Development of an Enhanced Mechanistically Driven Mode of Action Classification Scheme for Adverse Effects on Environmental Species.

This study developed a novel classification scheme to assign chemicals to a verifiable mechanism of (eco-)toxicological action to allow for grouping, read-across, and in silico model generation. The new classification scheme unifies and extends existing schemes and has, at its heart, direct reference to molecular initiating events (MIEs) promoting adverse outcomes. The scheme is based on three broad domains of toxic action representing nonspecific toxicity (e.g., narcosis), reactive mechanisms (e.g., electrophilicity and free radical action), and specific mechanisms (e.g., associated with enzyme inhibition). The scheme is organized at three further levels of detail beyond broad domains to separate out the mechanistic group, specific mechanism, and the MIEs responsible. The novelty of this approach comes from the reference to taxonomic diversity within the classification, transparency, quality of supporting evidence relating to MIEs, and that it can be updated readily.

Fate and exposure modeling in regulatory chemical evaluation: new directions from retrospection.

The development and application of fate and exposure modeling has undergone fundamental changes over the last 20 years. This has, in part, been driven by different needs within the regulatory community to address chemicals of concern using different approaches. Here we present a retrospective look at fate and exposure model application over the last two decades keeping an international regulatory perspective and using the Government of Canada's Chemicals Management Plan to illustrate concepts. We discuss the important role fate and exposure modeling has played to help address key data gaps when evaluating the risk of chemicals for both human health and ecological reasons. Yet limitations for more widespread model application within a regulatory context remain. Consequently, we identify specific data gaps and regulatory needs with an eye towards new directions for 21st century chemical evaluation. We suggest that one factor limiting greater model application is the need for increased awareness and agreement of what chemical exposure assessment encompasses within the risk assessment paradigm. This is of particular importance today because of the increased availability of computational and high-throughput data and methods for chemical assessment allowing evaluators to potentially examine exposure from site of release to site of toxic action, thus linking exposure with toxicology. We further suggest there is a need for discussion at a global level to promote the awareness of new tools and approaches available for fate and exposure modeling and suggest that this could be organized using the aggregate exposure pathways concept.

Review of existing terrestrial bioaccumulation models and terrestrial bioaccumulation modeling needs for organic chemicals.

Protocols for terrestrial bioaccumulation assessments are far less-developed than for aquatic systems. This article reviews modeling approaches that can be used to assess the terrestrial bioaccumulation potential of commercial organic chemicals. Models exist for plant, invertebrate, mammal, and avian species and for entire terrestrial food webs, including some that consider spatial factors. Limitations and gaps in terrestrial bioaccumulation modeling include the lack of QSARs for biotransformation and dietary assimilation efficiencies for terrestrial species; the lack of models and QSARs for important terrestrial species such as insects, amphibians and reptiles; the lack of standardized testing protocols for plants with limited development of plant models; and the limited chemical domain of existing bioaccumulation models and QSARs (e.g., primarily applicable to nonionic organic chemicals). There is an urgent need for high-quality field data sets for validating models and assessing their performance. There is a need to improve coordination among laboratory, field, and modeling efforts on bioaccumulative substances in order to improve the state of the science for challenging substances.