vvEPA
United States
Environmental Protection
Agency
Office of Water
4305
EPA-823-F-99-015
September 1999
Fact Sheet
Polychlorinated Dibenzo-p-dioxins and Related Compounds
Update: Impact on Fish Advisories
Dioxins are a group of synthetic organic chemicals that contain 210 structurally related individual chlorinated
dibenzo-p-dioxins (CDDs) and chlorinated dibenzofurans (CDFs). For the purposes of this fact sheet, the term
"dioxins" will refer to the aggregate of all CDDs and CDFs. These chemically related compounds vary in their
physical and chemical properties and toxicity. Dioxins have never been intentionally produced, except in small
quantities for research. They are unintentionally produced as byproducts of incineration and combustion processes,
chlorine bleaching in pulp and paper mills, and as contaminants in certain chlorinated organic chemicals. They are
distributed widely in the environment because of their persistence. Dioxin exposure is associated with a wide array
of adverse health effects in experimental animals, including death. Experimental animal studies have shown toxic
effects to the liver, gastrointestinal system, blood, skin, endocrine system, immune system, nervous system, and
reproductive system. In addition, developmental effects and liver cancer have been reported. Skin rashes and a
severe form of acne have been documented in humans following exposure to relatively high doses; however, other
effects of dioxin exposure in humans are not well understood. There are some studies that suggest liver damage
and cancer can occur in people exposed to dioxins. The available data do not provide sufficient evidence that
dioxins are genotoxic; however dioxins are classified by EPA as probable human carcinogens (Group B2). As of
1998, 19 states have issued 59 fish advisories for dioxins. These advisories inform the public that dioxins 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 dioxins. 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 mercury, PCBs, and
toxaphene are available at http://www.epa.gov/OST/fish. Future revisions will be posted on the web as they
become available.
Sources of Dioxins in the Environment
Dioxins are formed primarily as unintentional by-
products of incomplete combustion and various
chemical processes. Although forest fires and
possibly other natural sources may produce dioxins,
these sources are small compared with anthropogenic
sources. Dioxins are produced in small quantities
during the combustion of fossil fuels, wood, municipal
and industrial waste. Bleaching processes which were
used in pulp and paper production produced dioxins,
and they occur as contaminants during the production of
some chlorinated organic chemicals, such as chlorinated
phenols.
Currently, the major environmental source of dioxins
is incineration. Dioxins have been detected in soil,
surface water, sediment, plants, and animal tissue in
all regions of the earth.
Dioxins are highly persistent in the environment with
reported half-lives in soil and sediment ranging from
months to years. Because dioxins have very low
solubility in water and low volatility, most are
contained in soil and sediments that serve as
environmental reservoirs from which dioxins may be
released over a long period of time. Volatilization and
particle resuspension from environmental reservoirs
are probably important contributors to global
distribution.
Fate and Transport of Dioxins
The global cycling of dioxins consists of particle
resuspension and evaporation from soils and surface
waters to the atmosphere and redeposition back to
land and surface water. However, volatilization is
slow. Adsorption to sediments and bioaccumulation
are the primary loss mechanisms from surface water.
Photolysis is an important transformation process for
dioxins that are exposed to sunlight.
Dioxins in surface waters and sediments are
accumulated by aquatic organisms and bio-
accumulated through the aquatic food chain.
Concentrations of dioxins in aquatic organisms may
be hundreds to thousands of times higher than the
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concentrations found in the surrounding waters or
sediments. Bioaccumulation factors vary among the
congeners and generally increase with chlorine
content up through the tetra congeners and then
generally decrease with higher chlorine content. For
example, experimental bioconcentration factors
(BCFs) for fish exposed to 2,3,7,8-TCDD in water
ranged from 37,900 to 128,000; whereas, BCFs for
OCDD ranged from 34 to 2,226. In the presence of
both water and sediment, BCFs were reduced by
15% to 82% (compared to water only experiments)
for various congeners, with the greatest reduction
associated with OCDD.
Six dioxin congeners and nine dibenzofuran
congeners were measured in fish tissue and shellfish
samples in the EPA's National Study of Chemical
Residues in Fish (NSCRF). The various dioxin
congeners were detected at 32% to 89% of the 388
sites surveyed, while the furan congeners were
detected at 1% to 89% of the 388 sites surveyed. As
shown in Table 1, the dioxin/furan congeners
detected at more than 50% of the sites included four
CDD compounds and three CDF compounds;
1,2,3,4,6,7,8 HpCDD (89%), 2,3,7,8 TCDF (89%),
2,3,7,8 TCDD (70%), 1,2,3,6,7,8 HxCDD (69%),
2,3,4,7,8 PeCDF (64%), 1,2,3,4,6,7,8 HpCDF (54%),
and 1,2,3,7,8 PeCDD (54%). The most frequently
detected CDD/CDF compounds (1,2,3,4,6,7,8-
HpCDD and 2,3,7,8-TCDF) were also detected at the
highest concentrations: 249 ppt and 404 ppt,
respectively. The mean concentrations of these two
compounds were considerably lower, at 10.5 and
13.6 ppt, respectively. The dioxin congener 2,3,7,8-
TCDD, believed to be the most toxic to mammals,
was detected at 70% of the sites at a maximum
concentration of 204 ppt and a mean concentration of
6.8 ppt.
Potential Sources of Exposure and
Occurrence in Human Tissues
Dietary intake is the most important source of
exposure to dioxins for the general population. Meat,
dairy products, fish and other seafood products,
contribute more than 90% of the daily intake for the
general population.
Individuals who may be exposed to higher than
average levels of dioxins include those who ingest
food containing higher concentrations of dioxins than
are found in the commercial food supply. These
groups include recreational and subsistence fishers
who routinely consume large amounts of locally
Table 1. Maximum and Average Concentrations of
Dioxins Reported in Fish3
Chemical
Percent Maximum Mean
of Sites Concen- Concen-
Where trationb trationb
Detected (pg/g) (pg/g)
Dioxins
1,2,3,4,6,7,8-
HpCDD
2,3,7,8-TCDD
1,2,3,6,7,8-HxCDD
1,2,3,7,8-PeCDD
1,2,3,7,8,9-HxCDD
1,2,3,4,7,8-HxCDD
89 249 10.5
70 204 6.89
69 101 4.3
54 54 2.38
38 24.8 1.16
32 37.6 1.67
Furans
2,3,7,8-TCDF
2,3,4,7,8-PeCDF
1,2,3,4,6,7,8-
HpCDF
1,2,3,4,6,7,8-
PeCDF
1,2,3,4,7,8-HxCDF
2,3,4,6,7,8-HxCDF
1,2,3,6,7,8-HxCDF
1,2,3,4,7,8,9-
HpCDF
1,2,3,7,8,9-HxCDF
89 404 13.6
64 56.4 3.06
54 58.3 1.91
47 120 1.71
42 45.3 2.35
32 19.3 1.24
21 30.9 1.74
4 25.7 1.24
1 0.96 1.22
aSpecies included freshwater, estuarine, and marine finfish;
and a small number of marine shellfish.
""Concentrations reported on a wet weight basis (parts per
trillion).
Source: U.S. EPA, 1992.
caught fish; subsistence hunters who routinely
consume the meat and organ tissues of marine
mammals, and subsistence farmers living in a
contaminated area who consume farm-raised beef
and dairy products. In addition, persons who live near
industrial or municipal incinerators, and persons who
live near hazardous waste sites contaminated with
dioxins could be exposed to higher levels of dioxins
than the general population.
Analytical methods can be used to measure dioxins
in blood, lipid tissues, and breast milk.
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
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population, including recreational and subsistence
fishers, as well as sensitive subpopulations (such as,
pregnant women/fetus, nursing mothers, and
children). These advisories inform the pubic that high
concentrations of chemical contaminants 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).
General recommendations regarding food
preparation, such as trimming the fat and skinning the
fish prior to cooking, also may be included in general
advisory information. Lipophilic chemicals, such as
dioxins, accumulate mainly in fatty tissues (belly flap,
lateral line, subcutaneous and dorsal fat, dark
muscle, gills, eye, brain, and internal organs).
Therefore, removal of internal organs and skin and
trimming the fat before cooking will decrease
exposure. In addition, various cooking procedures
can also reduce the amount of dioxins consumed
(see Appendix section "Dose Modification Due to
Food Preparation and Cooking" of EPA's Guidance
for Assessing Chemical Contaminant Data for Use in
Fish Advisories, Volume 2).
As of December 1998, dioxins/furans were the
chemical contaminants responsible, at least in part,
for the issuance of 59 fish consumption advisories by
19 states (see Figure 1). Only 2% of all advisories
issued in the United States are a result of dioxin/furan
contamination in fish and shellfish. The number of
advisories for dioxins/furans fluctuated between 54
and 65 from 1993 through 1998. The maximum
number of advisories for dioxin were in effect in 1997.
Dioxins/furans are one of several chemical
contaminants for which fish advisories have been
rescinded by several states, in part because many
pulp and paper mills have changed their bleach kraft
processes, thereby reducing effluent levels of dioxins
and furans.
The decline in the number of dioxin advisories in
1998 can be attributed primarily to the rescinding of
advisories in three states (Arkansas, Michigan, and
Virginia).
Figure 1. Fish Advisories for Dioxins.
1998
D American Samoa
D Guam
D Virgin Islands
D Puerto Rico
O States issuing advisory (19)
• Statewide Coastal Marine Advisories
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It should also be noted that no states currently have
statewide advisories in effect for dioxins/furans in
their freshwater lakes and/or rivers. Three states
(Maine, New York, and New Jersey) have statewide
dioxin/furan advisories in effect for their coastal
marine waters. To date, 65% of the 59 dioxin
advisories in effect have been issued by the following
five states; New Jersey (9), New York (8), Maine (8),
West Virginia (6), and North Carolina (5).
Fish Consumption Limits—Table 2 shows the
recommended monthly fish consumption limits for
dioxins/furans for fish consumers based on EPA's
default values for risk assessment parameters. .
Consumption limits have been calculated as the
number of allowable fish meals per month, based on
the ranges of dioxins/furans 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 (30.44d)
# EPA's cancer slope factor for dioxin
(1.56 x 105 per mg/kg-d) from EPA's Health
Effects Assessment Summary Tables (U.S. EPA,
1997)
# Maximum acceptable cancer risk level
(10~5 over a 70-year lifetime)
For example, when dioxin levels in fish tissue are 0.1
ppq, then four 8-oz. meals per month can safely be
consumed.
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 dioxins/furans.
Additional information on calculating specific limits for
these sensitive populations is available in EPA's
Guidance for Assessing Chemical Contaminant Data
for Use in Fish Advisories, Volume 2, Section 3.
Toxicity of Dioxins
Pharmacokinetics—Dioxins are absorbed through
the gastrointestinal tract, respiratory tract, and skin
and distributed throughout the body. Absorption is
congener-specific, with decreased absorption of
hepta- and octa-congeners compared with dioxins
with fewer chlorines. Because of their lipophilic
nature, dioxins tend to accumulate in fat and the liver.
Dioxins are slowly metabolized by oxidation or
reductive dechlorination and conjugation, and the
major routes of excretion are the bile and feces.
Reported half lives in the body range from 5 to 15
years. Small amounts may be eliminated in the urine.
Table 2. Monthly Fish Consumption
Limits for Dioxins/Furans
Risk Based
Consumption Limit
Fish meals/month
16
12
8
4
3
2
1
0.5
None(<0.5)a
Cancer Health
Endpoints
Fish Tissue
Concentrations,
(pptrb,-TEQ)
>0.019- 0.039
>0.039- 0.052
>0.052- 0.077
>0.077-0.15
>0.15-0.21
>0.21 -0.31
>0.31 -0.62
>0.62-1.2
>1.2
aNone = No consumption recommended.
bpptr = parts per trillion on a wet weight basis.
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 to determine safe
consumption limits.
The current evidence indicates that metabolites are
less toxic than the parent compounds.
The predominant forms retained in the tissues are the
2,3,7,8-substituted congeners. Tissue deposition
depends on the route of exposure, congeners
present, dose, and age. Based on a study of a human
volunteer, about 87% of a single dose of dioxins
dissolved in corn oil was absorbed, and about 90% of
the absorbed dose was distributed to fatty tissue.
The half-lives for various dioxin congeners in humans
are reported to range from 2.9 to 26.9 years. Some
studies suggest longer half-lives in individuals with
higher levels of body fat.
Dioxins induce mixed function oxidases and hepatic
aryl hydrocarbon hydroxylase (AHH). Dioxins bind to
a cytosolic protein, the Ah receptor, which regulates
the synthesis of a variety of proteins. The Ah receptor
has been found in many human tissues, including the
lung, liver, placenta, and lymphocytes. Although
evidence indicates that the Ah receptor is involved in
many biological responses to dioxins, the diversity of
biological effects observed cannot be accounted for
by characteristics of this receptor alone.
Acute Toxicity—The LD50 values for dioxins vary
over several orders of magnitude depending on the
congener, species, and strain of animal tested. The
most toxic congener is 2,3,7,8-TCDD, with LD50
values ranging from 22 to 340 mg/kg in various
strains of laboratory rats. Guinea pigs are the most
sensitive species tested (LD50 values from 0.6 to 2.1
mg/kg), and hamsters are the most resistent (LD50
values from 1,157 to 5051 mg/kg). In all studies, the
animals died from a pronounced wasting syndrome
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characterized by weight loss and depletion of body fat
that lasted 1 to 6 weeks. By contrast, laboratory
animals have survived acute doses of 1 to 4 g/kg of
2,7-DCDD and OCDD. Single exposures to dioxins
have also affected the heart, liver, kidneys, blood,
stomach, and endocrine systems of laboratory
animals. No human deaths have been directly
associated with exposure to dioxins.
Chronic Toxicity—In animal studies, numerous
effects have been documented, including hepatic,
gastrointestinal, hematological, dermal, body weight
changes, endocrine, immunological, neurological,
reproductive, and developmental effects. Most of the
studies have involved oral exposure. Despite the
variety of adverse effects observed in animals
exposed to dioxins, adverse health effects in humans
have generally been limited to highly exposed
populations in industrial factories or following
chemical accidents and contamination episodes. The
adverse human health effect most commonly
associated with high-level exposure to dioxin-like
agents is the skin disease chloracne, a particularly
severe and prolonged acne-like skin disorder.
Adverse human health effects were also noted
following consumption of heated rice oil contaminated
with PCBs and CDFs. Conclusive evidence of other
adverse human health effects at lower dioxin
exposure levels is generally lacking because of
incomplete exposure data, concomitant exposure to
other compounds, and/or small numbers of study
participants. Some epidemiological studies have
suggested that dioxins may cause immuno-
suppression, respiratory effects, cardiovascular
effects, and liver effects in humans.
Developmental Toxicity—Dioxins have been shown
to cause adverse developmental effects in fish, birds,
and mammals at low exposure levels. Several studies
in humans have suggested that dioxin exposure may
cause adverse effects in children and in developing
fetuses. These include effects on the skin, nails, and
meibomian glands; psychomotor delay; and growth
retardation. However, study limitations, including lack
of control for confounding variables, and deficiencies
in the general areas of exposure make it difficult to
interpret these results. Overall, the human data are
inconclusive; however, the animal data suggest that
developmental toxicity is a concern.
In mammals, learning behavior and development of
the reproductive system appear to be among the
most sensitive effects following prenatal exposure. In
general, the embryo or fetus is more sensitive than
the adult to dioxin-induced mortality across all
species.
Mutagenicity—The majority of mutagenicity assays
of dioxins have been negative. An increased
incidence of chromosomal aberrations was found in
fetal tissue but not in maternal tissue in a group of
women exposed to dioxins following an industrial
accident in Italy; however, cases treated for chloracne
did not have an increased incidence of chromosomal
aberrations. Animal studies also are inconclusive.
The available data do not provide strong evidence
that dioxins are genotoxic.
Carcinogenicity—Dioxins are classified by EPA as
Group B2 (sufficient evidence in animals, insufficient
evidence in humans) when considered alone and
Group B1 (sufficient evidence in animals, limited
evidence in humans) when considered in association
with chlorophenols and phenoxyherbicides. This is
based on studies that have found multiple-site
sarcomas and carcinomas in rats and mice exposed
to various dioxin mixtures and congeners.
Epidemiological studies suggest an increased
incidence of cancer mortality (all types of cancers
combined) and of some specific cancers (soft-tissue
sarcoma, non-Hodgkin's lymphoma, respiratory tract
cancer, and gastrointestinal cancers). In addition,
there is evidence that 2,3,7,8-TCDD acts as a tumor
promoter. As with all epidemiological studies, it is
very difficult to obtain clear unequivocal results
because of the long latency period required for
cancer induction and the multiple confounders arising
from concurrent exposures, lifestyle differences, and
other factors. The currently available evidence
suggests that dioxins may cause cancer in humans.
Summary of EPA Health Benchmarks
# Carcinogenicity: 1.56 x 105 per mg/kg-d
(U.S. EPA, 1997)
Special Susceptibilities—There is evidence that
children are more susceptible than adults to the
dermal toxicity of dioxins. Animal data suggest that
the developing reproductive, immune, and nervous
systems of the fetus are sensitive to dioxin toxicity.
Interactive Effect—Environmental exposure to
dioxins includes various mixtures of CDDs and CDFs.
These mixtures of dioxin-like chemicals cause
multiple effects that vary according to species
susceptibility, congeners present, and interactions.
Risk assessment of these complex mixtures is based
on the assumption that effects are additive, and there
is some experimental evidence to support this.
However, there also is evidence that some
interactions may result in inhibition and others in
potentiation. Co-treatment of mice with various
commercial PCS mixtures (Aroclors) and 2,3,7,8-
TCDD has resulted in inhibiting some of the Ah
receptor mediated responses. An increased
incidence of cleft palate was reported when mice
were treated with both 2,3,7,8-TCDD and a
hexachlorobiphenyl compared with treatment with
2,3,7,8-TCDD alone. Both synergistic and
antagonistic responses have been observed following
co-exposure of 2,3,7,8-TCDD with other chemicals as
well.
Critical Data Gaps—The following data gaps have
been identified for dioxins: inhalation and dermal
toxicity studies; toxicity studies of dioxin compounds
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other than 2,3,7,8-TCDD; continued medical
surveillance of individuals with known past high
exposures to dioxins; mechanistic studies; immune
function tests in human cohorts; neurological tests in
ongoing prospective studies of humans; congner-
specific human toxicokinetic studies to better assess
human dosimetry; further studies to identify potential
biomarkers for exposure and effects; and additional
studies to support exposure modeling.
EPA Regulations and Advisories
# Maximum Contaminant Level in drinking
water = 3E-08 mg/L
# Water Quality Criteria:
Human health (ingesting water and
organisms) = 1.3E-08 ug/L
- Human health (ingesting organisms
only)= 1.4E-08ug/L
# Listed as a hazardous air pollutant under
Section 112 of the Clean Air Act
# Reportable quantity = 1 Ib
# Listed as a hazardous substance
Sources of Information
ATSDR (Agency for Toxic Substances and Disease
Registry). 1998. Toxicological Profile for Chlorinated
Dibenzo-p-dioxins. U.S. Department of Health and
Human Services, Public Health Service, Atlanta, GA.
U.S. EPA (Environmental Protection Agency). 1992.
National Study of Chemical Residues in Fish, Volume
I. Office of Science and Technology, Washington,
DC. EPA 823-R-92-008a.
U.S. EPA (Environmental Protection Agency). 1994.
Health Assessment Document for 2,3,7,8-
Tetrachlorodibenzo-p-Dioxin (TCPD) and Related
Compounds (External Review Draft) (3 volumes).
Office of Research and Development, Washington,
DC. (EPA/600/BP-92100/C).
U.S. EPA (Environmental Protection Agency). 1997.
Health Effects Assessment Summary Tables. FY
1997 Update. Office of Research and Development,
Office of Emergency and Remedial Response,
Washington, DC. EPA-540-R-97-036.
U.S. EPA (Environmental Protection Agency). 1999.
Fact Sheet: Update: National Listing of Fish and
Wildlife Advisories. Office of Water. Washington, DC.
EPA-823-F-99-005.
U.S. EPA (Environmental Protection Agency). 1999.
Guidance for Assessing Chemical Contaminant Data
for Use in Fish Advisories. Volume 2, 3rd Edition,
Risk Assessment and Fish Consumption Limits.
Office of Water. Washington, DC. EPA 823-B-97-009.
Zabik, M.E. and M.J. Zabik. 1995. Tetra-
chlorodibenzo-p-dioxin residue reduction by
cooking/processing offish fillets harvested from the
Great Lakes. Bulletin of Environmental Contamination
and Toxicology. 55:264-269.
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 MSt. SW(4305)
Washington, DC 20460
Bigler.Jeff@epa.gov
202260-1305
202 260-9830 (fax)
The 1998 update of the database National
Listing of Fish and Wildlife Advisories is
available for downloading from the following
Internet site: http://www.epa.gov/OST
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