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Carcinogenicity
Some pesticides have been evaluated
for their ability to cause cancer by the U.S.
EPA, International Agency for Research
on Cancer (IARC), National Institutes
of Health (NIH), or the State
of California. All of these groups use a weight-of-the-evidence
approach, where a panel of scientists evaluate the available data
for a particular chemical. The absence of a chemical on any of these
lists does not necessarily mean it is not a carcinogen. It may mean
that it has not yet been evaluated.
 PAN
Summary Carcinogen Categories
U.S.
EPA-OPP Carcinogen List
U.S.
EPA Toxics Release Inventory Carcinogen List
IARC
Carcinogen List
U.S.
NTP Carcinogen List
State
of California Proposition 65 Carcinogen List
Pesticide
Action Network (PAN) Summary Carcinogen Categories
There are several
organizations that evaluate and rank chemicals for their carcinogenicity.
Because
carcinogenicity designations from different sources sometimes conflict
with each other, PAN created a summary carcinogen designation that
reflects the most toxic ranking assigned by any organization.
In addition, the different terms used by different organizations
to describe carcinogen status were translated into a consistent
set of terms. The equivalences between the different ranking systems
are shown in the table below.
For a chemical
to be classified as a PAN
Bad Actor, it must be in either the Known or Probable
PAN summary category.
| PAN
category |
Equivalence
in other ranking systems |
| Known |
IARC:
Known
U.S. EPA: Known, Known/Likely, Carcinogenic to humans
U.S. NIH: Known
|
| Known,
P65 or TRI only |
CA
Proposition 65: Known to the State of California to be a
carcinogen. California's ranking does not distinguish between
different carcinogenic potencies, using a Yes/No format.
U.S. EPA TRI: Listed as a carcinogen on the Toxics Release
Inventory list. This ranking does not distinguish between different
carcinogenic potencies, using a Yes/No format.
Any pesticide listed as a Prop 65 or TRI carcinogen but NOT
as a Known carcinogen by IARC, EPA or U.S. NIH is listed separately
as Known, P65 or TRI only. |
| Probable |
IARC:
Probable
U.S. EPA: Probable (B1 and B2), Likely to be carcinogenic
to humans, Likely (high doses)/not
likely (low doses)
U.S. NIH: Reasonably anticipated to be a human carcinogen
CA Proposition 65: No parallel category
|
| Possible |
IARC:
Possible
U.S. EPA: Possible, Suggestive evidence of carcinogenicity
CA Proposition 65: No parallel ranking
U.S. NIH: No parallel category
|
| Unclassifiable |
IARC:
Unclassifiable
U.S. EPA: Not classifiable as to human carcinogenicity,
Unclassifiable, Not classifiable, Not amenable to classification,
Can not be determined, Data are inadequate for an assessment
of human carcinogenic potential. This ranking also includes
chemicals ranked as "Not Classified" and "Deferred."
CA Proposition 65: No parallel category
U.S. NIH: No parallel category
|
| Not
Likely |
IARC:
Probably not a carcinogen
U.S. EPA: Evidence of noncarcinogenicity, Unlikely,
Not likely, Not likely to be carcinogenic to humans
CA Proposition 65: No parallel category
U.S. NIH: No parallel category
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U.S.
EPA Office of Pesticide Programs (OPP) Carcinogen List
The U.S. EPA-OPP
maintains a List of Chemicals Evaluated for Carcinogenic Potential,
which classifies pesticides by their role in causing cancer in humans
and laboratory animals. The process by which chemicals are ranked
involves first selecting the chemicals to evaluate, than bringing
together a panel of scientists who evaluate the available data and
make a decision about a cancer ranking based on the weight of the
evidence. The data evaluated includes both epidemiological studies
on humans exposed to the chemical in the course of their daily lives,
as well as studies on laboratory animals. Chemicals that have been
studied extensively are more likely to have an accurate rating; however,
this means that newer chemicals that have been on the market for less
time may not have been studied sufficiently for scientists to conduct
a complete evaluation.
U.S. EPA's
classification of carcinogenicity has changed three times over the
last 15 years. The
categories used by U.S. EPA between 1986 and 1996 (1) are:
- Category A: Known
to cause cancer in humans
Generally based on epidemiological data showing sufficient evidence
to support a causal association between exposure to the substance
and cancer.
- Category B: Probable
human carcinogen
Known to cause
cancer in animals but not yet definitively
shown to cause cancer in humans. Category B is further split into:
- B1: Sufficient
evidence of carcinogenicity from animal studies with limited
evidence of carcinogenicity from epidemiologic studies in
humans.
- B2: Sufficient
evidence of carcinogenicity from animal studies with inadequate
or no data from epidemiologic studies in humans.
- Category C:
Possible human carcinogen
The data show
limited evidence of carcinogenicity in the absence of human data.
- Category D:
Not classifiable as to human carcinogenicity
This category is for chemicals for which the data are either
incomplete, inadequate or ambiguous and is labeled "not classifiable"
or "cannot be determined." This category is appropriate when
tumor effects or other key data are suggestive or conflicting
or limited in quantity and are thus not adequate to convincingly
demonstrate carcinogenic potential for humans. In general, further
chemical-specific and generic research and testing are needed
to be able to describe human carcinogenic potential.
- Category E:
Probably not carcinogenic, with no evidence of carcinogenicity
in at least two adequate animal tests in different species in
adequate epidemiologic and animal studies. This classification
is based on available evidence and does not mean that the agent
will not be a carcinogen under any circumstances.
The categories used by U.S.
EPA between 1996 and 1999 (quoted directly from reference 2) are:
- Known/Likely:
This category of descriptors is appropriate when the available
tumor effects and other key data are adequate to convincingly
demonstrate carcinogenic potential for humans; it includes:
- Agents
known to be carcinogenic in humans based on either epidemiologic
evidence of a combination of epidemiologic and experimental
evidence, demonstrating causality between human exposure and
cancer.
- Agents
that should be treated as if they were known human carcinogens,
based on a combination of epidemiologic data showing a plausible
causal association (not demonstrating it definitively) and
strong experimental evidence.
- Agents
that are likely to produce cancer in humans due to the production
or anticipated production of tumors by modes of action that
are relevant or assumed to be relevant to human carcinogenicity.
- Cannot
be determined: This category of descriptors is appropriate
when available tumor effects or other key data are suggestive
or conflicting or limited in quantity and thus, are not adequate
to convincingly demonstrate carcinogenic potential for humans.
In general, further agent-specific and generic research and testing
are needed to be able to describe human carcinogenic potential.
The descriptor 'cannot be determined' is used with a subdescriptor
that further specifies the rationale:
- Agents
whose carcinogenic potential cannot be determined, but for
which there is suggestive evidence that raises concern for
carcinogenic effects.
- Agents
whose carcinogenic potential cannot be determined because
the existing evidence is composed of conflicting data (e.g.,
some evidence is suggestive of carcinogenic effects, but other
equally pertinent evidence does not confirm any concern),
agents whose carcinogenic potential cannot be determined because
there are inadequate data to perform an assessment.
- Agents
whose carcinogenic potential cannot be determined because
no data are available to perform an assessment.
- Not likely:
This is the appropriate descriptor when experimental evidence
is satisfactory for deciding that there is no basis for human
hazard concern, as follows (in the absence of human data suggesting
a potential for cancer effects):
- Agents
not likely to be carcinogenic to humans because they have
been evaluated in at least two well conducted studies in two
appropriate animal species without demonstrating carcinogenic
effects.
- Agents
not likely to be carcinogenic to humans because they have
been appropriately evaluated in animals and show only carcinogenic
effects that have been shown not to be relevant to humans
(e.g., showing only effects in the male rat kidney due to
accumulation of alpha(2u)-globulin).
- Agents
not likely to be carcinogenic to humans when carcinogenicity
is dose or route dependent. For instance, not likely below
a certain dose range (categorized as likely by another route
of exposure). To qualify, agents will have been appropriately
evaluated in animal studies and the only effects show a dose
range or route limitation, or a route limitation is otherwise
shown by empirical data.
- Agents
not likely to be carcinogenic to humans based on extensive
human experience that demonstrates lack of effect (e.g., phenobarbital).
The categories used by U.S.
EPA from 1999 to the present (quoted directly from reference 2)
are:
- Carcinogenic
to humans: This descriptor is appropriate when there is convincing
epidemiologic evidence demonstrating causality between human exposure
and cancer. This descriptor is also appropriate when there is
an absence of conclusive epidemiologic evidence to clearly establish
a cause and effect relationship between human exposure and cancer,
but there is compelling evidence of carcinogenicity in animals
and mechanistic information in animals and humans demonstrating
similar mode(s) of carcinogenic action. It is used when all of
the following conditions are met:
- There
is evidence in a human population(s) of association of exposure
to the agent with cancer, but not enough to show a causal
association, and
- There
is extensive evidence of carcinogenicity, and
- The
mode(s) of carcinogenic action and associated key events have
been identified in animals, and
- The
key events that precede the cancer response in animals have
been observed in the human population(s) that also shows evidence
of an association of exposure to the agent with cancer.
- Likely
to be carcinogenic to humans: This descriptor is appropriate
when the available tumor effects and other key data are adequate
to demonstrate carcinogenic potential to humans. Adequate data
are within a spectrum. At one end is evidence for an association
between human exposure to the agent and cancer and strong experimental
evidence of carcinogenicity in animals; at the other, with no
human data, the weight of experimental evidence shows animal carcinogenicity
by a mode or modes of action that are relevant or assumed to be
relevant to humans.
- Suggestive
evidence of carcinogenicity, but not sufficient to assess human
carcinogenic potential: This descriptor is appropriate when
the evidence from human or animal data is suggestive of carcinogenicity,
which raises a concern for carcinogenic effects, but is judged
not sufficient for a conclusion as to human carcinogenic potential.
Examples of such evidence may include; a marginal increase in
tumors that may be exposure-related, or evidence is observed only
in a single study, or the only evidence is limited to certain
high background tumors in one sex of one species. Dose-response
assessment is not indicated for these agents. Further studies
would be needed to determine human carcinogenic potential.
- Data
are inadequate for an assessment of human carcinogenic potential:
This descriptor is used when available data are judged inadequate
to perform an assessment. This includes a case when there is a
lack of pertinent or useful data or when existing evidence is
conflicting, e.g., some evidence is suggestive of carcinogenic
effects, but other equally pertinent evidence does not confirm
a concern.
- Not likely
to be carcinogenic to humans: This descriptor is used when
the available data are considered robust for deciding that there
is no basis for human hazard concern. The judgement may be based
on:
- Extensive
human experience that demonstrates lack of carcinogenic effect
(e.g., phenobarbital).
- Animal
evidence that demonstrates lack of carcinogenic effect in
at least two well designed and well conducted studies in two
appropriate animal species (in the absence of human data suggesting
a potential for cancer effects).
- Extensive
experimental evidence showing that the only carcinogenic effects
observed in animals are not considered relevant to humans
(e.g., showing only effects in the male rat kidney due to
accumulation of alpha-2u-globulin).
- Evidence
that carcinogenic effects are not likely by a particular route
of exposure.
- Evidence
that carcinogenic effects are not anticipated below a defined
dose range.
About
the Data:
Accuracy, currency, comprehensiveness and source
The present U.S.
EPA-OPP cancer list contains 443 chemicals. It was last updated
by U.S. EPA on March 15, 2002. The list is presently not downloadable,
but the address for requesting a hard copy of the list is:
Communication
Services Branch (7506C)
Office
of Pesticide Programs
US Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460
Phone: (703) 305-5017; Fax: (703) 305-5558
Although there
is a note that this data will be updated twice each year, in practice
it seems to be published only once per year.
Reference:
- Office
of Pesticide Programs List of Chemicals Evaluated for Carcinogenic
Potential, August 25, 1999, U.S.
Environmental Protection Agency.
- Office
of Pesticide Programs List of Chemicals Evaluated for Carcinogenic
Potential, August 30, 2000, U.S.
Environmental Protection Agency.
- Office
of Pesticide Programs List of Chemicals Evaluated for Carcinogenic
Potential, March 15, 2002, U.S.
Environmental Protection Agency.
U.S.
EPA Toxics Release Inventory List
In 1986, Congress
passed the Emergency Planning and Community Right-To-Know Act (EPCRA)
and the Pollution Prevention Act (PPA), with the intent of increasing
the transparency of the use and disposal of chemicals in manufacturing,
mining, and other activities. Section 313 of the EPCRA and section
6607 of the PPA required companies that release toxic materials
to provide information to U.S. EPA on the identity and amounts of
these toxic chemicals they are releasing to air, land and water.
This information is made available to the public through U.S. EPA
as the Toxics Release Inventory (TRI), providing valuable information
on the release and transport of toxic chemicals in the U.S.
U.S. EPA publishes
a list of chemicals that must be reported. A chemical is placed
on the list if it is toxic to humans or damaging to the environment.
The current TRI toxic chemical list contains approximately 650 individually
listed chemicals and 30 chemical groups. Of this group, only 350
individual chemicals and 25 chemical groups are pesticides or related
compounds. Of these pesticide chemicals, only 222 have been formally
ranked through the TRI program for their toxicity.
Toxicity categories
evaluated for the TRI list of chemicals includes acute toxicity,
carcinogenicity, reproductive and developmental toxicity, environmental
toxicity and toxicity to organ systems including cardiovascular,
liver, gastrointestinal, kidney, immune, hematological, and respiratory
systems.
Environmental Defense
maintains a web site called Scorecard,
at which you can find information on the TRI chemicals being released
in your neighborhood, with a map showing the location of the responsible
facilities.
References:
- Toxics
Release Inventory and Community Right to Know, U.S. EPA.
Viewed on October 29, 2002.
- What
is the Toxics Release Inventory?, U.S. EPA, Viewed on
October 29, 2002.
- Hazard
Information on Toxic Chemicals Added to EPCRA Section 313 Under
Chemical Expansion, U.S. EPA, Viewed on October 29, 2002.
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International
Agency for Research on Cancer (IARC) Carcinogen List
A list of chemicals is maintained by IARC, an international organization
that evaluates chemicals for carcinogenicity and assigns a ranking
to them. The IARC system gives the following designations:
- Group 1: Known
carcinogens
- Group 2a: Probable
carcinogens
- Group 2b:
Possible carcinogens
- Group 3:
Unclassifiable because the data are incomplete or ambiguous.
- Group 4: Probably
not carcinogens
About
the Data: Accuracy,
currency, comprehensiveness and source
The complete IARC
carcinogen list includes carcinogen rankings for 885 agents, mixtures
and exposures, not all of which are pesticides. IARC publishes peer-reviewed
monographs detailing the basis for their carcinogen rankings. IARC last published a new
list in December 2002, and appears to update the list several times
a year. PAN updated this data on August 10, 2003.
Reference:
Lists
of IARC Evaluations, International Agency for Research
on Cancer. Viewed on August 10, 2003.
U.S.
National Toxicology Program (NTP)
Carcinogen List
A list of carcinogenic substances is constructed by the National Toxicology
Program, the U.S. Dept. of Health and Human Services, and the Public
Health Service. This list is published by the U.S. National Institutes
of Health (NIH). Section 301 (b)(4) of the Public Health Service Act
mandates that the Secretary of the Department of Health and Human
Services (DHHS) shall publish a biennial report that contains a list
of all substances:
- which either are known
to be human carcinogens or may reasonably be anticipated to be
human carcinogens, and
- to which a significant
number of persons residing in the United States are exposed.
The U.S. NTP system ranks
chemicals as "Known Carcinogens" or "Reasonably Anticipated
to Be a Carcinogen."
About
the Data: Accuracy,
currency, comprehensiveness and source
The U.S. NTP has
an extensive, ongoing project to assess carcinogenicity. Although
the complete list is only published every 2 years, there are occasional
updates. See reference 2 for ongoing U.S. NTP cancer information
and interim recommendations for the 11th report. The U.S. NTP dataset
includes rankings for roughly 350 chemicals, not all of which are
pesticides. The information in the PAN Pesticide Database was taken
from the 10th Report on Carcinogens, released in December 2002.
PAN last checked the currency of this data set
on December 11, 2003.
References:
- 10th
Report on Carcinogens 2002, U.S. National Toxicology Program.
Viewed on December 11, 2003.
- NIH
Report on Carcinogens Homepage. Viewed on December 11, 2003.
State
of California Proposition 65 Carcinogen List
A list of
chemicals "known to the State to cause cancer" is maintained by the
State of California under the Safe Drinking Water and Toxic Enforcement
Act of 1986 (Proposition 65).
Unlike other rating systems, California does not rank chemicals for
their carcinogenicity, but simply designates a chemical as a "Known"
carcinogen.
The absence of a chemical
on this list does not necessarily mean it is not a carcinogen.
It may mean that it has not yet been evaluated by the agencies responsible.
More detail is given in the "About the Data" section.
About
the Data
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Last updated
June 22, 2005
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