„ . „.                                       FINAL DRAFT
     United States                              .- > Y ' -  rp»n rru rnoo
, v  ., x Environmental Protection                        * f'  '•><-c ECAO-CIN-bOyj
vu A Agency                                        March, 1991

CT>
     Research  and
     Development
     HEALTH  AND ENVIRONMENTAL  EFFECTS DOCUMENT
     FOR ENDOSULFAN
     Prepared for
     OFFICE OF SOLID WASTE AND
     EMERGENCY RESPONSE
     Prepared by
     Environmental  Criteria and Assessment Office
     Office of  Health and Environmental  Assessment
     U.S. Environmental Protection Agency
     Cincinnati, OH  45268
                   DRAFT: DO NOT CITE OR QUOTE   HEADQUARTERS LIBRARY
                                          ENVIRONMENTAL PROTECTION AGENCY

  **                                       WASHINGTON, D.C. 20460
  o_                        NOTICE
  LU
   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 1s being circulated for comments
on its technical accuracy and policy implications.

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                                  ORD CLEARANCE FORM
[1 EPA Report No. 2. Series 3. Lab/Office Draft No. 4. Cc
EPA/600/8 ECAO-Cin- G093 Q ,
Final Document Title:
1th and Environmental Effects Document for Endosulfan
SB. Final Document Title, if changed:
6. Authcirts), Affiliation, and Address (identify
fPA nuthors with Lab/Office)
10. OU/Obj./PPA/Project/Deliverable Output No.
D109 Y105
11. Technical Information (Program) Manager
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Signature'' ~ Dap (
JlJiigninure of sender (if other than Tl(P)M) Date to CERI
W^f S w**ture/ Date ^-^
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Document Manager ' '
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Braneti A-362(CinM*»*3/87)

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                                  DISCLAIMER

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

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                                    PREFACE
    Health and  Environmental  Effects  Documents (HEEDs) are  prepared  for  the
Office of Solid  Waste  and Emergency Response  (OSWER).  This  document series
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  1n  this document
and  the  dates  searched   are  Included 1n  "Appendix:  Literature  Searched."
Literature search  material  1s current up  to  8 months previous  to  the  final
draft  date  listed  on  the front  cover.   Final  draft document  dates  {front
cover) reflect the date the document 1s sent to the  Program Officer (OSWER).

    Several  quantitative  estimates  are  presented  provided  sufficient  data
are available.   For systemic  toxicants,  these  Include Reference doses (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  Ufespan.  This  type of
exposure estimate  has  not been  extensively used,  or rigorously  defined as
previous risk assessment  efforts  have  focused  primarily on  lifetime exposure
scenarios.   Animal data   used   for  subchronlc  estimates  generally  reflect
exposure durations of 30-90  days.   The  general methodology  for  estimating
subchronlc RfOs  is  the same as  traditionally  employed for  chronic  estimates,
except that subchronlc data are utilized  when  available.

    In the case  of suspected  carcinogens,  RfDs are  not estimated.   Instead,
a  carcinogenic  potency   factor,  or  q-j*  (U.S.   EPA, 1980a),  is  provided.
These potency  estimates  are  derived  for  both  oral  and inhalation  exposures
where possible.  In addition, unit  risk  estimates for air  and drinking water
are presented based on inhalation and oral  data,  respectively.
    Reportable quantities  (RQs)  based on both chronic  toxlclty  and carcino-
genicity are derived.  The  RQ  is  used to determine the quantity of a hazard-
ous substance  for  which notification  is  required in the event  of
as  specified under  the Comprehensive  Environmental  Response,
and Liability  Act  (CERCLA).   These  two  RQs  (chronic  toxicity
genlcHy) represent  two  of  six scores developed  (the  remaining
ignitabilUy,  reactivity,  aquatic toxlclty,  and acute  mammalian  toxlclty}.
Chemical-specific RQs reflect  the  lowest  of  these six  primary criteria.   The
methodology  for  chronic toxlclty  and cancer based  RQs are  defined  in  U.S.
EPA, 1984 and 1986, respectively.
   a release
Compensation
and carcino-
four reflect
                                      111

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                               EXECUTIVE  SUMMARY

    Endosulfan  1s  the common name  for  l,4,5,6,7,7-hexachloro-8,9,10  trlnor-
born-5-en-2,3,yleled1methylsulph1te.  Two  Isomers  of  this  compound  exist  and
are  commonly   referred   to   as   either   a-endosulfan  and  B-endosulfan   or
endosulfan I or endosulfan  II.   The two  endosulfan  Isomers  can  Interconvert
with one  another.   Technical grade  endosulfan  1s  a  brown  crystalline  solid
with an odor of sulphur  dioxide  (Worthing and Walker, 1987).  The pure endo-
sulfan  Isomers  are  colorless  solids at  room temperature  {Wlndholz,  1983).
They are  slightly  soluble In water  (Worthing and Walker,  1987)  and  soluble
In most  common  organic  solvents  (Wlndholz,  1983).  Endosulfan Is  stable In
mineral acids,  but It  rapidly hydrolyzes  In  alkaline solutions (Worthing  and
Walker,  1987).   The  sole U.S.  producer  of  endosulfan  Is SureCo, Inc.,  In
Fort Valley, GA (SRI,  1989).  It Is produced  by  the D1els-Alder  reaction of
hexachlorocyclopentadlene with  butenedlol,  followed  by a  condensation  with
thlonyl chloride.  Commercial  endosulfan  Is  a mixture of  the  alpha (64-67%)
and  beta   (29-32%)    Isomers,   endosulfan  sulfate  and   endosulfan   dlol.
Endosulfan  1s   a wide-range,  nonsystemlc  contact  and  stomach  Insecticide
effective  against  numerous  Insects and  certain   mites  on  cereals,  coffee,
cotton,  fruit,  oilseeds, potatoes,  tea, vegetables  and  numerous  other  crops
(Worthing and Walker, 1987).
    In  soil,   the   major  removal   processes  of   endosulfan   are   probably
biological degradation and,  1n basic soils,  hydrolysis.   Blodegradatlon  has.
occurred  In  soil under  aerobic  (Martens, 1976,  1977;  Miles  and Hoy,  1979)
and anaerobic conditions  (Martens,  1977).  Losses  of  endosulfan  in  soil  from
hydrolysis were 8% at pH 6.3,  28%  at  pH 7  and  90% at  pH 8 after 10  days
(Martens,  1976).   Endosulfan  1s  expected  to adsorb   strongly  to  soils.
                                      Iv

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Volatilization of endosulfan  from  the soil surface to  the  atmosphere Is not
expected to be significant.
    If released  to  water, endosulfan  1s  expected to adsorb  to  sediment and
suspended  organic  matter,  moderately  bloconcentrate  1n  fish  and  aquatic
organisms and undergo destructive  removal  by  hydrolysis.   The rate constants
for  hydrolysis   of  a-endosulfan and  B-endosulfan  have been  experimentally
determined (Ellington et  al.,  1988),  and the calculated  half-lives  for  each
Isomer are  5.1x10=  and  5.6xl05  days at  pH 6,  9.0 and  7.8 days  at  pH  7
and 4.2  and  2.8 days at  pH  8, respectively.   Limited  data are  available  on
the  blodegradatlon  of  endosulfan   In  water,  and  Us  fate  by  this  process
cannot  be  determined.    Volatilization   of   endosulfan from  water  to  the
atmosphere  1s  expected  to  be  a   significant  process,  with  an  estimated
volatilization half-life from a model  river of between 3 and 7 days.
    Data  regarding  the fate  of endosulfan  In  the  atmosphere  are  limited.
Direct photochemical degradation In the  air   Is not expected  to  occur  to any
significant extent.   Endosulfan has  been  detected In  rainwater;  therefore,
removal  from  the  atmosphere  by  rain  washout  may  occur.   Endosulfan  1s
expected to exist primarily In the  vapor  phase In  the atmosphere.
    The  general  population may be  exposed to endosulfan  through  Inhalation
and 1ngest1on of contaminated  food.   The  U.S. Food  and  Drug Administration's
market basket survey, conducted from  1968-1984, found that  the average dally
Intake (normalized  for  body  weight)  for  adult  males 16-19 years  old  ranged
from  trace  to  22  ng/kg  bw  (both   a- and  B-lsomer combined)  from all  food
groups.   Endosulfan was  commonly  found  In   the   potato,  leafy  vegetable,
garden fruit, fruit, o^l,  fat  and  shortening  food  groups.   The average dally
Intake of  endosulfan for  Infants  and toddlers ranged  from not detected  to
15.5 ng/kg bw and  not  detected to  15.6  ng/kg bw,  respectively (both  Isomers

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combined).   The average  yearly  Intake  of endosulfan,  determined  during  a
Canadian  market basket survey  performed  1n Ontario  during  1985, was  140.1
Mg/year for A-endosulfan and 690.4 Mg/year  for 8-endosulfan.
    In  the National  Pesticide  Monitoring  Program  conducted  In  1970-1972,
endosulfan was  only found  In the first year In  6/16 of the states monitored.
In  1970,   6.6%  of  the samples   tested  positive  for  A-endosulfan,  and  1%
tested positive for 8-endosulfan.
    Occupational  exposure   to  endosulfan   1s  expected  to occur  for  those
Involved  1n  the production, formulation  or application  of  this  Insecticide.
A  farmer  applying this Insecticide  to his  fields Inhaled between 4490  and
36,570  ng/m1nute  during mixing, and  between  68  and  155 ng/mlnute  during
spraying (Oudbler et al.,  1974).
    The acute toxlclty  of  technical  grade endosulfan has  been assessed  with
at  least   17  freshwater  fish  and  Invertebrate  and  14  saltwater  fish  and
Invertebrate   natively-reproducing    species   using   currently   acceptable
bloassay  techniques  (Butler,   1963,  1964;  Holcombe  et  al.,  1983;  Korn  and
Earnest, 1974;  Johnson and  Flnley, 1980;  Joshl and Rege, 1980;  Joshl  et  al.,
1981;  Kleiner  et  al.,  1984; Lemke,  1980; LI and  Chen,  1981;  Macek  et  al.,
1969,  1976;  Mayer and  Ellersleck,  1986;  Naqvl  and Hawkins,  1988; Naqvl  et
al.,  1987;  Nebeker, 1982;  Nebeker  et al., 1983;  Pesch and  Hoffman,  1985;
Pickering and Henderson, 1966;  Sanders,  1969,  1972; Sanders and  Cope,  1968;
Schlmmel,   1981;  Schlmmel  et al.,  1977;   Schoettger,  1970a;  U.S. EPA,  1979,
1980c;  Verma  et  al.,  1981).   Acute  toxldty  values  for  freshwater  fauna
ranged  from a  96-hour LC--  of  0.17  Mg/P  for   S.  galrdnerl  to a  48-hour
EC5Q  of  750  Mg/P  for  0. magna {Lemke,  1980),  with  fishes  and  benthlc
Invertebrate species being  generally  less  sensitive than planktonlc  Inverte-
brates.   Acute  toxlclty  for   saltwater   fauna  ranged  from  0.04  Mg/P  with
                                      v1

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pink  shrimp,  P.  duorarum  (Schlmmel  et al.,  1977),  to  730 Mg/P with  the
benthlc  marine   worm,   N.   arenaceodentata   (Pesch  and   Hoffman,   1985).
Additional  acute  toxic  responses  to  endosulfan  (with nonnatlvely-reprodudng
species, with  unreported  forms  or  emulslflable  endosulfan formulations  or
for  other  toxic  endpolnts)  provide  supporting  evidence  of  the  degree  and
type  of  toxic  effects  that may  result  among  exposed aquatic  fauna  (Deoray
and  Wagh,  1987;  Devi  et  al.,  1981; Ferrando  et al., 1987;  Gopal et  al.,
1981,  1985; Haider  and  Inbaraj,  1986, 1988; Joshl et  al.,  1981;  Matthlessen
and  Logan,  1984;  Huley and  Mane,  1986,  1987;  Nebeker, 1982; Paul  and  Raut,
1987;  Rao  and  Murty,  1980b,  1982; Rao  et  al.,  1981; Roberts,  1975a;  Singh
and Naraln. 1982; Swarup et al.,  1981).
    Acute  tests  of endosulfan conducted with  the same  species In the  same
laboratory by both  static  nominal  and flowthrough  measured  techniques  showed
good agreement In most  cases.  Conflicting  data  have  been  reported regarding
effects of  water  hardness  (as CaCCL) on endosulfan  toxlclty (Pickering  and
Henderson,   1966;   Paul  and  Raut, 1987).   There  appears  to be  a positive
correlation between endosulfan  toxldty and  pH  and  temperature   (Almar  et
al., 1988;  Ferrando et al., 1987;  Macek  et  al.,  1969;  Paul  and  Raut, 1987).
    Chronic toxlclty  data  are available for one freshwater  Invertebrate  and
three  fishes, and for one  saltwater  Invertebrate  and one  fish  (Breteler  et
al.,  1982;  Joshl  et  al.,  1981;   Macek  et  al.,   1976;  Nebeker  et  al.,  1983;
U.S.  EPA,  1980b).   Chronic  values  ranged from  0.2-108  Mg/P  among  fresh-
water  forms,  and  for  marine  fauna  were 0.40  and 0.69  Mg/P  for M.  bah1a
and C. varleqatus,  respectively.   Fish and  M. bahla were more  sensitive than
D.  magna.   Additional  chronic toxlclty  data  regarding sublethal  effects  or
other  lethal endpolnts  support the  above  range  of toxlclty (Dalela et  al.,
1978;  Gopal  et  al.,  1982;  Haider  and Inbaraj,  1988;  KhUlare  and  Wagh,

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1987; Kleiner et  al.,  1984;  Mlshra  et  al..  1986;  Najml  et a!., 1986; Pandey,
1988;  Pesch  and  Hoffman,  1985; Rao  and  Nagabhushanam,  1987;  Sastry  and
Slddlqul, 1982; Shukla and Pandey, 1986;  Vasantha  and Parveen,  1988).
    New  significant  data  to  Influence  values for the Acute-Chronic  Ratio or
the  Final  Chronic   Value  were  not  located  In  the  available  literature;
therefore,  deferral  Is  recommended to  the extant  Freshwater Criteria  and
Saltwater  Criteria  derived  by  the  U.S.  EPA  (1980c)  for the  protection of
aquatic  life from endosulfan (Section 7.2.}.
    B1oconcentrat1on data  were  not  located  In the available  literature  for
freshwater  species,  and data derived from  saltwater  values  are Inconclusive.
Highly disparate  values  were reported for  C.  varleqatus {U.S.  EPA,  1980c)
and M. cephalus  {Schlmmel  et al.,  1977).   Data derived  with  Hytllus  edulls
do  not   Include  analyses  of endosulfan  sulfate,  the  predominant  form  In
tissues  of  other  exposed  species (Roberts,  1972).  Available  data,  however,
suggest  that  endosulfan   residues   are  quickly  metabolized  or  purged  to
nondetectable concentrations when  fish are  removed  from  endosulfan-polluted
waters.
    Exposure  of  seven  species  of  blue-green  algae  to   5-20  mg/P   of  endo-
sulfan (purity not  reported) Induced  retarded growth and decreased  nitrogen
fixation  (Shlvaprakash and Shetty,  1986).   C_.  vulgaMs was not  sensitive to
exposures  <10,000  Mg/P   HC-endosulfan  (technical   grade)   (Gohrbach  and
Knauf,  1971).   Growth   Inhibition  was  noted  at  2000   Mg/P  with  exposure
of Chlorella  to  an  emulslflable  concentrate  (Knauf  and  Schulze, 1973).   A
LOEC  of   1  Mg/mp  of  endosulfan  was  reported  for  the freshwater  algae,
Anabaena  sp.  and  Auloslra   sp.  (Tandon   et   al.,   1988),  and  a   maximum
acceptable  toxicant  concentration  of  <47  Mg/P  for  the marine red  algae,
Champ1a  sp. (Thursby et al.,  1985).

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    Endosulfan  had  a  48-hour   LCcn  of  24  yg/cm2  In  the  earthworm,   £.
foetlda  (Roberts  and  Dorough,   1984).   Direct  contact  L05Q  values  ranged
from  1.53-14.94   wg/g   In   PhllUplne   plant  and   leaf-hoppers   and   from
7.33-96.07  ug/g  In  their   arthropod  predators   (Fabellar  and  Helnrlchs,
1986).   Endosulfan  was  not  as  toxic   to  Colorado  potato  beetle  strains
previously  exposed   to  similar   pesticides,   having  direct  contact  LD_0
values  of  207-251   yg/g.   It  produced  a  relatively  mild   Increase   1n
mortality of  spotted tentlform  leafmlner eggs  exposed  by spray  (Hayden  and
HowHt,  1986)  and  produced  no  mortality  at  all  1n  green lace-wing  eggs,
larvae   or   adults  exposed  to   0.0754  solution   (Krlshnamoorthy,   1985).
Dose-related Increases In mortality were seen 1n larval and  adult  Orosophlla
exposed  to  25-100 ppm  (Creus  et al.,  1983).   Endosulfan was  less  toxic  to
very  young  ducklings  (LDC   =   27.8  mg/kg)   and  full  grown ducks  (LDC
                          50
50
34.4  mg/kg)  than  to   ducklings  of  Intermediate  ages  (LD.n  =  6.47-7.89
mg/kg) (Hudson et al.,  1972).
    Soil algae  populations  declined  1n  a  dose-related manner  upon  exposure
to endosulfan at  50-100 ppm.   C.  arJeUmim plants exposed to  0-10  ppm  had  a
concentration-related  decrease  In  root  and shoot growth  (Agarwal  and  Beg,
1982).  Exposure  to 1000 ppm  reduced pollen  germination  and  length of  the
pollen  tube  In   cucumbers  (Gentile  et  al.,  1978).   Concentration-related
growth Inhibition was  reported 1n V.  radlata exposed  to  >1500 ppm endosulfan
(Gupta and Gupta, 1980).
    Oral exposure studies with  rats  Indicate  that  -80%  of   the endosulfan
dose  1s  absorbed  In  48  hours  from  the gastrointestinal  tract  (Dorough et
al.,  1978).   The highest levels  occurred   In  male  reproductive  tissues  and
kidneys after  repeated  oral  exposures  (Ansarl  et  al.,  1984).  Endosulfan
does  not  accumulate In  fat  but  Is  distributed  to  the  brain  (Gupta,  1978;
                                      1x

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Khanna et al., 1979).  Data reviewed  1n Chapter  6  Indicate  that  the  kidneys,
male  reproductive  tissues  and  CNS  appear   to  be  the   main   targets   of
endosulfan  toxlclty.   Endosulfan  Is  excreted  primarily In  the feces  from
bile.  Single  and repeated-dose oral studies  with rats Indicate that  fecal
and  urinary  excretion of  endosulfan  and  metabolites  Is  ~60-7Q and  10-20%,
respectively  (Dorough et  al.,  1978).    The   major  excretory  products  are
unidentified  polar  metabolites.   Nonpolar  metabolites  of   endosulfan   In
orally  treated  rats  Include  endosulfan  dlol,  endosulfan  a-hydroxy  ether
and endosulfan lactone.  Appreciable  quantities  of endosulfan  or metabolites
1n the  feces  and tissues  are  In an  unidentified  bound  (unextractable)  form
{Dorough et al.,  1978).
    Effects on kidneys,  testes  and  Immunologlc  and central nervous  systems
In animals  have  been attributed  to  subchronlc and  chronic oral  exposure to
endosulfan.  Rats treated with 7.5 but not  2.5 mg/kg/day doses of endosulfan
for 60 days experienced  Increased liver and lung weights,  slightly  decreased
testes weight,  hyperactlvlty,  tremors,  clonlcotonlc  convulsions and  death
(Ansarl et  al.,  1984).   Immunosuppresslve effects occurred In  rats  adminis-
tered  diets  containing  10 and  20 ppm endosulfan, but  not  5  ppm,  for  8-22
weeks  (Banerjee  and  Hussaln,   1986);   these  Included  decreased   antigen
(tetanus  toxold   1nject1on)-1nduced  serum  globulin  (computed  as  ratios  to
albumin)  and   IgG  levels,  decreased  antibody  tUres,  decreased  leucocyte
migration  Inhibition  (blood  leukocytes),  decreased   macrophage  migration
inhibition  (peritoneal macrophages),  and  decreased  spleen  weights.   Similar
Immunosuppresslve effects  occurred  In rats  administered diets  containing  >3Q
ppm  endosulfan,  but not  10  ppm, for 6 weeks (Banerjee and Hussaln,  1987).
Decreased  testes  weight,  degenerative testlcular  alterations  (e.g.,  tubules
devoid  of  spermatogenlc  elements)  and  mortality occurred  1n  rats  orally

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exposed to 10 mg/kg/day  but  not 5 mg/kg/day doses  of  endosulfan  for  15 days
(Gupta and  Chandra, 1977).   Rats that  were  orally administered  endosulfan
for 58 days  showed reduced activity  of  alkaline phosphatase  In  the  ventral
prostate  at   >Q.625 mg/kg/day,  decreased  weights   of  reproductive  tissues
("ventral  prostate",  decreased epldldymls,  seminal vesicle and  coagulating
gland) at >2.5  mg/kg/day,  and  decreased  number  and motlllty  of  spermatozoa
1n  the  vas  deferens  at   >2.5  mg/kg/day  (Gupta   and  SMvastava,   1980).
Although  similar  findings  were reported  by Gupta  et  al.  (1981)  and  Ansarl
and Gupta (1981),  reproductive  performance was not  evaluated  In any of these
studies.
    A  review of  the neurologic  effects of  endosulfan  by  Gupta  and  Gupta
(1979) describe  the  prominent symptoms  of poisoning  1n  rats  and mice  as
hyperactlvlty, tremors  and convulsions of  clonlc  nature followed  by  death,
as  well   as  decreased  respiration,   dyspnea   and   salivation.   Neurotoxlc
effects  reported  1n rabbits  dosed  with  225   mg/kg  endosulfan  by  dermal
application  Include  hyperesponslveness  to sudden sound and  tactile stimuli,
fine  tremors  (whole  body),   moderate   tremors,   and   episodes   of   clonlc
convulsions.   In  dogs  administered   an  oral   dose  of  200-500  mg/kg  of
endosulfan Increased  salivation,  vomiting,  and   tonic and clonlc  cramps were
reported.  Sheep  grazing on  strawberry  fields   sprayed  with  35%  endosulfan
(two  sheep   Ingesting  a maximal  dose  estimated at 5  mg/kg) exhibited  an
unsteady  gait followed  by  an Inability  to stand up.  Srlkanth and  Seth
(1990)  reported   that  endosulfan   Induces  amlnopyrIne-n-demethylase  and
aniline hydroxylase activities  In  the  brain  of   rats  and that  endosulfan
potentiates  malathlon  neurotoxlclty  In  these  rats.   Agrawal  et  al.  (1983)
determined   that   long-term   endosulfan   exposure   (3  mg/kg   l.p.)   caused
aggressive  behavior  (foot-shock-induced  fighting   behavior)  1n  8-week-old
                                      x1

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male albino  rats  which was  Inhibited  by  a serotonin blocker.  Zaldl  et  al.
{1985}  determined  that  repeated  administration  of  the  1.0  mg/kg  dose
produced significant  Increases  In  labeled  serotonin  receptor  binding  as  well
as  foot-shock-induced  fighting  behavior,  effects   seen  even  8  days  after
cessation  of  treatment.    Seth  et  al.   (1986)  described  the  effects  of
endosulfan  on  various  neurotransmltter  receptors   In  pre-  and  postnatally
exposed pups  and  adult rats.   Repeated administration of endosulfan  during
geatatlon produced a  significant  decrease  In  the  affinity  and maximum number
of strlatal dopamlnerglc receptors of  rat  pups  without  affecting  the  binding
characteristics of other  receptors.   Endosulfan-dosed neonatal rats  did  not
exhibit  a  dopamlne  receptor  effect.   However,  there  was   an  Increase  In
serotonin and  benzodlazeplne receptors resulting 1n  a  serotonerglc mediated
aggressive  behavior.    In  comparison  to  adult rats  the  developing  animals
exhibited  a   greater  sensitivity  and   a   differential  response   towards
endosulfan.  Furthermore, these changes In adults were  reversible  whereas 1n
neonates  these  differences  persisted   even   8  days   after  cessation  of
treatment.    Anand et  al.   (1985)  reported  that  rats  exposed to  3  mg/kg
endosulfan  by  l.p.   Injection  demonstrated  significant   alterations   1n
neurological behavior.
    An  NCI  (1978) bloassay  was  conducted  1n  which  endosulfan was adminis-
tered In diets  to male  rats  at  TWA concentrations of 408 ppm for  78 weeks or
952 ppm for  63 weeks  (observed for  3  or  10 additional  weeks, respectively),
female  rats  at TWA concentrations of  223 or  445 ppm For  78  weeks  (observed
for 33  additional  weeks),  male mice at TWA concentrations of  3.5  or  6.9 ppm
for  78  weeks  (observed for  14  additional  weeks)  and female  mice   at  TWA
concentrations  of  2  or 3.9  ppm  for  78  weeks  (observed  for  14  additional
weeks).  Toxic effects attributable to  treatment  occurred   in  rats   at  all
                                      xil

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concentrations;  these  Included  marked   early   mortality  in  males,  high
Incidences  of  toxic  nephropathy   In   both  sexes  and  testlcular  atrophy.
Survival was  markedly  reduced In mice  that  were treated  with endosulfan by
gavage  at  doses of  1  or  2.15 mg/kg/day  on  days 7-28  of age,  followed by
treatment  In  the diet  at  concentrations  of  3 or  6  ppm,  respectively,  for
73-76 weeks (BRL, 1968).   Dogs treated with endosulfan  1n capsules  at doses
<0.75 mg/kg,  6 days/week  for  1  year showed no  treatment-related  effects on
growth,   organ  weights,   biochemical   and   hematologlcal   Indices,   urine
chemistry or gross  or hlstologlcal  appearance of tissues (Keller, 1959a).
    Available  evidence  Indicates   that   endosulfan   Is  maternally  toxic,
fetotoxlc and  teratogenlc.   Effects In  rats  treated  with  5  or  10 mg/kg/day
oral  doses   of   endosulfan    during  gestation   Included   maternal   deaths,
resorptlons and  fetuses with  skeletal abnormalities  (Gupta  et  al.,  1978).
Maternal  effects  (reduced body  weight  and signs  of  CMS stimulation)  and
fetal   effects   (unspecified   skeletal,   visceral   and   external  anomalies,
reduced  size  and weight)  occurred  In  rats  orally  treated with  6 mg/kg/day
but not  2 mg/kg/day  doses  of  endosulfan (Raltech  Scientific Services,  1960).
Reproductive  and fetal  developmental effects were  not  observed  In  rats  fed
3-75  ppm dietary  endosulfan  1n  a  2-generatlon  study  (Huntlngton  Research
Center,  1984),  but   toxic  alterations  occurred In  the  kidneys  of  F,.  males
at  all   levels.  Fetotoxlc  and  developmental  effects were not observed In
rabbits  orally treated with  0.3-1.8  mg/kg/day  doses  of  endosulfan  during
gestation, but maternal toxlclty (Including death) occurred at 1.8 mg/kg/day.
    Raltech Scientific  Services  (1980),  summarized by  the U.S.  EPA (1982),
yielded  fetal  effects  Including unspecified skeletal,  visceral  and  external
anomalies with  reduced size  and weight  at  6  mg/kg bw/day.   Data necessary
for  a  full evaluation  are  unavailable.   Gupta  et  al.  (1978)  demonstrates

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fetal  anomalies  (teratogenlc  effects)  at  5 mg/kg  bw/day.   Fetal  skeletal
malformations  Included  a  missing fifth  sternebrae,  flth metacarpus  or  an
extra   rib.    Studies   detailing  teratogenlc  effects  of   endosulfan   are
considered unreliable (U.S. EPA, 1982).
    Signs  of  acute  oral  endosulfan  Intoxication  In  animals Include  hyper-
activity,  depression,  salivation, lacrlmatlon,  labored  respiration,  tremors
and  tonlcoclonlc  convulsions  (U.S.  EPA,  1982;  WHO,  1984).   Oral  LD^s  of
9-121,  85  and 118  mg/kg  have  been  reported  for rats,  mice and  hamsters,
respectively.  Estimated oral doses of  250-2500 mg/kg were lethal  for  humans
(Tsa1  et  al., 1988); manifestations  of poisoning Included  gastrointestinal
Irritation, CNS  Irritability  manifested as  seizures,  respiratory  depression
and cardiovascular collapse.   Symptoms  of  occupational  exposure  (respiratory
and dermal) to endosulfan  are  similar to  those  of oral  poisoning (Israeli et
al.,  1969; Tlberln  et  al.,  1970).   Four-hour  LC5Q  values  of  350 and  80
mg/m3  were determined  for  male and  female  rats, respectively  (Ely et  al.,
1967).
    There  Is  limited evidence  describing  endosulfan  cardnogenlclty.   In NCI
(1978),  Increased  Incidences  of  tumors  were not  observed  In male  rats  fed
diets  containing >408 ppm, female rats  fed  >223  for 78  weeks, male mice fed
>3.5  for   78  weeks   or  female  mice  fed  >2 ppm  for 78  weeks.   High  early
mortality  precluded  evaluation  of cardnogenlclty In the male rats  and  male
mice  In  this  study.   Tumor  Incidences  were not  Increased In rats  fed  diets
containing 0,  10,  30 or  100 ppm  endosulfan  for  2 years  (Keller, 1959b), but
lack   of   additional  Information   precludes   evaluation  of   these   data.
Treatment-related Increased  Incidences  of  tumors did  not occur In mice  of
either sex that were treated with endosulfan by gavage  at  doses  of  1 or  2.15
mg/kg/day  on  days  7-28  of age,  followed  by endosulfan administered  in the
                                      x1v

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diet at  concentrations  of  3  or  6 ppm,  respectively,  for 73-76 weeks  (BRL,
1968;  Innes  et  al.,  1969).   Relatively small  numbers  of  animals  (10-18/
group)  and  high mortality  In both  sexes of  B6C3F1  mice  (both doses)  and
B6AKF1  mice  (high  dose)  may have  precluded  detection  or  development  of
tumors  1n this study.  Tumor  Incidences  did  not  Increase  In  B6C3F1  or  B6AKF1
mice of  either  sex 18  months following  a  single  2.15  mg/kg  subcutaneous
Injection of endosulfan (BRL,  1968).
    Endosulfan Induced mutation,  gene  conversion and chromosome aberrations
1n  S.  cerevlsae  (Yadav  et  al.,  1982),  mutation 1n  L5178Y mouse  lymphoma
cells  In vitro (McGregor et al.,  1988),  sex-linked recessive lethal  mutation
and  sex-chromosome  loss  In PxosoRhljA  (Velazquez et al., 1984),  chromosome
aberrations In bone marrow cells  of  Syrian hamsters treated  by  Intraperlto-
neal Injection  (Dzwonkowska and  Hubner, 1986) and sister chromatld  exchange
1n human lymphold cells In  vitro  (Sobtl  et al.,  1983).   Lack of  mutagenldty
In  bacteria   (Fahrlg,  1974;  Dorough  et al.,  1978; MoMya et  al.,   1983;
Pednekar  et al.,  1987),  dominant lethality  In  mice  (Arnold, 1972), chromo-
some aberrations In orally treated  rats (Dlkshlth and  Datta, 1978;  Dlkshlth
et al., 1978) or mlcronucle!  1n orally  treated  mice  (Usha Rani  et  al.,  1980)
Indicate that the evidence  for mutagenldty  and  clastogenlclty  of  endosulfan
should  be regarded as  Inconclusive.
    Data were not  sufficient  to  derive  RfD  values for Inhalation  exposure.
An  RfD of  0.0002 mg/kg/day  for   subchronlc  oral  exposure to endosulfan  was
based  on the LOAEL  of  0.15 mg/kg/day associated  with kidney  toxlclty  in  the
2-generation rat  study  by Huntlngton  Research  Center  (1984).   An  RfD  of
0.00005 mg/kg/day for  chronic  oral  exposure  was  based  on the same  data.   An
RQ  of  10  for  chronic  (noncancer)  toxlclty  was  based on  Increased  mortality
In mice (BRL,  1968).
                                      XV

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    Cardnogenlclty  data  In  humans  were  not  available  In the  literature.
Endosulfan  was   assigned  to  U.S.  EPA Group  D:  not  classifiable  as   to
carclnogenlcHy  to humans.   Data  were not  sufficient  to  derive  slope factors
for Inhalation or oral  exposure.  A cancer-based RQ was not derived.
                                     xvl

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                              TABLE  OF  CONTENTS

                                                                       Page

1.  INTRODUCTION	1-1

    1.1.   STRUCTURE AND CAS NUMBER	1-1
    1.2.   PHYSICAL AND CHEMICAL PROPERTIES 	  1-1
    1.3.   PRODUCTION DATA	1-3
    1.4.   USE DATA	1-3
    1.5.   SUMMARY	1-3

2.  ENVIRONMENTAL FATE AND TRANSPORT	2-1

    2.1.   AIR	2-1
    2.2.   WATER	2-1
    2.3.   SOIL	2-4
    2.4.   SUMMARY	2-6

3.  EXPOSURE	3-1

    3.1.   WATER	3-1
    3.2.   FOOD	3-1
    3.3.   INHALATION	3-3
    3.4.   DERMAL	3-6
    3.5.   OTHER	3-6
    3.6.   SUMMARY	3-7

4.  ENVIRONMENTAL TOXICOLOGY	4-1

    4.1.   AQUATIC TOXICOLOGY 	  4-1

           4.1.1.   Acute Toxic Effects on Fauna	4-1
           4.1.2.   Chronic Effects on Fauna	4-23
           4.1.3.   Effects on Flora	4-26
           4.1.4.   Effects on Bacteria 	  4-27

    4.2.   TERRESTRIAL TOXICOLOGY 	  4-28

           4.2.1.   Effects on Fauna	4-28
           4.2.2.   Effects on Flora	4-30

    4.3.   FIELD STUDIES	4-30
    4.4.   AQUATIC RISK ASSESSMENT	4-31
    4.5.   SUMMARY	4-36

5.  PHARMACOKINETICS 	 5-1

    5.1.   ABSORP1ION	5-1
    5.2.   DISTRIBUTION	5-1
    5.3.   METABOLISM	5-4
    5.4.   EXCRETION	5-7
    5.5.   SUMMARY	5-11
                                    xv11

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                          TABLE OF CONTENTS (cont.)

                                                                        Page

 6.  EFFECTS	6-1

     6.1.   SYSTEMIC TOXICITY	6-1

            6.1.1.    Inhalation Exposure 	   6-1
            6.1.2.    Oral  Exposure	6-1
            6.1.3.    Other Relevant Information	6-8

     6.2.   CARCINOGENICITY	6-16

            6.2.1.    Inhalation	6-16
            6.2.2.    Oral	6-16
            6.2.3.    Other Relevant Information	6-18

     6.3.   MUTAGENICITY	6-18
     6.4.   DEVELOPMENTAL  TOXICITY 	   6-21
     6.5.   OTHER REPRODUCTIVE EFFECTS 	   6-22
     6.6.   SUMMARY	6-25

 7.  EXISTING GUIDELINES AND STANDARDS 	   7-1

     7.1.   HUMAN	7-1
     7.2.   AQUATIC	7-1

 8.  RISK ASSESSMENT	8-1

     8.1.   CARCINOGENICITY	8-1

            8.1.1.    Inhalation	8-1
            8.1.2.    Oral	8-1
            8.1.3.    Other Routes	8-2
            8.1.4.    Weight of Evidence	8-2
            8.1.5.    Quantitative  Risk Estimates  	   8-3

     8.2.   SYSTEMIC TOXICITY	8-3

            8.2.1.    Inhalation Exposure 	   8-3
            8.2.2.    Oral  Exposure	8-3

 9.  REPORTABLE QUANTITIES 	   9-1

     9.1.   BASED ON SYSTEMIC TOXICITY 	   9-1
     9.2.   BASED ON CARCINOGENICITY	9-5

10.  REFERENCES	10-1

APPENDIX A: LITERATURE SEARCHED	A-l
APPENDIX B: SUMMARY TABLE  FOR ENDOSULFAN 	   B-l
APPENDIX C: DOSE/DURATION  RESPONSE GRAPH(S) FOR EXPOSURE TO
            ENDOSULFAN	C-l
                                     XV111

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4»
                               LIST OF TABLES
No.                               Title                                Page
1-1     Selected Chemical and Physical Properties of the
        Isomerlc Endosulfans	1-2
2-1     Calculated Half-Lives for the Hydrolysis of Endosulfan.  ...   2-3
3-1     Levels of Endosulfan In Surface Water and Sediment	3-2
3-2     Summary of Endosulfan Intake from FDA's Market  Basket
        Survey	3-4
3-3     Average Dally Intake of Endosulfan for Toddlers  and Infants  .   3-5
4-1     Acute ToxIcUy of Endosulfan to Natively-Reproducing
        Aquatic Fauna 	   4-2
4-2     Acute Lethality of Endosulfan to Nonnatlve Fauna	4-18
4-3     Additional Sublethal Effects of Endosulfan on Aquatic  Fauna  .   4-21
4-4     Chronic Values for Endosulfan 	   4-24
4-5     Genus Species/Mean Acute Values for Endosulfan	4-32
5-1     Distribution Patterns of A- and B-Isoraers of Endosulfan
        In Tissues of Rat After Oral Administration for  60  Days  .  .  .   5-3
5-2     Distribution of Endosulfan 1n a Human Following  Acute
        Ingestlon	5-5
5-3     Extraction Characteristics of Residues 1n Excreta and
        Tissues of Rats Treated with [HC]Endosulfan	5-8
6-1     Acute Oral Lethality of Endosulfan In Animals 	   6-9
6-2     Genotoxlclty Testing of Endosulfan	6-19
9-1     Oral ToxIcUy Summary for Endosulfan	9-2
9-2     Oral Composite Scores for Endosulfan	9-4
9-3     Endosulfan: Minimum Effective Dose (MED) and Reportable
        Quantity (RQ)	9-6
                                             xtx

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                               LIST OF  FIGURES
4-2
                          Title                                Page

Organization Chart for Listing GHAVs, GMCVs and BCFs
Required to Derive a Numerical Water Quality Criteria by
the Method of U.S. EPA/OWRS (1986) for the Protection of
Freshwater Aquatic Life from Exposure to Endosulfan 	  4-34

Organization Chart for Listing GHAVs, GHCVs and BCFs
Required to Derive a Numerical Water Quality Criteria by
the Method of U.S. EPA/OWRS (1986) for the Protection of
Saltwater Aquatic Life from Exposure to Endosulfan	
5-1
Metabolism of Endosulfan 1n Animals
4-35

5-6

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                             LIST  OF  ABBREVIATIONS
ADI                     Acceptable dally Intake
AEL                     Adverse effect level
BCF                     Bloconcentratlon factor
CAS                     Chemical Abstract Service
CBI                     Confidential business Information
CNS                     Central nervous system
CS                      Composite score
DMSO                    Dimethyl sulfoxlde
DNA                     Oeoxyrlbonuclelc add
ECso                    Concentration effective to 50% of recipients
                        (and all other subscripted dose levels)
FEL                     Frank effect level
GMAV                    Genus mean acute value
GMCV                    Genus mean chronic value
Ig                      ImmunoglobulIn
Koc                     Soil sorptlon coefficient
Kow                     Octanol/water coefficient
LC5Q                    Concentration lethal to 50% of recipients
                        (and all other subscripted dose levels)
1050                    Dose lethal to 50% of recipients
LM1                     Leucocyte migration Inhibition
LOAEL                   Lowest-observed-adverse-effect level
LOEC                    Lowest-observed-effect concentration
MATC                    Maximum acceptable toxicant concentration
MEO                     Minimum effective dose
MMI                     Macrophage migration Inhibition
                                      xx1

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NOAEL
NOEL
ppb
ppm
ppt
RfO
RfDso
RNA
RQ
RVd
RVe
TWA
 LIST OF  ABBREVIATIONS  (cont.)

No-observed-adverse-effect level
No-observed-effect level
Parts per billion
parts per million
Parts per trillion
Reference dose
Subchronlc oral reference dose
Rlbonuclelc acid
Reportable quantity
Dose-rating value
Effect-rating value
Time-weighted average
                                     xx11

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                               1.   INTRODUCTION
1.1.   STRUCTURE AND CAS NUMBER
    Endosulfan Is the common name for 6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-
hexahydro-6,9-methano-2,4,3-benzod1oxath1ep1n-3-ox1de  or   1,4,5,6,7,7-hexa-
chloro-8,9,10  tr1norborn-5-en-2,3-yleled1methylsulph1te.   It  Is  also  known
by  the trade names Thlodan,  BeosU  and  Cyclodan  (Royal  Society of Chemistry,
1983}.   Two  Isomers  of  endosulfan  exist  and  can  Interconvert  with  one
another.   These  are  normally   referred   to  as   either   a-endosulfan  and
B-endosulfan,  or  endosulfan  I  and  endosulfan  II  (Chemllne.  1989).   The
structure,  CAS Registry number,  empirical  formula  and  molecular weight  of
each Isomer, as well as the commercial mixture of Isomers,  are given below.
                                           B-endosulfan
                                           33213-65-9
                            mixture
                            15-29-7
                    a-endosulfan
CAS Registry No.:   959-98-8
Empirical formula:  CQH,C1,00S
                     3D  00
Molecular weight:  406.95
1.2.   PHYSICAL AND CHEMICAL PROPERTIES
    Technical grade endosulfan  1s  a brown crystalline solid with an  odor  of
sulphur dioxide  (Worthing and Walker, 1987).  The pure  Isomers  of endosulfan
are colorless solids  at  room temperature.  They are soluble In most  organic
solvents  and stable  In mineral  acids,   but  they hydrolyze rapidly  1n  the
presence  of  alkalies  (Wlndholz,   1983).   Selected  chemical   and  physical
properties of the endosulfan Isomers are  listed  1n Table 1-1.
0253d
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1.3.   PRODUCTION DATA
    According to  SRI  (1989), SureCo,  Inc.,  1n  Fort Valley, GA,  1s  the  sole
producer of endosulfan In  the United  States.  Data  on  U.S.  production volume
were not located In the available literature cited 1n Appendix A.
    This  Insecticide  1s  synthesized  by  the dels-Alder  reaction of  hexa-
chlorocyclopentadlene  with  butenedlol,  followed  by  a  condensation  with
thlonyl chloride.  Commercial endosulfan  1s a mixture of  the  alpha  (64-67%)
and beta  (29-32%) Isomers, endosulfan sulfate and  endosulfan  dlol (Worthing
and Walker, 1987).
1.4.   USE DATA
    Endosulfan  1s  a  wide-range, nonsystemlc  contact and stomach  Insecticide
effective  against numerous  Insects  and  certain mites  on cereals,  coffee,
cotton, fruit,  oilseeds,  potatoes,  tea, vegetables and  numerous  other crops
(Worthing and Walker, 1987).
1.5.   SUMMARY
    Endosulfan  Is the common name  for 1,4,5,6,7,7-hexachloro-8,9,lO-tr1nor-
born-5-en-2,3,yleled1methylsulph1te.   Two  Isomers of  this  compound exist and
are commonly  referred to  as either  a-endosulfan  and  S-endosulfan  or endo-
sulfan  I or endosulfan  II.   The two endosulfan  Isomers can Interconvert with
one another.   Technical  grade  endosulfan  1s  a  brown  crystalline  solid  with
an  odor of  sulphur dioxide (Worthing and  Walker,  1987).   The  pure endosulfan
Isomers are colorless solids at room temperature  (Wlndholz, 1983).  They are
slightly  soluble In water  (Worthing and  Walker,  1987)  and soluble  in  most
common  organic  solvents  (Wlndholz,  1983).   Endosulfan  Is  stable  in mineral
acids,  but  1t  rapidly hydrolyzes  1n alkaline solutions (Worthing  and Walker,
1987).   The  sole U.S.  producer  of  endosulfan  Is  SureCo,   Inc.,   in  Fort
Valley,  GA  (SRI,  1989).   It  is   produced  by  the  D1els-Alder  reaction  of

0253d                                1-3                              10/02/89

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hexachlorocyclopentadlene with  butenedlol, followed  by  a condensation  with
thlonyl chloride.   Commercial endosulfan  Is  a mixture of the  alpha  (64-67%)
and   beta   (29-32%)  Isomers,   endosulfan  sulfate  and  endosulfan   dlol.
Endosulfan  Is  a wide-range,  nonsystemlc  contact and  stomach  Insecticide
effective  against  numerous  Insects  and  certain  mites  on  cereals,  coffee,
cotton, fruit,  oilseeds,  potatoes,  tea, vegetables and  numerous  other  crops
(Worthing and Walker, 1987).
0253d
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10/02/89

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corresponding  values  for   B-endosulfan   are  7.4x10 3  8,/mol-hour,  3.7xlO~3
8./hour  and  1.5x10*  8,/mol-hour.   At  neutral   pH,  the  author  calculated
hydrolysis  half-lives  of  218  hours   (9.1  days)  for  the  a-1somer  and  187
hours  (7.8 days)  for  the  B-lsomer  (Ellington  et  al.,  1988).   Calculated
half-lives  for  the hydrolysis of endosulfan at  the environmentally .signifi-
cant  pH  range  (25°C), derived  from the  above  rate constants, are given  1n
Table 2-1.
    Data  regarding the blodegradatlon of  endosulfan In water  were  limited.
In  a  screening  test using  a settled domestic  wastewater   sludge  Inocolum,
a-endosulfan  at  an Initial  concentration  of   5  or  10 mg/i  underwent  0%
degradation  after  a  7-day  test  under aerobic  conditions.  No  degradation
ensued  through  the  second  and  third  subcultures.   Results  for B-endosulfan
were  Identical  (Tabak et  al.,   1981).   Greve and  WH  (1971)  reported  that
endosulfan  can  be  degraded  In aerobic  waters  at  pH 7,  with  a half-life of ~1
week.  The loss of  endosulfan  from a sediment/water sample was  slower  than
In  pure water (Walker  et al., 1988),  Indicating  that blodegradatlon  In water
may not be  significant.
    Endosulfan  Is  expected  to adsorb  significantly to  sediment  and suspended
matter  In  water.   In a study of  the  environmental  fate  of  Insecticides  that
entered the Rhine  River after a  fire  at  a chemical warehouse, endosulfan was
listed as  the only nonmercury compound  that  was  sorptlve enough to remain In
the  sediment  (Cape! et al., 1988).  This  Is consistent with  the estimated
K     of   2.89xl03   (Section  2.3.),   which   suggests   that   adsorption   1s
expected to be a significant  fate process.
    Endosulfan  Is  expected to moderately bloconcentrate In  fish  and  aquatic
organisms.  An  experimental  BCF  of  602  has  been  determined  for  endosulfan In
mussels,  Mytllus  edulls (Hawker  and  Connell,  1986).   A BCF  of  480  can  be


0254d                               2-2                              11/06/89

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                                  TABLE 2-1
            Calculated Half-Lives for the  Hydrolysis  of Endosulfan
            PH
                                     Half-life (days)
            5.0
            6.0
            8.0
            9.0
5.1x10*
S.lxlO5
9.0
0.42 (10 hours)
5.6x10*
5.6xl05
7.8
0.28 (6.7 hours)
0254d
           2-3
                    10/03/89

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calculated  for  a-endosulfan  using  the  experimental   K    of  3.83  (Hansch
and Leo,  1985)  and  the  regression equation  log  BCF = 0.76  log KQW  -  0.23
(Bysshe,  1982).   A  Henry's   Law  constant  for   a-endosulfan  of   l.OxlO'5
atm-mVmol  can  be  calculated  based on  the water  solubility  at 20°C  {0.51
mg/l)  (Bowman  and  Sans,  1983)  and a  vapor  pressure  of  0.998xlO~5  mm  Hg
at  25°C  (Suntlo   et al.,  1988).   A  calculated   Henry's  Law  constant  of
2.94xlO~5  atm-mVmol  at   20°C   has  been   reported  In  the  literature   for
endosulfan, although  no  Isomer  was specified  (Suntlo  et  al.. 1988).  Based
on  these  values,   the volatilization  half-life  of  endosulfan  from a model
river 1 m deep,  flowing  at 1  m/sec with  a  wind velocity  of 3 m/sec  1s  -3-7
days (Thomas, 1982).  Therefore,  volatilization from water  to  the atmosphere
1s expected to be a significant  fate process.
2.3.   SOIL
    The  major  pathways  for removal  of  endosulfan  from  soil  are  probably
mlcroblal  degradation and  hydrolysis  In alkaline  soils.   Of  28   fungi,  49
bacteria  and  10 actlnomycetes  Isolated  from  soil,  pure  cultures  of  16,  15
and  3   of  these  species,  respectively,  degraded  endosulfan  under  aerobic
laboratory  conditions.   Metabolites  from the  biological  breakdown  of endo-
sulfan were endosulfan sulfate,  endosulfan  dlol and endosulfan hydroxyether,
along  with two  unidentified products   (Martens,  1976).    Endosulfan  at  an
Initial concentration of  10 ppm  was blodegraded under aerobic, anaerobic and
flooded  conditions  1n  seven   different  soils  from  Germany.  England   and
Thailand  (Martens,  1977).  Endosulfan  and  Us  known blodegradatlon products
underwent   aerobic   blodegradatlon  when  Incubated  with   a   mixed  culture
obtained  from  a sandy loam at  pH 6.5,  and  the half-lives were as  follows:
a-endosulfan,   1.1  weeks;  B-endosulfan,   2.2  weeks;   endosulfan   ether,   6
weeks;   endosulfan  a-hydroxy ether,  8 weeks;  endosulfan  sulfate,   11  weeks;
0254d                               2-4                              10/03/89

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endosulfan dlol,  14 weeks;  and  endosulfan  lactone,  5.5  hours  {probably not a
result  of  biological  processes)  (Miles   and  Hoy,  1979).  Degradation  of
endosulfan  In  soil can also  occur  by hydrolysis.  In  a  soil  blodegradatlon
study,  losses  of  endosulfan  from  hydrolysis  were  2% at  pH 5.5,  8% at pH 6.3,
28% at  pH 7 and 90% at pH 8 after 10 days (Martens,  1976).
    The  persistence  of  endosulfan  has   been  measured  In  field  studies,
although  the  exact mechanisms  of  removal  cannot be determined.  Endosulfan
applied to a field at  a  rate of 2 Ib/acre  on two occasions  In Hay, 1963, was
found  In  the  soil during August  of the same year at concentrations  of 0.12
and 0.14  ppm,  or -14%  of  the original  amount applied  (Byers et  a!.,  1965).
In  soil samples  taken  from  eight  orchard  and  vegetable plots  In  Colorado
where 0.25-1.25  ppm endosulfan  had  been applied  2-7 years  earlier,  only one
sample  tested positive for  residues  of  this  compound  (Hulllns  et  a!.,  1971).
The persistence  of endosulfan In  soils  from  India was  determined by measur-
ing the residue after 17.6  ppm  was  applied to a wet soil, and 19.7,  89.6 and
8.0 ppm were  applied  to dry  soils.  After  60  days,  3.2, 1.8, 1.1  and 0.9%
remained  In  the  fields, respectively (Rao  and  Murty,  1980a).    The  authors
concluded that  the persistence of  endosulfan  In  soils  Is  shorter than that
of other organochlorlne pesticides,  and that  Us  persistence  In dry  soils Is
directly related to the Initial rate of  application.
    Endosulfan Is  expected  to adsorb strongly to soils.  In  the  laboratory,
endosulfan  applied at  concentrations  <43.2   vq/g  to  a  sandy   clay  loam
column  did not  leach  >17  cm  (6.7 Inches)  from  the  top  over a period  of  300
days when pure water  was used  as an eluent simulating  0.25 cmVday of rain
(El Belt et al.,  1981).   Similar  results were  obtained  In  Identical  experi-
ments using a Gezlra soil and another sandy  clay  loam  (El Belt  et al., 1981,
1983).  Endosulfan applied  to soil  plots  In  India  (0.2-0.5%  organic  carbon)

0254d                               2-5                               11/06/89

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was not  found  at a  depth  >4 Inches after  100  days when  the  Initial  appli-
cation  rate  was  between  8.0 and  89.6  ppm (Rao and  Murty,  1980a}.   These
results   are   consistent   with   a   K     of   2.89xl03   for   a-endosulfan
                                       oc
obtained  from   the  regression  equation   log  K    =  0.544  log  K   *  1.377
(Lyman,  1982)  using a  K    of  3.83  (Hansch and  Leo,  1985).  A  K   between
2000 and 5000 suggests slight mobility In soil (Swann et al., 1983).
    Volatilization   of   endosulfan   from   soil  1s   not   expected   to   be
significant.   In an  experiment that  measured  the  volatility of  endosulfan
from  plant  surfaces,  loss of a-endosulfan  was  greater  than that  of  B-endo-
sulfan  under  controlled conditions.   After 10 days,  86%  (a-) and 99% (8-)
of  the  amount  applied to  bean  plant  leaves remained  (Beard and  Ware,  1969).
In  addition,  the  strong   adsorption  of  endosulfan  to  soil  Is  expected  to
reduce  the  rate  of  volatilization  from the  soil  surface  to a  negligible
level.
2.4.   SUMMARY
    In   soil,   the   major  removal   processes   of  endosulfan  are  probably
biological degradation  and,  In  basic  soils,  hydrolysis.   Blodegradatlon  has
occurred  In  soil under aerobic (Martens,  1976,  1977;  Miles and  Hoy,  1979)
and anaerobic conditions  (Martens,  1977).   Losses of  endosulfan  In soil from
hydrolysis were 8% at  pH 6.3,  28% at pH  7  and  90% at pH 8 after 10 days
(Martens,  1976).   Endosulfan  Is   expected  to   adsorb  strongly  to  soils.
Volatilization  of endosulfan  from  the soil  surface to  the atmosphere  Is  not
expected to be significant.
    If  released  to  water, endosulfan  Is  expected to adsorb to  sediment  and
suspended  organic  matter,   bloconcentrate  moderately  In   fish  and  aquatic
organisms and undergo destructive  removal by  hydrolysis.   The  rate constants
for  hydrolysis   of  a-endosulfan and  8-endosulfan  have been  experimentally
0254d                               2-6                              01/22/91

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determined  (Ellington  et  al.,  1988),  and the calculated half-lives  for  each
Isomer  are S.lxlO5  and  5.6xl05  days at  pH 6,  9.0 and  7.8 days  at pH  7
and 4.2  and 2.8 days  at  pH  8,  respectively.  Limited data are  available  on
the blodegradatlon  of  endosulfan  1n  water, and  Us fate  by  this  process
cannot  be  determined.   Volatilization  of  endosulfan  from  water  to  the
atmosphere  Is  also  expected  to be  a  significant process, with  an  estimated
volatilization half-life from a model  river of  between 3  and  7 days.
    Data  regarding  the fate  of  endosulfan  In  the  atmosphere  are  limited.
Direct photochemical degradation  In the  air Is  not  expected  to  occur  to any
significant extent.   Endosulfan has  been  detected  1n rainwater;  therefore,
removal  from  the  atmosphere  by  rain  washout  may occur.   Endosulfan  Is
expected to exist primarily 1n the vapor  phase  In the atmosphere.
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                                 3.  EXPOSURE

    Endosulfan may enter the atmosphere during application  to  control  animal
and plant pests  In agricultural  and  residential  settings,  from manufacturing
and  formulating  procedures and  through  commercial application.   Pesticides
may enter air  during application  of  dusts  and  aerosols In target areas  and
may drift Into the atmosphere of  nontarget  areas  (Kutz  et  al., 1976).   Spray
application   Is  probably  the  major  source   of  atmospheric  contamination  by
pesticides (Lewis and Lee,  1976).
3.1.   WATER
    The levels of endosulfan detected  1n  surface  water  are  reported  In Table
3-1.  Endosulfan has  also  been  detected  In  well  water  samples obtained from
54  private  and municipal  wells  1n  California,  although the  concentrations
were not  quantified  (Maddy et  al., 1982).   In 36  and 52X of  50 rainfalls on
the  Canadian side  of  the Great  Lakes   1n 1976,  a-endosulfan and  B-endo-
sulfan were  found  at mean  (maximum)  concentrations of  1.5 and  4.9  ng/s,  (15
and  45  ng/l),  respectively (Strachan  and   Huneault,  1979).    Another  study
In  the  Great Lakes ecosystem found  both  the a-  and B-endosulfan  Isomers In
rainwater  samples  at a  concentration  ranging  from   1-10  and  1-12  ngA,
respectively (Elsenrelch et al., 1981).
3.2.   FOOD
    The market basket survey conducted by the U.S.  Food and Drug Administra-
tion, which  analyzed  samples collected In retail  food outlets  throughout  the
United  States,  routinely  found  endosulfan residues  1n  the  following  food
groups:  potatoes,  leafy vegetables,  garden fruits,  fruits,  oils,  fats  and
shortenings   (Cornellussen,  1972;  Ouggan  and Cornellussen,  1972;  Hanske  and
Cornellussen,  1974;   Hanske  and  Johnson,   1975,  1977;   Johnson and  Manske,
0255d
3-1
10/02/89

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1976, 1977;  Johnson  et  al., 1981a,b, 1984a,b; Podrebarac,  1984a,b;  Gartrell
et al., 1985a,b,c, 1986a,b;  Gunderson,  1988).  Values for  the  average  dally
Intake  of  endosulfan   from  all  food groups  1n  these   studies  for  16- to
19-year-old males can be found  In Table  3-2.   Corresponding data  for Infants
and toddlers are reported In Table 3-3.
    The estimated annual dietary  Intake  of endosulfan from  the  Ingestlon of
fresh food  grown In  Ontario, Canada,  In  1985  obtained from quantitative data
on  residues  In  fruits,  leafy vegetables,  milk  and eggs/meat,  was  140.1
yg/year  for  a-endosulfan  and  690.36   pg/year   for  0-endosulfan   (Davles,
1988).  Endosulfan has  also  been  found 1n  vegetable  oil  (4 ppb),  and the oil
of groundnut  (8  ppm),  sesame {22 ppm) and mustard seeds  (832  ppm)  purchased
In Lucknow, India (Olkshlth et  al.,  1989).
3.3.   INHALATION
    According  to Kutz  et  al.   (1976),  Inhalation Is  an  Important   route of
exposure  to  pesticides for  the  general   population.    A  farmer  routinely
applying  endosulfan  to  his fields  Inhaled  4490-36,570  ng/m1nute   of  endo-
sulfan during  mixing and 68-155  ng/mlnute  during spraying  (Oudbler  et  al.,
1974).
    a-Endosulfan  was  found 1n  the  air  of  Columbia,   SC,  at  an  average
concentration  of 0.078 ng/m3,   but  not  In  the air  of Boston,  MA  (Bldleman,
1981).  Data collected  at urban and  rural  sites  1n  14 states during 1970 and
at  16  sites   during   1971-1972  Indicate   that   neither  a-endosulfan  nor
B-endosulfan was detected 1n samples  taken  during the latter two  years.  For
1970,  6.61%  of the samples   tested positive  for   a-endosulfan  and  1.02%
tested positive  for  0-endosulfan, with  mean  concentrations  for  the positive
samples   of  111.9   and  22.0   ng/m3,  respectively.   The  maximum  values
detected  were  2256.5  ng/m3  (a-)   and  54.5  ng/m3  (8-).   Endosulfan  was
0255d
3-3
10/02/89

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                                  TABLE  3-2

        Summary of  Endosulfan  Intake  from FDA's Market Basket Survey3'^
Fiscal Year
1968
1969
1976
1977
1978
1979
1977-1980
1980
1980-1982
1981-1982
1982-19846
Intake (ng/kg
a
id
Traced
3
2.6
2.5
3
NR
3
NR
9
2.7
bw/day]
B
NR
NR
3
3.1
3.4
2
NR
8
NR
13
5.0
I ntake
a
NR
NR
NR
NR
NR
NR
0.216
NR
0.596
NR
NR
( tig/da y)c
B
NR
NR
NR
NR
NR
NR
0.549
NR
0.898
NR
NR
aSources:   Cornellussen,  1972;  Ouggan and  Cornellussen,  1972;  Manske  and
 Cornellussen,  1974;  Manske  and Johnson,  1975,  1977;  Johnson  and  Manske,
 1976,  1977;  Johnson et  al., 1981a,b, 1984a,b;  Podrebarac, 1984;  Gartrell
 et al., 1985a,b,c, 1986a,b; Gunderson, 1988

bFor adult males aged 16-19 years

cBody weight taken to be 69.1  kg

dlsomer not specified

eFor males aged 14-16 years

NR = Not reported
0255d
3-4
10/02/89

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                                  TABLE 3-3

         Average Dally Intake of Endosulfan for  Toddlers  and Infants*
Fiscal Year
1975
1976
1977
1978
1979
1980
1981-1982


a
NO
11
ND
ND
1
ND
ND
Intake
Infant
B
ND
4.5
ND
0.2
5
1
3
(nq/kg bw/day)
Toddler
a
ND
7.8
0.4
5.0
6
1
6


3
ND
7.8
1.2
5.5
3.7
2
11
*Sources:  Johnson et  al.,  1981a,  1984a;  Gartrell  et  a!.,  1985a,  1986a;
 Podrebarac, 1984a

ND = Not detected
0255d                               3-5                              10/02/89

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found  In  air  samples from 6/16 states monitored  In  this  study  (Kutz  et  al.,
1976).   Endosulfan  has also  been  detected In  the  air  over the  Great  Lakes
{E1senre1ch et al., 1981).
    In  the  relatively small city  of  Delft In  the  densely  populated  western
Netherlands,  atmospheric  concentrations  for  a-endosulfan for  1979-1981  had
mean  and  maximum  values  of  168  and  1130  pg/m3.   The  estimated dally  and
yearly  Intake based  on  this  data  and on  an  Inhalation  rate  of 20  mVday
was given as 3.4 ng/day and 1.2 jig/year (Gu1cher1t and Schultlng,  1985).
3.4.   DERMAL
    Data  regarding  dermal  exposure  to endosulfan were  limited.   Endosulfan
may persist  on  the hands  of  workers spraying  this  Insecticide for <32  days
after use (Kazen et al.,  1974).
3.5.   OTHER
    a-Endosulfan was  detected at  a  concentration  of 0.01  ppm  in 0.07%  (1
sample) of  1506 samples  taken from 35 states  as  part  of the  National  Soil
Monitoring Program  during fiscal  year  1970.    In  a similar  study  performed
the following year,  of 1486  samples  from  37  states, o-endosulfan was  found
In  0.1% (2 sites)  of the samples  at concentrations of  0.05 and 0.23  ppm.
For B-endosulfan,  corresponding  values  were  0.27% positive  (4  sites)  and
0.2%  positive (3  sites),  with maximum concentrations  of 0.07  and  1.24  ppm,
respectively  (Carey  et   al.,  1978;   Crockett  et  al.,  1974).   Endosulfan
(a- and  B-lsomer   or  endosulfan   sulfate)  was   found  In  13  high  organic
content  soils  taken  from 28  vegetable  farms  during  1S76  In  southwestern
Ontario,  Canada,  at  concentrations  ranging  from  0.03-1.79  ppm  (Miles  and
Harris, 1978).  Soil  pesticide levels  were measured  at  51  locations  through-
out  the United  States that  represented   areas  of  regular,  limited  and  no
pesticide  use  In  1965-1967.   Endosulfan  was  not  found  In  the  latter  two
0255d
3-6
10/02/89

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areas but was  found  In regular-use areas In  the  following  crops  and concen-
trations:  vegetable   and/or  cotton,  32%  positive  at   0.01-1.22  ppm;  tree
fruits,  30%  at  0.02-4.63  ppm;  and  small   grains  and  root  crops,  9%  at
0.07-0.92  ppm (Stevens  et  al.,   1970).   Endosulfan was  found  In  31  soil
samples  taken from   apple  orchards  In Ontario,  Canada  during   1975  at  a
concentration  range  from not  detected  to 2.63  ppm (mean  =  0.26 ppm)  at  a
depth of 0-15  cm,  and not detected to 1.01 ppm (mean =  0.06  ppm)  at a  depth
of 15-30 cm (Frank et al., 1976).
    Endosulfan was  qualitatively  detected  1n Connecticut  bee apiaries  and
brood comb  (Anderson  and Wojtas,  1986).  It was  found  In the eggs of Chinook
salmon  returning  from  Lake  Michigan  1n fall  1982, at  a concentration  of
0.6-27.8 yg/kg (median, 6.61) (Glesy, 1988;  Glesy et al., 1986).
3.6.   SUMMARY
    The  general  population may be exposed  to endosulfan  through  Inhalation
and 1ngest1on  of contaminated  food.  The U.S.  Food and  Drug Administration's
market basket  survey, conducted from 1968-1984,  found that  the average  dally
Intake  (normalized for  body  weight) for adult males 16-19 years  old  ranged
from  trace  to 22  ng/kg  bw  (both a- and  B-lsomer  combined)  from  all  food
groups.   Endosulfan   was   commonly found  In   the  potato,  leafy  vegetable,
garden fruit,  fruit,  oil,  fat  and shortening  food groups.   The average  dally
Intake  of  endosulfan for  Infants and   toddlers  ranged  from  not  detected  to
15.5 ng/kg  bw  and  not detected to 15.6  ng/kg bw,  respectively (both Isomers
combined).    The  average  yearly  Intake  of endosulfan,  determined  during  a
Canadian market  basket survey  performed  In  Ontario during 1985, was  140.1
pg/year for o-endosulfan and  690.4 pg/year  for 8-endosulfan.
    In  the National  Pesticide Monitoring  Program  conducted  In  1970-1972,
endosulfan was only  found  In the  first  year 1n 6/16 of  the states monitored.


0255d                               3-7                              10/02/89

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In  1970,  6.6%  of  the  samples  tested  positive  for a-endosulfan,  and  1%
tested positive for B-endosulfan.
    Occupational  exposure  to   endosulfan  1s  expected  to  occur  for  those
Involved  1n  the production, formulation or application  of this  Insecticide.
A  farmer  applying this  Insecticide  to his  fields Inhaled  between  4490  and
36,570  ng/mlnute during  mixing, and  between  68  and  155  ng/mlnute  during
spraying (Oudbler et al., 1974).
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                         4.  ENVIRONMENTAL TOXICOLOGY
4.1.   AQUATIC TOXICOLOGY
4.1.1.   Acute Toxic  Effects on  Fauna.   Acute  median  toxic  responses  from
endosulfan exposure  have been assessed with >7  freshwater  Invertebrates,  10
freshwater fishes,  8 saltwater  Invertebrates  and 6  saltwater  fishes (Table
4-1).   Data  presented  In  this  table  are  from  studies  assaying  technical
grade endosulfan  using  natively-reproducing species.   Saltwater species were
generally  more  sensitive   to  endosulfan than   freshwater  forms.   The  most
sensitive  species  was   the  pink  shrimp,  Penaeus   duorarum   (LC5Q  =  0.04
         Median  response  concentrations  for  freshwater   forms ranged  from
a  96-hour  LC5Q  of  0.16  jig/s,  for  rainbow  trout,  Sal mo  qa1rdner1.  to  a
48-hour  EC5Q  for  the  water  flea,  Daphnla magna.   Fishes and  most  benthlc
Invertebrates  were  two or   three  orders  of  magnitude  more   sensitive  to
endosulfan  than was  the planktonlc D. magna.   In saltwater forms,  a  simi-
larly  disparate sensitivity among  species  was  apparent.  In this  case,  the
benthlc  Invertebrates, Neanthes  arenaceodentata  and  Crassostrea  Virginia.
were   the   highly resistant   forms.    Differences  In  sensitivities  among
organisms raise questions  regarding the validity  of  the data,  especially In
the case  of D_.  magna ,  since  It  1s  usually among  the  most sensitive  of test
species.  In  this case, however,  the data  for  D_.  magna were gathered by six
laboratories  that conducted  round-robin  tests  (Nebeker,  1982).   These data
showed good agreement.  Data  obtained  with N. arenaceodentata were similarly
obtained  and  also  showed   good  agreement.   C_.  vlrglnlca  data  may  be less
reliable, since  they  were provided  by only one  laboratory and  derived by
older methods (Butler, 1963, 1964).
0256d                               4-1                              11/07/89

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