of evidence from one category to another. The categories are presented in decreasing order of strength of evidence.

  1. Positive data derived from human germ-cell mutagenicity studies, when available, will constitute the highest level of evidence for human mutagenicity.

  2. Valid positive results from studies on heritable mutational events (of any kind) in mammalian germ cells.

  3. Valid positive results from mammalian germ-cell chromosome aberration studies that do not include an intergeneration test.

  4. Sufficient evidence for a chemical's interaction with mammalian germ cells, together with valid positive mutagenicity test results from two assay systems, at least one of which is mammalian (in vitro or in vivo). The positive results may both be for gene mutations or both for chromosome aberrations; if one is for gene mutations and the other for chromosome aberrations, both must be from mammalian systems.

  5. Suggestive evidence for a chemical's interaction with mammalian germ cells, together with valid positive mutagenicity evidence from two assay systems as described under 4, above. Alternatively, positive mutagenicity evidence of less strength than defined under 4, above, when combined with sufficient evidence for a chemical's interaction with mammalian germ cells.

  6. Positive mutagenicity test results of less strength than defined under 4, combined with suggestive evidence for a chemical's interaction with mammalian germ cells.

  7. Although definitive proof of nonmutagenicity is not possible, a chemical could be classified operationally as a nonmutagen for human germ cells if it gives valid negative test results for all endpoints of concern.

  8. Inadequate evidence bearing on either mutagenicity or chemical interaction with mammalian germ cells (EPA 1986, Pp 9-10).

METHODS FOR DERIVATION OF INHALATION REFERENCE CONCENTRATIONS AND APPLICATION OF INHALATION DOSIMETRY

The culmination of the hazard identification phase of any risk assessment involves integrating a diverse data collection into a cohesive, biologically plausible toxicity “picture”; that is, to develop the weight of evidence that the chemical poses a hazard to humans. The salient points from each of the laboratory animal and human studies in the entire data base should be summarized as should the analysis devoted to examining the variation or consistency among factors (usually related to the mechanism of action), in order to establish the likely outcome for exposure to this chemical. From this analysis, an appropriate animal model or additional factors pertinent to human extrapolation may be identified.



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