• , ,:
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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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(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
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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
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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
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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
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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
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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
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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
-------
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B-30
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B-31
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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
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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
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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
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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
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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
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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.
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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.
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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««»
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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.
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