Little Pro on 2016-04-26 Views:  Update:2018-04-02

A carcinogen is a chemical substance or a mixture of chemical substances that induces cancer or increases its incidence. Substances and mixtures that have induced cancer in experimental animal studies are considered to be presumed or suspected human carcinogens unless there is strong evidence to indicate the mechanism of tumor formation is not relevant to humans (definition from GHS).

A tumor (neoplasm) is simply an uncontrolled growth of cells. Benign tumors grow at the site of origin, do not invade adjacent tissues or metastasize and generally are treatable. Malignant tumors (cancer) invade adjacent tissues or migrate to distant sites (metastasis). They are more difficult to treat and often cause death.

Dose Descriptor and Risk Assessment of Carcinogens

It is generally recognized that some chemicals (non-threshold carcinogens) will cause carcinogenic risks even at the smallest exposure concentration. For these chemicals the conventional NOAEL and safety factor approach to derive exposure safety standards is not appropriate.

Two useful dose descriptors for carcinogenicity are T25 and BMD10. They may be obtained from two-year carcinogenicity rodent bioassay (in rat or mice). 

  • T25:The chronic dose rate that will give 25% of the animals’ tumors at a specific tissue after correction for spontaneous incidence, within the life time of that species.
  • BMD10: derived bench mark dose assumed to give 10% of the animals’ tumors at a specific tissue after correction for spontaneous incidence, within the life time of that species.

Under EU REACH regulation, linear extrapolation from T25 or the BMD10 to a risk of 10^(-5) is proposed to derive the so-called "derived minimum effect level" (DMEL), a reference risk level considered to be of very low concern. For the risk characterisation this value is compared with exposure concentrations to humans. If the eposure level is lower than the DMEL, the risk level is seen as tolerable.

GHS Classification Criteria for Carcinogenicity

Category Criteria
Category 1A Chemicals known to have carcinogenic potential to humans - largely based on human evidence

Mixtures containing ≥ 0.1% of such a category 1A carcinogen.

Category 1B Chemicals presumed to have carcinogenic potential to humans - largely based on animal evidence.

Mixtures containing ≥ 0.1% of such a category 1B carcinogen.

Category 2 Suspected human carcinogen - evidence from human and/or animal studies is limited

Mixtures containing ≥ 0.1% of such a category 2 carcinogen.

Carcinogen classification should be based on strength of evidence and other considerations (e.g., weight of evidence). Expert judgment is always necessary in applying the classification criteria. Good references include National Toxicology Program (NTP) “Report on Carcinogens” and International Agency for Research on Cancer (IARC) "Monographs on the Evaluation of Carcinogenic Risks to Humans".

Testing Guidelines

  • Carcinogenicity Studies (OECD TG 451)
  • Combined Chronic Toxicity/Carcinogenicity Studies (OECD TG 453)


You have learned the definition of carcinogen, neoplasm and cancer, dose descriptor for carcinogenicity (T25 and BMD10), GHS classification criteria for carcinogenicity and  testing guidelines.

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 Tags: Topics - CRAToxicology and Health Risk Assessment

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