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mutagenic effect, mutagenicity

mutagenic substances or agents are, those, which induce mutation in living cells. Mutagenicity refers to the induction of permanent transmissible changes in the amount or structure of the genetic material of cells or organisms. These changes may involve a single gene or gene segment, a block of genes or chromosomes.

Alterations to the genetic material of cells may occur spontaneously or be induced as a result of exposure to ionising or ultraviolet radiation, or genotoxic substances. In principle, human exposure to substances that are mutagens may result in increased frequencies of mutations above baseline. Heritable damage to the offspring, and possibly to subsequent generations, of parents exposed to substances that are mutagens may follow if mutations are induced in parental germ cells (reproduction cells). Mutations in somatic cells (cells others than reproduction cells) may be lethal or may be transferred to daughter cells with deleterious consequences for the affected organism. There is considerable evidence of a positive correlation between the mutagenicity of substances in vivo and their carcinogenicity in long-term studies with animals. The aims of testing for mutagenicity are to assess the potential of substances to induce effects which may cause heritable damage in humans or lead to cancer.

Mutagens are usually chemical compounds or ionizing radiation. Mutagens can be divided into different categories according to their effect on DNA replication:

  • Some mutagens act as base analogs and get inserted into the DNA strand during replication in place of the substrates.
  • Some react with DNA and cause structural changes that lead to miscopying of the template strand when the DNA is replicated.
  • Some work indirectly by causing the cells to synthesize chemicals that have the direct mutagenic effect.
Mutagenic, Carcinogenic, Reprotoxic
Mutagenic, Carcinogenic, Reprotoxic and Respiratory Sensitizers
mutagenicity and carcinogenicity

mutagenicity refers to the induction of permanent transmissible changes in the amount or structure of the genetic material of cells or organisms. These changes may involve a single gene or gene segment, a block of genes or chromosomes.
Alterations to the genetic material of cells may occur spontaneously or be induced as a result of exposure to ionising or ultraviolet radiation, or genotoxic substances. In principle, human exposure to substances that are mutagens may result in increased frequencies of mutations above baseline. Heritable damage to the offspring, and possibly to subsequent generations, of parents exposed to substances that are mutagens may follow if mutations are induced in parental germ cells (reproduction cells). Mutations in somatic cells (cells others than reproduction cells) may be lethal or may be transferred to daughter cells with deleterious consequences for the affected organism. There is considerable evidence of a positive correlation between the mutagenicity of substances in vivo and their carcinogenicity in long-term studies with animals. The aims of testing for mutagenicity are to assess the potential of substances to induce effects which may cause heritable damage in humans or lead to cancer.

Chemicals are defined as carcinogenic if they induce tumours, increase tumour incidence and/or malignancy or shorten the time to tumour occurrence. Carcinogenic chemicals have conventionally been divided into two categories according to the presumed mode of action. Non-genotoxic modes of action include epigenetic changes, i.e., effects that do not involve alterations in DNA but that may influence gene expression, altered cell-cell communication, or other factors involved in the carcinogenic process. The objective of investigating the carcinogenicity of chemicals is to identify potential human carcinogens, their mode(s) of action, and their potency.
Once a chemical has been identified as a carcinogen, there is a need to elucidate the underlying mode of action, i.e. whether the chemical is directly genotoxic or not. For genotoxic carcinogens it is assumed that, unless exception, there is no discernible threshold and that any level of exposure carries a risk. For non-genotoxic carcinogens, no-effect-thresholds are assumed to exist and to be discernable. Human studies are generally not available for making a distinction between the above mentioned modes of action; and a conclusion on this, in fact, depends on the outcome of mutagenicity testing and other mechanistic studies. In addition to this, animal studies may also inform on the underlying mode of carcinogenic action.
The cancer hazard and mode of action may also be highly dependent on exposure conditions such as the route of exposure. Therefore, all relevant effect data and information on human exposure conditions are evaluated.

Source: REACH