IUPAC Glossary of Terms Used in Toxicology
| A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z |
ANNEX 3
CLASSIFICATION OF CARCINOGENICITY
1. Classification according to IARC [16]Classification based on the weight of the evidence and not on potency as follows.
- Sufficient evidence. Causal relationship has been established
between exposure to the
agent and human cancer: a positive relationship has been observed
between exposure to the agent and cancer in studies in which
chance, bias and confounding could be ruled out with reasonable
confidence.
- Limited evidence. Positive association has been observed
between exposure to the agent and cancer for which a causal
interpretation is considered to be credible, but chance, bias or
confounding could not be ruled out with reasonable
confidence.
- Inadequate evidence. Available studies are of insufficient
quality, consistency or statistical power to permit a conclusion
regarding the presence or absence of a causal association.
- Evidence suggesting lack of carcinogenicity. There are
several adequate studies covering the full range of doses to
which human beings are known to be exposed, which are mutually
consistent in not showing a positive association between exposure
to the agent and any studied cancer at any observed level of
exposure. A conclusion of “evidence suggesting lack of
carcinogenicity” is
inevitably limited to the cancer sites, circumstances and doses
of exposure and length of observation covered by the available
studies. In addition, the possibility of a very small risk at the levels of exposure studied
can never be excluded.
- Overall evaluation. Total body of evidence is taken into
account; the agent is described according to the wording of one
of the following categories, and the designated group is given.
The categorization of an agent is a matter of scientific
judgement, reflecting the strength of the
evidence derived from studies in humans and in experimental
animals and from other relevant data.
| Group 1 |
The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used only when there is sufficient evidence
of carcinogenicity in humans. |
| Group 2 | This category includes agents, mixtures and exposure circumstances for which, at one extreme, the degree of evidence of carcinogenicity in humans is almost sufficient, as well as those for which, at the other extreme, there are no human data but for which there is evidence of carcinogenicity in experimental animals. Agents, mixtures and exposure circumstances are assigned to either 2A (probably carcinogenic to humans) or 2B (possibly carcinogenic to humans) on the basis of epidemiological and experimental evidence of carcinogenicity and other relevant data. |
| Group 2A |
The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans. |
| Group 2B |
The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans This category is generally used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group. |
| Group 3 |
The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and
exposure circumstances for which the evidence of
carcinogenicity is inadequate in humans and inadequate or
limited in experimental animals. |
| Group 4 |
The agent (mixture) is probably not carcinogenic to humans. This category is used for agents or mixtures for which there is evidence suggesting lack of carcinogenicity in humans and in experimental animals. In some circumstances, agents or mixtures for which there is inadequate evidence of carcinogenicity in humans but evidence suggesting lack of carcinogenicity in experimental animals, consistently and strongly supported by a broad range of other relevant data, may be classified in this group. |
3. Classification according to the USEPA [17, 18]
Group A: “Human Carcinogen”
“This group is used only when there is sufficient evidence
from epidemiologic studies to support a causal association
between exposure to the agents and cancer.”
Group B (1 and 2): “Probable Human
Carcinogen”
“This group includes agents for which the weight of
evidence of human carcinogenicity based on epidemiologic studies
is “limited” and also includes agents for which the
weight of evidence of carcinogenicity based on animal studies is
“sufficient”. The group is divided into two
subgroups. Usually, Group B1 is reserved for agents for which
there is limited evidence of carcinogenicity from epidemiological
studies. It is reasonable, for practical purposes, to regard an
agent for which there is “sufficient evidence of
carcinogenicity” in animals as if it presented a
carcinogenic risk to humans. Therefore, agents for which there is
“sufficient” evidence from animal studies and for
which there is “inadequate evidence” or “no
data” from epidemiologic studies would usually be
categorized under Group B2.”
Group C: “Possible Human
Carcinogen”
“This group is used for agents with limited evidence of
carcinogenicity in animals in the absence of human data. It
includes a wide variety of evidence, e.g., (a) a malignant tumor
response in a single well-conducted experiment that does not meet
conditions for sufficient evidence, (b) tumor responses of
marginal statistical significance in studies having inadequate
design or reporting, (c) benign but not malignant tumors with an
agent showing no response in a variety of short-term tests for
mutagenicity, and (d) responses of marginal statistical
significance in a tissue known to have a high or variable
background rate.”
Group D: “Not Classifiable as to Human
Carcinogenicity”
“This group is generally used for agents with inadequate
human and animal evidence of carcinogenicity or for which no data
are available.”
Group E: “Evidence of Non-Carcinogenicity for
Humans”
“This group is used for agents that show no evidence for
carcinogenicity in at least two adequate animal tests in
different species or in both adequate epidemiologic and animal
studies.
The designation of an agent as being in Group E is based on the
available evidence and should not be interpreted as a definitive
conclusion that the agent will not be a carcinogen under any
circumstances.”
For the purpose of classification and labelling and having regard to the current state of knowledge, such substances are divided into three categories:
Category 1
Substances known to be carcinogenic to man. There is sufficient
evidence to establish a casual association between human exposure
to a substance and the development of cancer.
Category 2
Substances which should be regarded as if they are carcinogenic
to man. There is sufficient evidence to provide a strong
presumption that human exposure to a substance may result in the
development of cancer, generally on the basis of:
- appropriate long-term animal studies,
- other relevant information.
Category 3
Substances which cause concern for man owing to possible
carcinogenic effects but in respect of which the available
information is not adequate for making a satisfactory assessment.
There is some evidence from appropriate animal studies, but this
is insufficient to place the substance in category 2.
A1: Chemical substances that are confirmed to be carcinogenic for humans
A2: Chemical substances that are suspected to be carcinogenic for humans
A3: Chemical substances that are carcinogenic for animals
A4: Substances that are not classified as carcinogenic
A5: Substances that are not suspected to be carcinogenic for humans