Human Health Risk Assessment for Priority Substances

Appendix C -- Criteria for Classification of Mutagenicity in Germ Cells

Chemicals are classified into six categories on the basis of the following criteria¹⁰

Group I -- Human Germ Cell Mutagen

Group I -- Data from adequate epidemiological studies indicate that there is a causal relationship between exposure of humans to a substance and an increased incidence of inherited mutations in live or dead offspring.

Group II -- Probable Human Germ Cell Mutagen

Group II -- Data from epidemiological studies to assess germ cell mutagenicity are inadequate: however, there is sufficient evidence of germ cell mutagenicity in animal species (i.e., there is an increased incidence of gene mutations, structural or numerical chromosomal aberrations, or inherited congenital malformations in the live offspring of exposed animals; or an increase in dominant lethal mutations in the potential offspring of exposed animals).

Group III -- Possible Human Germ Cell Mutagen

Group III.A -- Data from epidemiological studies indicate an association between exposure and human germ cell mutagenicity, but alternative explanations such as chance, bias, or confounding cannot be excluded.

Group III.B -- Data from epidemiological studies to assess germ cell mutagenicity are inadequate: however, there is sufficient evidence of somatic cell mutagenicity (in vivo gene mutations or chromosomal aberrations) in humans or animal species, and sufficient evidence of exposure to germ cells in humans or animal species.

Group III.C -- Data from epidemiological studies to assess germ cell mutagenicity in humans are inadequate or lacking. There is sufficient data in animals to indicate that the chemical is a germ cell mutagen, but available data indicate that the induction of mutations occurs through an epigenetic threshold-based mechanism.

Group III.D -- Data from epidemiological studies to assess germ cell mutagenicity in humans are inadequate. There is sufficient evidence of mutagenicity of somatic cells in humans or animal species (in vivo gene mutations or chromosomal aberrations), but evidence of exposure to germ cells is inadequate or lacking.

Group IV -- Unlikely to Be a Human Germ Cell Mutagen

Group IV.A -- There is no evidence of human germ cell mutagenicity in sufficiently powerful and well-designed epidemiological studies. There is evidence of mutagenicity of somatic cells in well-designed and well-conducted studies in humans or animals, but there is no evidence of exposure of human or animal germ cells in well-designed studies.

Group IV.B -- Data on germ cell mutagenicity in epidemiological studies in humans are inadequate; there is no evidence of mutagenicity in vivo in germ or somatic cells in well-designed and properly conducted studies in animals.

Group V -- Probably Not a Human Germ Cell Mutagen

Group V.A -- There is no evidence of germ cell mutagenicity in sufficiently powerful and well-designed epidemiological studies; there is no evidence of germ cell mutagenicity in animal species.

Group V.B -- There is no evidence of germ cell mutagenicity in sufficiently powerful and well-designed epidemiological studies; data in animal species are inadequate.

Group V.C -- Data from epidemiological studies to assess germ cell mutagenicity in humans are inadequate, but evidence of the lack of germ cell mutagenicity in animal species is strongly supported by other data on mutagenicity in vivo.

Group VI -- Unclassifiable with Respect to Germ Cell Mutagenicity in Humans

Group VI.A -- Data from epidemiological and/or animal studies are inadequate (i.e., because of major qualitative limitations, the studies cannot be interpreted as showing either the presence or absence of germ cell mutagenicity).

Group VI.B -- There are no in vivo mutagenicity data available for evaluation.

Group VI.C -- Results of epidemiological studies in human populations and experimental studies in animal species are conflicting, without an identifiable mechanistic basis.

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^10.Though criteria for several subgroups of each category are specified, they are presented as representative examples only of possible combinations of results and are not exhaustive. This does not preclude inclusion of compound in the category for which available data do not precisely fulfil the exact criteria specified in one of the subgroups.