United States
                      Environmental Protection
                                  Office of Water
September 1999
Fact Sheet
Toxaphene Update:   Impact on Fish  Advisories

Toxaphene is the tradename for an organochlorine pesticide that is comprised of a mixture of at least
670 chlorinated camphenes. Toxaphene was first introduced in 1947 and was probably the most heavily used
pesticide in the United States during the 1970s after DDT was banned. In the United States, toxaphene was banned
for most uses in 1982 and all uses were banned in 1990. However, due to its relatively long half-life, toxaphene
persists in  the environment.  The soil half-life is approximately 1 to 14 years. Toxaphene can enter waterbodies from
soil runoff and can also volatilize and be transported to waterbodies  via the atmosphere. Toxaphene absorbed by
organisms accumulates in fatty tissues and has been shown to affect the central nervous system and the liver. EPA
has classified toxaphene as a probable human carcinogen (Group B2). As of 1998, four states have issued a total of
six fish advisories for toxaphene. These advisories inform the public that high concentrations of toxaphene have
been found in local fish at levels of public health concern. State advisories recommend either limiting or avoiding
consumption of certain fish from specific waterbodies or, in some cases, from specific waterbody types (e.g., all
freshwater lakes or rivers).
  The purpose of this fact sheet is to summarize current information on sources, fate and transport, occurrence
  in human tissues, range of concentrations in fish tissue, fish advisories, fish consumption limits, toxicity, and
  regulations for toxaphene. The fact sheets also illustrate how this information may be used for developing fish
  consumption advisories. An electronic version of this fact sheet and fact sheets for dioxins/furans, mercury,
  and PCBs, are available at http://www.epa.gov/OST/fish. Future revisions will be posted on the web as they
  become available.
Sources of Toxaphene in the

In the United States, all uses of toxaphene were
banned in 1990. As a result, no entries for toxaphene
are reported in EPA's Toxic Chemical Release
Inventory (TRI). In the past, toxaphene entered the
environment as an insecticide. Toxaphene entered
surface waters through runoff from rain, by direct
application to lakes as a pesticide, by wastewater
release from manufacturing facilities, and through
activities related to disposal of waste pesticides.
Toxaphene adsorbs to soil particles, and may enter
waterbodies in this form. Virtually all of the
toxaphene in waterbodies is in the particulate and
sediment fractions. Toxaphene was also applied
directly to soil as an insecticide for agricultural crops.

Fate and Transport of Toxaphene

Once toxaphene enters the environment, it breaks
down very  slowly. Therefore, even though the use of
toxaphene has been banned in the United  States for
more than  10 years, exposures may still occur. After
releases to surface water or soils or application to
crops, the more volatile components of toxaphene
readily partition to the atmosphere where they
persist. The atmosphere is the most important
environmental medium for the transport of toxaphene
and it can also be transported to  surface water and
soil by wet and  dry deposition. As a result, toxaphene
can be carried far from its original release  site. In
                               soil, toxaphene binds to soil particles; therefore,
                               leaching to ground water is not of great concern. In
                               surface water, the toxaphene that does not volatilize
                               is eventually deposited in sediments.

                               Toxaphene can bioconcentrate in the tissues of
                               aquatic organisms and may also be biomagnified in
                               the aquatic food chain. In 1984 and 1985, the U.S.
                               Fish and Wildlife Service collected 321  composite
                               samples of whole fish from 112 stations nationwide
                               as part of the National Contaminant Biomonitoring
                               Program (NCBP). Toxaphene was detected in
                               freshwater fish at 69% of 112 stations sampled in the
                               NCBP study. Maximum and geometric mean tissue
                               concentrations of toxaphene in  1984 were 8.2 and
                               0.14 ppm (wet weight), respectively. An analysis of
                               all 1984-1985 data from the NCBP study on
                               toxaphene in bottom-feeding and predatory fish
                               species showed there was no significant difference in
                               residues in these two trophic groups of fish. Mean
                               tissue concentrations of toxaphene were 0.19 + 0.63
                               and 0.17 + 0.35 ppm,  respectively, for bottom
                               feeders and predator species. Results of a more
                               recent study  show the range of total toxaphene
                               concentrations (wet weight) measured in various fish
                               species in  the Great Lakes from 1992-1994 (see
                               Table 1).

       Table 1. Mean Concentrations of
        Toxaphene Reported in Great
           Lakes Fish3 (1992-1994)
Error of
   Species included only freshwater finfish.
 b Concentrations are reported on a wet weight basis.
 Source: Glassmeyer et a/., 7997.
Potential Sources of Exposure and
Occurrence in Human Tissues

Because the use of toxaphene was banned in the
United States, potential sources of exposure are
limited. Low-level exposures may occur in the
general  population through ingestion of contaminated
food. Because toxaphene may accumulate in fish
and shellfish, persons who consume large quantities
of these foods may be at greater risk of higher level
exposure than the general population. Additionally,
persons who eat large quantities of wild game from
areas where toxaphene was  heavily used as a
pesticide may also be at higher risk. An additional
source of potential exposure is contact with
toxaphene-contaminated media near toxaphene
waste disposal sites. Before toxaphene was banned,
major sources of exposure resulted during its
manufacture and use as an insecticide. These
exposures were primarily dermal or by inhalation.

Analytical methods can be used to measure
toxaphene in blood, urine, breast milk,  and body
tissues.  Similar to PCBs, toxaphene analysis can be
conducted for specific congeners using high
resolution spectrometry or gas chromatography with
electron-capture negative ionization. However, there
currently are no standard methods for these
analyses. At this time, EPA's Office of Water
recommends analysis of total toxaphene until further
development of congener-specific analyses.
Fish Advisories

The states have primary responsibility for protecting
their residents from the health risks of consuming
contaminated noncommercially caught fish. They do
this by issuing consumption advisories for the
general population, including recreational and
subsistence fishers, as well as sensitive
subpopulations (such as pregnant women/fetus,
nursing mothers, and children). These advisories
inform the public that high concentrations of
chemical  contaminants, such as toxaphene, have
been found in local fish. The advisories recommend
either limiting or avoiding consumption of certain fish
from specific waterbodies or, in some cases, from
specific waterbody types (such as lakes or rivers).

As of December 1998, toxaphene was the chemical
contaminant  responsible, at least in part, for the
issuance  of a total of six fish consumption advisories
by four states: Arizona (3), Georgia (1), Oklahoma
(1), and Texas (1) (see Figure 1). This contaminant
accounts  for  less than 0.2 % of all advisories issued
in the United States.  The number of advisories for
toxaphene has remained relatively unchanged from
1993 through 1998. Currently, no states have issued
statewide or  regionwide advisories for toxaphene in
their freshwater  lakes and/or rivers or in their coastal
marine waters.

Fish Consumption Limits—Table 2 shows the
recommended monthly fish consumption limits for
toxaphene for fish consumers based on EPA's

     Table  2. Monthly Fish Consumption
            Limits for Toxaphene

None (<0.5)a
Fish Tissue
s (ppm, wet
Fish Tissue
(ppm, wet weight)
>0.0027 - 0.0055
>0.0055 - 0.0073
>0.0073 - 0.01 1
>0.011 -0.022
>0.022 - 0.029
>0.029 - 0.044
>0.044 - 0.088
 aNone = No consumption recommended.
 Note: In cases where >16 meals per month are
 consumed, refer to EPA's Guidance for Assessing
 Chemical Contaminant Data for Use in Fish Advisories,
 Volume 2, Section 3 for methods to determine safe
 consumption limits.

                              Figure 1. Fish Advisories for Toxaphene.
D American Samoa
D Guam
D Virgin Islands
D Puerto Rico
                                                                     EH States issuing advisory (4)
values for risk assessment parameters.
Consumption limits have been calculated as the
number of allowable fish meals per month, based on
the ranges of toxaphene in the consumed fish tissue.
The following assumptions were used to calculate the
consumption limits:

#   Consumer adult body weight of 72 kg
#   Average fish meal size of 8 oz (0.227 kg)
#   Time-averaging period of 1 month (30.44 d)
#   EPA's reference dose for toxaphene
    (2.5 x 10~4  mg/kg-d) from EPA's Reference Dose
    Tracking Report (U.S.  EPA, 1997)
#   EPA's cancer slope factor for toxaphene
    (1.1 per mg/kg-d) from EPA's Integrated Risk
    Information System (U.S. EPA, 1999b)
#   Maximum acceptable cancer risk level (10~5 over
    a 70-year lifetime).

For example, when toxaphene levels in fish tissue are
1 ppm, then sixteen 8-oz. meals per month (based
on the noncancer health endpoint-EPA's reference
dose) or a half  an 8-oz. meal per month (based on
the cancer health endpoint-EPA's cancer slope
factor) can safely be consumed. EPA recommends
using the more conservative  of the two limits; for
toxaphene, this is the consumption limit based on the
                            cancer health endpoint. For sensitive populations,
                            such as pregnant women, nursing mothers, and
                            young children, some States have issued either "no
                            consumption" advisories or "restricted consumption"
                            advisories for toxaphene. Additional information on
                            calculating specific limits for these sensitive
                            populations is available in EPAs Guidance for
                            Assessing Chemical Contaminant Data for  Use in
                            Fish Advisories,  Volume 2, Section 3.

                            Toxicity of Toxaphene

                            Pharmacokinetics—Most of the components of
                            toxaphene are rapidly degraded in mammals via
                            dechlorination, dehydrodechlorination, and oxidation,
                            primarily through the action of the mixed function
                            oxidase system and other hepatic microsomal
                            enzymes. Conjugation may occur but is not a major
                            route of metabolism.  Each  component of toxaphene
                            has its own  rate of biotransformation, making the
                            characterization  of toxaphene pharmacokinetics
                            complex. Some components of toxaphene  are highly
                            lipophilic and poorly metabolized; these components
                            may accumulate in body fat.

                            Acute Toxicity—Acute high-level exposures  to
                            toxaphene and toxaphene-contaminated food have

resulted in death in adults and children with an
estimated minimum lethal dose of 2 to 7 g, which is
equivalent to 29 to  100 mg/kg for an adult male. LD50
values in rats were 80 mg/kg  for females and 90
mg/kg for males. Transient liver and kidney effects
and periods of memory loss have been observed in
humans after single large oral exposures. In animals,
the most sensitive organ is the liver. Toxicity to  the
central nervous  system, kidneys, and adrenal glands
has also been observed.

Chronic  Toxicity—Chronic exposure to toxaphene
may result in damage to the following organ
systems: liver, kidney, adrenal, immunological,  and
neurological. Chronic exposure to toxaphene may
cause hormonal alterations. A study on chronic
exposure found  increased levels of hepatic
metabolism of the hormones estradiol and estrone
and a decrease  in their uterotropic action. Some
adverse effects of toxaphene  that do not occur with a
single exposure  may result from repeated exposure
totaling a lower cumulative dose. Exposures at  0.06
mg/kg-d over 5 weeks caused adrenal hormone
reductions, whereas a single dose of 16 mg/kg  did
not cause effects.

Developmental Toxicity—Women exposed to
toxaphene after  entering a field that had recently
been sprayed with the chemical exhibited a higher
incidence of chromosomal aberrations in cultured
lymphocytes than did unexposed women. Dermal
and inhalation uptake were the probable routes  of
exposure; however, the  exposure was not quantified.
Animal study results suggest that toxaphene does
not interfere with fertility in experimental animals at
the doses tested (up to 25 mg/kg-d).

Adverse developmental effects, including
immunosuppressive and behavioral, were noted in
experimental animals at levels below those required
to induce maternal toxicity. Immunosuppression
(reduction in macrophage levels, cell-mediated
immunity, and humoral immunity) was observed in
test animals exposed during gestation and nursing,
as were alterations in kidney and liver enzymes and
delayed bone development. Other adverse effects
noted in offspring of maternally exposed animals
included  histological changes in the liver, thyroid,
and kidney.

Toxaphene is known to be rapidly conveyed into
breast milk after maternal exposure to the chemical.
The half-life of toxaphene in milk has been estimated
at 9 days.

As noted above, toxaphene accumulates in body
tissue; consequently, exposure occurring prior to
pregnancy can contribute to the overall maternal
body burden and result in exposure to the developing
individual. Therefore, it is necessary to reduce
exposure to children and women with childbearing
potential to reduce overall body burden. Depending
on the timing and extent of an individual's prior
exposure to toxophene, the outcome of that
pregnancy may be affected even if exposure is
reduced during pregnancy.
  Children may be at greater risk for toxic
  effects caused by toxaphene because their
  immune systems are not fully developed until 10
  to 12 years of age. Immunosuppressive effects
  have been demonstrated in animals after
  chronic exposure to toxaphene. These studies
  have also suggested that immature animals
  cannot detoxify a toxaphene mixture as
  efficiently as they can the single components of
  the mixture.
Mutagenicity—Changes in human genetic material
have been noted  in workers exposed to toxaphene.
There are also numerous positive mutagenicity
assays of toxaphene: the Ames test, sister chromatid
exchange, chromosomal aberrations in toxaphene-
exposed  humans, and forward mutation assays. The
implications of this for human germ cells are not
known. One assay designed to assess the dominant
lethal effects on implantations in mice yielded
negative  results. Some data suggest that the polar
fraction of toxaphene may be more mutagenic than
the nonpolar fraction.

Carcinogenicity—Toxaphene  is classified as a
probable  human carcinogen (Group B2) by EPA
based on oral studies in animals. No conclusive
human epidemiological studies are available for
toxaphene. Oral administration of toxaphene resulted
in an increased incidence of hepatocellular
carcinomas and neoplastic nodules in  mice and
thyroid tumors in rats.

Toxaphene has recently been observed to have
estrogenic effects on human breast cancer estrogen-
sensitive  cells. Xenoestrogens have been
hypothesized to have a role in human breast cancer.
In addition to potential carcinogenic effects,
toxaphene may also cause disruption of the
endocrine system due to its estrogenic activity.
     Summary of EPA Health Benchmarks

  #  Chronic Toxicity—Reference Dose:
     2.5 x 1Q-4 mg/kg-d (U.S. EPA, 1997)

  #  Carcinogenicity: 1.1 per mg/kg-d (U.S.
     EPA, 1999b)
Special Susceptibilities—A protein-deficient diet
may increase the toxicity of toxaphene approximately
threefold based on an LD50 study in rats. Individuals
with  latent or clinical neurological diseases, such as

epilepsy or behavioral disorders, may be at higher
risk for toxaphene toxicity.  In addition, children may
be especially susceptible to toxaphene-induced
neurotoxicity based on early reports of acute
ingestion toxicity.

Other individuals who may be at higher risk are those
with diseases of the renal,  nervous, cardiac, adrenal,
and respiratory systems. Individuals using certain
medications are also at potential risk due to the
induction of hepatic microsomal enzymes by
toxaphene (discussed further in the following

Interactive Effects —Metabolism of some drugs and
alcohol may be affected by toxaphene's  induction of
hepatic microsomal enzymes. This was observed in
a man using warfarin as an anticoagulant while he
used toxaphene as an insecticide. The effectiveness
of the drug was reduced because toxaphene's
induction of microsomal enzymes increased the
drug's metabolism.

Based on acute studies in animals and anecdotal
reports of acute exposure in humans, exposure to
chemicals that increase microsomal mixed-function
oxidase systems (e.g., lindane) are likely to reduce
the acute toxicity of other chemicals detoxified by the
same system (e.g., toxaphene) because the system
is functioning at a higher than normal level.
Toxaphene, in turn, may reduce the acute toxicity of
chemicals that require this system for detoxification.

Critical Data Gaps —The following data gaps have
been  identified for toxaphene.
#   mammalian germ cell genotoxicity,
#   studies that investigate sensitive developmental
    toxicity endpoints including behavioral effects,
#   epidemiological and animal studies of
#   long-term neurotoxicity studies in animals using
    sensitive functional and neuropathological tests
    and  behavioral effects on prenatally exposed
#   epidemiological studies evaluating multiple
    organ systems,  and pharmacokinetic studies.
                                    EPA Regulations and Advisories

  #   Maximum Contaminant Level in drinking water = 0.003 mg/L

  #   Listed as a hazardous air pollutant under the Clean Air Act

  #   Reportable Quantity = 1 Ib

  #   Toxaphene Effluent Standard = 0-15 ug/L discharge/day

  #   Effluent Guidelines and Standards: Electroplating—Definition of Total Toxic Organic = > 0.01 mg/L

  #   Effluent Guidelines and Standards: Metal Finishing—Definition of Total Toxic Organic = >0.01 mg/L

  #   Chemicals and chemical categories to which this part applies (Toxic Release Inventory) = 25,000 Ib
      manufactured or processed, 10,000 Ib otherwise used

  #   Extremely Hazardous Substances and Their Threshold Planning Quantities (Camphechlor) =
      500/10,000 Ib

  #   Municipal Solid Waste  Landfills: Design Criteria—MCL for Upper Aquifer = 0.005 mg/L

  #   Municipal Solid Waste Landfills: Appendix II = 2 ug/L (Practical Quantitation Limit)

Sources of Information

ATSDR (Agency for Toxic Substances and Disease
Registry). 1996. Toxicological Profile for Toxaphene
(Update). U.S. Department of Health and Human
Services, Public Health Service, Atlanta, GA.

Davis,  D.L., H.L. Bradlow, M. Wolff, T. Woodruff,
D.G. Hoel, and H. Anton-Culver. 1993. Medical
hypothesis: Xenoestrogens as preventable causes of
breast cancer. Environmental Health Perspectives
101(5): 372-377.

Glassmeyer ST., D.S. Devault, T.R. Meyers, and
R.A. Hites. 1997. Toxaphene in Great Lakes fish: a
temporal, spatial, and trophic study. Environmental
Science and Technology 31 (1 ):84-88.

HSDB (Hazardous Substance Data Bank). 1998.
National Library of Medicine, National Toxicology
Program, Bethesda, MD.

Kidwell, J.M., L.J. Phillips, and G.F. Burchard. 1995.
Comparative analyses of contaminant levels in
bottom feeding and predatory fish  using the National
Contaminant Biomonitoring Program data. Bulletin of
Environmental Contamination and  Toxicology.

MIXTOX. 1992. Database on toxicological
interactions available on disk for personal computers.
Version 1.5. Environmental Criteria and Assessment
Office,  U.S. Environmental Protection Agency,
Cincinnati, OH.

Soto, A.M., K.L.Chung, and C. Sonnenschein.1994.
The pesticides endosulfan, toxaphene, and dieldrin
have estrogenic effects on human  estrogen-sensitive
cells. Environmental Health Perspectives 102(4):380-
U.S. EPA (Environmental Protection Agency) 1997.
Reference Dose Tracking Report. Office of Pesticide
Programs, Health Effects Division. Washington, DC.

U.S. EPA (Environmental Protection Agency). 1999a.
Guidance for Assessing Chemical Contaminant Data
for Use in Fish Advisories.  Volume 2, 3rd edition. Risk
Assessment and Fish Consumption Limits. EPA
823-B-99-008. Office of Water. Washington, DC.

U.S. EPA (Environmental Protection Agency). 1999b.
IRIS (Integrated Risk Information System) for
Toxaphene. National Center for Environmental
Assessment, Office of Research and Development.

U.S. EPA (Environmental Protection Agency). 1999c.
Fact Sheet: Update: National Listing of Fish and
Wildlife Advisories.  EPA-823-F-99-005. Office of
Water, Washington, D.C.
  For more information about the National Fish
  and Wildlife Contamination program, contact:

               Mr. Jeffrey Bigler
      U. S. Environmental Protection Agency
        Office of Science and Technology
             401 M St. S.W. (4305)
             Washington, DC 20460
              (202) 260-9830 (fax)

  The 1997 update of the database National
  Listing of Fish and Wildlife Advisories is available
  for downloading from the following Internet site: