•    , ,:
              United States         Office of Water         EPA 440/5-80-076
              Environmental Protection     Regulations and Standards    October 1980
              Agency            Criteria and Standards Division
                             Washington DC 20460       /» I
SEPA       Ambient
              Water Quality
              Criteria  for
              Toxaphene

-------
       AMBIENT  WATER  QUALITY  CRITERIA  FOR

                 TOXAPHENE
                 Prepared By
    U.S. ENVIRONMENTAL PROTECTION AGENCY

  Office of Water Regulations and Standards
       Criteria and Standards Division
              Washington, D.C.

    Office of Research and Development
Environmental Criteria and Assessment Office
              Cincinnati, Ohio

        Carcinogen Assessment Group
             Washington,  D.C.

    Environmental  Research Laboratories
             Corvalis, Oregon
             Duluth,  Minnesota
           Gulf Breeze,  Florida
        Narragansett,  Rhode  Island

-------
                              DISCLAIMER
     This  report  has  been  reviewed by the  Environmental  Criteria and
Assessment Office, U.S.  Environmental  Protection  Agency,  and approved
for publication.   Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
                          AVAILABILITY  NOTICE
       This  document is available  to  the public  through  the National
Technical Information Service, (NTIS), Springfield, Virginia  22161.
                                     ii

-------
                               FOREWORD

    Section 304  (a)(l)  of  the  Clean Water Act of  1977  (P.L.  95-217),
requires the Administrator  of  the Environmental  Protection Agency  to
publish criteria  for water  quality accurately reflecting  the  latest
scientific knowledge on the kind  and extent of all identifiable effects
on  health  and  welfare which  may  be  expected from  the presence  of
pollutants in any body of water, including ground water.  Proposed water
quality criteria  for the 65  toxic  pollutants  listed  under section 307
(a)(l) of  the  Clean Water  Act  were developed and  a notice  of  their
availability was published for public comment on March 15, 1979 (44 FR
15926)  July 25, 1979 (44 FR 43660), and  October 1, 1979 (44 FR 56628).
This document  is a revision of  those proposed criteria  based  upon a
consideration of  comments  received  from  other  Federal  Agencies,  State
agencies,  special interest  groups,  and  individual  scientists.   The
criteria contained in this document replace any previously published EPA
criteria  for the 65  pollutants.    This criterion  document is  also
published  in satisfaction of paragraph  11 of the Settlement Agreement
in  Natural  Resources Defense Council, et.  al. vs.  Train,  8  ERC 2120
(D.O.C. 1976), modified, 12 ERC  1B33 (D.D.C. 19/9).

    The term "water  quality criteria" is used  in  two sections of the
Clean Water Act,  section 304 (a)(l) and  section 303 (c)(2). The term has
a different  program  impact in  each section.   In section 304, the term
represents  a non-regulatory, scientific  assessment  of  ecological ef-
fects. The criteria  presented  in this publication are such scientific
assessments.   Such  water  quality  criteria associated  with  specific
stream uses when  adopted as State water quality standards  under section
303 become enforceable maximum  acceptable levels  of a  pollutant in
ambient waters.   The water  quality  criteria adopted  in the  State water
quality standards could have the same  numerical limits as the criteria
developed  under section 304. However, in  many situations States may want
to  adjust  water quality criteria developed under  section  304 to reflect
local  environmental  conditions  and   human  exposure  patterns  before
incorporation  into water  quality standards.   It is  not until  their
adoption  as part  of the State water quality standards that the criteria
become regulatory.

     Guidelines  to assist  the  States  in  the  modification of criteria
presented  in  this  document,   in   the development  of  water quality
standards, and in other water-related  programs of this Agency,  are  being
developed  by EPA.
                                     STEVEN SCHATZOW
                                     Deputy Assistant Administrator
                                     Office of  Water Regulations  and Standards
                                   111

-------
                           ACKNOWLEDGEMENTS
Aquatic Life Toxicology:

   William A. Brungs, ERL-Narragansett
   U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian lexicology and Human Health Effects:
   Phillip H. Howard (author)
   Syracuse Research Corporation


   Steven D. Lutkenhoff (doc. mgr.)
   ECAQ-Cin
   U.S. Environmental Protection Agency

   Bonnie Smith  (doc. mgr.)
   ECAO-Cin
   U.S. Environmental Protection Agency

   Edward Calabrese
   University of Massachusetts

   Kenneth Cheever
   National  Institute for Occupational
     Safety  & Health

   Patrick Durkin
   Syracuse  Research Corporation

   Larry  Fradkin
   ECAO-Cin
   U.S. Environmental Protection Agency

   Gerald Marquardt
Douglas L. Arnold
Health and Welfare
Canada

Joseph Borzelleca
Medical College of Virginia
William B. Buck
University of Illinois
Jaqueline V. Carr
U.S. Environmental Protection Agency

'<.  Diane Courtney
U.S. Environmental Protection Agency
 Pamela  Ford
 Rocky Mountain  Poison  Center

 A,  Wallace Hayes
 University of Mississippi


 Gordon  Newell
    U.S.  Environmental  Protection Agency    National  Academy of Sciences
    Fred Oehme
    Kansas State University

    Jerry F.  Stara
    ECAO-Cin
    U.S. Environmental  Protection Agency
 Herb Pahren,  HERL
 U.S. Environmental  Protection Agency
 Technical Support Services Staff:  D.J. Reisman, M.A. Garlough, B.L. Zwayer,
 P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,
 M.M. Denessen.

 Clerical Staff:  C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
 B.J. Quesnell, T. Highland,  R. Rubinstein.
                                   IV

-------
                           TABLE OF CONTENTS

                                                            Page

Criteria Summary

Introduction                                                A-l

Aquatic Life Toxicology                                     B-l
     Introduction                                           B-l
     Effects                                                B-l
          Acute Toxicity                                    B-l
          Chronic Toxicity                                  B-3
          Plant Effects                                     B-5
          Residues                                          B-5
          Miscellaneous                                     B-6
          Summary                                           B-6
     Criteria                                               B-8
     References                                             B-30

Mammalian Toxicology and Human Health Effects               C-l
     Exposure                                               C-l
          Ingestion from Water                              C-l
          Ingestion from Food                               C-4
          Inhalation                                        C-ll
          Dermal                                            C-15
     Pharmacokinetics                                       C-15
          Absorption                                        C-15
          Distribution                                      C-l9
          Metabolism                                        C-20
          Excretion                                         C-21
     Effects                                                C-22
          Acute, Subacute, and Chronic Toxicity             C-22
          Synergism and/or Antagonism                       C-28
          Teratogenicity                                    C-31
          Mutagenicity                                      C-32
          Carcinogenicity                                   C-34
     Criterion Formulation                                  C-48
          Existing Guidelines and Standards                 C-48
          Current Levels of Exposure                        C-53
          Special Groups at Risk                            C-54
          Basis and Derivation of Criterion                 C-54
     References                                             C-59

Appendix I                                                  C-74
     Summary and Conclusions Regarding the
          Carcinogenicity of Toxaphene                      C-74
     Derivation of the Water Quality Criterion
          for Toxaphene                                     C-76

-------
                        CRITERIA DOCUMENT
                            TOXAPHENE
CRITERIA
                          Aquatic  Life
     For toxaphene the criterion to protect  freshwater aquatic life
as derived using the Guidelines  is  0.013 ug/1 as a 24-hour average,
and the concentration should not exceed 1.6 ug/1 at any time.
     For  saltwater  aquatic  life  the  concentration of  toxaphene
should not exceed 0.070  ug/1 at any time.  No data are available
concerning the chronic toxicity  of  toxaphene to sensitive saltwater
aquatic life.

                          Human Health
     For the maximum protection of human health from the potential
carcinogenic effects due  to  exposure of toxaphene through ingestion
of  contaminated  water   and  contaminated  aquatic  organisms,  the
ambient water concentration  should  be zero based on  the non-thresh-
old assumption  for  this  chemical.   However,  zero level may not be
attainable at  the present  time.  Therefore, the  levels  which may
result in incremental increase of cancer  risk over  the lifetime are
estimated at 10"  ,  10  , and 10.   The  corresponding recommended
criteria are 7.1 ng/1, 0.71  ng/1, and 0.07 ng/1, respectively.  If
the above estimates  are  made for consumption  of aquatic organisms
only, including consumption of water,  the  levels are 7.3 ng/1, 0.73
ng/1, and 0.07  ng/1, respectively.
                               VI

-------
                           INTRODUCTION
     Toxaphene is a commercially produced, broad  spectrum, chlori-
nated  hydrocarbon  pesticide  consisting primarily  of chlorinated
camphene  and  a mixture of related compounds  and  isomers.   It was
introduced  in  the  United States in 1948 as  a contact insecticide
under  various  trade  names and  is  currently  the most heavily used
insecticide in the  United States,  having replaced  many of the agri-
cultural  applications of DDT, for which  registration  has been can-
celled.  Annual production of  toxaphene exceeds  100 million pounds,
with primary usage  in  agricultural crop application, mainly cotton.
     On May 25,  1977,  the U.S.  EPA issued a  notice  of rebuttable
presumption  against   registration  and  continued   registration  of
pesticide products containing toxaphene  (42 FR 26860) .
     Toxaphene is  a  complex  mixture  of polychlorinated camphenes
and bornanes with  the  typical empirical formula  C].oHioC18  and an
average molecular weight of 414.  It  is an amber,  waxy solid with  a
mild terpene odor,  a  melting point  range  of 65  to  90°C,  a vapor
pressure 0.17 to 0.40  mm Hg at 25°C,  and a density of 1.64 at 25°C
(Brooks, 1974;  Metcalf,  1966) .  Toxaphene has  a solubility in water
of approximately 0.4  to 3.0  mg/1 and  is readily  soluble  in rela-
tively nonpolar solvents, with  an  octanol/water partition coeffi-
cient of 825 (Brooks,  1974; Edwards,  1973;  Metcalf, 1966;  Sanborn,
et al.  1976).   Paris,  et al.   (1977)  reported a toxaphene partition
coefficient value of 3,300.  Gas chromatographic analysis suggests
the presence of approximately  177 components in technical toxaphene
(Holmstead, et al.  1974).   Infrared  absorptivity at 7.2  microns
                               A-l

-------
aids  in  distinguishing toxaphene  from other  chlorinated terpene
products such as strobane.  Although  tricyclene  may accompany the
camphene, the commercial  mixture contains less  than 5 percent of
other terpenes.
     Toxaphene is commercially  produced  by reacting camphene with
chlorine in the presence of ultraviolet radiation and certain cata-
lysts to yield chlorinated camphene with  a chlorine content of 67
to 69 percent (Metcalf, 1966).   The chlorine content of the commer-
cial product is  limited to this  narrow range since the  insecticidal
activity peaks sharply at those percentage levels.   Toxaphene is
available in various  formulations  as  an emulsifiable concentrate,
wettable powder, or dust.
     The commercial product  is  relatively stable but may dehydro-
chlorinate upon  prolonged  exposure to  sunlight, alkali, or tempera-
tures above 120°C (Metcalf, 1966; Brooks, 1974).
                               A-2

-------
                            REFERENCES








Brooks, G.T.   1974.   Chlorinated  Insecticides.   CRC Press, Cleve-



land, Ohio.







Edwards, C.A.   1973.   Persistent Pesticides in  the Environment.



2nd ed.  CRC Press, Cleveland, Ohio.








Holmstead,  R.L., et  al.   1974.   Toxaphene composition analyzed by



combined gel chromatography-chemical ionization mass spectrometry.



Jour. Agric. Food Chem.  22: 939.








Metcalf, R.L.  (ed.)   1966.   Kirk-Othmer  Encyclopedia of Chemical



Technology.  John Wiley and Sons,  Inc., New York.








Paris, D.F., et al.  1977.   Bioconcentration of  toxaphene by micro-



organisms.   Bull. Environ. Contain. Toxicol.  17: 564.








Sanborn, J.R., et al.   1976.  The fate of chlordane  and toxaphene in



a terrestrial-aquatic model ecosystem.  Environ. Entomol.  5: 533.
                               A-3

-------
Aquatic Life Toxicology*
                                 INTRODUCTION
    Toxaphene has  been used  as an  insecticide for  many years.   Its  acute
toxicity, particularly to fishes, prompted  its  use  to control  populations of
undesirable  fishes.   Toxaphene  is  a  mixture  of  numerous chlorinated  ter-
penes, but which terpenes are most toxic to  aquatic biota is  unknown because
they have not been tested individually.
    The acute toxicity, persistence,  and bioconcentration potential of toxa-
phene  have  been well  documented.   Chronic  toxicity of toxaphene  to  fresh-
water  and  saltwater  fish and  invertebrate  species  has been  documented  only
recently.
                                    EFFECTS
Acute Toxicity
    Available data  for freshwater invertebrate species  (Table  1)  include 13
acute  values for  11  species;  six species represent  rather different decapods
and  insects.   There  are toxicity  data from only  three tests  using flow-
through  procedures.   LC5Q  values  range from 1.3  to 180 ug/1.   The  stone-
fly,  Claassenia sabulosa,  is  the most sensitive  species  among those tested;
the midge, Chironomous plumosus. is least sensitive.
    As shown in Table  1,  57 acute toxicity  values  are  available for 18  spe-
cies  of  freshwater  fishes.   Nine  of the  57  LC5Q values  are  from flow-
through  tests,  and  the remainder are  from  static  tests.   Johnson and Julin
(1980) showed that exposures of  bluegill and channel  catfish to  toxaphene  in
 *The  reader is  referred  to the  Guidelines for  Deriving  Water  Quality Cri-
 teria  for  the Protection of Aquatic  Life  and  Its  Uses in order to better un-
 derstand  the following discussion  and  recommendation.   The following tables
 contain  the appropriate data that were found  in  the literature,  and at the
 bottom of  each  table are calculations  for  deriving various measures of tox-
 icity  as described  in the Guidelines.
                                      8-1

-------
flow-through test systems did not produce an  appreciable  increase  in  toxici-
ty  values  over  static test  systems;  however,  fathead  minnows  were  three
times more  susceptible to  toxaphene poisoning  in  the flow-through  system.
Channel  catfish  was the most  sensitive  species, with  a 96-hour  LC5Q  value
of  0.8  ug/l, and  goldfish  was  least  sensitive, with  a  96-hour  LC5Q  value
of 28 ug/l.
    The Freshwater Final Acute Value for toxaphene, derived  from the  species
mean  acute  values listed in  Table 3  using the procedure  described  in  the
Guidelines, is 1.6 ug/l.
    The 10  saltwater  invertebrate  species  tested were highly disparate  in
species sensitivity  to toxaphene (Table 1).   Crustaceans varied  greatly  in
species sensitivity.  The blue crab  was  relatively insensitive; the  96-hour
LCgg  values  range  from 370 to  2,700 ug/l  (McKenzie,  1970).  Several  life
stages of the pink shrimp were nearly  identical  in sensitivity to  toxaphene,
with  the  96-hour LC5Q  values  in the range from 1.4  to  2.2  yg/1  (Courtenay
and Roberts,  1973;  Schimmel,  et  al. 1977).  However, sensitivity  of  indivi-
duals of five early life stages  of the drift-line crab exposed to toxaphene
in  96-hour  toxicity  tests  was  inversely  related  to  the age  of  the  crabs
tested.  For example,  the  96-hour  LC50 of stage  I  larvae  was 0.054  ug/l;
that  for megalopa  (the oldest stage tested) was 8.4  ug/l (Table  1).   Other
than  stage  I drift-line crab  larvae,  the  most sensitive crustacean  tested
was  the copepod,  Acartia  tonsa,  with a  96-hour LC5Q  value  of  0.11  yg/1
(Khattat and  Farley, 1976).  The hard clam,  Mercenaria  mercenaria, was  the
least sensitive  species (Table  1) with  a  species  mean acute  value of  1,120
ug/l  (Davis and Hidu, 1969).
    In  flow-through  toxicity  tests  with  five  saltwater fish  species  (Tables
1  and  6),  96-hour  LC   values were in   the range  from  0.5  to 8.6
                                      B-2

-------
(Katz, 1961;  Korn  and Earnest,  1974;  Schimmel, et  al.  1977).  Katz  (1961)
exposed the threespine stickleback to toxaphene  in  static  tests at 5  and  25
g/kg  salinity and  reported  96-hour LC5Q  values of  8.6  and  7.8  wg/l,  re-
spectively.
    The Saltwater Final  Acute  Value for toxaphene, derived from the  species
mean  acute values  listed  in Table 3  using the procedure  described   in  the
Guidelines, is 0.07 wg/l.
Chronic Toxicity
    Chronic, data are available  for  three  freshwater invertebrate  species
(Table 2). The  chronic  values for Daphnia magna,  scud (Gammarus pseudolimn-
aeus),  and midge  (Chironomus  plumosus)  are 0.09,  0.18,  and  1.8  Pg/l,  re-
spectively.  These  differ by  a  factor  of 20,  indicating  a sensitivity dif-
ference  among the  tested species.  Acute-chronic  ratios  for  the  three in-
vertebrate species tested were in  the range  from 100  to 133 (Table 2).
    Two  chronic  tests have been conducted with freshwater fish species, pro-
viding  chronic values of 0.037 and 0.059 ug/l for fathead minnow and  channel
 catfish, respectively (Table  2).  Acute-chronic ratios are  265 for  fathead
 minnow and 71 for channel catfish.  A third chronic test result with  brook
 trout is included in Table  6  because even  at the  lowest concentration tested
 there was an effect on growth.
     The  geometric  mean  of acute-chronic  ratios  for  freshwater  species  is
 123.  Dividing the value of 123 into the Freshwater  Final  Acute Value of 1.6
 ug/l  provides the Freshwater Final Chronic Value of 0.013  wg/l (Table 3).
     Chronic  studies  on  toxaphene with  saltwater  fish species  indicate  that
 concentrations  that  do  not affect individuals  in their early stages differ
 little  from  96-hour LC5Q  values.   Goodman,   et  al.  (1978)  conducted  an
 early-life-stage study  with the  sheepshead  minnow in which toxaphene was not
                                       B-3

-------
 lethal  to  embryos at  concentrations  as high  as 2.5 ug/l.   Combined embryo
 and larval mortality during  a  28-day exposure to 2.5 wg/l  was  significantly
 greater than  control  mortality, but at  1.1  wg/l mortality was  not  greater.
 Therefore, concentrations  not  affecting survival  or growth  of  sheepshead
 minnows in  an early-life-stage  test  (Table  2)  (Goodman,  et al.  1978)  were
 similar to the  96-hour LC5Q (1.1  yg/l)  of toxaphene to juvenile  sheepshead
 minnows (Table  1)  (Schimmel,  et  al.  1977).   The  acute-chronic  ratio  for
 sheepshead minnow is 0.66, two orders of magnitude  lower than the  freshwater
 ratios.
     The chronic  data  for  the  saltwater sheepshead  minnow contrast  sharply
 with chronic  test  data for  freshwater  fish  species  (Table 2).   The  acute
 value   of  toxaphene for  the channel  catfish  (4.2  ug/l)  was  85  times  the
 highest concentration  that produced  no  observable deleterious effects  in a
 chronic study? that for the  fathead  minnow  (9.8  pg/1) was nearly 400 times.
 Data for four other pesticides  support  the hypothesis that differences  be-
 tween  acute and  chronic effect  concentrations  in  freshwater and  saltwater
 fish species  are similar  (Parrish,  et  al. 1978).   Possibly the  early-life-
 stage test was not  a sensitive  measure of chronic effects,  or it may be that
 saltwater fish species  differ from  freshwater  fish species  in chronic sensi-
 tivity  to  toxaphene due to  innate  differences between saltwater and fresh-
 water fishes or to  phylogenetic  factors  such  as those reported by  Macek and
 McAllister (1970).
     In   another early-life-stage  study with a saltwater fish  species, Schim-
mel, et al. (1977) exposed the embryos and larvae  of the  longnose killifish,
Fundulus similis,  to  toxaphene  for  28  days (Table  6).   The results  of the
test could  not be used  to establish  a chronic  value because the  lowest  con-
centration  tested caused substantial  mortality.
                                     B-4

-------
    The acute-chronic  ratio for sheepshead  minnow was  not  used because  it
was two orders of magnitude  lower  than  the other five values,  and  therefore
a Saltwater Final Chronic Value was not calculated.
Plant Effects
    A  single test on  a freshwater algal  species,  Selenastrum capricornutum
(Table  4-)  provided  an EC5Q of  0.38  yg/1  (U.S.  EPA, 1980).   Ukeles  (1962)
found  that five  species of saltwater algae varied  greatly  in sensitivity to
toxaphene  (Table 4).   The most sensitive organism was  the dinoflagellate,
Monochrysis  lutheri, its growth being  inhibited at a concentration  of 0.15
wg/U   Data  from Butler (1963) indicated  that  1,000 wg/1 caused a 90.8 per-
cent decrease  in productivity  of natural phytoplankton communities.
Residues
    Table  5  contains steady-state bioconcentration data  for  three freshwater
fish- species.   Bioconcentration  factors  (BCF)  ranged  from  3,400  for brook
trout (Mayer,  et al. 1975)  to  52,000  for fathead minnow  (Mayer,  et al.  1977).
     The bioconcentration of toxaphene  in  tissues of saltwater animals  has
 been well studied  (Table 5),  Lowe, et al. (1970) exposed  eastern  oysters,
 Crassostrea  virqinica, to a concentration of 0.7  ug/l for 36 weeks,  followed
 by a 12^week  depuration period.  The maximum BCF,  32,800, was attained after
 24 weeks.  Mo toxaphene was found in oyster tissues  after the 12-week  depur-
 ation  period.   Goodman, et aU (1978)  exposed  sheepshead minnow embryos  and
 fry to toxaphene  for 28 days and reported  an  average  BCF of 9,800.   Schim-
 mel, et al.  (1977)  exposed  newly-hatched  and juvenile  longnose killifish for
 28 days and reported average BCF values of 27,900 and 29,400, respectively.
     Dividing  a BCF value  by the  percent lipid  value  for   the  same  species
 provides a  BCF  value  adjusted to  1  percent lipid content;  this resultant BCF
                                       B-5

-------
 value is referred to as the normalized bioconcentration factor.  The geomet-
 ric mean of normalized BCF values for toxaphene for freshwater and saltwater
 aquatic  life is  4,372  (Table 5).
     Dividing the U.S.  Food and Drug Administration (FDA) action level of 5.0
 mg/kg for edible fish  by the  geometric mean of normalized BCF values (4,372)
 and by a  percent  lipid value of 15  for  freshwater species (see Guidelines)
 gives a  freshwater residue value based on marketability  for  human consump-
 tion of  0.076 wg/1.   Dividing the  FDA action level  (5.0  mg/kg)  by the geo-
 metric mean  of normalized  BCF  values  (4,372)  and  by a percent lipid value of
 15  for saltwater species (see  Guidelines)  gives  a saltwater residue value of
 0.071 wg/1.   Also  based on marketability  for  human consumption using the FDA
 action level and the highest  BCF for  edible  portion  of a consumed fish spe-
 cies  (7,800  for channel catfish for freshwater),  a freshwater residue  value
 of  0.64  wg/1  is obtained  (Table 5).   No  appropriate  BCF value  for  edible
 portion of a consumed fish species is available for saltwater.
    The  lowest  freshwater residue  value  of those  calculated  becomes  the
 Freshwater Final  Residue Value of  0.076  wg/1.  The Saltwater Final  Residue
 Value is  0.071  wg/1.   The  Final  Residue  Values  may be too high  because,  on
 the average, the concenration  in 50 percent of species  similar to  those used
 to derive the values will exceed the FDA action level.
 Miscellaneous
    Table 6,  containing data  for other effects not  listed  in  the  first five
 tables, does not indicate any  significant effect  levels that would  alter the
 conclusions discussed previously.
 Summary
    The freshwater  acute data base  for toxaphene  contains  data  for 11  in-
 vertebrate and 18 fish  species.  Acute  values  for  invertebrate species  range
from  1.3  w9/l for  the stonefly, Claassenia  sabulosa,  to  180 ug/1 for  the
                                     B-6

-------
midge,  Chlronomus  plumosus.   Species  mean  acute  values  for  fish  species
range from 2 Pg/l for  largemouth bass  to 20 ug/1 for  guppy.  Chronic values
are  available  for  three  freshwater  invertebrate and  two fish species,  and
range from 0.037 wg/l for the fathead minnow to  1.8  ug/1  for  midge, Chirono-
mus_ plumosus.  Acute-chronic ratios for  freshwater species  were in the range
from 71 to 265.
    The  saltwater  acute  data  base for toxaphene contains  data for  10  in-
vertebrate  and four fish  species.   Species mean  acute  values  for inverte-
brate  species  range from 0.11  ug/1  for  a copepod,  Acartia  tonsa,  to 1,120
ug/l  for  the  hard  clam,  Mercenaria  mercenaria.   Acute  values  for  fish
species  range  from  0.5  vg/l  for  pinfish to  8.2  ug/1  for the threespine
stickleback,   A chronic value of 1.66  ug/1  is  available for the sheepshead
minnow.
     A single  EC5Q  value of 0.38  yg/l  is  available for a  freshwater algal
species,  and a wide range  of  toxaphene concentrations  (0.15 to  1,000 ug/1)
has  been  reported to cause  deleterious  effects  to saltwater  plant  species.
     Bioconcentration factors for  toxaphene and freshwater fish species range
from 3,400 for brook  trout fillets to 52,000 for whole  body fathead  minnow.
The  bioconcentration  factor  for  a  single  saltwater  invertebrate  species,
Eastern  oyster,  is 32,800 in  edible  tissue;  bioconcentration  factors  in
saltwater fish  species  range  from 1,270 in  ova  of  exposed adult  longnose
killifish to  29,400  in  juvenile  longnose killifish.   Freshwater and Salt-
water Final  Residue  Values of  0.076  and 0.071  u9/l were  calculated.    It
should be  pointed  out that these Final  Residue Values  may  be too high  be-
cause, on the average, the concentration in 50  percent of  species  similar  to
 those used to derive the value will exceed the FDA action level.
                                      B-7

-------
                                   CRITERIA
    For  toxaphene  the criterion  to  protect freshwater  aquatic  life as  de-
rived using  the  Guidelines  is 0.013 wg/l as a 24-hour average,  and  the  con-
centration should not exceed 1.6 ug/1 at any time.
    For saltwater aquatic life the concentration of toxaphene  should  not  ex-
ceed 0.070 ug/1  at  any time.  No data  are  available  concerning the  chronic
toxicity of toxaphene to sensitive saltwater aquatic life.
                                    B-8

-------
                                                                 T»t>lf 1*   Acutf values for toxaphene
to
u>
Species Mean
UC50/EC50 Acute Value
c 	 i^« Method* (iig/l> 
FRESHWATER SPECIES
Cladoceran, S» U t9
Slmocephalus serrulatus
Cladoceran, S, U 10 M
Slmocephalus serrulatus
Cladoceran, Sf U 15 15
Daphnla pulex
Cladoceran, rT, M 10 10
Daphnla magna
Si i ^*5 —
» u ^
Garomarus fasclatus
e it fi 14
Scud, S, U o n
Gammarus fasclatus^
Scud, S, U 26 26
Gammarus lacustrls
Scud, FT, M 24 24
Gammarus pseudol Imnaeus
Glass shrimp, S, U 28 28
Palaemonetes kadlakensls
Midge (larvae), FT, M 180 180
Chlronomus plumosus
Stonef ly. S, U 2.3 2.3
Pteronarcys callfornlca
Stonef ly. S, U 3.0 3.0
Pteronarcel la bad la
Stonef ly, S, U 1.3 U*
Claassenla sabulosa
Coho salmon, S, U 9.4
Oncorhynchus klsutch

Reference

Sanders & Cope,

Sanders * Cope,

Sanders i Cope,

Sanders, 1980

Sanders, 1972


Sanders, 1972


Sanders, 1969

Sanders, 1980

Sanders, 1972

Sanders, 1980

Sanders & Cope

Sanders & Cope

Sanders & Cope

Katz, 1961




1966

1966

196$

















, 1968

, 1968

, 1968




-------
                                   Tabl*  tt   (Continued)
to

H
O
Species
Coho salmon,
Oncorhynchus ktsutch
Chinook salmon,
Oncorhynchus tshawytscha
Rainbow trout,
Salop galrdnerl
Rainbow trout,
Sal mo galrdnerl
Rainbow trout,
Salmo galrdnerl
Brown trout,
Salmo trutta
Brook trout,
Salvellnus fontlnalls
*
Stonero) ler,
Campostoma anomalum
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Carp,
Cyprlnus carplo
Golden shiner,
Notemlgonus crysoleucas
Bluntnose minnow.
• Method*
S, U
s, u
s, u
8, U
s, u
s, u
FT, M
S, U
s, u
$, u
s, u
s, u
s, u
s, u
LC50/EC50
(Ud/l)
8
2,5
8.4
9.4
11
3
10,8
14
5.6
28
14
4
6
6.3
Species Neon
Acute Value
(uo/l)
8.7
2.5
-
-
9.?
3
11
14
13
4
6
6.3
Reference
Macek & McAl
1970
Katz, 1961
Katz, 1961
Mahdl, 1966
Macek & McAl
1970
lister,



lister,
Macek & McAllister,
1970
Mayer, et al. 1975
Mahdl, 1966
Henderson, et al,
1959
Mahdl, 1966
Macek & McAllister,
1970
Macek & McAllister,
1970
Mahdl, 1966
Mahdl, 1966


                                    Plmephales notatus

-------
                                   Table !,  (Continued)
w

H
H

Species
Fathead minnow,
Pltnephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Black bullhead.
1 eta 1 urus me las
Black bullhead.
1 eta 1 urus me las
Channel catfish.
1 eta 1 urus punctatus
Channel catfish.
1 eta 1 urus punctatus
Channel catfish,
1 eta 1 urus punctatus

Method*
S, U

fTf U

s, g

§» u

s, g

s, u

s, g

FT, g

FT, g

s, g

s, g

s, u

FT, g

FT, g

Species Mean
I.C50/EC5Q Acute Value
(wa/l) (tia/l)
7,5

7,2

5,1

14

13

20

23

7,0

5,0 9,8

1,8

5 3.0

13

16.5

5.5


Reference
Henderson, et a|.
1 Acn
1959
Mayer, et al, 197?

Henderson, et 9U
1959
Macek «, McAllister,
1970
Cohen, et a|, I960

Johnson 4 Julln, 1980

Johnson & Julln, 1980

Johnson & Julln, 1980

Johnson & Julln, 1980

Mahdl, 1966

Macek & McAllister,
1970
Macek & McAllister,
1970
Mayer, et al. 1977

Johnson 4 Julln, 1980


-------
                                  Table 1.  (Continued)
M
I
Species
Channel catfish.
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
1 eta 1 urus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Guppy,
Method*
FT, U
S, U
S, U
S. U
S, U
S, U
S, U
S, U
S, U
S, U
S, U
S, U
S. U
S. U
LC50/EC50

-------
                                  Table  1.   (Continued)
(-•
CO

Cf\AC 1 AC
«jy^y i y *•
B 1 ueg III,
Lepomls macroch 1 rus
Blueglll,
Lepomls macroch 1 rus
Blueglll,
Lepomls macroch 1 rus
Blueglll,
Lepomls macroch 1 rus
Blueglll,
Lepomls roacrochlrus
Blueglll,
Lepomls macroch 1 rus
Blueglll,
Lepomls macroch 1 rus
Blueglll,
Lepomls macroch 1 rus
B 1 ueg III,
Lepomls macrochlrus
Blueglll,
Lepomls macrochlrus
B 1 ueg III,
Lepomls macrochlrus
Redear sun fish,
Lepomls mlcrolophus
Largemouth bass.
Micropterus salmoldes
Yel low perch.
Species Mean
LC50/EC50 Acute Value
Method* (ua/U (wo/l)
S, U 3.2

S, U 2.6

S, U 2.4

S, U 5.0

S, U 7.8

S, U 3.5
S, U 18

S, U 2.4

S, U 2.6

FT, U 3.4

FT, U 4.7 4.1

S, U 13 13

S, U 2 2

S, U 12 12

Reference
MaceK, at al. 1969

Macek, et al. 1969

Macek, et al. 1969

Isensee, et al. 1979

1 senses, et al. 1979

Henderson, et al.
1959
Macek & McAl lister,
1970
I y i\j
Johnson 4 Julln, 1980

Johnson & Julln, 1980

Johnson & Julln, 1980

Johnson & Julln, 1980

Macek 4 McAllister,
1970

Macek & McA 1 1 1 ster ,
1970

Macek & McAl lister,
1970
                                    Perca flavescens

-------
                                 Table 1.  (Continued)
w
Species
Eastern oyster,
Crassostrea vlrojnlca
Eastern oyster,
Crassostrea virgin lea
Eastern oyster,
Crassostrea vlrglnlca
Hard clam (embryo),
Mercenarla mercenarla
Copepod,
Acartia tonsa
Mysld shrimp (juvenile),
Mysldopsls bah la
Mysld shrimp (adult),
Mysldopsls bah la
Blue crab,
Ca 1 1 1 nectes sap 1 dus
Blue crab,
Ca 1 1 1 nectes sap 1 dus
Blue crab,
Ca 1 1 1 nectes sap 1 dus
Blue crab,
Ca 1 1 1 nectes sap 1 dus
Blue crab,
Ca 1 1 1 nectes sap 1 dus
Blue crab.
Method*
FT, M
FT, U
FT, U
s, g
S, U
FT, M
FT, M
S, U
S, U
S, U
S, U
S, U
S, U
Species Mean
LC50/EC50 Acute Value
(iig/l) lva/n
SALTWATER SPECIES
16
63
57 16
1,120 1,120
o.u»« o.n
6.32
3.19 4.5
580
900
370
960
380
770
Reference
Schlmnel, at al, 1977
Butler, 1963
Butler, 1963
Davis & Hldu, 1969
Khattat & Farley,
1976
Nlmmo, 1977
Nlmmo, 1977
McKenzle, 1970
McKenzle, 1970
McKenzle, 1970
McKenzle, 1970
McKenzle, 1970
McKenzle, 1970
                                 Calllnectes sapldus

-------
                                Table 1,
tfl
H
ui
Species Mean
UC50/EC50 Acute Value
Species j£ 	 	 HSH
Blue crab, S. U 1,200
Cal 1 Inectes sapldus
Blue crab, S, U 2,700
Calllnectes sapldus
Blue crab, S. U 1,000 824
Cal 1 Inectes sapldus
Korean shrimp, s» U 2°»3
Palaemon macrodacty 1 UA
Korean shrimp, FT, U 20,6 21
Palaemon macrodacty 1 UA
Grass shrimp, FT, M 4.4 4.4
Palaemonetes puglo
c-r u 1 A "•
Pink shrimp, FT, M L*
Penaeus duorarum
Pink shrimp (naupllus), S, U 2,2
Penaeus dourarum
Pink shrimp (protozoea), S, U 1.8
Penaeus duorarum
Pink shrimp (mysls), S, U 1.4 '•«
Penaeus duorarum
Mud crab (stage 1 larva), S, U 43.75 43.8
Rh 1 thropanopeus harr 1 s 1 1
Or 1 ft- line crab (stage 1 S, U 0.054
larva).
Sesarma clnereum

Reference
McKenzle, 1970

McKenzle, 1970

McKenzle, 1970

Schoettger, 1970

Schoettger, 1970

Schlmmel, et a). 1977

Schlmmel, et al. 1977


Courtenay 4 Roberts,
1973

Courtenay 4 Roberts,
1973

Courtenay 4 Roberts,
1973

Courtenay 4 Roberts,
1973

Courtenay 4 Roberts,
1973


                                  Drift-line  crab  (stage  II
                                   larva),
                                  Sesarma  clnereum
S, U
                                                                              0.76
Courtenay 4 Roberts,
1973

-------
                                  Table |.   (Continued)
to
Species
Drift-line crab (stage III
larva),
Sesarma clnereum
Drift-line crab (stage IV
larva),
Sesarma clnereum
Drift-line crab (megalopa),
Sesarma clnereum
Sheepshead minnow,
Cyprlnodon varlegatus
Threesplne stickleback,
Gasterosteus aculeatus
Threesplne stickleback,
Gasterosteus aculeatus
Striped bass,
Morone saxati 1 Is
Plnflsh,
Lagodon rhomboldes
Method*
S, U
S, U
s, u
FT, M
S, U
S, U
FT, U
FT, M
LC50/EC50
(HO/1)
0,74,
6.6
8.4
M
8,6
7.8
4.4
0.5
Species Mean
Acute Value
(wo/1)
-
-
I.I
LI
8.2
4.4
0.5
Reference
Courtenay &
1973
Courtenay &
1973
Courtenay &
1973
Schlmmel, et
Katz, 1961
Katz, 1961
Roberts,
Roberts,
Roberts,
al, 1977

Korn & Earnest, 1974
Schlmmel, et al. 1977
                                 * S = static; FT = flow-through; U * unmeasured; M = measured
                                 **LC50 recalculated using problt analysis method of FInney (1971),

-------
Cd
                                                              Table 2.  Chronic values for toxaphene


                                                                         Units     Chronic Value
                                                                                       (ug/|)        Reference
spa^ias •«*»•
Cladoceran, LC
Daphnla magna
Scud, LC
Gammarus pseudol Imnaeus
Midge (larva), LC
Chlronomus plumosus
Fathead minnow, LC
Plmephales promelas
Channel catfish, LC
Ictalurus punctatus
FRESHWATER SPECIES
0.07-0. \2

0.13-0.25

1.0-3.2

0.025-0.054

0.049-0.072


0.09 Sanders, 1980

0.18 Sanders, 1980

1.8 Sanders, 1980

0.037 Mayer, et al.

0,059 Mayer, et al.








1977

1977

SALTWATER SPECIES
S heaps head minnow, ELS
Cyprlnodon varlegatus
* LC = life cycle or partial life
1.1-2.5

cycle, ELS = early
1.66 Goodman, et al. 1978

1 1 fe stage


Acute-Chronic Ratios
Acute Chronic
Value Value
Species
Cladoceran,
Daphnla magna
Scud,
(ug/n (v
10

24
q/|) Ratio

0.09 111

0.18 133




Gammarus pseudol Imnaeus

-------
                                    Table 2.   (Continued)
                                                                      Acute-Chronic Ratios
Midge (larvae),
Chlronomus plumosus
Fathead minnow,
Plmephales promelas
Channel catfish,
Ictalurus punctatus
Sheepshead minnow,
Cyprlnodon varlegatus
Acute
Value
(ug/l)
180
9.8
4.2
1.1
Chronic
Value
(ug/l)
1.8
0.037
0.059
1.66
Ratio
100
265
71
0.66
(D
I
M
00

-------
                                 Table 3.  Species Man acute values and acute-chronic ratios for toxaphene
w

H-1
ID
Rank*
29
28
27
26
25
24
23
22
21
20
19
18
17
Species
Midge,
Chlronomus plumosus
Glass shrlnp,
Palaemonetes kadlakensls
Scud,
Gamnarus lacustrls
Scud,
Gammarus pseudol Imnaeus
Guppy,
Poecllla retlculata
Cladoceran,
Daphnla pulex
Scud,
Gammarus fasclatus
Stonerol ler,
Campostoma anomalum
Cladoceran,
Slmocephalus serrulatus
Goldfish,
Carasslus auratus
Radear sunflsh,
Lepomls mlcrolophus
Yel low perch,
Perca flavescens
Brook trout.
Species Mean
Acute Value
(IIO/D
FRESHWATER SPECIES
180
28
26
24
20
15
14
14
14
13
13
12
11
Species Mean
Acute-Chronic
Ratio

100
-
133

"
"


"

-
                                              Salvellnus fontlnalIs

-------
Table 3.  (Continued)
Rank*
16
15
14
13
12
It
10
9
B
7
6
5
4
3
Species Mean
Acute Value
Species (uq/l)
Cladoceran,
Daphnla magna
Fathead minnow,
Plmephales promelas
Rainbow trout,
Salmo gairdnerl
Coho salmon,
Oncorhynchus klsutch
Bluntnose minnow,
Plmephales notatus
Golden shiner,
Notemlgonus crysoleucas.
Channel catfish,
Ictalurus punctatus
Blueglll,
Lepomls macrochlrus
Carp,
Cyprlnus carplo
Black bul (head,
Ictalurus me las
Stonef ly,
Pteronarce 1 1 a bad 1 a
Brown trout,
Salmo trutta
Chinook salmon,
Oncorhynchus tshawytscha
Stonef ly.
10
9.8
9.2
8.7
6.3
6
4.2
4.1
4
3.0
3.0
3
2.5
2.3
Species Mean
Acute-Chronic
Ratio
111
265
-
71
-
           Pteronarcys ca11fornIca

-------
01
to
H
Species Mean
Acute Value
r 1 r tUO/l)
Rank* SpecleA 	 " 	
2
2 Largemouth bass,
Mlcropterus salrooldes
1 Stonefly, '*3
Claassenla sabulosa
SALTWATER SPECIES
14 Hard clam, l't20
Mercenarla mercenarte
13 Blue crab,
Calllnectes sapldus
12 Mud crab, 43'8
Rhithropanopeus narrlsn
\\ Korean shrimp, 2I
Palaemon macrodactylus
10 Eastern oyster,
r.ra«ostrea virgin lea
9 Threesplne stickleback, 8«2
Gasterosteus aculeatus
8 Mysld shrimp, 4*5
Mysldopsis bah I a
7 Grass shrimp, 4'4
Palaamonetes puglo
6 Striped bass, 4'4
Morone saxattlls
5 Pink shrimp, U4
Panaeus duorarum
4 Drift-line crab, '•'
Species Mean
Acute-Chronic
Ratio
-
Sasarma clnereum

-------
Table 3.  (Continued)

                                       Species Mean      Species Mean
                                        Acute Value      Acute-Chronic
Rank*      Species                         (ug/l)           Ratio

 3         Sheepshead minnow,                I.I              0.66
           Cyprlnodon varlegatus

 2         Plnflsh,                          0.5
           lagodon rhomboldes

 1         Copepod,                          0.11
           Acartla tonsa
* Ranked from least sensitive to most sensitive based on species mean acute
  vaIue.


  Freshwater Acute-Chronic Ratio = 123

  Freshwater Final Acute Value = 1.6 ug/l

  Freshwater Final Chronic Value - 1.6 ug/l r 123 - 0.013 ug/l


  Saltwater Final Acute Value - 0.07 ug/l

-------
                                                                 Table 4.  Plant values for toxaphene
CD

to
U)
Species
Alga,
Sel enastrum caprlcornutum
Alga,
Chlorel la sp.
Dlnof lagel late,
Dunal lei la euchlora
Dlnof lagel late,
Monochrysls lutherl
Alga,
Phaecodacty 1 urn tr 1 cornutum
Alga,
Protococcus sp.
Natural phytop lankton
communities
Result
Effect (ug/ll
FRESHWATER SPECIES
EC50 0.38
SALTWATER SPECIES
No growth 70
Lethal 150
No growth 0.15
Letha 1 40
No growth 150
90. 8% 1,000
decrease In
productivity;
Reference
U.S. EPA, 1980
Ukeles, 1962
UKeles, 1962
Ukeles, 1962
Ukeles, 1962
Ukeles, 1962
Butler, 1963

-------
                                                        Table 5.  Residues for toxaphene
w
Species
Brook trout,
Salvellnus fontlnalls
Brook trout,
Salvellnus fontlnalls
Fathead minnow,
Plroephales proinelas
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish fry,
Ictalurus punctatus
Eastern oyster,
Crassostrea virgin lea
Sheepshead minnow,
Cyprlnodon varlegatus
Longnose kllllflsh (fry),
Fundulus slml 1 Is
Longnose kllllflsh
(juvenile),
Fundulus slml Us
Longnose kllllflsh (adult),
Fundulus slml 1 Is
Longnose kllllflsh,
Fundulus slml 1 is
Tissue
Whole body
Fl 1 let
Whole body
Whole body
Fl | let
Whole body
Edible tissue
Whole body
Whole body
Whole body
Whole body
Ova of exposed
adults
Llpld Bloconcentratlon
(1) Factor
FRESHWATER SPECIES
10,000
3,400
9.3 52,000
7.8 22.000
7,800
4.7 40,000
SALTWATER SPECIES
32,800
3.6* 9,800
27,900
29,400
5,400
1,270
Duration
(days)
140
161
98
100
137
90
168
28
28
28
32
14
Reference
Mayer, et al. 1975
Mayer, et al. 1975
Mayer, et al. 1977
Mayer, et al. 1977
Mayer, et a). 1977
Mayer, et al. 1977
Lowe, et al. 1970
Goodman, et al. 1978
Schlmnel, et al. 1977
Schlnmel, et al. 1977
Schlmnel, et al. 1977
Schlmnel, et al. 1977

-------
f
Table 5.  (Continued)
                                            Llpld        Bloconcentratlon     Duration
Species                        Tissue        (?)              Factor           (days)      Reference

Longnosekll.lflsh,          Ova of exposed   -             3.700                  32      Schl—1, rt .1. 1977
Fundulus slmllls             adults



* Percent  llpld data from Hansen, 1980


                                    Maximum Permissible Tissue Concentration

                                                      Concentration
                           Action Level                   
-------
                 Table 5.   (Continued)
                 Freshwater Final Residue Value * 0.076 ug/l
                 Saltwater Final Residue Value = 0,071 ug/l
W
N)

-------
                                                                  Table 6.  Other data for toxaphene
a

K>
-J
Species
Duration
Effect
Result
(no/I)
FRESHWATER SPECIES
Cladoce.ran,
Daphnla magna
Midge.
Chlronomus pluroosus
Brook trout,
Salvellnus fontlnalls
Brook trout,
Salvellnus fontlnalls
Brook trout,
Salvellnus fontlnalls
Fathead minnow,
Plmephales promelas
Fathead minnow (fry),
Plmephales promelas
Fathead minnow,
Plmephales promalas
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Channel catfish,
1 eta 1 urus punctatus
Channel catfish,
1 eta 1 urus punctatus
Channel catfish.
14 days
20 days
161 days
It days
161 days
30 days
30 days
7 days
24 days
16 days
5 days
12 days
29 days
Reduced
reproduct Ion
Delayed
emergence
Growth Inhibition
and mortality
LTC«
Decreased
reproduct Ion
(embryo viability)
Growth Inhibition
Growth Inhibition
LTC
LTC
LTC
LTC
LTC
LTC
0.12
3.2
0.288
4,1
0.068
0.097
0.054
5.3
2.6
1.5
15.2
3.7
1.9
Reference





Sanders, 1980




Sanders, 1980




Mayer, et a).  1975




Mayer, et a I,  1975




Mayer, et al.  1975





Mayer, et a I.  1977




Mayer, et al.  1977




Mayer, et al.  1977




 Johnson  & Julln, 1980




 Johnson  & Julln, 1980




 Mayer, et al.  1977




 Johnson & Julln, 1980




 Johnson & Julln, 1980
                                 Ieta Iurus punctatus

-------
Table 6.  (Continued)
W
to
00
Species
Channel catfish,
Ictalurus punctatus
Channel catfish (fry),
Ictalurus punctatus
Blueglll,
Lepomls macrochlrus
Blueglll,
Lepomls Itaacrochlrus
Eastern oyster,
Crassostrea vlrglnlca
Eastern oyster,
Crassostrea virgin lea
Mactrld clam,
Rang la cuneata
Blue crab,
Calllnectes sapldus
Grass shrimp,
Pa 1 aemonetes puglo
PlnK shrimp,
Penaeus duorarum
Brown shrimp,
Penaeus aztecus
Mysld shrimp,
Mysldopsls bah la
Duration
Result
Effect (u
-------
                                Table $.   (Continued)
                                Longnose kllllflsh
                                (fry 48 hrs),
                                .Fundulus s(mills
K>
VO
Duration          Effect

  28 days    LC50
Remit
(yg/l)     Reference

  1.3      Schlmmel, et al.  1977
Longnose kllllflsh
(Juvenile),
Fundulus slmllls
Longnose kllllflsh
(adult),
Fundulus slmllls
Spot,
Leiostomus xanthurus
Spot,
Leiostomus xanthurus
White mullet,
Mug II curema
28 days
14 days
144 hrs
2 days
2 days
LC50
95| mortality
50* mortality
LC50
LC50
0,9
1.7
0.5
1.0
5.5
Schlnmel, et at.
Schlmel, et al,
Lowe, 1964
Butler, 1964
Butler, 1963
1977
1977


                                * LTD » lethal  threshold concentration

-------
                                  REFERENCES

Butler,  P.A.   1960.   Effect  of  pesticides  on  oysters.   Natl.  Shellfish
Assoc.  51: 23.

Butler, P.A.   1963.   Commercial  fisheries  investigations,  pesticide-wildlife
studies: A  review of  Fish  and Wildlife  Service  investigations during  1961
and 1962.  U.S. Dep. Inter.  Fish Wild!. Circ.   167:  11.

Butler, P.A.   1964.   Pesticide-wildlife  studies,  1963:  A review of  Fish and
Wildlife Service  investigations  during the calendar year.  U.S.  Dep.  Inter.
Fish Wild!. Circ.  199: 5.

Chaiyarach, S., et  al.  1975.  Acute toxicity of the  insecticides  toxaphene
and  carbaryl  and the  herbicides propanil  and  molinate to  four species  of
aquatic organisms.  Bull. Environ. Contain. Toxicol.   14: 281.

Cohen, J.M., et al.   1960.   Effect of fish poisons on  water  supplies.  Part
1, Removal of toxic materials.  Jour. Am. Water Works Assoc.  52:  1551.

Courtenay,  W.R.,  Jr. and M.H.  Roberts,  Jr.  1973.  Environmental  effect on
toxaphene  toxicity  to selected fishes and crustaceans.   EPA-R3-73-035.  U.S.
Environ. Prot. Agency.

Davis, H.C. and H.  Hidu.   1969.   Effects of pesticides on embryonic develop-
ment of clams and  oysters  and on survival and  growth of  the  larvae.  U.S.
Dep.  Inter., Fish Wildl.  Bull.  67: 393.
                                     B-30

-------
 Finney, D.J.  1971.  Probit Analysis..  University Press, Great Britain.

 Goodman, L.R., et  al.   1978.   Effects  of heptachlor and toxaphene on labora-
 tory-reared  embryos  and fry of  the sheepshead minnow.  30th  Annu.  Conf. SE
 Assoc. Game  Fish Comm.  p. 192.

 Hansen, D.   1980.  Memorandum to C.E. Stephan.  U.S. EPA.  July.

 Henderson, C., et  al.   1959.   Relative toxicity of ten chlorinated hydrocar-
 bon insecticides to four species of fish.  Trans. Am. Fish. Soc.  88: 23.

 Isensee, A.R., et  al.   1979.   Toxicity and fate of  nine toxaphene fractions
 in an aquatic ecosystem.  Jour. Agric.  Food Chem.  27:  1041.

 Johnson, W.W. and A.M.  Julin.  1980.   Acute toxicity of toxaphene to fathead
 minnows,  channel  catfish, and  bluegills.  EPA-600/3-80-005.   U.S.  Environ.
 Prot. Agency.

 Katz, M.   1961.   Acute toxicity of  some organic insecticides  to  three  spe-
 cies of salmonids  and  to  the  threespine stickleback.  Trans. Am.  Fish.  Soc.
 90: 264.

 Khattat, F.H. and S. Farley.  1976.  Acute toxicity  of certain  pesticides to
Acartia tonsa Dana.  EPA-600/3-76-003.   U.S. Environ. Prot.  Agency.

Korn,   S.   and  R.  Earnest.   1974.   Acute  toxicity of 20  insecticides  to
striped bass, Morone  saxatilis.   Calif. Fish Game.   60:  128.
                                     B-31

-------
Lowe, J.I.   1964.   Chronic exposure of  spot,  Leiostomus xanthurus, to  sub-
lethal  concentrations  of  toxaphene  in   seawater.   Trans.  Am.  Fish.  Soc.
93: 396.

Lowe, J.I., et al.  1970.  Chronic exposure of  oysters  to  DDT,  toxaphene and
parathion.  Proc. Natl. Shellfish Assoc.   61:  71.

Macek, K.J.  and  W.A.  McAllister.  1970.   Insecticide susceptibility of  some
common fish family representatives.   Trans.  Am.  Fish.  Soc.   99:  20.

Macek, K.J., et al.  1969.  The  effects  of  temperature  on  the susceptibility
of bluegills and rainbow  trout  to selected pesticides.  Bull.  Environ.  Con-
tarn. Toxicol.  4: 174.

Mahdi, M.A.  1966.  Mortality of some species of fish  to  toxaphene  at three
temperatures.  U.S. Dep. Inter.  Fish Wild!.  Ser.  10:  1.

Mayer, F.L., et  al.  1975.  Toxaphene effects  of reproduction, growth,  and
mortality of brook trout.  EPA-600/3-75-013.  U.S. Environ. Prot. Agency.

Mayer, F.L., et  al.  1977.  Toxaphene:  Chronic toxicity to  fathead minnows
and channel catfish.  EPA-600/3-77-069.  U.S.  Environ.  Prot. Agency.

McKenzie, M.D.   1970.   Fluctuations in  abundance  of  the blue  crab  and  fac-
tors  affecting mortalities.  South  Carolina Wild!. Resour. Dep.  Tech.  Rep.
1: 27.
                                     B-32

-------
Nimmo,  D.W.   1977.   Toxaphene:   Its  effects   on   mysids.    Memorandum  to
F. Hagtnan.  U.S. Environ. Prot. Agency,  Washington,  O.C.

Parrish,  P.R.,  et  al.   1978.   Chronic  toxicity of chlordane,  trifluralin,
and   pentachlorophenol   to  sheepshead   minnows   (Cyprinodon   variegatus).
EPA-600/3-78-010.  U.S. Environ. Prot. Agency.

Sanders,  H.O.   1969.   Toxicity of  pesticides  to   the  crustacean  Gammarus
lacustris.  Tech. Pap. No. 25.   Bur. Sport Fish. Wild!.  January.

Sanders,  H.O.   1972.  Toxicity  of  some  insecticides to four  species of mala-
costracan crustaceans.  Tech. Pap. No. 66.  Bur. Sport Fish.  Wild!.  August.

Sanders,  H.O.   1980.   Sublethal effects  of  toxaphene on  daphnids,  scuds, and
midges.   EPA 600/3-80-006.  U.S. Environ. Prot. Agency.

Sanders,  H.O. and O.B.  Cope.   1966.   Toxicities of  several  pesticides to two
species of  cladocerans.  Trans. Am. Fish. Soc.  95:  165.

Sanders,  H.O.  and  O.B.  Cope.  1968.   The relative  toxicities  of several
pesticides  to  naiads  of  three  species of  stoneflies.  Limnol.  Oceanogr.
13:  112.

Schimmel, S.C., et al.   1977.   Uptake and toxicity  of  toxaphene  in several
estuarine organisms.  Arch. Environ.  Contam. Toxicol.  5: 353.
                                      B-33

-------
Schoettger, R.A.   1970.   Progress in  sport fishery research.   Fish-Pestic.
Res. Lab. U.S. Oep. Inter. Bur. Sport Fish Wildl.  Resour.  Publ.   106.

Ukeles,  R.   1962.   Growth of  pure cultures of  marine phytoplankton  in  the
presence of toxicants.  Appl.  Microbiol.  10:  532.

U.S. EPA.  1980.   Unpublished  laboratory  data.   Environmental Research Lab.,
Duluth, Minnesota.

U.S. Food  and  Drug Administration.   1979.   Administrative Guideline 7420.08,
Attachment K, July 5.
                                     B-34

-------
Mammalian Toxicology and Human Health Effects
                             EXPOSURE
Ingestion from Water
     Several,  routine  monitoring studies of  United States surface
waters conducted prior to 1975 did not detect toxaphene  (Brown and
Nishioka,  1967;  Lichtenberg, et  al. 1970;  Manigold and Schulze,
1969; Mattraw, 1975;  Schafer,  et al. 1969;  Schulze,  et al.  1973;
Weaver,  et al.  1965).    Lichtenberg (1971)  and Schulze,  et al.
(1973) placed the  toxaphene lower detection limit at  0.5  to 1.0
yg/1, whereas other organochlorides can  be  detected  near  concentra-
tions two orders of magnitude lower.
     Toxaphene,  however,  had been  detected before  1975 in water
around areas  where  it was applied  to crops as an insecticide.  In
California, Johnston, et al. (1967) detected toxaphene residues in
60  of 61  analyses of  surface  effluents  in Panoche  Drain  Water
(average 2.009 ug/1 and range of 0.100 to  7.900  ug/1) and in 13 of
66 analyses of San Joaquin Valley tile drainage  effluents (average
0.528 ug/1 and range of  0.130 to 0.950 yg/1).  Also,  in California,
Bailey and Hannum  (1967) found toxaphene in 17 of 26 surface water
samples  (average concentration  0.23  ug/1).   The San Joaquin Dis-
trict, California Department of Water Resources  (1963-1969) detect-
ed  toxaphene  in 51  of  422  (12 percent)  tile  drainage effluents
(0.02  to 0.5  ug/1),  in  216 of 447  (48  percent)  surface drains in
Central Valley  (0.04  to 71.00 ug/D, in 88 of 712  (12 percent) of
Central Valley surface waters (0.02  to 0.93 ug/1), and in 8 of 200
(4 percent) California bays and surface waters.
                               C-l

-------
     In Alabama, the Flint Creek watershed was monitored during the
years 1959  to 1965  (Cohen,  et al.  1961;  Grzenda  and  Nicholson,
1965; Grzenda,  et  al.  1964; Nicholson,  1969;  Nicholson,  et  al.
1964, 1966).  This watershed drains an agricultural district where
the major  pesticide source  is  from small cotton  farms  which  are
major users of  toxaphene (Nicholson, et  al.  1964).  During this
study,  toxaphene  was  detected   (carbon  absorption  followed  by
chloroform extraction) in paired samples of raw  Flint Creek water
and treated drinking water  obtained from Flint  Creek.   Toxaphene
concentrations ranged from the limits of detection to 0.410 ug/1,
with a mean of approximately 0.07 ug/1.   However, since  the recov-
ery was approximately 50 percent  (i.e., 48 percent for  the 1 ng/1
spiked  samples  and 42 percent  for the 0.5 ng/1 samples), actual
residues may have averaged about 0.14 ug/1.   The toxaphene concen-
trations in treated  and  untreated  water samples  were not signifi-
cantly different, indicating that treatment of drinking  water does
not reduce toxaphene concentrations.
     Although Mattraw  (1975)  did  not detect  toxaphene  in surface
water in an organochlorine residue  survey in Florida, toxaphene was
found in 3.2 percent of the sediment samples (claimed lower detec-
tion  limit of  0.05  ug/D •   Barthel,  et al.  (1969) also found
detectable toxaphene residues in sediments at  11  sites on the lower
Mississippi River.  Herring and Cotton (1970) detected toxaphene in
11 of 20 Mississippi Delta Lakes at a maximum concentration  of 1.92
ug/1.   Sediments from 10 of  these lakes  had a  maximum  toxaphene
concentration of 2.46 ug/1*
                               C-2

-------
      Toxaphene  contamination also has  been documented in an  area
"surrounding  a toxaphene manufacturing  plant.   The University  of
 Georgia. Marine  Institute   (Reimold,  1974;  Reimold  and Durant,
 1972a,bf  1974?  Durant and  Reimold,  1972)  has monitored  toxaphene
 contamination in surface waters,  sediment,  and  biota of waters re-
 ceiving the  effluent of  the Hercules, Inc. plant which is located
 on Terry Creek,  Brunswick,  Georgia and is  the  largest producer  of
 toxaphene  in  the United States.  The average monthly toxaphene  con-
 centration in the  plant's  effluent has decreased  from a high  of
 2,332 yg/1 in August 1970  to a low of 6.4 yg/1  in  June 1974.   Dye
 experiments  have shown that the  effluent  is diluted by a  factor  of
 10 after it  reaches  Terry  Creek  (Reimold,  1974).   The  Institute
 (Reimold and Durant, 1972a,b; Durant and Reimold,  1972)  analyzed
 sediment at  three  locations downstream  of  the  plant   outfall.
 Samples were collected prior to a dredging operation in  June  1971
 at three sites  downstream:   0.2  miles from the  outfall at a loca-
 tion  50 yards from  an  intersection with another creek;  0.8 miles
 from  the plant outfall; and 1.4 miles from the plant outfall  and  50
 yards  from  the  end  of  Terry Creek  (junction  with Back River) .
 Reimold and Durant  (1972b)  measured 32.56 ug/1 as the average toxa-
 phene concentration  in  sediment cores within  Terry Creek  Marsh.
 The highest residue concentration measured in the surrounding water
 was 15 ug/1  before  dredging.
      Recently,  a  survey of commercial drinking  water samples  con-
 ducted by the  U.S.  EPA  (1976a)  during  1975  and  1976  found  no
 detectable levels  of toxaphene in 58 samples;  the  limit  of  detec-
 tion  was 0.05 ug/1.
                                C-3

-------
Ingestion from Food
     Estimates of  toxaphene exposure  from dietary  intake  can be
made from the U.S.  Food and Drug Administration  (FDA) market basket
survey, the  FDA  survey  of unprocessed food  and feed samples, and
the U.S. Department of Agriculture (USDA) survey of meat and poul-
try.   In  the FDA market basket survey,  food samples are prepared
for consumption (i.e., cooked or otherwise processed) prior to mon-
itoring for  pesticide residues  (Duggan and McFarland,  1967).   The
market  basket  items are grouped  by  commodity  class  (e.g.,  dairy
products, leafy vegetables, legume vegetables) and are intended to
represent a  2-week  diet for a 16- to 19-year-old male  (Duggan and
Corneluissen,  1972).   The  results  of  these surveys,  from their
inception to the most recently published report, are summarized in
Table 1.  From 1964 to 1972,  food samples  were obtained from five
cities:  Boston,  Mass., Baltimore, Md., Los Angeles, Calif., Kansas
City,  Mo.,  and  Minneapolis,  Minn.   Of the 26  positive  samples
encountered during  this period,  there were 19 in Los Angeles, 4 in
Baltimore,  and  1  each  in  Boston,  Minneapolis and Kansas  City.
Based  on  the estimates of  daily  intake made  by Duggan and  Cor-
neluissen (1972)  and assuming an average body weight of 70 kg, the
estimated daily  dose of dietary toxaphene  over  the  period  of June
1964 to April 1970 was 0.021 ug toxaphene/kg  body weight/day.  This
estimate is based on food samples from a limited number of cities,
most of which are not located in areas of high toxaphene  usage.  The
more recent (1972 to 1975)  results of the market basket survey sug-
gest  that  the  current  daily  dietary  dose  may  be substantially
lower;  however,  it  is equally possible that  the dietary doses for
                               C-4

-------
                                                            TABLE 1

                                   Toxaphene Residues Found in Food and Drug Administration
                                              Market Basket Survey, 1964  to 1975*
     Monitoring
       Period
 No. of     No.  of
Composite  Coraposits
           Positive
    %       Commodities Contaminated
Occurrence    (No. of composits of
           each commodity contaminated)
 Range of    Daily
 Levels      Intake
 (mg/kg)
Reference
June 1964-April 1965    216        0

June 1965-April 1966    312        3


June 1966-April 1967    360        0


June 1967-April 1968    360        4



June 1968-April 1969    360       13
                         0.0

                         1.0


                         0.0


                         1.1



                         3.6
           Leafy vegetables(1)
           and garden fruits(2)
           Meat, fish, or poultry(l),
           leafy vegetables(l), and
           garden fruits(2)

           Garden fruits(6), meat, fish,
           or poultry(l), legume vege-
           tables (2),  root vegetables
           (1), and  leafy vegetables(3)
             0      Duggan, et al. 1966

0.048-0.38   0.002  Duggan, et al. 1967
             0      Martin and Duggan,
                      1968

0.064-0.375  0.002  Corneliussen, 1969
0.022-0.33   0.004  Corneliussen, 1970
n June 1969-April 1970 360 * 1.1 Leafy vegetables(2) and
1 garden fruits{2)
Ul
June 1970-April 1971 360 1 0.3 Root vegetables (1)

June 1971-July 1972 420 1 0.2 Leafy vegetables (1)
Aug. 1972-July 1973 360 0(1)** 0.0

Aug. 1973-July 1974 360 3 0.8 Garden fruits(3)

Aug. 1974-July 1975 240 1 0.4 Leafy vegetables (1)
0.080-0.132 0.001 Cocneliussen, 1972
trace Manske and Cornelius
sen, 1974
0.1 Manske and Johnson,
1975
(0.005)** Johnson and Manske,
1975
trace-0.163 Manske and Johnson,
1976
0.118 Johnson and Manske,
1977
 *Source: Duggan  and Corneliussen,  1972
 **Strobane

-------
 individuals  located  in the Mississippi Delta  (an area of high toxa-
~phene  usage)  could be substantially  higher.
     The U.S. EPA (1977) recently compiled the  results  of  the FDA
 survey on unprocessed   food  and  feed  samples.    As indicated  in
 Table  2, the percent of  occurrence  of toxaphene  contamination sug-
 gests  a low  incidence of contamination.
     The only published  information encountered  in the USDA survey
 of meat and  poultry is  contained in  the World Health Organization
 (WHO,  1974a) monograph  on  toxaphene.  This  information is summa-
 rized  in Table 3.
      Similar but unpublished information covering  the years 1973 to
 1978 has been  obtained  from the  USDA (1978)  and  is summarised in
 Table  4.  These data indicate that toxaphene is found consistently
 from year to year in the fat of  cattle,  although  the incidence of
 contamination  is extremely  low.   During  this  survey period, only
 six samples were in excess  of the  tolerance  limit  (7.0 mg/kg; see
 Existing Guidelines  and Standards section).  Of  these six viola-
 tions,  five were in fat samples from cattle, one of  which occurred
 in  the first  quarter  of 1978.   The data summarized  in Tables  3
 and 4  indicate that toxaphene is not a  widespread  contaminant in
 meat  and poultry products.
       As detailed in the Aquatic Toxicology section of this  criteria
 document, toxaphene in water can  be bioconcentrated in  fish by fac-
 tors  of 50,000 and more, based on laboratory studies  and  measure-
 ments of whole  body residues.   However, in  assessing potential
 human dietary exposure, the primary concern is with residues bio-
 concentrated in the edible portion or fillet.   Working with  adult
                                 C-6

-------
                                                   TABLE 2



                       Toxaphene Residues Found in Food and Drug Administration Survey

                             of Unprocessed Food and Feed Samples, 1972 to 1976*
o
i
Year
1972

1973

1974
1975
1976
No. of
Commodities
Contaminated
10

15

8
12
15
No. of
Samples
Checked
3516

2906

1919
2317
4228
No. of
Positive
Samples
118

150

109
118
257
No. of
Occurrence
3.3

4.8

4.6
5.0
6.0
Commodity most
Frequently
Contaminated
Leaf & Stem
Vegetables
Leaf & Stem
Vegetables
Fish
Fish
Fish
         *Source:  U.S.  EPA,  1977,

-------
                                               TABLE 3

                         Residues of Toxaphene in Meat  and  Poultry  Products'
a

00
Species
Meat
Cattle
Calves
Swine
Sheep
Goats
TOTAL
Poultry
Young chickens
Mature chickens
Turkeys
Ducks
Geese
Other
TOTAL
No,
1969

739
142
1964
312
12
3169

1909
78
169
42
1
_
2199
of Tissues
Analyzed
1970(6 mos)

583
67
1076
137
8
1871

1405
67
8
2
4
1486
No. with
1969

712
141
1741
303
10
2907

1898
77
164
41
1
-
2181
a Residue
1970 (6 mos)

NA*
NA
NA
NA
NA
1721

NA
NA
NA
NA
NA
NA
1472
No. with
Toxaphene

1969 1970

2
0
0
0
0
2

2
0
0
0
0
0
2

0
0
2
1
o.
3

0
0
0
0
0
u
0
      aSource:  World Health Organization,  1974a
      *Breakdown by species not available  from 1970 interim report

-------
                                                          TABLE 4

                             Residues of Toxaphene in Fat Samples of Meat and Poultry Products
                                             at  Slaughter  in  the  United  States4
Number of Positive Samples/Total Number
O
1
vo








Animal
Cattle
Calves
Sheep & Goats
Swine
Chicken
Turkeys
Ducks & Geese
Rabbits
Horses
TOTAL
1973
9/710
1/84
2/289
4/232
3/530
3/517
0/95
0/19
0/44
22/2520
(1.27)
(1,19)
(0.69)**
(1.72)
(0.57)
(0.58)
(0.0)
(0.0)
(0.0)
(0.87)
1974
2/1117
0/284
1/371
2/329
1/1138
0/735
0/148

3/266
9/4388
(0.18)
(0.0)
(0.27)
(0.61)
(0.09)
(0.0)
(0.0)

(1.13)
(0.21)
1975
3/1733
0/269
0/356
0/324
0/777
0/554
0/246
0/11
0/261
3/3971
(0.17)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.08)
of Samples (*)
1976
3/1785
0/327
0/250
1/442
0/927
0/456
0/267
0/65
0/217
4/4736
(0.17)
(0.0)
(0.0)
(0.23)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.08)
1977
4/880
0/124
0/100
0/215
1/375
0/303
0/186
0/21
0/112
5/3216
(0.45)
(0.0)
(0.0)
(0.0)
(0.27)
(0.0)
(0.0)
(0.0)
(0.0)
(0.22)
1978*
1/432
0/62
0/36
0/179
0/191
0/64
0/39
0/14
0/20
1/1037
(0.23)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.10)
  Source: U.S. Department of
 *first two quarters only
**listed as lamb
Agriculture, 1978

-------
brook trout, Mayer, et al. (1975) found that toxaphene was biocon-
centrated in the fillet by a  factor of 8,000 when fish were kept in
water containing toxaphene at  0.5 yg/1  for  161 days.   The biocon-
centration factor  for  the fillet was less than  2,400.   Toxaphene
residues found  in  fish from  toxaphene-treated lakes are generally
consistent with levels  obtained during laboratory studies and indi-
cate  that  fish  bioconcentrate toxaphene by  a factor  of several
thousand.  For  example,  Terriere,  et al. (1966)  found  that total
mean body residues in rainbow  trout in lakewater were several U9/9
compared to approximatley 0.5 ug/1 in water (bioconcentration fac-
tor of  9,000  to 19,000),  which is comparable to the bioconcentra-
tion  observed  experimentally by Mayer,  et  al.  (1975)  with total
body residues in brook trout.
     A bioconcentration factor (BCF)  relates the concentration of a
chemical in aquatic  animals  to the concentration  in  the  water in
which they  live.   The steady-state BCFs  for  a lipid-soluble com-
pound in the tissues  of various aquatic animals  seems to be propor-
tional  to  the  percent  lipid  in the tissue.   Thus, the per capita
                                      •
ingestion of a lipid-soluble  chemical can  be estimated from the per
capita consumption of fish and shellfish,  the  weighted average per-
cent lipids of consumed fish and shellfish, and a  steady-state BCF
for the chemical.
     Data from a recent survey on fish and shellfish consumption in
the United States was  analyzed  by  SRI   International  (U.S.  EPA,
1980).  These data were  used to  estimate that the per capita con-
sumption of  freshwater and  estuarine  fish  and shellfish  in  the
United  States  is  6.5  g/day  (Stephan,  1980).   In addition, these
                               C-10

-------
 data were  used with data on the fat content of the edible portion of
 the  same  species  to estimate  that the  weighted  average  percent
 lipids  for consumed  freshwater  and estuarine fish  and shellfish is
 3.0  percent.
      Two laboratory  studies,  in which  percent  lipids and a steady-
 state BCP  were measured,  have  been conducted  on  toxaphene.   The
 mean of  the BCF values, after normalization to 1 percent lipids, is
 4,372 (see Table  5  in Aquatic Toxicology, Section B).   An  adjust-
 ment factor  of  3  can be used to adjust the mean normalized  BCF to
 the  3.0  percent lipids that  is  the  weighted average for  consumed
 fish and shellfish.   Thus,  the weighted average  bioconcentration
 factor  for toxaphene  and  the edible portion of all  freshwater  and
 estuarine  aquatic organisms  consumed by Americans  is calculated to
 be 13,100.
 Inhalation
      The highest toxaphene residues in air have been found in areas
 where toxaphene  is  applied  for  agricultural purposes  (especially
 cotton  production)  (Arthur,  et  al.  1976;  Miss. Agric.  Exp.  Sta.,
 1976; Stanley, et al. 1971; Tabor,  1965 and  1966).  Studies  in cot-
 ton  growing  areas demonstrate  that  airborne  residues are highest
 during the  cotton  growing  season and decrease to lower levels  after
 harvesting, but spring  tilling  releases soil residues to the air.
 The recent  identification  of  toxaphene  at ng/m   concentrations over
 the  Atlantic  Ocean, where it has not been applied,  indicates that
 toxaphene residues move with air currents analagous  to DDT  (Bidle-
man,  et al. 1976;  Bidleman and Olney, 1975).
                              Oil

-------
     Arthur,  et al.  (1976)   reported  a  3-year  (January  1972 to
December  1974)   study  of  toxaphene  air  residues  at  Stoneville,
Miss.,  which  is located  in  the southern cotton  belt.   Over  this
period, toxaphene concentrations were  highest in August  (1,540.0,
268.8,  and 903.6  ng/m  )  and  lowest  in  January  (0.0,  0.0,  10.9
ng/m ).  The mean monthly concentration  was 167 ng/m .  In  a  more
recent  unpublished  survey of the Mississippi area, conducted  from
January 1976 to  July  1976, the mean  measured toxaphene concentra-
tion in air was 18.7 ng/m ,  with  the  highest concentration found
during June and July  (42.09 ng/m )  (Miss. Agric. Exp. Sta.,  1976).
Earlier  studies  (Tabor,  1965,  1966)  conducted  in seven  southern
agricultural  communities detected  toxaphene at  only  two  sites:
Leland, Miss., where toxaphene levels ranging from 1.2  to  7.5 ng/m
were found in 6 of 15  samples  from July  to September  1963;  and
Newellton,  Tex., where  toxaphene  levels  ranging  from 3.1  to 15
ng/m  were found in  6 of 10 samples.  Both of these  communities  were
in cotton  growing areas.
     Comparative geographic  studies of   toxaphene  air concentra-
tions  suggest  that toxaphene  contamination is  most  pervasive in
southern states.  From 1967 to 1968 Stanley, et  al.  (1971)  attempt-
ed to  monitor  toxaphene at nine locations:   Baltimore,  Md.;  Buf-
falo, N.Y.; Dothan, Ala.; Fresno, Calif.; Iowa City, Iowa;  Orlando,
Fla.;  Riverside, Calif.;  Salt Lake City,   Utah;  and  Stoneville,
Miss*   Toxaphene was  found  in  only three  locations,  all  in the
southern part of the country:  Dothan  (11 of 90 samples at 27.3 to
79.0 ng/m3), Orlando  (9 of 79  samples  at  20.0 to 2,520 ng/m3), and
Stoneville  (57 of 98  samples  at 16.0 to  111.0 ng/m ).   Similarly,
                               C-12

-------
Bidleman, et al.  (1976) monitored toxaphene at five sites  in North
America.   As indicated in  Table  5,  the more  southern sites evi-
denced considerably higher  concentrations of toxaphene.
     Toxaphene has also been  monitored  in the  atmosphere over  the
east  coast of  the U.S,,  near Bermuda,  and- over  the open ocean
(Bidleman and Olney,  1975).  With respect to the above discussion
of geographic distribution and since substantial amounts  of toxa-
phene are used in the  South on cotton, it is not too  surprising that
a sample taken at Sapelo Island, Ga.  is  substantially greater  (mean
of  2.8  ng/m3)  than  the  samples  taken  at  Bermuda  (mean  of 0.79
ng/m3) or over the open ocean  (mean  of  0.53 ng/m  ).
     These monitoring  studies clearly suggest  that toxaphene is  a
prevalent atmospheric  contaminant in areas  where  this pesticide is
used, particularly in  the southern United States.   Taking  the mean
monthly  toxaphene concentration  of  167 ng/m  noted  by Arthur,  et
al.  (1976) over  a 3-year  period in Stoneville, Miss., and  assuming
 (1)  that the average  human weighs 70 kg and breathes 24 m  of  air
per day and (2)  that all of the  toxaphene breathed into the  lungs is
absorbed,* the average daily dose of toxaphene from air is  approxi-
mately  0.057 ug/kg.**  This  is approximately  twice  the estimated
daily  intake of  toxaphene  from the  diet (see Ingestion from Food
section)  based  on the FDA  1964 to 1970 market basket survey.   An
  'Assuming  100  percent   absorption  is  common EPA  policy, but in
   this  case is  very  conservative since  human studies of  occupa-
   tionally  exposed individuals suggest no  absorption (see Absorp-
   tion  section).
**It should be noted  that  0.057  ug/kg  is a maximum  or worst  case
   value  due  to  (1) assumption of  100 percent absorption and (2)  use
   of a mean monthly toxaphene  concentration from a high  toxaphene
   use  area.
                               C-13

-------
                                      TABLE  5



           Toxaphene Residues  in Air  Samples  at  Five North American  Sites*
Location and Date
Kingston, Rhode Island, 1975
Sapelo Island, Georgia, 1975
Organ Pipe Cactus National Park, Arizona, 1974
o Hays, Kansas, 1974
*• Northwest Territories, Canada, 1974
Number
of
Samples
6
6
6
3
3

0
1
2
0
0
Range
(ng/m3
.04 -
"7 _.
,7 -
.083 -
.04 -
,
0.
5.
7.
2.
0.

4
2
0
6
13
*Source: Bidleman, et al.  1976

-------
average national  level of toxaphene  exposure from  air  cannot be
estimated from  the available data.   However, taking  the average
concentration monitored by Bidleman and Olney (1975) over the open
ocean (0.53  ng/m3), the daily intake of  toxaphene  from air would be
0.18 ng/kg.
Dermal
     No direct information is available on the importance  of dermal
absorption in total human exposure to  toxaphene.   Data from toxi-
city  studies  with  laboratory mammals  (see  Acute,  Subacute,  and
Chronic Toxicity section) indicate that toxaphene can  be absorbed
across the skin in toxic amounts  by humans.  However, incidences of
dermal absorption of toxaphene by humans are restricted to occupa-
tional or accidental exposures to large amounts of toxaphene.  For
those exposed to  only  background levels of  toxaphene,  dermal ab-
sorption is not likely to be a significant route of entry.
                         PHARMACOKINETICS
Absorption
     The  recently  completed U.S.  EPA  (1978) study  suggests cnat
inhalation exposures to  toxaphene do not result  in sufficient ab-
sorption by humans to cause quantifiable levels in the blood.  The
study found no  detectable  levels of  toxaphene in  the  blood  of 54
workers occupationally  exposed to  toxaphene.   However, of 53 per-
sonal air samples  analyzed, 30 had quantifiable levels of toxaphene
and 19  had  trace  levels.   In the  same  study, one individual not
occupationally  exposed to  toxaphene  was  found  to  have  elevated
toxaphene blood levels  associated with the  consumption  of  toxa-
phene-contaminated  fish  (see Excretion  section),  indicating sig-
nificant absorption after oral exposure.

                              C-15

-------
      Inferences  on the absorption of toxaphene by  laboratory  mam-
mals  can be made from some of the available toxicity data.  Absorp-
tion  across  the alimentary  tract,  skin,  and respiratory tract  is
indicated by the adverse effects elicited  by toxaphene after oral,
dermal,  and  inhalation exposures.   Based  on toxicity studies de-
tailed  in  the  Acute, Subacute, and  Chronic Toxicity section, the
vehicle used in the administration of toxaphene has a marked influ-
ence on lethality.   This effect is probably attributable  to differ-
ences in the extent  and/or rate of absorption.  In  oral  exposures,
toxaphene has a much lower LD5Q when administered  in  a readily ab-
sorbed vehicle, e.g., corn oil or peanut oil,  than  when given in  an
indigestible vehicle such as kerosene.  Similarly,  dermal applica-
tions of  toxaphene in solution with  mineral oil,  dimethyl phtha-
late, or  water  are much more  toxic than  similar  applications  of
toxaphene in powder  preparations  (Lackey,  1949a,b; Conley, 1952).
Documented cases of human poisoning by toxaphene indicate that man
may absorb toxic levels following oral,  dermal,  or  inhalation expo-
sures {McGee, et al. 1952;  Pollock,  1958? Warraki,  1963).   When
administered or  applied  in  comparable  lipophilic  solvents,  the
ratio of oral LD5Q to dermal LD5Q is about 0.1 (Tables  6 and 7).
This  suggests  that  toxaphene  is  absorbed  more completely and/or
more  rapidly from  the alimentary tract  than  from  the skin.   The
pronounced variability in  time to  death after toxaphene  ingestion
indicates marked individual  differences in the rate  of  toxaphene
absorption and/or differences in susceptibility  to toxaphene intox-
ication.
                              C-16

-------
O
                                                  TABLE  6
                      Acute Oral Toxicity of Technical Toxaphene to Laboratory Mammals
             Organism
       Rats:
         Unspecified strain
         Wistar, male,
         (3-4 weeks, 50-60 g)
         fasted
         Sherman, male,
         (i>90 days,>. 175 g)
         fasted
         Sherman, female,
         (:»90 days,>-175 g)
         fasted
        Mice

        Cats

        Dogs



        Rabbits
        Guinea Pigs
    Vehicle
         *+ standard error.
        **9~5 percent confidence
 Unspecified

 Cottonseed oil

 Peanut oil

 Peanut oil

 Peanut oil
 Peanut oil
 Corn oil
 Corn oil
 Corn oil
 Unspecified oil
 Peanut oil
 Unspecified oil
 Peanut oil
 Corn  oil
 Unspecified oil
 Peanut oil
 Corn  oil
 Unspecified oil

interval.
   LD50
 (mg/kg)
                                                                              Reference
       69       Lehman,  1951

 220 + 33*     Boyd and Taylor,  1971


90(67-122)**   Gaines,  1960

 80(70-91)**   Gaines,  1960

       40      Shelanski and Gellhorn, undated
       90      Hercules Inc., undated
  120-125      Shelanski and Gellhorn, undated
       60      Hercules Inc., undated
       112      Hercules Inc., undated
       80      Rico, 1961
     25-40      Hercules Inc., undated
       100      Rico, 1961
       25      Lackey,  1949a
       49      Hercules Inc., undated
       100      Rico, 1961
    75-100      Hercules Inc., undated
       270     Hercules Inc., undated
        80     Rico,  1961

-------
                                                TABLE 7
                                               i


                       Acute Dermal Toxicity of Toxaphene  to Laboratory  Mammals
o
i
M
oo
Organism
Rats
Sherman, male,
O-90 days, >- 175 g)
unfasted
Rats
Sherman, female,
O-90 days, >*175 g)
Rats
Rabbits
Rabbits
Vehicle

Xylene

Xylene
Xylene
Dust
Peanut
oil
Dose
(mg/kg)

1075
(717-1613)

780
(600-1014)
930
p>4000
<250
Response

LD50
(95% Confidence
Interval)

LD5Q
(95% Confidence
Interval)
LD50
LD5Q
LD5Q
Reference

Gaines, 1960 and 1969

Gaines, 1960 and 1969
Hercules, Inc., undated
Hercules, Inc. , undated
Hercules, Inc., undated

-------
Distribution
     Toxaphene  is readily  distributed throughout  the body,  with
highest  residues  found in  fat  tissue.   Three  hours  after  single
intubations  of    Cl labeled  toxaphene in a mixture of peanut oil
and acacia, rats had detectable levels of   Cl activity in all tis-
sues examined  (kidney, muscle, fat,  testes,  brain, blood,  liver,
intestines,  esophagus, spleen,  and stomach).   The highest  levels
were found  in  the stomach and  blood.   By nine days after  dosing,
6.57 percent of the  administered  dose (measured as    Cl  activity)
remained  in  the organism, with most  of  the activity  found  in the
fat, blood, liver, and intestines (Crowder and Dindal,  1974).  In  a
similar single dose  study using rats,  with  corn oil as the  vehicle
                             14
(Ohsawa,  et al. 1975), both  C labeled toxaphene (8.5 mg/kg)  and
  C  labeled  2,2,5-endo-,  6-exo-,  8,9,10-heptachloroborane  (2.6
mg/kg)  (a component  of toxaphene) were found primarily in the fat,
liver,  kidneys, and blood after  14 and 9  days,  respectively.   These
patterns are consistent with toxaphene redistribution  from  the fat
via the  circulatory  system to  kidneys and  liver  prior to  urinary
and fecal elimination  (see Metabolism  and Excretion sections).
     The predominance  of fat storage has also been demonstrated in
12-week feeding studies with  rats  (Clapp,  et  al.  1971) and  2-year
feeding studies with rats and dogs (Lehman, 1952a; Hercules,  Inc.,
undated).  In all  these studies, toxaphene residues were highest in
fat tissue but remained below the levels administered  in the  diet.
This is consistent with the relatively rapid  elimination  of  toxa-
phene by mammals (see Excretion section).
                              C-19

-------
 Metabolism
      Toxaphene undergoes reductive  dechlorination,  dehydrochlori-
 nation,  and hydroxylation in mammalian systems.
      In  the study by Crowder and Dindal  (1974)  using  36C1 labeled
 toxaphene,  about 68  percent of  the  activity was  recovered as ionic
 chloride.   Similarly,  Ohsawa,  et al.  (1975)  found that  of seven
   Cl labeled  toxaphene  fractions  administered   by  intubation  to
 rats,  all were  dechlorinated by about 50  percent.   Based  on  the
 recovery of both  14C  and 36C1  labeled  toxaphene, these  investi-
 gators  concluded that only  3 percent  of  the original dose  is  ex-
 creted   unchanged  and  only  2  percent  is  eliminated  as  carbon
 dioxide.
     For technical  (i.e., commercial grade)  toxaphene, both  reduc-
 tive dechlorination and dehydrochlorination occur in reduced  bovine
 blood  hematin solutions, and 50 percent  dechlorination has been
 noted in toxaphene incubated with rat  liver microsomes and reduced
 nicotinamide  adenine dinucleotide phosphate (NADPH)  under anaero-
 bic  conditions (Khalifa,  et al. 1976).   Reductive dechlorination
 has  also been demonstrated   for  heptachloroborane,  a  component of
 toxaphene (Saleh, et al. 1977; Chandurkar, 1977;  Pollock, 1978).
     Toxaphene has  been shown  to .yield a  type  I binding spectra
with hepatic  cytochrome P-450  of rats,  mice, and rabbits,  which
suggests that  toxaphene may serve as  a substrate for  the hepatic
microsomal mixed-function oxidase system  (Kulkarni,  et al.  1975).
Type II  binding  has not been observed.  Metabolism by the hepatic
microsomal mixed  function oxidase  system is  further  suggested  by
the potentiation of toxaphene by piperonyl butoxide (Saleh,  et al.
                              C-20

-------
 1977)  and the demonstrated  NADPH  dependence for the  in  vitro  hy-
 droxylation  of  nonachloroborane   (a  toxaphene  component)  by  rat
 liver  microsomes  (Chandurkar,  1977).
     In  comparing the chromatographic patterns  of  toxaphene  resi-
 dues found  in  the liver,  feces,  and fats, both  Pollock  (1978)  and
 Saleh, et al.  (1977)  have noted that only fat  residues approximate
 those  of whole  toxaphene,  while   residues  in both  the liver  and
 feces  are consistently more  polar.
 Excretion
     The  half-life  of   C  or   Cl labeled toxaphene in  rats  after
 single oral doses appears to be from 1 to 3  days, with most of  the
 elimination occurring via the  urine and feces  (Crowder and Dindal,
 1974; Ohsawa, et  al.  1975).  Only  a small portion of the  urine  and
 fecal  metabolites are eliminated  as glucuronide  or   sulfate con-
 jugates  (Chandurkar,  1977).
     As  mentioned in the  Absorption section,  elevated  toxaphene
 blood  levels  in  one individual in the U.S.  EPA  (1978) study were
 associated  with   the  consumption  of toxaphene-contaminated  fish
 (catfish  fillet  with  a  toxaphene  residue of  52  yg/g  wet weight).
 On the first day  that blood  samples were taken, toxaphene  was  found
 in the blood  of  this individual  at a concentration of 142  ug/1-
Eleven days after this measurement, the concentration  of  toxaphene
 in the blood had  fallen to 47  ug/1.   By  14 days  after the initial
measurement, toxaphene blood levels were  below the limit of detec-
 tion (30  ug/1).
                              C-21

-------
                              EFFECTS
"Acute,  Subacute,  and  Chronic  Toxicity
      Information  on the acute oral toxicity of toxaphene to labora-
 tory animals  is summarized in Table 6.  In cases of acute intoxica-
 tion, toxaphene,  like  most  chlorinated hydrocarbon  insecticides,
 appears to act as  a central  nervous  system stimulant.   However,
 unlike  DDT,  toxaphene does not significantly affect  conduction  in
 the  rat  superior  cervical  ganglion   (Whitcomb  and  Santolucito,
 1976).   Published reports  of  cases of  acute poisoning of humans  by
 ingestion of  toxaphene are summarized  in Table 8.   In these cases,
 convulsions are the most consistent clinical signs of intoxication.
 Similar effects have been observed in  both rats  and dogs (Lehman,
 1951).    Along  with convulsions,  hyperreflexia  has been  noted  in
 dogs (Lackey, 1949a,b), rats (Boyd and Taylor,  1971),  and humans
 (Haun and Cueto,  1967). Additional unpublished reports (U.S. EPA,
 1976d)  of poisoning  in humans describe the major  symptoms of oral
 intoxication  as vomiting,  convulsions, cyanosis, and  coma.   Based
 on a review of  the  acute toxicity  of toxaphene to experimental mam-
 mals and cases of human poisoning, Conley  (1952)  has estimated the
 minimum lethal oral dose of toxaphene for man to be between 30 and
 103 mg/kg body weight.  In rats, pathological effects of toxaphene
 include cloudy swelling and congestion of  the kidneys,  fatty degen-
 eration  and  necrosis of  the liver, and  decreased spermatogenesis
 (Boyd and Taylor, 1971).  Mehendale (1978) has reported that toxa-
 phene (100 mg/kg  in the diet  for eight  days)  inhibits hepatobiliary
 function in  rats.
                                C-22

-------
                                                             TABLE 8

                 Case Studies of Toxaphene Poisoning in Humans in which Ingestion is the Primacy Route of Entry
Case No.
Subject(s)
Nature of
toxaphene
Dose
Time to react
O to onset of
1 symptoms
Symptoms
Outcome
Time to death
or recovery
1* 2*
Male, Male, 4 yrs
2 yrs 8 mo
Wax Emulsion in
water
Unknown Unknown
xv-7 hours 2 hours
Convulsions Convulsions
2-5 minute
intervals
Death Death
9.5 hours 6 hours
3* 4* 5*
Male, Male, 2 yrs Female, 20 yrs
1 yr 5 mo Female, 16 yrs
Female, 12 yrs
60% in 20% in solution Residue of spray
solvents in food
100 mg/kg Unknown 9.5-47 mg/kg
N)S] N]S1 1.5-4 hours
Convulsions Convulsions, Nausea; vomiting
intermittent intermittent; convulsions
mild cerebral
excitement; aim-
less jerking
motion and ex-
cessive muscular
tensions of ex-
tremities, marked
pharyngeal and
laryngeal spasms;
labored respira-
tion; cyanosis
Death Recovery Recovery
11 hours 12 hours ^-^12 hours
6* 7**
Male, adult Female, 9 mo.
Male, young
Female, adult
Residue of Powder, 13.8%
spray in toxaphene,
food 7.04% DDT
Unknown Unknown
4 hours A few hours
No nausea; Vomiting; diarrhea;
spontaneous convulsions; hyper-
vomiting; reflexia; tachycar-
convulsions dia; b.p. 140/100;
jerking and labored respiration;
transitory respiratory failure
movements;
muscular
rigidity;
periods of
unconscious-
ness; amnesia (?)
Recovery Death

-------
     The  acute  dermal  toxicity of  toxaphene  is  summarized  in
-Table 7.  Toxaphene  appears  to be somewhat less toxic when  admin-
 istered dermally.  In rats the ratios of dermal to oral LD5Qs range
 from 10 to 12 (Gaines, 1960,  1969; Hercules,  Inc.,  undated).   With-
 out providing  documentation, Hayes  (1963) estimates  the  hazardous
 dermal dose  for  humans  at  46 g.   For  a  70  kg  man,  this is approxi-
 mately  660  mg/kg.   Dermal LD5Qs for rats  range  from 780 to 1075
 mg/kg  (Gaines,  1960,  1969; Hercules  Inc.,  undated).
     Table  9 summarizes the  effects of subacute oral administration
 of  toxaphene to  laboratory  mammals.   Except for convulsions  ob-
 served  in dogs given  5  mg/kg/day, none of the exposures detailed in
 Table  9  resulted  in  clinical signs  of  toxaphene poisoning.   The
 ability  of  dogs to  tolerate large  cumulative  doses (176  to 424
 mg/kg)  when given at 4 mg/kg/day suggests a rather sharp threshold
 level  for central nervous system stimulation.   This is  consistent
 with  information discussed  in the Excretion  section,  showing that
 toxaphene is eliminated relatively  rapidly.   A similar  pattern is
 seen  in  rats on  intraperitoneal injection.   Ohsawa  and coworkers
 (1975)  have found that male rats  injected  with 50  mg toxaphene
 (approximately 300 mg/kg)  every  48 hours tolerated cumulative doses
 of 700 to  2,000 mg/kg  (over 10 times  the single  oral  LD5Q dose)
 before marked lethality occurred.
      In subacute exposures  that do not >cause apparent central ner-
 vous system stimulation, no  increases in mortality are noted.  How-
 ever, pathological  changes  of  the  kidneys  and  liver,  as well as
 changes in blood chemistry,  seem to  be  common features of  subclini-
 cal toxaphene intoxication.
                                C-24

-------
                                                         TABLE 9

                                           Subacute Oral Toxicity of Toxaphene





0
1
to
cn


Organism

Mice, both albino
and wild strains

Rats

Rats

Vehicle Duration

Diet Several weeks
or months

Diet 12 weeks

N.S.** 7 months

Dose
ing/kg/day or
ppm in diet)
50 mg/kg/day
(250-480 ppm)

189 ppm

1.2-4. & ma /ka /riai
Estimated
cumulative
dose
(rog/kg)
300



/ 9<;n_innn

Response*

Changes in blood
chemistry and
urine protein
No apparent adverse
effects



Reference

Baeumler,

Clapp, et
1971


1975

al.


Rats, Sherman, male    Diet      2-9 months
 and female, '^lOO g

Rats and guinea pigs   Diet      6 months
50 and 200 ppm


100-800 ppm
Temporary change in
 blood chemistry

Questionable liver
 pathology

No significant
 effect
                                                                                                      Grebenyuk,  1970
Ortega, et al.
 1957

Shelanski and
 Gellhorn, undated
Dogs corn oil
Corn oil


Corn oil


"A few days"
44 days


106 days


5
4


4


mg/kg/day
mg/kg/day


mg/kg/day


^15-35
176


424


Convulsion
Questionable liver
pathology: renal
tubular degeneration
Questionable liver
pathology: renal
tubular degeneration
Lackey,
Lackey,


Lackey,


1949a
1949a


1949a


**N.S.  - not specified.

-------
     Ortega,  et  al.  (1957)  (using rats) and Lackey  (1949a)  (using
-flogs) have noted similar changes in liver  histology after  toxaphene
administration.  Morphologically,  these changes  appear  as vacuoles
of  plasma with  occasional  red  blood  cells found  within  hepatic
cells.   This condition,  referred  to as hydropic accumulation,  is
distinct  from fatty degeneration.   In neither  rats nor  dogs  was
hydropic  accumulation associated  with the destruction of hepatic
cells.  However, Ortega, et al. (1957)  also noted occasional masses
of  red blood cells invading the cytoplasm of liver  cells in areas
of  hypertrophy  and  margination.    In  addition  to  liver  damage,
Lackey (1949a)  also noted  widespread  degeneration of  the tubular
epithelium,  occasionally accompanied by inflammation of the pelvis
of  the kidney.   Identical  pathological changes were seen in dogs
surviving prolonged  dermal  exposures to toxaphene (Lackey, 1949b).
Ortega,  et  al.   (1957),  however,  did not  note any  pathological
changes attributable to toxaphene in the  kidneys of  rats.
      As noted in  Table 9,  alterations in clinical  chemistry have
 also been seen in subacute  oral toxaphene exposures.  Mice with no
clinical signs  of intoxication evidenced consistent  increases in
 serum  acid  phosphatase,  glutamicpyruvic transaminase,  and gamma-
 glutyamyl transpeptidase activities,  along  with increased neutro-
 phil counts  and changes  in urine protein (Baeumler, 1975).   At a
 much lower daily dose, rats had only a transient increase  in serum
 alkaline phosphatase during the fifth  month of ingestion  and  showed
 no variation  in  urine hippuric acid (Grebenyuk, 1970).   Increases
 in all of the above enzyme activities  are consistent with the mild
 liver pathology associated with subacute toxaphene  exposure.
                                C-26

-------
     Lehman  (1952b) states that the 90-day dermal LD5Q of toxaphene
~(as  a  dry  wax)  is  40  mg/kg in rabbits.  No details of symptoms or
pathology  are provided.
     Hercules Inc.  (undated)  has  exposed human volunteers to toxa-
phene.   Both dermal and  inhalation  routes  of exposure  were used.
Toxaphene  doses of  300  mg/day applied  to the  skin of  50 volunteers
for  30 days produced no observable toxic effects.  Similarily, cot-
ton  patches  treated with  toxaphene  produced  neither  sensitization
nor  primary  skin irritation  when  applied  to  the skin of  200 sub-
jects.   Shelanski  (1974)  indicates that  humans exposed to toxaphene
mists  of 500 mg/m3 of air for 30 minutes daily  for  10 consecutive
days followed by three  daily exposures three  weeks later showed no
adverse  effects, based on physical  examinations as well  as blood
and  urine  tests.
     However,  Warraki  (1963) has  attributed two  cases  of acute
bronchitis with miliary  lung shadows  to  inhalation  of toxaphene
during applications of toxaphene  formulation spray.   Warraki does
not  specify  the carriers used during  the toxaphene  spray applica-
 tions  of  the cases that  he summarized.  However, he  did indicate
 that toxaphene  is  usually applied as  an emulsifiable concentrate
 containing 60  percent  toxaphene, 35  percent kerosene,  3 percent
 xylol, and 2 percent emulsifier.   Both  individuals,  male adults,
 had  been  exposed  to  toxaphene sprays from 1.5  to 2  months before
 the  onset of pulmonary insufficiency.   Maximum  breathing capacity
 was between  19 and  22 percent of  normal.    Both adverse affects
 observed (pulmonary insufficiency and  lung lesions) were reversible
 within three months after toxaphene exposure was discontinued.  No
                                C-27

-------
 central nervous system effects  were  noted.   One case of  allergic
"rhinitis  in a worker exposed to  toxaphene  by inhalation  has  been
 reported.   However, details  on  the duration of his exposure  were
 not  given  (U.S.  EPA, 1976d).  As  with  most  reports  of occupational
 poisoning,  the possible role of exposure to other compounds compli-
 cates  the  interpretation  of  these case studies.
     Long-term  exposures to  low dietary levels of toxaphene  are
 summarized  in Table 10.  All studies note some form of liver patho-
 logy in rats at dietary levels of 100 mg/kg or above.  At 100 mg/kg,
 cytoplasmic vacuolization similar  to  that   seen  on subacute  oral
 exposure was noted by Kennedy, et al.   (1973).  Lehman (1952a) noted
 both cytoplasmic vacuolization and fatty degeneration of the liver
 in  rats fed 100 mg/kg.   With a 25  mg/kg diet, Fitzhugh  and Nelson
 (1951)  observed  increased  liver  weight with minimal   liver  cell
 enlargement.   Unpublished  studies on  rats,  dogs,  and  monkeys  by
 Hercules  Inc.   (undated)  are  in  general agreement  with the above
 published  reports.  The lowest dietary  level of toxaphene producing
 unequivocal liver damage over a 2-year feeding period is  20 mg/kg
 diet.   Only at  relatively  high concentrations, i.e., 1,000 mg/kg
 diet,  does  chronic toxaphene exposure  elicit central nervous system
 effects characteristic  of acute  intoxication.
     No cases  of chronic human intoxication have been encountered
 in  the literature.
 Synergism  and/or Antagonism
      Induction   of  hepatic   microsomal  mixed-function   oxidase
 appears to account for most of the interactions of  toxaphene with
 other  compounds.   In  rats  pretreated with  aldrin  or dieldrin and
                               C-28

-------
                                                 TABLE 10

                Chronic Toxicity of Toxaphen^ at Low Dietary Levels to Laboratory Mammals
       Organism
  Duration
 of Feeding
    Toxaphene
  Concentration
      in Diet
     Response*
    Reference
o
i
(O
VD
    Rats,
     Sprague-Dawley
    Rats
    Rats
    Rats
    Dogs

    Dogs
    Dogs


    Monkeys
3 generations
Lifetime
Lifetime
2 years
2 years
2 years

2 years
1360 days
 ( 3.7 years)

2 years
         25   mg/kg**   No effect

        100   mg/kg     Liver  pathology

         25   mg/kg     No effect

        100   mg/kg     Liver  pathology

         25   mg/kg     Liver  pathology
         25   mg/kg
        100   mg/kg

  1000-1600   mg/kg

       5-20   mg/kg

         40   mg/kg


        200   mg/kg


          5
          mg/kg/day*
No effect
Slight liver damage

CNS stimulation

No effect

Slight liver
 degeneration

Moderate liver
 degeneration

Liver necrosis
      10-15   mg/kg    No clinical or
(  0.64-0.78             histological
          nig/kg/day)   effects
                     Kennedy, et al. 1973
                     Lehman, 1952a
Fitzhugh and Nelson,
 1951

Hercules, Inc., undated
Hercules, Inc., undated

Hercules, Inc., undated


Hercules, Inc., undated


Hercules, Inc., undated


Hercules, Inc., undated
     *Administered  in capsules containing toxaphene dose  in corn oil;  5 mg/kg/day  equivalent  to  200
      mg/kg in diet.
    **Diets prepared fresh weekly.   (The other studies  in  this  table  did  not  specify  frequency).

-------
evidencing  increased  liver  0-dealkylase and 0-demethylase  activi-
ties,  toxaphene  96-hour LD50 values  were  approximately two times
higher  (indicating decreased toxicity)  than those of rats given no
pretreatment.  Similarly, pretreatment with DDT,  a known  inducer of
hepatic microsomal mixed-function oxidase,  resulted in  a 3-fold in-
crease in the 96-hour  LD50 of toxaphene in  rats  (Deichmann and Kep-
linger, 1970).   Piperonyl butoxide, which inhibits the metabolism
of  many toxicants by  mixed-function  oxidase,  has  been  shown to
potentiate the toxicity of toxaphene  in house flies (Saleh, et al.
1977).
     When administered  by intubation  to  rats,  equitoxic combina-
tions of toxaphene with parathion, diazinon, or trithion wer= less
toxic  than  would be expected,  based  on the  assumption of simple
similar action (Keplinger and Deichmann, 1967).
     Cases of  acute  human intoxication by toxaphene-lindane mix-
tures have been  reported.  In one  instance,  (Pollock,  1958) a 70-
year-old male  had his  hands  in contact with  a toxaphene-lindane
solution for  two hours.  After  10 hours,   the  following symptoms
developed:  headache,  poor coordination, lassitude, severe nausea,
and vomiting.  Over the  next week,  this individual  exhibited mild
hyperthermia, flaccid musculature, and decreased response to stim-
uli.  Only after nine days did the individual become semicomatose.
At  no  time  were convulsions or  hyperreflexia  noted.   These signs
and symptoms are  not characteristic of  toxaphene or lindane poison-
ing  (Matsumura,  1975) and differ markedly  from the previously de-
scribed cases of acute  oral  toxaphene  poisoning  in  humans.   While
clinical signs of intoxication may be expected to show some varia-
                              C-30

-------
tion  with different routes  of  entry, such  profound variation  is
uncommon  with  the chlorinated insecticides.   Gaines (1960,  1969)
noted  no  difference between signs  of intoxication in rats orally
and dermally exposed to a variety of  pesticides.   Lackey  (1949a,b)
similarly noted  no  remarkable  differences in the  response of dogs
to subacute oral and dermal doses of  toxaphene.
     Two  cases of  acute  aplastic  anemia associated  with dermal
exposure  to  toxaphene/lindane mixtures  have been reported  (U.S.
EPA, 1976d).   One of these cases resulted in death due to acute mye-
lomonocytic  leukemia which was  presumed to  be secondary  to the
development of aplastic anemia.   Thus,  while toxic anemia has not
been reported  in laboratory mammals  experiencing  acute  toxaphene
poisoning, such an effect  may be  hazardous in  man in  instances also
involving lindane exposure.
Teratogenicity
     In a study  by  Kennedy, et  al.  (1973) ,  male  and female rats
were fed toxaphene at dietary levels of 25 and 100 mg/kg.  Gross and
microscopic pathology  of  F_ weanlings  revealed no  indication of
teratogenic effects.  Further,  no statistically signficiant varia-
tions from controls were noted in either dose group for any of the
following parameters:   mating  index, fertility  index,  pregnancy
index, parturition  index, mean viable litter  size, live  birth in-
dex, 5-day survival  index, lactation index, or weaning body weights
of offspring.   One of sixteen females  from each dose group resorbed
an entire litter.    This was  not seen  in any  of the 32  control
females but did occur in tests  with another pesticide, Delna
                              C-31

-------
     In multigeneration studies of mice given toxaphene at  25 rag/kg
diet, no effects on fertility, gestation, viability, lactation, or
survival indices were observed (Keplinger, et al. 1970).
     In  addition to  these long-term  dietary studies,  one study
(Chernoff and Carver,  1976)  has  been conducted in which toxaphene
in corn oil was administered to pregnant female rats and mice from
days 7 to 16 of  gestation  at doses of 15, 25,  and 35 mg/kg/day.  All
doses produced  signs  of maternal and  fetal  toxicity  but  did not
produce teratogenic effects.
     DiPasquale  (1977)  has examined  the effects of  toxaphene on
fetal guinea pig development.  In this study, toxaphene was admin-
istered to pregnant females at a  dose of  15 mg/kg body weight oral-
ly from day 21  to  day  35  of  gestation.  No  effects  were noted on
anatomical development of  the fetus.  The only sign of fetotoxicity
was a decrease in collagen-containing structures.  This was attrib-
uted to a functional deficiency of vitamin C  related to mixed-func-
tion oxidase induction.  Maternal guinea pigs showed a slight loss
of body weight,  but no effects attributable  to toxaphene exposure
were seen on maternal liver weight or mortality.
Mutagenicity
     Epstein,  et al.  (1972)  have used a modified  dominant lethal
assay in mice to evaluate  the  mutagenic  potential  of  a variety of
chemical agents  including  toxaphene.  In  this study, four groups of
male ICR/Ha  Swiss mice were given toxaphene either intraperitoneal-
ly (single doses of 36  mg/kg or 180 mg/kg) or orally (five doses of
8  mg/kg/dose or  16  mg/kg/dose).   After dosing,  the  treated males
were mated  to groups  of untreated females over  an  8-week  period.
                              C-32

-------
Based on  measurements of early fetal deaths per pregnancy and  the
percent of  females  with  early fetal deaths, the toxaphene-treated
groups did  not  differ significantly from controls.  Thus, in this
strain of mice,  toxaphene  apparently does not produce chromosomal
abnormalities that preclude zygote development.
     Hill  (1977)  has  summarized  information on  the mutagenicity
testing of  toxaphene in bacterial  systems.   Ames  tests have been
conducted  on  Salmonella  typhimurium  strains  TA 1535,  TA 1537,
TA 1538, TA 98, and TA 100 with and without metabolic activation by
noninduced  mammalian liver fractions.   Positive  results were  ob-
tained  for  strains  TA 98  (frameshift mutation) and TA 100   (base
pair substitution) only in tests without metabolic  activation.   All
other  tests were  negative.    A "high  temperature"  toxaphene  has
elicited  positive dose  response  increases  in  strains  TA 98   and
TA 100 only with metabolic activation.   All the  above tests were
conducted by Litton Bionetics  Inc. for Hercules, Inc.
     In addition  to  these  studies,  work has been  conducted on  the
mutagenicity  of toxaphene  in  the  Salmonella  system  by Dr.   Kim
Hooper of Bruce Ames1 group in Berkeley,  Calif.  (Hill, 1977).   His
results indicate that  toxaphene  and  toxaphene subtractions   are
mutagenic to strain TA 100 with and  without activation by Aroclor^-
induced rat microsomes.  Mutagenic activity was decreased in those
tests using microsomal activation.
     A recently completed study by U.S.  EPA (1978)  found no signif-
icant differences in the  rates  of chromosomal aberrations in leuko-
cytes between groups of individuals  occupationally  exposed to toxa-
phene and  groups with no occupational exposures to toxaphene.

                               C-33

-------
Carcinoqenicity
     Under contract  to  the National Cancer  Institute  (NCI),  Gulf
South Research Institute has  recently  completed a carcinogenicity
bioassay of  toxaphene  (NCI,  1979) .   It should  be noted that this
study, which was conducted from  1971 to  1973,  did not follow cur-
rent NCI protocols (NCI, 1977).   Specifically,  only 10 animals were
used in each matched control group,  and were  not pair-fed.  In this
study, groups  of Osborne-Mendel rats  and  B6C3F]_  hybrid mice were
exposed  to technical-grade  toxaphene  in  the  diet for  80 weeks.
Details  of the dose schedule and number of  animals used are pro-
vided in Tables  11 and  12,
     Toxaphene  was  added to  the feed  in acetone.  In addition,  2
percent  corn oil was  added  to  the diet  as  a dust suppressant.
Actual  dietary toxaphene  concentrations,  which were confirmed  by
gas-liquid chromotography, did not deviate  from the nominal concen-
tration  by more  than 6.9 percent.   In  addition to the matched con-
trol  groups  indicated  in these tables, pooled  control groups were
used  in the statistical analyses.  For rats,  pooled controls con-
sisted of  matched controls from similar bioassays on captan,  chlor-
aben, lindane, malathion,  and picloram, as well as the matched con-
trols from the toxaphene bioassay.   For  mice,  pooled controls con-
sisted  of matched controls from  similar bioassays on lindane, mala-
 thion,  phosphamidon, and tetrachlorvinphos,  as well as  the matched
controls  from the  toxaphene study.  Organisms used  in  all pooled
 control groups were of the  same strains,  from the same suppliers,
 and examined by the same pathologists.
                                C-34

-------
                                                  TABLE 11

                                 Toxaphene  Chronic Feeding  Studies  in  Rats3
O
u>
ui
Sex and
Test Group
Male
Matched-Control
Low- Dose



High-Dose



Female
Matched-Control
Low- Dose


High-Dose


Initial
No. of
Animals (b)

10
50



50




10
50


50


Toxaphene
in Diet(c)
(rag/kg)

0
1,280
640
320
0
2,560
1,280
640
0

0
640
320
0
1,280
640
0
Time on
Dosed (d)


2
53
25

2
53
25



55
25

55
25

Study (weeks) Time-Weighted
Observed (e) Average^DoaeCf )

108-109
556


28
1,112


28

108-109
540

30
1,080

30
         Source:  National  Cancer  Institute,  1979.
         All  animals were  5  weeks of  age when  placed  on  study.
        clnitial  doses shown were toxic; therefore, doses  were  lowered  after  2  weeks and again at
         53 or  55 weeks, as  shown.
         All  animals were  started on  study on  the  same day.
        eWhen diets containing  toxaphene were  discontinued,  dosed  rats  and their matched controls were
         fed  control diets without  corn oil  for  20 weeks,  then  control  diets  (2 percent corn oil added)
         for  an additional 8 weeks.
         Time-weighted average  dose  =
 (dose in ppm x no. of weeks at that dose)
'  (no. of weeks receiving each dose)

-------
                                                  TABLE 12


                                 Toxaphene Chronic Feeding Studies in Mice
O
i
00
a\
Sex and
Test Group
Male
Matched-Control
Low-Dose


High-Dose


Female
Matched-Control
Low-Dose


High-Dose


Initial
No. of
Animals (b)

10
50


50



10
50


50


Toxaphene
in Diet(c)
(mg/kg)

0
160
80
0
320
160
0

0
160
80
0
320
160
0
Time on Study (weeks) Time-Weighted
Dosed (d) Observed (e) Average^Doseff )

90-91
19 99
61
11
19 198
61
10

90-91
19 99
61
11
19 198
61
10
        a
         Source:  National Cancer Institute,  1979.

        bAll animals were 5 weeks of age when placed on study.

        clnitial doses shown were toxic; therefore, doses were lowered at 19 weeks, as shown.

        dAll animals were started on study on the same day.

        eWhen diets containing toxaphene were discontinued,  dosed mice and their matched controls
         were fed control diets without corn oil for 7 weeks, then control diets (2 percent corn oil
         added)  for an additional 3 to 4 weeks.
        f       .  ^  „         j      .g(dose in ppm x no. of weeks at that dose)
        ^Time-weighted average dose = -	(no. of weeks receiving each dose)

-------
     During tt   course of this study, both rats and mice evidenced
signs of general toxic effects.   Both  male and female rats in the
high-dose group developed body tremors  at week  53.  From week 52 to
week 80, other  clinical  signs, which occurred  primarily  in toxa-
phene-dosed  rats,  included  diarrhea,  dyspnea,  pale  mucous  mem-
branes, alopecia,  rough hair coats, dermatitis, ataxia, leg paraly-
sis, epistasis, hematuria, abdominal  distention, and vaginal bleed-
ing.  Female rats  in  both dose groups  had lower mean body weights
than the matched controls. No dose-related effect on mortality was
noted in any of the rat test groups.  In mice, males and females in
each dose group displayed a significant increase in mortality when
compared to  the matched  controls.   In high-dose male  mice,  mean
body weights were generally lower  than  those in  the matched control
group.  Clinical signs of toxicity in mice included abdominal dis-
tention, diarrhea, alopecia,  rough hair coats, and dyspnea.
     The effects of dietary  toxaphene  on  tumor  incidence  in male
rats,  female  rats, male  mice,  and female mice are  summarized in
Tables 13, 14,  15, and 16, respectively.
     In male rats  in  the high  dose  group, a significant increase
was noted in the incidence of follicular-cell carcinomas or adeno-
mas of the thyroid.  Of the nine thyroid tumors that were found in
this group, two were carcinomas.  A significant increase of folli-
cular-cell adenomas of the thyroid was also noted in the high-dose
group of female rats; however,  no  carcinomas were  found.   In both
of  these  groups,  the development  of  thyroid  tumors was  dose-
related.  A significant increase was  also  noted  in the incidence of
chromophobe adenomas, chromophobe  carcinomas,  and  adenomas of the
                               C-37

-------
o
I
co
CO
                                                    TABLE 13

             Analyses of  the  Incidence of Primary Tumors  in Male  Rats  Fed Toxaphene in the Diet3'
Topography; Morphology Matched Control Pooled Control Low Dose
Liver: Neoplastic Nodule (c)
p Values (d)
Weeks to First Observed Tumor
Pituitary: Chromophobe Adenoma,
Carcinoma, NOS, or Adenoma,
NOS(c)
p Values (d)
Weeks to First Observed Tumor
Adrenal: Adenoma, NOS, Cortical
Adenoma, or Carcinoma
p Values(d,e)
Weeks to First Observed Tumor
Spleen: Hemangioma(c)
p Values (d)
Weeks to First Observed Tumor
Thyroid: Follicular-cell
Carcinoma or Adenoma (c)
p Values (d)
Weeks to First Observed Tumor
1/9 (11)
N.S.
109


3/7 (43)
N.S.
102

4/9 (44)
p = 0.019 (N)
—
0/9 (0)
N.S.
—

1/7 (14)
N.S.
109
1/52 (2)
N.S.
—


8/46 (17)
N.S,
—

5/52 (10)
N.S.
—
0/49 (0)
N.S.
—

2/44 (5)
p = 0.007
—
6/44 (14)
p = 0.034**
p = 108


13/42 (31)
N.S.
85

5/41 (12)
p = 0.043 (N)*
p = 85
3/45 (7)
N.S.
83

7/41 (17)
N.S.
104
High riose
4/45 (9)
N.S.
94


5/31 (16)
N.S.
95

3/37 (8)
p = 0.020 (N)*
p = 85
3/42 (7)
N.S.
85

9/35 (26)
p = 0.008**
56
        ^Source:  National Cancer Institute,  1979.
         Dosed groups received time-weighted average doses of 556 or 1,112 ppm.
        °Number of tumor-bearing animals/number of animals examined at site (percent).
         Beneath the incidence of tumors in  a control group is the probability level for the Cochran-
         Armitage test when p less than 0.05; otherwise,  not significant (N.S.) is indicated.  Beneath
         the incidence of tumors in a dosed  group is the  probability level for the Fisher exact test
         for the comparisons of that dosed group with the matched-control group (*) or with the pooled-
         control group (**) when p less than 0.05 for either control group; otherwise, not significant
         (N.S.) is indicated.                                                   .
        eA negative trend  (N) indicates a lower incidence in a dosed group than in a control group.

-------
                                       TABLE  14




Analyses of the Incidence of Primary Tumors in Female Rats Fed Toxaphene in the Diet
Topography; Morphology Matched Control
Integumentary System: Malignant
Fibrous Histiocytoma of the
Subcutaneous Tissue (c)
p Values (d)
Weeks to First Observed Tumor
Mammary Gland: Fibroadenoma (c)
p Values (d)
Weeks to First Observed Tumor
Liver: Hepatocellular Carcinoma
*? or Neoplastic Nodule (c)
^ p Values (d)
Weeks to First Observed Tumor
Pituitary: Chromophobe Adenoma,
Carcinoma, or Adenoma, NOS(c)
p Values (d)
Weeks to First Observed Tumor
Thyroid: Follicular-cell
Adenoma (c)
p Values(d)
Weeks to First Observed Tumor

0/10 (0)
N.S.
—
1/10 (10)
N.S.
87
1/10 (10)
N.S.
109
3/8 (38)
p = 0.046
85
0/6 (0)
p = 0.022
—
Pooled Control

0/55 (0)
N.S.

6/55 (11)
N.S.
—
1/55 (2)
N.S.
—
17/51 (33)
p = 0.012
—
1/46 (2)
p = 0.008
—
Low Dose

1/50 (2)
N.S.
105
10/50 (20)
N.S.
19
5/42 (12)
N.S.
108
15/41 (37)
N.S.
75
1/43 (2)
N.S.
102
High Dose

3/49 (6)
N.S.
83
10/49 (20)
N.S.
67
4/40 (10)
N.S.
109
23/39 (59)
p = 0.013**
79
7/42 (17)
p = 0.021**
105

-------
                                             TABLE 14  (continued)
o
i
Topography: Morphology
Adrenal: Cortical Adenoma or
Carcinoma (c)
p Values (d)
Weeks to First Observed Tumor
Uterus: Endometrial Stromal
Polyp (b)
p Values (c)
Weeks to First Observed Tumor
aSource: National Cancer Institute,
Matched Control
0/8 (0)
N.S.
—
0/9 (0)
N.S.
—
1979.
Pooled Control
3/50 (6)
N.S.
—
5/53 (9)
N.S.
—
f a A f\ ^r- i nan m<-i
Low Dose
3/44 (7)
N.S.
104
9/41 (22)
N.S.
87
/L-n
High Dose
6/43 (14)
N.S.
87
5/45 (11)
N.S.
109

       °Number  of  tumor-bearing animals/number  of  animals examined at site (percent).

       dBeaneath the incidence of tumors  in  a control group is the probability level  for the Cochran-
        Armitage test when p less than 0.05; otherwise not significant (N.S.)  is indicated.  Beneath
        the incidence of tumors in a dosed group is  the probability level for  the Fisher exact test
        for the comparison of that dosed  group  with  the matched-control group  (*) or  with the pooled-
        control group (**)  when p less than  0.05 for either control group;  otherwise, not signifi-
        cant (N.S.)  is indicated.

-------
                                                   TABLE 15
             Analyses  of  the  Incidence of Primary Tumors  in Male Mice  Fed  Toxaphene  in the  Diet
                                                                                               a,b
o
i
*>•
Tononrflphv Morphology Matched Control Pooled Control
Liver: Hepatocellular
Carcinoma(c) 0/10 (0) 4/48 (8)
pValues(d) P -c 0.001 p^ 0.001
Weeks to First Observed Tumor
Liver: Hepatocellular Carcinoma
or Neoplastic Nodule (c) 2/10 (20) 7/48 (15)
pvalues(d) p^ 0.001 p^ 0.001
Weeks to First Observed Tumor 90
Low Dose
34/49 (69)
p^O.OOl*
p <; 0.001**
73
40/49 (82)
p^. 0.001*
p <. 0.001**
73
High Dose
45/46 (98)
p ^c.0.001*
p -^0.001**
59
45/46 (98)
p-c. 0.001*
p^c. 0.001**
59
       aSource: National Cancer Institute, 1979.

       bDosed groups received time-weighted average doses of 99 or 198 mg/kg.

       GNumber of tumor-bearing animals/number of animals examined at site  (percent).

       dBeneath the incidence of tumors in a control group is the probability level  for  the Cochran-

        Armttage test when p less than 0.05; otherwise not significant  (N.S.) is  indicated.  Beneath

        the incidence of tumors in a dosed group is the probability level for the Fishe,: exact  test

        for the comparison of that dosed group with the matched-control group (*) or with  the pooled

        control group (**) when p less than 0.05 for either control group;  otherwise, not  signifi-

        cant  (N.S.) is  indicated.

-------
                                                   TABLE 16

            Analyses of  the Incidence of  Primary Tumors in  Female Mice Fed Toxaphene in the Diet
o
i
>£*
K)
Topography: Morphology
Liver: Hepatocellular
Carcinoma (c)
p Values (d)

Weeks to First Observed Tumor
Liver: Hepatocellular
Carcinoma or Neoplastic
Nodule (c)
p Values (d)

Weeks. to First Observed Tumor
Matched Control Pooled Control Low Dose
0/9 (0) 0/48 (0) 5/49 (10)
p^O.OOl p ^,0.001 p = 0.030**

89
0/9 (0) 0/48 (0) 18/49 (37)
p^c.0.001 p
-------
pituitary in the high-dose group of  female  rats.  However, an exam-
ination of historical  control  data  on the  incidence  of pituitary
tumors  in  female rats  suggested  that an  association  between the
administration of toxaphene and the development of pituitary tumors
could not be maintained.
     In both male and female mice, significant increases were noted
in the  incidence of hepatocellular carcinomas and in the incidence
of hepatocellular  carcinomas combined with  neoplastic nodules of
the liver.  Based on the results of this study, the NCI (1979) has
concluded:   "Toxaphene is carcinogenic  in  male  and female BSCSF-^
mice, causing  increased incidences of  hepatocellular   carcinomas.
The test results also  suggest carcinogenicity of toxaphene for the
thyroid of male and female Osborne-Mendel rats."
     Litton Bionetics,  Inc.  (1978)  reported a study in the E6C3l?l
strain  of male  and  female  mice fed  at doses  of  7,  20, and 50 ppm
toxaphene in the diet.  This study showed a  statistically signifi-
cant excess of  hepatocellular  tumors  (hepatocellular  adenoma plus
hepatocellular  carcinoma)  in  male  mice, but  only at the  50 ppm
dose.   Toxaphene  in  a  corn oil premix was  added to the basal diet
and blended;  the control  diets contained an equal amount of added
corn oil.  Animals  were maintained  on dietary toxaphene treatment
for  18  months,  followed  by  a  6-month   period   of   observation
(Table  17) .   At the end  of  this 2-year study,  surviving animals
were sacrificed and histopathologic examination of  the  major organs
was initiated.   Intercurrent deaths were evaluated by  histopathol-
ogy as  they occurred.
                               C-43

-------
                                TABLE  17

              Toxaphene  Chronic Feeding  Studies  in  Mice*
Sex and Test Group

Group 1
Group 2
Group 3
Group 4

Group 1
Group 2
Group 3
Group 4
Male
Matched-Control
Low-Dose
Med-Dose
High-Dose
Female
Matched-Control
Low-Dose
Med-Dose
High-Dose
Initial
No. of
Animals**

54
54
54
54

54
54
54
53
Toxaphene
in Diet
(mg/kg)

0
7
20
50

0
7
20
50
Dosed
(weeks)

78
78
78
78

78
78
78
78
Observed
(weeks)

105
105
105
105

105
105
105
105
 *Source:  Litton Bionetics, Inc., 1978.

**Weanling B6C3Fi  mice were placed on study following seven days of
  acclimation.
                                C-44

-------
     Analysis of the combined hepatocellular tumor incidence indi-
cated a statistically significant  increase  (Fisher  Exact Test)  in
male mice  treated  with  50 ppm levels  of  toxaphene  (Table 18).  A
dose-related  increase  in  the incidence  of this  tumor  type  was
determined using the Cochran Armitage Trend Test.  Female mice did
not show a significant  increase  in hepatocellular tumor  incidence
at any level of toxaphene  treatment  (Table  19).
     The major  increase  in tumor  incidence  for male mice adminis-
tered  50  ppm levels of  toxaphene  was in hepatocellular  adenomas.
This nonmalignant tumor type occurs with increasing  age in controls
of the B6C3F-L strain of  mice.
                                C-45

-------
                                                  TABLE 18


              Analysis  of  the  Incidence  of Hepatocellular  Tumors in Male Mice Fed Toxaphene*
SEX
GROUP NUMBER
TYPE OF DEATH
NUMBER OF LIVERS EXAMINED
Hepatocellular adenomas
Hepatocellular carcinomas
Total hepatocellular tumors
Total number of livers
bearing hepatocellular tumors
MALES
GROUP 1
T I
(44) (9)
3 0
5_ 2
8 2

10/53 (19%)


T + I
(53)
3
J_
10
i-4-
r T


T
(47)
0
9^
9


MALES
GROUP 2
I
(7)
0
2
2

10/54 (19%)


T + I
(54)
0
11
11
4-4-
T T
o
I
£>•
CT>
SEX
GROUP NUMBER
TYPE OF DEATH
NUMBER OF LIVERS EXAMINED
Hepatocellular adenomas
Hepatocellular carcinomas
Total hepatocellular tumors
Total number of livers
bearing hepatocellular tumors


T
(45)
2
LO
12


MALES
GROUP 3
I T + I
(8) (53)
0 2
2 12_
2 14
4.4.
12/53 (23%T


T
(46)
11
11
22


MALES
GROUP 4
I
(5)
0
1
1
4.
18/51 (35%) '


T + I-
(51)
11
M
23


        *Source: Litton Bionetics, Inc., 1978

         T = Terminal kill

         I = Intercurrent death

           = Fisher's Exact Test  (Group 4 compared to Group 1): P = 0.048  (1 tailed)

        ++ = Cochran Armitage Trend Test: P = 0.020

-------
o
I
                                                 TABLE  19



              Analysis of  the  Incidence of Hepatocellular Tumors  in Female Mice Fed Toxaphene*
SEX
GROUP NUMBER
TYPE OF DEATH
NUMBER OF LIVERS EXAMINED
Hepatocellular adenomas
Hepatocellular carcinomas
Total hepatocellular tumors
Total number of livers
bearing hepatocellular tumors
SEX
GROUP NUMBER
TYPE OF DEATH
NUMBER OF LIVERS EXAMINED
Hepatocellular adenomas
hepatocellular carcinomas
Total hepatocellular tumors
Total number of livers
bearing hepatocellular tumors


T
(46)
1
1
2



T
(43)
1
3_
4


FEMALES
GROUP 1
I
(7)
0
()
0

2/53 (4%)
FEMALES
GROUP 3
I
(9)
0
0
0

4/52 (8%)


T + I
(53)
1
1
2



T + I
(52)
1
3
4




T
(46)
1

2



T
(45)
3
2
5


FEMALES
GROUP 2
I
(7)
0

0

2/53 (4%)
FEMALES
GROUP 4
I
(7)
0

1

6/52 (12%)


T + I
(53)
1

2



T + I
(52)
3

6


         *Source:  Litton Bionetics,  Inc.,  1978


         T  =  Terminal kill


         I  =  Intercurrent death

-------
                      CRITERION FORMULATION

Existing Guidelines and Standards

     Standards  for toxaphene  in air,  water,  and  food have  been

established  or  recommended  by  many groups.   However,  all  these

standards were set before the results of  the NCI bioassay  of  toxa-

phene for carcinogenicity were available.

     Both the Occupational Safety and Health Administration  (39  FR

23540)  and  the  American  Conference  of  Governmental   Industrial

Hygienists (ACGIH, 1977a)  established a time-weighted average  value

of 500 ug/m   for  toxaphene  in  the  air  of the working environment.

The  ACGIH  (1977b)  based  this standard on unpublished acute and

chronic toxicity studies conducted  in the  1950's and  on  comparisons

of the  toxicity  of toxaphene with DDT  and lindane.   In addition,

this group set a tentative short-term exposure limit  for toxaphene

of 1.0 mg/m3  (ACGIH, 1977a).

     The national interim primary drinking water standard for  toxa-

phene is 5 yg/1 (40 FR 11990; U.S.  EPA  1976b,c).   This  standard  is

based on the reported organoleptic effects of toxaphene  at concen-

trations above  5  yg/1  (Cohen, et  al.   1961;  Sigworth,   1965).   A

standard of  25  yg/1  was  also calculated  based  on  minimal  or  no

effects in  rats  after  they were fed toxaphene at a concentration  of

10 mg/kg in the diet,  which was estimated to give an  average daily

dose of 1 mg/kg body weight  (Lehman, 1965).   This  latter calcula-

tion used the following assumptions:


     weight of rat = 300 g
     daily food consumption of rat =  50 g
     weight of average human adult =  70 kg
     average daily water intake for man = 2 liters
     safety factor = 500
     dietary intake =  trace (assume zero)


                              C-48

-------
     From these assumptions, the maximum safe daily dose for human was
estimated to be  3.4 yg/kg  body  weight  (U.S. EPA,  1976b).   It should
be noted, however, that the assumption of 50 g daily food consump-
tion for a 300 g rat is probably excessively high.
     The  National  Academy of  Sciences   (NAS,  1977)  estimated the
acceptable daily intake of toxaphene  for man at 1.25 ug/kg.  This
was based on  a  study  by Fitzhugh and Nelson (1951) , summarized  in
Table 10,  in which  rats evidenced  increased  liver   weight and
hepatic  cell  enlargement after  exposure to  toxaphene at 25  mg/kg
diet for two years.  In their  estimation NAS  assumed  the daily dose
in rats during the Fitzhugh and Nelson study was equivalent  to 1.25
mg/kg body weight,  and  the application  of a  safety factor of  1,000
was appropriate.  Then, assuming a human body weight of 70 kg  and a
daily  water  consumption  of  2 liters,  NAS   set  the  suggested no-
adverse-effect  level  from water  at  8.75 ug/1 (assigning 20  percent
of the  total ADI to water) or 0.44 ug/1   (assigning 1  percent of  the
total ADI to  water).
     Tolerances established  by  the  FDA for toxaphene  residues  in
various agricultural  products  are given in  Table 20.
      In Canada,  the tolerance  for toxaphene  in citrus fruits is 7.0
mg/kg.   In both the Netherlands and West Germany, the corresponding
standard is  0.4 mg/kg (Gunther,  1969).
     WHO has not yet established an acceptable  daily  intake  level
for  toxaphene  (WHO,  1974a,b,  1976).  The following  information is
considered  necessary  by WHO  (1974b)   before  an  acceptable  daily
 intake can  be established:
                                C-49

-------
                                               TABLE  20

                   Tolerances  for  Toxaphene Residues in Various Agricultural  Products
o
i
Ul
o
         Residue
          level
         (mg/kg)
6

5



3

2

0.1
                                Product
Fat of meat from cattle, goats, and sheep
Fat of meat from hogs
Fat of meat from horses
Cranberries, hazelnuts, hickory nuts, horse-
  radish, parsnips, pecans, peppers, pimentos,
  rutabagas, walnuts
Collards, kale,  spinach

Crude soybean oil

Barley, oats, rice, rye, and wheat
Sorghum grain
Cottonseed

Pineapple and bananas*

Soybeans, dry form

Sunflower seeds
                                                       Reference
                                                                              22 FR 4615
                                                                              24 FR 4727
                                                                              27 FR 7492
22 FR 4615
27 FR 7492

31 FR 12435

23 FR 477
25 FR 5335
26 FR 11799

27 FR 4913

31 FR 9453

U.S. EPA, 1977
         *0f which not more than 0.3  mg/kg  shall be in pulp after the peel is removed and
          discarded.

-------
     1.    Adequate toxicological  information on  camphechlor
          (toxaphene)  as currently marketed,  including a car-
          cinogenicity study.

     2.    Comparative  studies  evaluating  the  toxicological
          hazard associated with polychlorinated  camphene  of
          different  manufacture  used  in worldwide  agricul-
          ture.

     3.    Before recommendations can be made concerning resi-
          dues from  the  use  of camphechlor, other  than that
          conforming  to FAO  specifications, information _ is
          needed on the composition, uses,  and residues aris-
          ing from such products.


Nonetheless, the guideline levels for toxaphene in specified foods

have been recommended by WHO  (1974a)  (Table 21).  These recommenda-

tions are based on levels  that might be expected if good applica-

tion practices are followed and do not reflect a judgment concern-

ing potential human hazard.

     The  International  Joint  Commission of  the  United States and

Canada  (1977) has  recommended  a water standard of  0.008  ug/1 for

the  protection  of aquatic  life.    This  standard is  based  on the

study by  Mayer, et al.  (1975)  which found  that toxaphene at 0.039

ug/1 caused  a significant increase in mortality and a  significant

decrease  in  growth  in brook  trout  fry over  a  90-day period.  The

standard  of 0.008 ug/1 is obtained  by applying  a safety  factor

of 5.

     Finally, effluent  standards  for toxaphene manufacturers have

been set  at  1.5 ug/1 for existing facilities and 0.1 ug/1 for new

facilities  (41 FR 23576).
                               C-51

-------
                                                TABLE 21

                           Guideline Levels for Toxaphene in Specified Foods*
                                  Pood
o
i
ui
N)
Fat of meat of cattle, sheep,
  goats, and pigs

Broccoli, brussels sprouts, cabbage, celery,
  collards, eggplant, kale, kohlrabi, lettuce,
  okra, peppers, pimentos, spinach, tomatoes,
  barley, rice (rough), rye, sorghum, bananas
  (whole), pineapple, beans (snap, dry, lima),
  peas, cauliflower, oats, wheat, shelled nuts,
  carrots, onions, parsnips, radishes,
  rutabagas

Soybeans, peanuts (ground-nut), cotton-seed
  oil (refined), rape-seed oil (refined),
  soybean oil (refined),  peanut oil (refined),
  maize, rice (finished)

Milk and milk products (fat basis)
                                                                 Level
                                                                                  mg/kg
                                                                             2     mg/kg




                                                                             0.5   mg/kg

                                                                             0.5   mg/kg
              *Source: World Health Organization, 1974a

-------
Current Levels of Exposure

     Quantitative  estimates  of  human exposure  to  toxaphene are

extremely difficult  to make based  on the  data presented  in the

Exposure section.  The three major obstacles are:


     1.   The  wide  variation  in  toxaphene  concentrations
          noted in food, water, and air.

     2.   Conflicting  information  concerning  the  trend  of
          toxaphene residues in food.

     3.   The  marked  seasonal  and  geographic  difference in
          toxaphene concentrations found in air and  food.


Given  these  problems,  a conservative approach in estimating  expo-

sure to toxaphene  is necessary.

     An  early estimate of dietary  intake of  toxaphene was  0.021

ug/kg/day, based  on  the FDA's market  basket  surveys between  1964

and  1970  (Duggan  and  Corneliussen,  1972).   Although more  recent

market basket surveys indicate a decrease in  the  incidence of  toxa-

phene contamination  (see Table 1) and although the USDA survey sug-

gests that the incidence of toxaphene contamination of raw meat has

remained relatively  stable since 1969  (see Tables 2 and 3),  the FDA

survey of unprocessed  food samples shows an almost  2-fold increase

in  the incidence of toxaphene contamination between 1972 and 1976

 (see  Table  2) .   Given this conflicting  information,  the current

dietary  intake is  estimated to be 0.042 yg/kg/day, twice that noted

by  Duggan and Corneliussen  (1972).

     No  satisfactory estimate can be made of average national inha-

lation exposures.  In areas where toxaphene is not used, inhalation
                               C-53

-------
 exposure  may  be  negligible.   Even  in  areas  of  high use,  the appar-

 ent  low  absorption  of toxaphene  across the  lungs suggests  that

 inhalation  may not  be  a significant source  of  exposure.

     These  admittedly  tenuous exposure  estimates  are  summarized  as

 follows:


               Source              Estimated Intake

               Water               no estimate
               Food                0.042  yg/kg/day
               Air                 0


 Special Groups at Risk

     Individuals working  with toxaphene  or  living in areas where

 toxaphene is  used or produced would seem  to be at  higher risk  than

 the  general  population.   However, as   indicated  previously  (see

 Mutagenicity  section), an increased incidence of chromosomal aber-

 ration has  not been noted in groups  with occupational exposure  to

 toxaphene (U.S. EPA, 1978).   Further, of 32 samples of human  adi-

 pose tissue obtained in areas of high toxaphene usage from  autopsy

 or surgery  cases, only one sample contained detectable  levels  of

 toxaphene  (0.13  ppm)   (U.S.  EPA,  1978).   It  appears,  then,  that

 individuals who  live  in areas of  high  toxaphene  use or  who  have

occupational exposure to toxaphene  are not at greater  risk than the

general population.

Basis and Derivation of Criterion

     Various water  concentrations have already  been recommended for

toxaphene (see Existing Guidelines and  Standards  section).   These

concentrations,  with the rationale, are  summarized  in Table 22.
                              C-54

-------
                                               TABLE 22


                                  Water Concentrations for Toxaphene
o
i
Ul
(Jl
             Standard
5.0 yg/1


8.75 yg/1




0.44 yg/1




0.008 yg/1
                            Rationale
Organoleptic effects


Noncarcinogenic

 mammalian toxicity


Noncarcinogenic
 mammalian toxicity


Aquatic toxicity data
                                         Source
U.S. EPA, 1976b


HAS, 1977




NAS, 1977




Int. Joint Comm., 1977

-------
     Since  the  results of the NCI  bioassay  of toxaphene for car-
cinogenicity were positive (see Appendix I), estimated risk levels
for  toxaphene  in water can also  be calculated using a linearized
multistage  model as  discussed  in  the  Human  Health  Methodology
Appendices  to  the October 1980  Federal Register  notice  that an-
nounced the availability of this document.
     Under  the  Consent Decree  in  NRDC v. Train,  criteria  are to
state  "recommended  maximum permissible  concentrations (including
where appropriate, zero) consistent with the protection of aquatic
organisms, human health, and  recreational  activities."  Toxaphene
is  suspected  of being  a  human carcinogen.   Because  there  is no
recognized safe  concentration for a human carcinogen,  the  recom-
mended concentration of toxaphene  in water for maximum protection
of human health is zero.
     Because attaining a zero  concentration level may be infeasible
in some cases and in order to assist  the Agency and states  in the
possible future development of water quality regulations, the con-
centrations of  toxaphene corresponding  to several incremental life-
time cancer risk levels have  been  estimated.   A cancer risk level
provides an estimate of the additional  incidence of cancer that may
be expected in an exposed population.,  A risk of 10   for example,
indicates a probability of one additional case of cancer for every
100,000 people  exposed,  a risk  of  10   indicates  one additional
case of cancer  for every million people exposed, and so forth.
     In  the Federal  Register  notice  of  availability  of  draft
ambient water quality  criteria,  U.S.  EPA  stated  that it is  con-
                              C-56

-------
sidering setting criteria at an interim target risk level of  10"  ,


10~6, or 10~7 as shown in the following table.



Exposure Assumptions                Risk Levels
	(per day)	         and Corresponding Criteria  (1)

                             0      10"7       10~6       10"5


2 liters of drinking         0   0.071 ng/1   0.71 ng/1   7.1 ng/1
water and consumption
of 6.5 g fish and
shellfish.  (2)

Consumption of  fish and      0   0.073 ng/1   0.73 ng/1   7.3 ng/1
shellfish only.


 (1)   Calculations by applying a linearized multistage model as

      mentioned  above to  the animal  bioassay  data presented in

      Appendix  I.   Since the extrapolation model is  linear at

      low doses, the additional  lifetime risk is directly pro-

      portional  to  the  water concentration.   Therefore,  water

      concentrations corresponding  to  other  risk  levels  can be

      derived  by multiplying or dividing one of the risk  levels

      and corresponding water concentrations shown in the table

      by  factors such as  10,  100,  1,000, and  so forth.

 (2)   Approximately 98 percent of the toxaphene exposure results

      from  the consumption of aquatic organisms which  exhibit

      an  average  bioconcentration  potential of  13,100-fold.

      The  remaining 2  percent of  toxaphene  exposure  results


      from  drinking  water.



      Concentration  levels were derived assuming a lifetime exposure

 to  various amounts  of  toxaphene (1) occurring from the  consumption

 of  both  drinking  water and  aquatic life  grown in  waters containing
                               C-57

-------
the corresponding toxaphene concentrations and  (2) occurring solely
from consumption of aquatic life grown  in  the waters containing the
corresponding toxaphene  concentrations.    Because  data indicating
other  sources  of  toxaphene exposure  and their contributions  to
total body burden are inadequate for quantitative use, the figures
reflect the incremental risks associated with the indicated routes
only.
                               C-58

-------
                            REFERENCES







American Conference of Governmental Industrial Hygienists.  1977a.



TLVs: Threshold Limit Values  for  Chemical  Substances and Physical



Agents in the Workroom Environment with Intended Changes for 1977.



Cincinnati, Ohio.







American Conference of Governmental Industrial Hygienists.  1977b.



Documentation of the Threshold Limit Values.  3rd ed.  Cincinnati,



Ohio.







Arthur, R.D.,  et  al.   1976.  Atmospheric  levels  of pesticides in



the Mississippi delta.  Bull. Environ.  Contain. Toxicol.  15: 129.







Baeumler, W.   1975.   Side  effects  of toxaphene  on mice.   Anz.



Schaedlingskd., Pflanz. Umweltschutz.  48:  65.







Bailey, T.E. and J.R.  Hannum.  1967.  Distribution of pesticides in



California.   Jour.  San.  Eng.  Div.  Proc.  Am.   Soc.  Civil  Eng.



93: 27.







Barthel, W.F.,  et  al.   1969.  Pesticide residues  in sediments of



the lower Mississippi River and  its tributaries.   Pestic. Monitor.



Jour.  3: 8.
                              C-59

-------
Bidleman, T.F.  and C.E.  Olney.   1975.   Long range  transport of
toxaphene insecticide in the atmosphere of the western North Atlan-
tic.  Nature.  257: 475.

Bidleman, T.F.,  et al.   1976.  High  Molecular  Weight Chlorinated
Hydrocarbons in  the Air and  Sea:  Rates and Mechanisms  of Air/Sea
Transfer.   In; H.L. Windom and  R.E.  Dace  (eds.)f  Marine Pollutant
Transfer.  D.C. Heath & Co.

Boyd, E.M. and F.I. Taylor.   1971.  Toxaphene toxicity in protein-
deficient rats.  Toxicol. Appl.  Pharmacol.  18:  158.

Brown, E. and Y.A.  Nishioka.   1967.  Pesticides in selected western
streams - a contribution to the national program.  Pestic. Monitor.
Jour.  1: 38.

Chandurkar,  P.S.   1977.   Metabolism of  toxaphene  components in
rats.  Microfilmed by Photogr. Media Center, Univ. of Wisconsin.

Chernoff, N. and B.D. Carver.   1976.   Fetal toxicity of  toxaphene
in  rats and mice.  Bull. Environ.  Contam.  Toxicol.  15: 660.

Clapp, K.L., et al.  1971.  Effect of Toxaphene on  the  Hepatic Cells
of  Rats.  Ini Proc. Ann. Meet. Western Section, Am.  Soc. Anim.  Sci.
Fresno State College, Fresno, California.
                               C-60

-------
Cohen, J.M.,  et  al.   1961.  Effect  of  fish poisons on water sup-



plies.   III. Field  study at  Dickinson.    Jour.  Am.  Water Works



Assoc.  53: 233.







Conley, B.E.   1952.   Pharmacological properties of  toxaphene, a



chlorinated  hydrocarbon  insecticide.    Jour.  Am.  Med.  Assoc.



149: 1135.







Corneliussen, P.E.  1969.   Pesticide  residues in  total diet  samples



(IV).  Pestic. Monitor. Jour.  2: 140.







Corneliussen, P.E.  1970.   Pesticide  residues in  total diet  samples



(V).  Pestic. Monitor. Jour.  4: 89.







Corneliussen, P.E.  1972.   Pesticide  residues in  total diet  samples



(VI).  Pestic. Monitor. Jour.  5: 313.







Crowder, L.A. and E.F. Dindal.   1974.  Fate of chlorine-36-labeled



toxaphene in rats.  Bull.  Environ. Contam. Toxicol.   12: 320.







Deichmann, W.B.  and M.L. Keplinger.  1970.  Protection against  the



acute effects of  certain  pesticides  by pretreatment  with  aldrin,



dieldrin,  and DDT.    Pestic. Symp.  Collect.  Pap.  Inter-Am. Conf.



Toxicol. Occup.  Med., 6th, 7th, 1968-1970.
                              C-61

-------
DiPasquale, L.C.   1977.   Interaction of  toxaphene  with ascorbic
acid in  the pregnant  guinea pig.   Master's Thesis.   Wright State
University, 1976.  EPA in-house rep. 1977.  Summarized by K. Diane
Courtney, Environ. Toxicol.  Div., Health Eff. Res. Lab., U.S. Envi-
ron. Prot. Agency, in a Toxaphene review dated Nov. 16, 1977.

Duggan, R.E. and P.E.  Corneliussen.  1972.  Dietary intake of pes-
ticide chemicals in the United States (III).  June 1968-April 1970
(with summary of 1965-1970).  Pestic. Monitor.  Jour.  5: 331.

Duggan, R.E.  and  F.J. McFarland.   1967.   Assessments include raw
food and  feed  commodities,  market  basket  items  prepared  for con-
sumption, meat samples taken at slaughter.  Pestic. Monitor. Jour.
1: 1.

Duggan, R.E.,  et al.  1966.  Pesticide residues  in total diet sam-
ples.  Science.  151:  101.

Duggan, R.E.,  et al.  1967.  Pesticide residues  in total diet sam-
ples (II).  Pestic. Monitor. Jour.   1: 2.

Durant, C.J. and R.J.  Reimold.  1972.  Effects of estuarine dredg-
ing of toxaphene-contaminated sediments in Terry Creek, Brunswick,
Georgia - 1971.  Pestic. Monitor.  Jour.   6: 94.
                               C-62

-------
 Epstein,  S.S.,  et al.   1972.   Detection of chemical mutagen by the
 dominant  lethal  assay  in  the  mouse.    Toxicol.  Appl.  Pharmacol.
 23:  288.

 Fitzhugh,  O.G.  and A.A. Nelson.  1951.  Comparison of  chronic ef-
 fects produced  in rats  by several chlorinated  hydrocarbon insecti-
 cides.  Fed.  Proc.   10:  295.

 Gaines,  T.B.    1960.   The acute toxicity  of  pesticides  to  rats.
 Toxicol. Appl.  Pharmacol.   2:  88.

 Gaines, T.B.  1969.  Acute toxicity of  pesticides.   Toxicol.  Appl.
 Pharmacol.  14: 515.

 Grebenyuk, S.S.  1970.   Effect of polychlorocamphene on  liver  func-
 tions.  Gig.  Primen., Toksokol.  Pestits. Klin. Otravlenii.  8:  166.

 Grzenda, A.R. and H.P.  Nicholson.  1965.   Distribution and magni-
 tude of insecticide  residues  among various components of a stream
 system.     Trans.   South.  Water  Resour.  Pollut.  Control   Conf.
 14: 165.

Grzenda, A.R., et  al. 1964.   Water pollution by insecticides  in an
agricultural river basin.   II.  The  zooplankton,  bottom fauna and
fish.  Limnol. Oceanog.   9: 318.
                              C-63

-------
Gunther, F.A.   1969.   Insecticide residues  in  California citrus



fruits on products.  Residue Rev.  28: 1.







Haun, E.G.  and  C.  Cueto.   1967.   Fatal toxaphene  poisoning  in a



9-month-old infant.  Am. Jour. Dis. Child.   113: 616.







Hayes,  W.J.,  Jr.    1963.   Clinical Handbook  on Economic  Poisons.



Pub. Health Publ. No. 475.  U.S. Government Printing Office, Wash-




ington, D.C.







Hercules,  Inc.   Undated.   Hercules  toxaphene insecticide.  Bull.




T-105c.







Herring,  J.  and D.  Cotton.   1970.   Pesticide  residues of twenty



Mississippi delta  lakes.   Proc.  24th Annu. Conf. S.E. Assoc. Game



Fish Comm.  482.







Hill, R.N.  1977.   Memorandum to Fred Hageman.   Off.  Spec. Pestic.



Rev., U.S.  EPA.  December  15.







International Joint Commission, United  States  and Canada.   1977.



New and Revised Great  Lakes  Water Quality Objectives.   In:  Toxa-




phene.   Vol.  II.







Johnson, R.D. and  D.D.  Manske.   1975.  Pesticide residues in  total



diet samples  (IX).  Pestic. Monitor.  Jour.  9:  157.
                                C-64

-------
 Johnson, R.D. and D.D. Manske.  1977.  Pesticide and other chemical
 residues  in  total diet  samples  (XI).    Pestic.  Monitor.  Jour.
 11: 116.

 Johnston, W.R., et al.  1967.  Insecticides in tile drainage efflu-
 ent.  Water Resour. Res.  3:  525.

 Kennedy,  G.L.,  Jr.,  et  al.    1973.   Multigeneration  reproductive
 effects  of  three pesticides  in rats.   Toxicol.  Appl.  Pharmacol.
 25: 589.

 Keplinger, M.L. and W.B. Deichmann.   1967.  Acute  toxicity  of com-
 binations of pesticides.  Toxicol. Appl. Pharmacol.  10:  586.

 Keplinger, M.L., et al.   1970.  Effects of Combinations  of  Pesti-
 cides on  Reproduction in Mice.   In; Pestic.  Symp.  Collect.  Pap.
 Int. Am. Conf. Toxicol. Occup. Med.  6th, 7th.

 Khalifa, S., et al. 1976.  Toxaphene degradation by  iron (II)  pro-
 toporphyrin systems.  Jour. Agric. Food Chem.  24: 277.

 Kulkarni, A.P., et al.  1975.  Cytochrome P-450 optical  difference
 spectra of  insecticides.   Comparative  study.  Jour.  Agric.  Food
Chem.   23: 177.

Lackey,  R.w.  1949a.   Observations  on the  acute and chronic  toxi-
city of  toxaphene in the dog.  Jour. Ind. Hyg. Toxicol.   31:  155.
                              C-65

-------
 Lackey,  R.W.   1949b.  Observations on  the  percutaneous  absorption



 of  toxaphene  in  the rabbit  and dog.   Jour.  Ind.  Hyg.  Toxicol.




 31:  155.







 Lehman,  A.J.   1951.  Chemicals  in foods: A report  to  the Associa-



.tion of  Food  and  Drug Officials on current  developments.  Part II.



 Pesticides.   U.S. Q. Bull.  Assoc.  Food Drug Off.  15:  122.







 Lehman,  A.J.   1952a.   Oral toxicity of toxaphene.  U.S. Q.  Bull.



 Assoc. Food Drug Off.  16:  47.







 Lehman,  A.J.   1952b.   II.  Pesticides: Dermal  toxicity.   U.S. Q.



 Bull. Assoc.  Food Drug Off.  16: 3.







 Lehman,  A.J.  1965.  Summaries  of pesticide  toxicity.   Assoc.  Food



 Drug Off., Topeka, Kans. Summarized  in U.S.  Environ.  Prot. Agency,




 1976b.







 Lichtenberg,  J.J.  1971.   Aspects  of pesticidal use of toxaphene



 and  terpene  polychlorinates on man and the environment.  Cited by



 Hartwell,  et al.  1974.   Anal. Qual.  Control  Lab.    U.S. Environ.



 Prot. Agency, Cincinnati,  Ohio.







 Lichtenberg,  J.J., et al.   1970.  Pesticides  in  surface waters  of



 the United  States - a 5-year  summary,  1964-1968.   Pestic. Monitor.




 Jour.  4:  71.
                                C-66

-------
Litton  Bionetics,  Inc.   1978.   Carcinogenic  evaluation in  mice.
Toxaphene.   Final  rep.   LBI  Project No. 20602.   Kensington, MD.
Submitted to Hercules, Inc., Wilmington, Delaware.

Manigold, D.B.  and J.A.  Schulze.   1969.   Pesticides in selected
western  streams - a  progress  report.    Pestic.  Monitor.   Jour.
3: 124.

Manske, D.D. and P.E.  Corneliussen.   1974.   Pesticide residues  in
total diet samples (VII).  Pestic. Monitor. Jour.  8: 110.

Manske, D.D. and R.D. Johnson.  1975.  Pesticide  residues in  total
diet samples (VIII).   Pestic. Monitor. Jour.  9:  94.

Manske, D.D. and R.D.  Johnson.   1976.   Pesticide  and metallic  resi-
dues in total diet samples (X).  Pestic. Monit. Jour.  10: 134.

Martin, R.J. and R.E.  Duggan.   1968.   Pesticide residues in  total
diet samples (III).  Pestic.  Monitor. Jour.   1: 11.

Matsumura, F.  1975.   Toxicology of Insecticides.  Plenum Press.

Mattraw, H.C.  1975.   Occurrence of chlorinated hydrocarbon insec-
ticides - southern Florida - 1968-1972.   Pestic.  Monitor.   Jour.
9: 106.
                              C-67

-------
McGee, L.C.,  et al.   1952.   Accidental poisoning  by toxaphene.



Jour. Am. Med. Assoc.  149: 1124.







Mehendale, H.M.   1978.   Pesticide-induced modification of hepato-



biliary function: hexachlorobenzene, DDT and toxaphene.  Food Cos-




met. Toxicol.  16: 19.







Mississippi  Agricultural  Experiment  Station,  Dept.  of  Biochem-



istry.  1976.  Samples of air  received from  Delta  Branch Exp.  Sta-



tion.  Mississippi  State Univ.  Summarized in U.S.  Environ. Prot.




Agency,  1977.   (Unpubl.)







National Academy of  Sciences.  1977.  Drinking water and  health.   A



report  of the  Safe Drinking  Water  Committee Advisory  Center  on



Toxicology Assembly of  Life  Sciences,  National  Research  Council,




Washington,  D.C.







National Cancer Institute.   1977.   Guidelines for  carcinogenesis



bioassays in small rodents.  Tec. Rep. No. 1.  Publ.  No.  017-042-



 00118-8.  U.S.  Government Print. Off.,  Washington, D.C.







 National Cancer Institute.  1979.  Bioassay of toxaphene for possi-



 ble carcinogenicity.  DHEW Publ. No.  (NIH)  73-837.







 Nicholson, H.P.   1969.   Occurrence and  significance  of pesticide



 residue  in water.  Jour. Wash. Acad.  Sci.  59: 77.
                                C-68

-------
 Nicholson,  H.P.,  et al.   1964.   Water pollution by insecticides in
 an agricultural  river  basin.   I.  Occurrence  of  insecticides  in
 river and treated water.   Limnol.  Oceanog.   9:  310.

 Nicholson,  H.P.,  et al.   1966.   Water Pollution by Insecticides: A
 Six and  One-half  Year Study of a Watershed.  In; Proc. Symp. Agric.
 Waste Waters.  Rep. No. 10 of water Resour. Center.  Univ. of Cali-
 fornia.

 Ohsawa,  T., et al.  1975.  Metabolic dechlorination of toxaphene in
 rats.  Jour. Agric.  Food  Chem.   23: 98.

 Ortega,  P., et al.   1957.  Pathologic changes in the  liver  of rats
 after  feeding low levels  of various insecticides.   Am.  Med.  Assoc.
 Arch.  Pathol.  64:  614.

 Pollock,  G.A.   1978.   The toxicity  and metabolism of  toxaphene.
 Univ.  of  California, Davis.

 Pollock,  R.w.    1958.    Toxaphene-lindane poisoning  by  cutaneous
 absorption -  report of  a  case with recovery.    Northwest  Med.
 57: 325.

Reimold,  R.J.  1974.   Toxaphene interactions in estuarine ecosys-
tems.  Natl. Tech. Inf. Serv.  COM-75-10104/8GA.   Springfield, Vir-
ginia.
                              C-69

-------
Reimold, R.J. and C.J. Durant.  1972a.  Survey of toxaphene levels
in Georgia estuaries.   Tech.  Rep.  Ser. No. 72-2.  Georgia Mar. Sci.
Center, Skidaway Island.

Reimold, R.J. and C.J.  Durant.   1972b.   Monitoring toxaphene con-
tamination in a  Georgia estuary.   Natl. Tech. Inf.  Serv.  COM 73-
1072.  Springfield,  Virginia.

Reimold, R.J. and C.J. Durant.  1974.  Toxaphene content of estua-
rine fauna and flora before, during, and after dredging toxaphene-
contaminated sediments.  Pestic. Monitor. Jour.  8: 44.

Rico, A.   1961.  Chlorinated synthetic organic  insecticides and
their toxicology.  Red. Med. Vet. Ecole Alfort.  137: 761.

Saleh, M.A., et  al.   1977.   Polychlorobornane components of  toxa-
phene:   Structure-toxicity   relations   and   metabolic  reductive
dechlorination.  Science.  198: 1256.

San Joaquin District, Calif. Dept. of Water Resources.  1963-1969.
Annual  summaries of  water-borne chlorinated hydrocarbon pesticide
program.   In;  G.E.  Guyer, et al.  1971.   Toxaphene status report.
Spec. rep.  Hazard.  Mater. Adv. Comm., U.S. Environ. Prot. Agency.
                               C-70

-------
Schafer, M.L., et al.   1969.   Pesticides  in drinking water from the



Mississippi and Missouri Rivers.  Environ. Sci. Technol.  3: 1261.







Schulze,  J.A.,   et  al.   1973.   Pesticides  in  selected  western



streams - 1968.  Pestic. Monitor. Jour.  7: 73.







Shelanski, H.A.  1974.  Rep. to Hercules, Inc.  (Unpubl.)







Shelanski, H.A. and A. Gellhorn.   Undated.  Data cited by McGee, et



al. 1952.  (Unpubl.)







Sigworth, E.A.  1965.   Identification  and removal  of herbicides and



pesticides.  Jour. Am. Water Works Assoc.  57: 1016.







Stanley, C.W., et al.   1971.  Measurement of atmospheric levels of



pesticides.  Environ.  Sci. Technol.   5: 430.







Stephan, C.E.  1980.  Memorandum to J. Stara.  U.S. EPA.  July 3.







Tabor, E.G.  1965.   Pesticides  in  urban atmosphere.  Jour. Air Pol-



lut. Control Assoc.  15: 415.







Tabor, E.G.  1966.  Contamination of  urban air through  the use of



insecticides.  Trans.  N.Y. Acad.  Sci.  Ser. 2.  28: 569.







Terriere, L.C., et al.  1966.   The persistence of  toxaphene in lake



water and its uptake  by aquatic plants and animals.   Jour.  Agric.



Food Chem.  14: 66.
                              C-71

-------
U.S. Department of Agriculture.  1978.  Data courtesy of Dr.  Grace



~Clark, Residue Eval. Surveil. Div., Food Safety Qual. Serv.,  Wash-



ington, D.C.   (Unpubl.)







U.S. EPA.   1976a.  Laboratory examination  of drinking water pesti-



cide analysis.  Summarized  in U.S.  EPA, 1977.   (Unpubl.)







U.S. EPA.   1976b.  National Interim Primary Drinking Water Regula-



tions.  EPA-570/9-76-003, Off.  of  Water Supply.







U.S.  EPA.    1976c.   Quality Criteria  for  Water.   Report  No. EPA-



440/9-76-023.







U.S. EPA.   1976d.  Episode  summary  for reports involving toxaphene.



Pesticide  Episode Review  System,  Rep.  No. 81.   Pestic.  Episode




Resp.  Branch.







U.S.  EPA.   1977.   Toxaphene: Position document.







 U.S.  EPA.    1978.  Occupational exposure  to toxaphene.   Final rep.



 by the Epidemiol. Stud. Progr.   Off.  Tox. Subst., Washington, D.C.



 (Draft).







 U.S.  EPA.   1980.   Seafood  consumption  data  analysis.    Stanford



 Research Institute  International,  Menlov Park,  Calif.   Final rep.,



 Task II.  Contract  No. 68-01-3887.
                                C-72

-------
Warraki,  S.   1963.   Respiratory hazards of chlorinated  camphene.
Arch. Environ. Health.  7: 253.

Weaver,  L. ,  et al.   1965.   Chlorinated hydrocarbon -pesticides  in
major U.S. river basins.  Pub. Health Rep.  80: 481.

Whitcomb, E.R. and J.A. Santolucito.   1976.   The action  of pesti-
cides on  conduction  in  the  rat superior cervical ganglion.  Bull.
Environ.  Contain. Toxicol.   15: 348.

World Health  Organization.   1974a.  Evaluation  of  some  pesticide
residues  in foods: Camphechlor.  Pestic. Residues Ser. No. 3.

World Health  Organization.    1974b.   Pesticide  residues  in food.
Tech. Rep. Ser. No. 545.

World Health  Organization.    1976.   Pesticide residues  in food.
Tech. Rep. Ser. No. 592.
                              C-73

-------
                           APPENDIX  I

      Summary and Conclusions Regarding the Carcinogenicity
                          of Toxaphene*

     Toxaphene is a mixture  of  polychlorinated camphenes.   It was
found to be mutagenic for Salmonella typhimurium strains TA 98 and
TA 100 without metabolic activation.   Two  studies,  (1) the National
Cancer  Institute  (NCI)  bioassay  (dietary  study)  on  toxaphene in
mice and  rats,  and  (2)   the  Bionetics  Research Laboratory dietary
study (sponsored by  Hercules,  Inc.) in mice, have demonstrated  that

toxaphene is carcinogenic to both mice and rats.
     The  NCI  dietary  study using male  and female  BSCSF^  mice at
doses of 99 and 198  ppm  revealed a statistically significant excess
of hepatocellular carcinomas  in male and  female mice at both  dose
levels.  The Bionetics Research Laboratory study in the  same strain
 (B6C3F,)  of male and  female mice  fed at doses  of 7,  20, and 50 ppm
 in the  diet showed a statistically significant excess of hepatocel-
 lular  tumors  (hepatocellular adenoma plus hepatocellular carcino-

ma)  in  male mice, but only at the 50 ppm  dose.
     The  NCI  bioassay  study  also showed  a  carcinogenic response
 induced by toxaphene in  both  male  and female  Osborne-Mendel  rats
 only at the high dose level  (1,080 ppm),  consisting of  a  statisti-
 cally  significant excess of follicular-cell carcinomas and adenomas

 of  the  thyroid.
      In summary,  carcinogenic  responses have  been  induced  in  mice
 and  rats by toxaphene.   These  results, together with the  positive
 mutagenic response,  constitute  substantial evidence that  toxaphene

 is  likely to  be a human carcinogen.
                               C-74

-------
     The water  quality  criterion for toxaphene  is  based on inci-
dence of hepatocellular  carcinomas and neoplastic nodules from the
Litton Bionetics B6C3F1 male mice bioassay.   it  is  concluded that
the water concentration  of toxaphene should be less  than 7.1 ng/1
in order to keep the lifetime cancer risk below 10~5.
                                           Carolno««»
                             C-75

-------
     Derivation of the Water Quality Criterion  for  Toxaphene


     The water quality criterion  for toxaphene  is  derived from the

development of hepatocellular carcinomas  and  neoplastic nodules in

the B6C3F-L male mice given several doses of toxaphene in the Litton

Bionetics bioassay (Litton Bionetics,  1978).   The criterion is cal-

culated from the following parameters:


         Dose                           Incidence
     (mg/kg/day)               (no.  responding/no,  tested)

          0.0                            10/53

          0.91                           11/54

          2.6                            12/53

          6.5                            18/51



     le = 540 days            w  = 0.030 kg

     Le = 735 days            R  = 13,100  I/kg

     L  = 735 days


     With  these parameters,  the  carcinogenic  potency  factor for

humans, q,* is 1.131 (mg/kg/day)    .  The resulting water concentra-

tion of toxaphene calculated to keep the  individual  risk below 10

is 7.1 ng/1.
                               C-76


                                              . „ S. GOVERNMENT PWNTtNG OFFICE 1980  720-016/5955

-------