A theoretical approach for a weighted assessment of the mutagenic potential of nanomaterials.

Several approaches have recently been proposed for predicting the potential hazard and risk to human health of engineered nanomaterials (NMs). Here, we present a theoretical approach to assess the mutagenic potential of NMs, which could be incorporated into risk assessment tools. Following the weight of evidence approach recommended for chemicals, we describe criteria for evaluating and weighting existing literature information, based on current knowledge on the relevance and limitations of genotoxicity and mutagenicity assays used in testing NMs. The relevant assays are then categorized according to the genotoxic events detected in three categories: DNA damage, gene mutations and chromosomal damage - the former weighing lower than the two latter ones, since unrepairable alterations have more weight than those depicting primary DNA damage that can still be repaired. Besides, evidence from in vivo tests are given a higher weight than data coming from in vitro tests, because animal studies can more accurately predict secondary genotoxicity. Although studies conducted according to validated protocols have greater weight, studies that do not comply with conventional test guidelines are also considered, trying to make use of all available information for each NM. A threshold of agreement among studies belonging to the same category is required to consider this category positive or negative for mutagenicity. The final outcome is a statement on the mutagenic potential of the nanoform and the uncertainty of this evaluation. Finally, we discuss new methods and possible improvements in current assays that could be incorporated in future guidelines.