose
(-24 yg/kg)
Intravenous Dose
(10 yg/kg)
                                           nq/q of Tissue
Trachea
Lungs
Liver
Kidneys
Fat
Remaining carcass
292 + 170
420 * 250
539 7 72
3272 > 84
311 7 12
63 7 40
107.0 «• 65.0
71.5 * 55.2
3.6 * 1.9
29.5 + 20.2
2.8 + 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 7 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 f 4.6
aSources: Borough, 1980; Lawrence and Borough, 1982; U.S. EPA, 1986b

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 roean+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  1n  Individual  tissues  of animals  treated orally at  doses  of
 5-25 yg/kg.
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5.3.   METABOLISM
    Autoradlographs  of  urine  extracts   from rats  given  single  doses  of
14C-labeled  hexachlorocyclopentadlene  revealed   at  least  four  metabolites
(Mehendale, 1977).  These metabolites were not Identified or characterized.
    Yu and  Atallah (1981)  found  no unchanged hexachlorocyclopenta  dlene  1n
the  urine  or  feces  of  rats  given  single  oral doses  of  14C-hexachloro-
cyclopentadlene.    Both  the  urinary  and  fecal  metabolites  were  charac-
terized as  polar, with  11% of the  14C-content  soluble 1n 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  U.2,   1.6 and  10.6 hours,  respectively.   The  addition  of  mercuric
chloride  to the gut  contents  and fecal  homogenate as  a bacterlclde resulted
In an Increase In  half-lives  to 17.2 and 6.2 hours,  respectively.   Oenatura-
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  mutagenlclty 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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         N     H
                                                    -
       PanUchl
  Trtr»chloro-
eyelopcntadicnone
       Htxcchloro-
       c fc1open tadlcna
                                                                     Mucltophile
                                 FIGURE 5-1
                   Proposed Metabolic Formation of  Reactive
        Tetrachlorocyclopentadlenone from Chlorinated Cyclopentadlenes
                      Source:  Wggelmann et al.,  1978
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       -31-
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5.4.   EXCRETION
    Rats  given  single  oral  doses  of 14C-labeled  hexachlorocyclopentadlene
(5 yrnol)  excreted  33% of  the  dose 1n the urine  and  10% of the dose  In  the
feces 1n  7  days  (Mehendale,  1977).  About 87% of the  dose  eliminated  In  the
urine and 60% of the dose  eliminated  1n  the  feces were excreted 1n the first
24  hours.   Mehendale  (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  1*C-hexachlorocyclo-
pentadlene  given  to rats  was  excreted  1n the  lungs.  The  level of  fecal
excretion reported  In  the Mehendale  (1977)  study  was probably low  because
the feces were  dried and  powdered before analysis.  UhUacre  (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 In the feces and  -17% In the urine.
    In a  single-dose  study.  Dorough  (1979)  found that 73-96%  of  the  radio-
label of  l4C-hexachlorocyclopentad1ene was excreted  1n  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  ppra 14C-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 *4C-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 14C-hexach1orocyclopentad1ene  at  6  mg/kg  excreted  2-3
0077d                               -32-                             04/05/88

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times 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   14C-hexachlorocyclopentad1ene   are
presented 1n  Table  5-2 (El  Dareer  et al.,  1983).   This study  supports  the
observation  that  little   hexachlorocyclopentadlene   or  Us  metabolites  1s
excreted  1n the  respiratory  tract.   Following  oral and  Intravenous  exposure,
fecal excretion  predominates, while  a larger percentage  of  the radioactivity
1s excreted 1n the urine following Inhalation exposure.
5.5.   SUMMARY
    Comparative  pharmacok1net1c  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 toxlclty data  which  Indicate that  hexachlorocyclo-
pentadlene 1s more toxic following Inhalation exposure than  oral  exposure.
    Following    Inhalation    exposure   to    l*C-hexachlorocyclopentad1ene,
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 hi vivo and  \n_ 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.
0077d                               -33-                             04/05/88

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                                                 TABLE 5-2

                    Distribution of Radioactivity Expressed as Percentage of Administered
                 Dose from »4C-Hexachlorocyc1opentadlene  In  Rats  Dosed by  Various Routes3
Oral Dose (X)
Low Dose0
(4.1 mg/kg)
Feces
Urine
Tissues
C02
Other volatile
TOTAL RECOVERY
79
35
2
0
0
118
.4
.5
.4
.8
.2
.3
± 2.9
± 2.5
1 0.6
1 0.0
±0.0
1 3.0f
High Dosec
(61 mg/kg)
65.3
28.7
2.4
0.6
0.3
97.3
± *•*
± *-2
± 0.1
1 0.0
f 0.0
± 7.0
Intravenous Dose (X)c
(0.59 ng/kg)
34.0
15.8
39.0
0.1
0.1
89.0
± I-
± 1.
± I-
± o.
± o.
± 2-
oe
4
0
0
0
0
Inhalation Dose IX)
Group A<*
(1.0 mg/kg)
28.7 ± 4.3
41.0 t *-8
28.9 i 1.6
1.4 * 0.3
NR
(100)
Group Bc
(1.4 rag/kg)
47.5 ± 6
40.0 ± 6
11.5 * 0
1.0 i 0
NR
(100)
.4
.6
.8
.5



aSource: El Dareer et al.. 1983;  U.S.  EPA.  1986b

bThe values represent the mean % of dose ±  SD for  three  rats.

cAt 72 hours after dosing or exposure

dAt 6 hours after exposure

ePlus Intestinal contents

ffor  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  14C-hexachlorocyclopentad1ene,  the  radio-
activity  1s  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.
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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  nice and  four rats  to hexachlorocyclopentadlene  (89.5%
pure)  at  0.34  ppm (3.7 mg/ra3),  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  1n  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/m3,  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  1n  all  species.
Mice,  rats and  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  In  mice  exposed  to 0.15  ppm. and  no
effects In 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  (99.42X)  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/ma)  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)].

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Exposure-related changes  1n 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 In female rats  (Battelle  Northwest  Laboratories,  1984).   At 0.4
ppra, relative lung weights  were  higher In 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   1n  the
respiratory tract epithelium were  observed 1n  rats at >0.4 ppm.   The  changes
observed Included necrosis and acute Inflammation.  No  effects  were observed
1n rats at 0.15 ppm.
    In  mice  (Abdo  et al.,  1986),  body weight gains were 105C lower  In  both
sexes  at   0.4  ppm.   The  only change   1n  organ  weight  was  an   Increase  1n
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  Ulstar  rats were exposed  to  hexachlorocyclopentadlene (96% pure)  at
nominal concentrations  of  0,  0.05,  0.1  or  0.5 ppm  (0, 0.56,  1.1   or  5.6
mg/m»),  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.   Mild
degenerative  changes  In the  liver  and kidney  were also  observed In  a  few
rats  at  0.5  ppm,  with  kidney  weights significantly  Increased  In  females.
Changes In  organ weights or hlstopathologlcal  changes  were not  observed  1n
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/ma), 6 hours/day,  5 days/week
for up to 14 weeks.  No effects were  observed 1n 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  In  body weight  gain or food  or  water consumption.
At  12  weeks,   there  were  marginal,   but  not  statistically  significant.
Increases  In 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  \n  the  exposed rats  were similar  to
changes  described  In  the  Evans et  al.  (1978)  study.   The  toxlcologlcal
significance  of these  changes   1s  not  known.   The  Clara  cell  contributes
Important materials  to  the extracellular  lining  of the peripheral  airways,
and  1f  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 toxldty of other  chlorinated  cyclopenta-
dlenes  following  subchronlc  Inhalation  exposure were  not  located  1n  the
available literature cited In  Appendix A.
    6.1.1.2.    CHRONIC -- 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.    SUBCHRQNIC — IBT (1975)  fed groups  of 15 male and 15 female
albino  rats  hexachlorocyclopentadlene  In  the diet  at  concentrations of  0.
10,  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  histopathologic
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  (94.3-97.4X  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 In 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 kldney-to-braln and  I1ver-to-bra1n  weight
ratios was observed  1n females at  all  doses,  with Increases  1n  Iung-to-bra1n
weight also observed In females at 300  mg/kg.  Toxic nephrosls  was observed
1n  female mice  at doses >75 mg/kg.  This effect was not  observed  In  males.
Treatment at >38  mg/kg  resulted  1n forestomach  lesions,  Including  ulceratlon
and Inflammatory  changes  1n  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 In males at 38,  75  and 150 rag/kg  and  females  at 75 and  150  mg/kg.
The  I1ver-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 In females at >75  mg/kg.  A  dose-related  Incidence  of forestomach


0077d                               -40-                             04/05/88

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lesions (ulceratlon and  Inflammation)  was  observed beginning at 19 mg/kg  In
female  rats  and  at 38  mg/kg  1n  male rats.   No effects  were observed  1n
either sex at 10 mg/kg.
    Pertinent data  regarding the  toxldty  of other chlorinated  cyclopenta-
dlenes following  subchronlc  oral  exposure  were not located  In  the  available
literature dted 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  toxlclty data  for hexachloro-
cyclopentadlene are presented  1n  Table 6-1.   Reported  oral  LD...S In  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-
pentadlehe 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
LD~Q  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  In  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  1n 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 ToxIcUy of Hexachlorocyclopentadlene*
   Species, Age
             Results
 Reference
Rat, young adult


Rabbit, adult


Rat, young adult


Rat, young adult


House, young adult


Rat, weanling


House, weanling


Rabbit, adult


Rabbit, adult


Rat, young adult


Rat. young adult


Rabbit, adult
oral 1059: males - 510 mg/kg
           females - 690 mg/kg

oral 1059: females - 640 mg/kg
oral 1059: males and females -
926 mg/kg

oral 1059: males and females -
651 mg/kg

oral 1059: males and females -
600 mg/kg

oral 1059: males - 425 mg/kg
           females - 315 mg/kg

oral 1059: males and females -
680 mg/kg

dermal 1.059:. females - 780 mg/kg
dermal 1059: males - 200 mg/kg
             females - 340 mg/kg

3.5-hour Inhalation 1059: males
          and females - 3.1 ppro

4-hour Inhalation 1059: males -
         1.6 ppm, females - 3.5 ppm

3.5-hour Inhalation 1059:
females - 5.2 ppm
Treon et al.,
1955

Treon et al.,
1955

IRDC, 1968


Oorough, 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
House, adult
3.5-hour Inhalation 1059: males
and females - 7.1 ppm
3.5-hour Inhalation 1659: males
and females - 2.1 ppm
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


RabbH, adult           severe eye Irritant  (0.1 mi  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 In  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
0077d                               -43-                             04/05/88

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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  (97.7% pure)  at  0.  0.022.  0.11  or 0.5  ppm  (0,  0.25.  1.2 or  5.6
mg/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 1n males  at 0.022 and 0.11  ppm.  Body weights were significantly
reduced at  day  1  after  the   exposure  at  0.5  ppm  1n  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 1n the
lungs and  hlstopathologlc lesions  were  observed In  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 Haste-
water Treatment Plant  In Louisville, KY (Wilson  et al.. 1978; Morse et al..
0077d                               -44-                             04/05/88

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1979; Komlnsky et 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  (Norse  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  (Morse 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 (75%) of  the workers.  Indicated  that
the  most  common  symptoms  were  eye   Irritation (59X), headaches  (45X)  and
throat Irritation  (27X).  In 95X 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  In  27% and  protelnuHa 1n 15X.   No  clinical abnormali-
ties were reported 3 weeks later  (Morse et al.. 1978,  1979).
    During  the  cleanup,  the clinical  chemistry  parameters  of the  workers
were  monitored.   The only  abnormalities  noted were several  mlnlmal-to-mlld
abnormalities  In  liver  function tests  (SGOT, serum  alkaline  phosphatase,
serum  total  bH1rub1n,  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 (Horse et al.. 1979).
6.2.   CARCINOGENICITY
6.2.1.   Inhalation.    A   number   of   mortality   studies   (Shlndell   and
Associates, 1980,  1981; Wang  and MacNahon, 1979; Buncher et  al.,  1980)  have
not shown  Increased  cancer death rates  In  workers Involved 1n the  produc-
tion  of  hexachlorocyclopentadlene.  These  studies  are  reviewed  In U.S.  EPA
(1984a, 1986b).
    An NTP  Inhalation carclnogenlclty bloassay  of  hexachlorocyclopentadlene
In rats and mice Is In progress (NTP. 1987).
    Pertinent  data regarding  the  carclnogenlclty   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 carclnogenlclty of the  chlori-
nated  cylcopentadlenes  following  oral  exposure  were  not   located  In  the
available literature  cited In Appendix A.  A chronic  oral  toxldty 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. 19865).
6.2.3.   Other Relevant Information.   Pertinent  data  regarding the carclno-
genlclty  of  the  chlorinated  cyclopentadlenes  following  other  routes  of
exposure were not  located  In the available literature cited  In Appendix A.
6.3.   HUTAGENICITY
    .In vitro  and In  vivo  mutagen1c1ty data for the  chlorinated  cyclopenta-
dlenes are presented  In  Table  6-2.   Negative  results  for  hexachlorocyclo-
pentadlene have  been  reported In rautagenlcUy  assays  In bacteria (Gdggelmann

0077d                               -46-                             04/05/88

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                                                                                 TABLE  6-2


                                                           Mutagentclty Testing of Chlorinated Cyclopentadlenes
ro

x.
op
Assay
Reverse
•utatlon
Reverse
•utatlon
Reverse
•utatton
Reverse
•utatlon
Reverse
•utatlon
Reverse
•utatlon
Reverse
•utatlon
Indicator/
Organ 1 SB
Esther Ichla
coll fc!2
£. coll k!2
i. coll k!2
Saleonella
tvphlBurluM
TA1535.
TA1S38
S. tvphlMurluM
TA1535. IA1538
S. twhlBurluB
TA100
S. tvphlaairlua
TA98. TA100.
TA1S35. TA1S37
Coofiound
and/or
Purity
hexachloro-
cyclopenta-
dlene/gas-
chronato-
graphtcally
pure
pentachloro-
cyclopenta-
dtene/gas-
chronato-
graphlcally
pure
tetrachloro-
cyclopenta-
dlene/gas-
chronato-
graphlcally
pure
hexachloro-
cyclopenta-
dlene
tetrachloro-
cyclopenta-
dtene
hexachloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
d1ene/98X
Application
pratncuba-
batlon
prelncuba-
batlon
prelncuba-
batlon
BB
NR
vapor
pre Incuba-
tion
Concentration Activating
or Dose Syste*
2.7xlO'« - » Bouse liver
2.7x10'* N itcrosooal
protein
2.4x10'* - «• Bouse liver
2.4x10'* N ilcrosonal
protein
1.0x10"* - i Bouse liver
1.0x10'* N Btcrosoaal
protein
MR f Bouse liver
•Icrosooal
protein
NR «• aouse liver
•tcrosonal
protein
NR »S-9
3.3 pg/plate -S-9
100 tig/plate »S-9
Response Coownt
70X survival at 72 hours.
cytotoxlc at higher
concentrations
» Positive results with,
but not without oeta-
boltc activation
i Positive results with.
but not without meta-
bolic activation
NC
» HC
Exposure times of 30. 60
and 120 alnuies were used
which May not have been
long enough to observe
a Mutagentc effect.
Higher levels could not
be tested due to cyto-
toxlclty.
Reference
fifiggelnann
et al.. 1978
Otggelmann
et al.. 1978
Goggeloann
et al.. 1978
Greta
et al.. 1977
firela
et al.. 1977
1BT. 1977
Haworth
et al.. 1983

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                                                                            TABLE  6-2 (cant.)
00
Assay
Forward
mutation
DMA repair
Cell trans-
formation
Set-linked
recessive
lethal
Dominant
lethal
Indicator/
Organism
MUSB lymphoma
U17BV cells
rat primary
hepatocytes
BALB/3T3
cells
Drosoohlla
melanoaaster
CO-1 Mice
Compound
and/or
Purity
hexachloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
dlene
nexachloro-
cyclopenta-
dlene
hexachloro-
cyclopenta-
dlene
Application
added to
cultures
added to
cultures
added to
cultures
feeding
Injection
gavage.
S days
Concentration Activating
or. Dose Systea
1.25x10"* »S-9
n9/«t
10'» - NA
1(T« N
0-0.156 w»/|il
40 ppa NA
?00 ppM
0.1, 0.3 or NA
1 .0 agAg/day
Response Cement
Cytotoxlclty was ob-
served at higher con-
centrations.
NC
Doses selected allowed
00-10W survival.
NC
Nice were mated for
1 weeks.
Reference
Litton
Blonettcs.
Inc.. 1978b
Brat. 1983
Litton
Blonetlcs.
Inc.. 1977
Juodelka,
1983
Litton
Btonetlcs.
Inc..l978a
      NA » Not applicable;  NC - no comment; NR • not reported
M




CD

-------
et al.,  1978;  Grelm et al., 1977; IBT, 1977; Hauorth et al..  1983)  and  1n a
mutation  assay  In  mouse  lymphoma cells  (Litton  Blonetlcs,  Inc..  1978b).
Hexachlorocyclopentadlene  also  tested  negative for  cell  transformation  1n
BALB/3T3  cells (Litton  Blonetlcs,  Inc.,  1977).  DMA repair  In  rat  primary
hepatocytes  (Brat.  1983),  sex-linked  recessive lethal  mutations  In  Droso-
phlla melanoqaster  (Juodelka, 1983) and a dominant lethal mutation  study  In
mice (LUton Blonetlcs, Inc., 1978b).
    Studies of penta-  and  tetrachlorocyclopentadlene  1n  bacteria (Gdggelmann
et al.,  1978;  Grelm et al.,  1977)  have reported positive results for reverse
mutation  In  the  presence of metabolic  activation.  Goggelmann 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 rautagenlc activity.
6.4.   TERATOGENICITY
    In  a  teratogenlclty  study,  pregnant  Charles  River  CO rats  were treated
by gavage  with hexachlorocyclopentadlene  (98.25X pure)  1n corn  oil  at 3,  10
or  30  mg/kg  on  gestation  days  6-15  (IRDC. 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  In maternal  body weight  gain  observed.
Persistent anogenltal  staining was observed  In  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  1n the
number of external, soft tissue or skeletal  abnormalities.
    In  an .Irt 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 mg/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  White
rabbits by gavage with  hexachlorocyclopentadlene  1n cottonseed oil at  0.  5,
25 or 75 mg/kg/day.  Mice  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  Utters/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  Toss 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  1n 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  1n  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 1n the available  literature  cited  In
Appendix A.
6.6.   SUMNARY
    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  1n  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 1n 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  1n  mice
at   0.04   ppm    and    In   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 ppm,  with
deaths at  >1  ppm.   The animals  were  exposed 6 hours/day,  5  days/week.   A
chronic Inhalation study using rats  and mice 1s  1n  progress (NTP,  1987).
    A  13-week  gavage study  using rats and mice (SRI,  1981a;  Abdo et  al.,
1984)  found  ulceratlon of  the stomach In  mice treated 5 days/week at  >38
mg/kg, and  at >19 rag/kg  1n  rats.   No effects were observed  In mice at  19
rag/kg  or  1n  rats  at  10  mg/kg.   No effects  were  reported tn  rats  fed
hexachlorocyclo- pentadlene  In the  diet at up  to  300  ppm for 90  days  (IBT,
1975).
    The  lowest  oral  LD5_  1s 315  mg/kg  In  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 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  mg/ma  (Levin,  1980).   Questionnaires completed  by
workers  at  the  Morris  Forman  Wastewater  Treatment Plant  1n 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).
    Mortality studies  of  hexachlorocyclopentadlene  production workers  have
not  shown  Increased  cancer death rates.   No  animal studies of  the cardno-
genlclty of hexachlorocyclopentadlene were available.

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    Results of  mutagenlcUy  assays  of penta- and tetrachlorocyclopentadlene
In  bacteria  have  been positive  (Goggelmann et  al.t 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  1n  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 1n  mice
(LUton 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-TUA  of  0.01 ppm  (0.1  rag/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 1s  206  yg/l.   Using organoleptlc  data
for  controlling  undesirable  taste  and  odor,  the  estimated  level  1s  1
ug/l  (U.S.  EPA.  1980b).    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  mg/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  (19805)  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  cardnogenlclty of  the
chlorinated cyclopentadlenes following  Inhalation  exposure  were not located
1n the available literature cited  In  Appendix A.  An Inhalation cardnogen-
1c1ty bloassay of hexachlorocyclopentadlene  1s  In progress (NTP, 1987).
8.1.2.   Oral.   A  number  of  mortality  studies  (Shlndell  and  Associates,
1980, 1981;  Wang and HacMahon,  1979;  Buncher et al.,  1980)  have  not shown
Increased  cancer death  rates  In   workers  Involved  1n  the   production  of
hexachlorocyclopentadlene.  Animal  studies  regarding  the  cardnogenlclty of
chlorinated cyclopentadlenes following oral  exposure were not located In the
available literature  cited  1n  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  1n Appendix  A.
ff.1.4.   Height 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,  19865),  the  chlorinated  cyclopentadlenes  can  be
considered Group 0 -  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 Its  lacMmatory 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  100% of the  Individuals  on  a
panel  was  0.0017  mg/m*   (0.00015   ppm).    Multiplying   the   0.0017  mg/m3
concentration  by  20  m'/day,  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  1n Louisville. KY  (Norse et al., 1978.  1979)  1t 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  If 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/m3 (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/m3  (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  In females  at 0.6  and 2.2  mg/ma.   No  treatment-
related changes  In body weight,  food and  water consumption, and  gross  and
hlstopathology were  observed.   Electron microscopy  revealed  ultrastructural
changes 1n  the Clara cells 1n  rats  at all exposure concentrations, with  no
effects In 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  1n
the  Rand  et al.  (1982a)  study to be a NOAEL  1n 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   1n rats  and mice  at
lower concentrations, a new subchronlc Inhalation RfD will be derived.
    D. Clark  et  al. (1982) exposed  groups of  eight rats/sex  to hexachloro-
cyclopentadlene at  0,  0.56, 1.1 or  5.6 mg/ma  (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  In  males  and  pulmonary
degenerative changes were noted 1n both  sexes.   N1ld degenerative changes  1n
the  liver and kidney  were also  observed  In  a few  rats at  5.6 mg/m8  and
kidney weights Increased  significantly  1n  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  In  this  study was
0077d                               -58-                             04/05/88

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5.6  mg/ma,   a  concentration  associated  with  death.   Multiplying  the  5.6
mg/m*  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
raVday 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  1s  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 ppro), 6 hours/day,  5 days/week for  13 weeks.   Information
concerning  the mouse study was available  only  1n an abstract (Abdo  et  al..
1986).   All  rats  and  mice exposed to >11.1  mg/m3  died.  In  rats  (Battelle
Northwest Laboratories,  1984), body weight gain was  significantly  (p<0.05)
reduced  In  males  at  4.46  mg/m3;  a  similar  but  less severe  effect  was
observed  In  females.   At  0.4 ppra,  relative  lung  weights were higher  In
females  and  significantly  (p<0.5)  higher  In  males.   Relative  weights  of
heart,  kidney  and testes  In  4.46  mg/m3  males  were  also  Increased.   Dose-
related  hlstopathologlcal  changes In  the respiratory tract epithelium  were
observed  In rats  at >4.46  mg/m3.   The  changes  observed  Included  necrosis
and  acute Inflammation.   No effects  were observed 1n  rats  at  1.67  mg/m3.
Multiplying  the  LOAEL  (4.46  mg/m3)  and  NOAEL  (1.67 mg/m3)  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/m3,  and  body  weight  gains  were  10%  lower  1n  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
hlstopathologlcal  alterations   In   the  respiratory  epithelium.  Including
hyperplasla  and  metaplasia,  were  observed  In  mice  at  >1.67  mg/m8.   No
effects were  observed  1n mice  a.t 0.45  mg/ma.   Multiplying the  LOAEL  (1.67
rag/ma) and NOAEL  (0.45   mg/m8)  concentrations by  6/24 hours  and 5/7  days
to  expand  to  continuous  exposure,  multiplying  by  the  reference  mouse
Inhalation  rate  (0.039  m»/day)  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   In  the  NTP-sponsored  subchronlc   studies  1s   0.39
mg/kg/day,  a  dose  at  which  hyperplasla  and metaplasia  of the  respiratory
epithelium were  observed  1n mice.   The highest  NOAEL  below the  mouse  LOAEL
Is the rat NOAEL  of 0.2  mg/kg/day.   Application  of  an  uncertainty factor of
100  (10  for  Interspecles extrapolation and 10  to  protect sensitive  Indi-
viduals) and a modifying  factor  of 10 results  In  a  subchronlc  Inhalation RfD
of 0.0002  mg/kg/day  or 0.014  ing/day  for a  70 kg human.   The modifying factor
Is used  because of  the  steep dose-response curve Indicated In 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.
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Multiplying the O.QQQ2  mg/kg/day RfD by  70  kg body weight, and dividing  by
20  ma/day human  breathing  rate,  the  subchronlc  RfD  for  hexachlorocyclo-
pentadlene corresponds to a air concentration of 0.0007  mg/m3.
    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  1s  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  In  females  during  treatment followed by  a  decrease  during  the
recovery  period,  was  considered  the LOAEL.   A chronic  Inhalation  RfD  of
0.00006  mg/kg/day  or   0.0046  mg/day  was calculated  from 0.05  ppm  (0.56
rag/m3),  the  lowest concentration tested  (NOAEL).  using   a  rat  breathing
rate  of  0.26 mVday, 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 RfO  results 1n  a chronic  RfO of  0.00002
mg/kg/day (O.OOH rag/day), or a concentration of  0.00007  mg/m».
    As  stated  for  the  subchronlc Inhalation  RfO  for  hexachlorocyclopenta-
dlene, confidence 1n  the  chronic Inhalation RfO  1s medium.   The chronic  RfO
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  toxldty  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.  ISO or 300 rag/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  1n forestomach  lesions.  Including
ulceratlon 1n 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 mg/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  150  mg/kg and  female rats
at  75  and  150 mg/kg.   At 19  mg/kg,  the LOAEL.  forestomach lesions  were
observed 1n  female  but not male rats.   The  10  mg/kg dose level  was  a  NOAEL
1n both male and female rats.
    Because  stomach  lesions  were   observed  1n  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 ing/day for a  70  kg  human.   Confidence 1n  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 RfDs.
    8.2.2.2.   CHRONIC  EXPOSURES — There  are  no  chronic   oral  studies  of
hexachlorocyclopentadlene.   A chronic  oral   RfD  of 0.007 mg/kg/day or  0.5
rag/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 In  this RfD 1s
low.
    A lack  of  pertinent data regarding the  chronic oral  toxldty  of  other
chlorinated cyclopentadlenes precludes the derivation of chronic oral RfDs.
0077d                               -63-                             04/05/88

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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  In 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.t 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
1s not  presented In 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  ppra,  6  hours/day,  5  days/week  (a  transformed animal  dose  of   1.04
mg/kg/day). The  chronic human  MED of 0.56 mg/day corresponds  to  an RV.  of
5.9, while death corresponds to  an RV   of 10.
                                     C
    A CS of 59  corresponds  to an RQ  of  10  pounds.   This RQ 1s 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 CARCIN06EHICITY
    The lack of data precludes the derivation  of cardnogenldty based RQs.
0077d                               -64-                             04/05/88

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                                                                              TABLE 9-1

                                                            ToxicIty Sundry for HexachlOrocyclopentadtene
Ut
1
Species/
Route Strain Sex
Inhalation rats/Ulstar H.F
Inhalation rats/F344 H.F
Inhalation rats/F34« H.F
Inhalation m1ce/B6C3F1 R.F
Inhalation mtce/B6C3Fl H.F
Oral mlce/B6C3Fl H.F
Oral m!ce/B6C3Fl H.F
No. at Average
Start Height
(kg)
8/sex 0.35°
10/sex 0.22d
10/sex 0.22*
10/sex 0.03B
10/sex 0.03D
10/sex O.OSb
10/sex 0.03D
Vehicle/ Purity
Physical (X) Exposure
State
air 96 0.5 ppm
(5.6 mg/m«).
6 hours /day,
5 days/week,
for 30 weeks
plus 14 weeks
recovery
air 99.42 1 ppm (11.2
mg/B«».
6 hours/day.
5 days/week.
.for 13 weeks
air 99.42 0.4 ppm (4.5
mg/m«).
6 hours/day.
5 days/week.
for 13 weeks
air 99.42 0.4 ppm (4.5
mg/m«).
6 hours/day.
5 days/week.
for 13 weeks
air 99.42 0.15 ppn
(1.67 mg/m«).
6 hours/day.
5 days/week.
for 13 weeks
corn oil 94-97 300 mg/kg by
gavage. 5
days/week.
for 13 weeks
corn oil 94-97 ISO mg/kg by
gavage. 5
days/week.
for 13 weeks
Transformed Equivalent
Animal Dose Human Dose4 Response
(mg/kg/day) (mg/kg/day)
0.64C 0.11 Death of 4/8 males and
2/8 females; kidney,
liver and pulmonary
degenerative changes
1.45* 0.21 Death of all rats
0.58e 0.08 Decreased body weights of
males, necrosis and acute
Inflaomatlon of respira-
tory eplthella
1.04* 0.08 Death of 5/10 males and
2/10 feoales
0.39C 0.03 Hyperplasla and meta-
plasia of respiratory
eplthella
214.3' 16.2 Death of all males and
3/10 females
107. l' 8.1 Toxic nephrosls In fe-
males, stomach lesions,
depressed body weight
gain
Reference
Clark
et al.. 19B2b
Battelle
Northwest
Laboratories,
1984
Battelle
Northwest
Laboratories.
1984
Abdo et al..
1986
Abdo et al..
1986
SRI. 1981a;
Abdo et al..
1984
SRI. 1981a;
Abdo et al..
1984

-------
                                                                           TABLE 9-1 (cont.)
9>
I

Route

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 0.35<>



Vehicle/
Physical
State
corn oil



corn oil



Purity
(X) Exposure

94-97 ISO ag/kg by
gavage. 5
days/week ,
.for 13 weeks
94-97 1) ag/kg by
gavage. 5
days/week .
for 13 weeks
Transforaed
Anlaal Dose
(ag/kg/day)
107. lf



13.6'



Equivalent
Huain Dosea
(ag/kg/day)
18.3



2.3




Response

Death, toxic nephrosls
and s touch lesions


Stoaach lesions In
females



Reference

SRI. 19Bla;
Abdo et al..
1984

SRI. 1981a;
Abdo et al..
1984

'Calculated by Multiplying the anlaal  transformed dose by the cute root ratio of the anlaal body weight to the huaan  body weight  (70 kg)
^Reference rat (0.3S kg) and enuse (0.03 kg) body weights (U.S. EPA. 1985)
cCalcu1ated by  multiplying  the  concentration  by the  hours/day,  days/week, by  the anteal  Inhalation rate  (0.223 ••/day  rats;  0.039 ••/day  alee  (U.S.
 EPA (1985)] and by dividing by the anlaal  body weight
dfstlaated froa growth curves In the study
•Calculated as described In c except the Inhalation rate of O.U a»/day calculated froa I  - 0.105 (w/0.113J2/3 (U.S.  EPA. 1985) was  used
'Calculated by aultlplylng the dose by S days/7 days
ro

-------
g
                  TABLE  9-2

Composite Scores for Hexachlorocyclopentadlene
Species
Rat

Rat



Rat



Mouse

Mouse


Animal Dose
(mg/kg/day)
0.64

1.45



0.58



1.04

0.39


Chronic
Human MED*
(mg/day)
0.77

1.47



0.56



0.56

0.21


RVd Effect RVe
5.7 Death of 4/8 males. 10
2/8 females
5.2 Death 10



5.9 Decreased body weight, 4
necrosis and acute In-
flammation of respira-
tory epithelium
5.9 Death of 5/10 males. 10
2/10 females
6.5 Hyperplasla and met a- 6
plasla of respiratory
epithelium
CS RQ Reference
57 10 Clark
et al.. 1982b
52 10 Battelle
Northwest
Laboratories,
1984
23.6 100 Battelle
Northwest
Laboratories.
1984
59 10 Abdo et al..
1986
39 100 Abdo et al..
1986

         'The dose was divided by an uncertainty factor of 10 to approximate chronic exposure.
OB
00

-------
                                  TABLE 9-3
                          Hexachlorocyclopentadlene
          Minimum Effective Dose (MED) and Reportable Quantity (RQ)

Route:                  Inhalation
Species:                Mouse
Dose*:                  0.56 rag/day
Duration:               13 weeks
Effect:                 death
Reference:              Abdo et al., 1986; SRI.  1981a
RVd                     5.9
RVe                     10
Composite Score:        59
RQ:                     10
*Equ1valent human dose
Q077d                               -68-                             04/05/88

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                                  TABLE 9-4
               Chlorocyclopentadlene,  THchlorocyclopentadlene,
          Tetrachlorocyclopentadlene and Pentachlorocyclopentadlene
          Minimum Effective Dose (HED) and Reportable Quantity (RQ)
Route:
Dose:
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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Plant,  Metropolitan Sewer District. Louisville. KY.   NIOSH  Hazard Evaluation
and  Technical   Assistance Rep.  No.   TA-7739.   U.S.  DREW,  Cincinnati.  OH.
(Cited  In  U.S.  EPA. 1984a, 19865}

Komlnsky,  J.R., C.L.  Ulsseman  and D.L.  Morse.  1980.   Hexachlorocyclopenta-
dlene contamination  of  a municipal  wastewater  treatment  plant.  Am.  Ind.
Hyg. Assoc. J.   41: 52.   (Cited 1n U.S.  EPA.  1984a.  1986b)

Korte,   F.   1978.    Photomlnerallzatlon of   hexachlorocyclopentadlene  and
ecotox1colog1cal profile  analysis of hexachlorocyclopentadlene.   Unpublished
report  prepared  for  Velslcol Chemical  Corp..  Chicago, IL.   (Cited  1n  U.S.
EPA. 1984a)
0077d                               -78-                             04/05/88

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Kuohl, D.M., E.N.  Leonard,  B.C.  Butter-worth and K.L. Johnson.   1983.   Poly-
chlorinated chemical  residues  1n fish from major  watersheds near  the  Great
Lakes, 1979.  Environ. Int.  9: 293-299.

Lawrence,  L.J.  and  H.U.  Dorough.    1981.   Retention  and  fate  of  Inhaled
hexachlorocyclopentadlene  In the rat.  Bull. Environ.  Contam.  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.   Ooc.  #878211178.
Microfiche #0730205956.

Litton  BVonetlcs.  Inc.   1977.   Evaluation  of hexachlorocyclopentadlene  .Iri
vitro  malignant  transformation  In  BALB/313 Cells.   LBI  Project No.  29840.
Prepared  for  Velslcol Chemical  Corp.,  Chicago,  IL.   7 p.   (Cited 1n  U.S.
EPA, 19860)

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,  MO.  13 p.   (Cited In  U.S.
EPA, 1984a)
0077d                               -79-                             04/05/88

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LHton B1onet1cs, Inc.   1978b.   Hutagenldty evaluation of hexachlorocyclo-
pentadlene 1n  the  mouse lymphoma  forward  mutation assay.  LSI  Project No.
20839.  Prepared for Velslcol Chemical Corp., Chicago, IL.  10 p.  (Cited  In
U.S. EPA. 1984a)

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

Lu, P.Y.. R.L.  Netcalf.  A.P.  Hlrue and J.W.  Williams.  1975.  Evaluation  of
environmental   distribution  and  fate  of  hexachlorocyclopentadlene,  chloro-
dane, heptachlor and heptachlorepoxlde In  a  laboratory model ecosystem.   J.
Agrlc. Food Chera.  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  Dlv.,
Office of  Water Regulations and  Standards.  U.S.  EPA.  Washington. DC.  EPA
440/4-81-014,  p. 174.

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

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

Nehendale, H.H.   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.
Iii: Environmental Exposure from Chemicals,  Vol.  1,  W.B.  Neely and G.E. Blau,
Ed.  CRC Press.  Inc.. Boca Raton.  PL.  p.  207.

Morse,  D.L.,  P.J.  Landrlgan and  J.H. Flynt.   1978.   Internal  CDC  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.  Wlsseman,  III.   1979.   Occupational
exposure  to  hexachlorocyclopentadlene  (how safe 1s  sewage?).   3.  Am.  Med.
Soc.  241: 2177-2179.

Murray. F.J.,  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.  DHEW  (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 Water  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 M.A.Q. Khan.  1979.  Fate of hexachlorocyclopentadlene  1n
goldfish  (Carasslus   auratusl.    Paper   presented   at   the   Am.  Chem.  Soc.
Meetings, April. Honolulu. HI.   (Cited In  U.S.  EPA.  1984a)

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

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

Rand.  G.M.,  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.   T977a.   Soil  metabolism   of   l4C-hexachlorocyclopentad1ene.
Univ.  Kentucky.   Unpublished  report  prepared  for  Velslcol  Chemical  Corp..
Chicago, IL.  (CUed 1n U.S. EPA. 1984a)

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

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

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Shell  Oil  Company.   1982.   TSCA  8(D)  Submission  Hexachlorocyclopentadlene
(HEX): Acute toxldty to Selenastrum caprlcornutum.   Mlchroflche #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, 1986b)

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  1n U.S.
EPA. 1984a, 1986b)

Slnhasenl, P.. L.G.  D'Alecy,  R.  Hartung and M.  Shlater.   1982.  Hexachloro-
cyclopentadlene  Increases  oxygen  consumption  by Intact  rainbow trout  and
Isolated heart mitochondria.  Abstract  1n  Fed.  Proc.  March 1982.   (Cited In
U.S. EPA. 1984a)

Slnhasenl, P., L.G.  D'Alecy,  R.  Hartung and M.  Shlater.   1983.  Respiratory
effects  of  hexachlorocylopentadlene on Intact  rainbow  trout  (Salmo  galrd-
nerl) and on ox1datWe phosphorylatlon  of  Isolated  trout heart  mitochondria.
Toxlcol. Appl. Pharmacol.  67: 215-223.
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Spehar, R.L..  G.D.  Velth.  D.L.  DeFoe  and  B.V. Bergstedt.   1977.   A rapid
assessment  of  the  toxldty  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.D.  Velth,  D.L.  DeFoe and  B.V.  Bergstedt.  1979.  Toxldty
and  b1oaccumulat1on  of  hexachlorocyclopentadlene,   hexachloronorbornadlene
and  heptachloronorbornene  In  larval  and  early  juvenile  fathead minnows.
Plmephales promelas.  Bull.  Environ.  Contam. Toxlcol.   21:  576-583.

SRI  (Southern  Research  Institute).   1980.   Acute Toxldty  Report on Hexa-
chlorocyclopentadlene  (C53607) 1n  F1scher-344  and B6C3F1  Mice.   Unpublished
Report for NTP.  44 p.  (Cited In U.S. EPA,  1986b)

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

SRI  (Southern  Research  Institute).   1981b.  Subchronlc Toxldty Report  on
Hexachlorocyclopentadlene (C53607) 1n Flscher-344 Rats.  Report  for the NTP.
Project No. 4419-XXXVIII.  Doc.  #40-8349130. Microfiche #OTS0507497.

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   1n  the  United   States  using   STORET  database.
Environ. Toxlcol. Chem.  4:  131-142.

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Stevens,  a.E.   1979.   Chlorinated  derivatives  of  cyclopentadlene.    In:
Klrk-Othmer Encyclopedia of Chemical Technology, Vol.  5,  3rd  ed.t  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. Hashnl  and E.F.  Barth.   1981.   Blodegradabll-
1ty  studies  with  organic  priority  pollutant  compounds.   J. Water  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. Sc1.  16: 254-259.

thunia, M.K.,  P.E.  O'MelTl,  S.G.  Brownlee and  R.S. Valentine.  1978.   Bio-
degradation  of  spilled  hazardous  materials.    In.:  Control  of   Hazardous
Materials Spills.   Information Transfer.  Inc.. Rockvllle. MD.   p.  217-220.
(CUed In U.S. EPA. 1984a)

Treon. J.F.,  F.P.  Cleveland  and  J.  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.


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U.S. EPA.   1980a.  Guidelines  and Methodology  Used In  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  1n 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 1n. U.S. EPA, 1984a)

U.S.  EPA.    1983.   Methodology   and   Guidelines   for   Reportable  Quantity
Determinations  Based  on Chronic Toxlclty  Data.  Prepared  by  the  Office  of
Health  and  Environmental  Assessment.  Environmental Criteria and Assessment
Office. Cincinnati, OH  for the  Office  of Solid Waste and Emergency Response,
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  HexachlorocyclopentacMene.
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 Carclnogenlclty  In  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 Water  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.D., D.L. DeFoe and  B.V. Bergstedt.  1979.   HeasuHng and estimating
the  bVoconcentratlon  factor of chemicals  In  fish.   J. Fish Res. Board  Can.
36: 1040-1048.

VHkas,  A.G.  1977.   The acute toxlclty of  hexachlorocyclopentadlene  to the
water  flea,   Daphnla  maqna  straus.   Union  Carbide  Environmental  Services.
Prepared  for  Velslcol Chemical  Corp.,  Chicago.   IL.   (Cited  In U.S.  EPA.
1984a)

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)

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

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

Whltacre, D.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  1n  U.S.  EPA,
1984a)

Wilson, J.A..  C.P. Bladwln  and  T.J. McBrlde.   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. 1984a. 1986b)

Wolfe, N.L.,  R.G.  Zepp,  P.  Schlotzhauer  and M. Sink.   1982.   Transformation
pathways  of hexachlorocyclopentadlene  In  the  aquatic environment.   Chemo-
sphere.  11: 91-101.
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Yoshlda, K., T. SMgeoka and F. Yamauchl.  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, II.   (Cited 1n 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 In 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 1n U.S.  EPA,  1986b)

Zepp, R.G., P.P.  Schlotzhauer.N.S. Simmons, G.C.  Miller,  G.L.  Baughman  and
N.L. Wolfe.  1984.  Dynamics of pollutant photoreactlons  1n the  hydrosphere.
Fresenlus Z. Anal. Chera.  319: 119-125.
OQ77d                               -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.O.  and F.E.  Clayton.  Ed.   1982.  Patty's  Industrial
    Hygiene  and Toxicology.  3rd  rev.  ed.,  Vol.  2C.   John  Wiley  and
    Sons, NY.  p. 3817-5112.
0077d                               -91-                             04/05/88

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

    Hamilton,  A. and H.L. Hardy.  1974.  Industrial Toxicology, 3rd  ed.
    Publishing Sciences  Group,  Inc.,  Littleton,  HA.  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.  Ma bey.  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  Hostrand 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   1n
    Programs.   Registration  Standards   and  the  Data Call 1n Programs.
    Office of Pesticide  Programs,  Washington, DC.

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

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

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

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

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    In addition,  approximately 30  compendia  of aquatic  toxldty data were

reviewed. Including the following:


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

    Johnson, W.W.  and M.T. Flnley.   1980.  Handbook  of  Acute  Toxldty
    of Chemicals  to   Fish  and  Aquatic  Invertebrates.   Summaries   of
    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

Subchronlc      rat
           0.15 ppra (0.45 mg/ro*)
           6 hours/day,  5 days/week
           for 13 weeks  (0.2 rag/kg/day)
                                NOAEL     0.01  rag/day or
                                          0.0007 mg/ra8
                             Battelle Northwest
                             Laboratories.  1984;
                             Abdo et al.,  1986
Chronic
rat
0.15 ppra (0.45 mg/ro*)
6 hours/day, 5 days/week
for 13 weeks (0.2 mg/kg/day)
NOAEL     0.001 rag/day or
          0.00007 rag/ra8
                   Battelle Northwest
                   Laboratories, 1984;
                   Abdo et al.,  1986
Oral Exposure

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

Based on Chronic Toxlclty:

Based on CarclnogenlcHy:
                    10 pounds

                    ID
                                                             Abdo  et  al..  1986
ID = Insufficient data

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