ON THE USE AND FUTURE OF ALTERNATIVE TESTING STRATEGIES IN REGULATORY TOXICOLOGY

Regulatory toxicology has emerged as a necessary discipline to ensure that chemicals introduced into commerce are safe. Contemporary history has taught us the hard way that while many chemicals are not harmful to human health, there too are many chemicals that were found after introduction into commerce to cause harm. This is a serious public health concern. Regulatory toxicologists inform decisions in part based on alternative test methods in addition to traditional in vivo studies. This is in part due to legal constraints placed on regulators, and it has not been articulated in research what these constraints and data are, or how these considerations inform regulatory decisions. The findings of this body of research reveal that alternative test methods primarily inform decisions of the US Environmental Protection Agency’s New Chemicals Program, which administers the Toxic Substances Control Act. This research also finds that there exist data gaps that need to be filled so that the New Chemicals Program can be able to make more informed decisions. Various studies have blossomed in recent years on the potential of alternative test methods to inform decisions, which includes the work of the ToxCast program. ToxCast has been productive in research, but has yet to have a method validated and implemented by regulators. This study finds that there are ToxCast parameters that may be predictive of hepatocarcinogenesis, but further research is warranted. Finally, the US National Academies of Sciences has promoted the use of alternative test methods, specifically putting forward the notion that the perturbation of network motifs may be a means to fill information gaps. The literature on motifs to date is limited to basic research, but recurring motifs across species that were identified in this body of research can be applicable within toxicity testing moving forward