Factors influencing mutagenic mode of action determinations of regulatory and advisory agencies.

摘要: The determination of whether a chemical induces cancer through mutagenic or genotoxic mechanism frequently plays an important role in evaluating the risks associated with low dose exposure. Although various approaches are employed for making mode action decisions, systematic investigation to identify major factors that influence these determinations has not been performed. To accomplish this, over 40 risk assessments conducted by U.S. international regulatory agencies and organizations were reviewed components had played significant role, either directly indirectly, decision-making process. identified included properties agent, its metabolites degradation products; metabolism toxicokinetics; effects seen vivo, particularly target organ; structural metabolic similarities known nonmutagenic chemicals; characteristics tumors induced animal bioassays; origin observed effects. quality data, specific endpoint sensitivity assay conditions toxicity also considerations. In all cases, authoritative groups used weight-of-evidence approach and, most cases where evaluations more than one body, similar conclusions reached. summary, critical evaluation data as well expert judgment is necessary reaching conclusions. These should be made within broader context chemical's overall carcinogenicity.