Stuart Marshall

The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment

Abstract In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (United Kingdom) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (eg, transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments. In light of the growing number of examples of the application of omics data in the context of ecological risk assessment, we considered how omics datasets might continue to support the AOP framework. In particular, the role of omics in identifying potential AOP molecular initiating events and providing supportive evidence of key events at different levels of biological organization and across taxonomic groups was discussed. Areas with potential for short and medium-term breakthroughs were also discussed, such as providing mechanistic evidence to support chemical read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing robust extrapolations of species-sensitivity. Key challenges that need to be addressed were considered, including the need for a cohesive approach towards experimental design, the lack of a mutually agreed framework to quantitatively link genes and pathways to key events, and the need for better interpretation of chemically induced changes at the molecular level. This article was developed to provide an overview of ecological risk assessment process and a perspective on how high content molecular-level datasets can support the future of assessment procedures through the AOP framework.

Biodegradability of highly ethoxylated nonionic surfactants: Determination of intermediates and pathways of biodegradation

Existing data regarding alcohol ethoxylate (AE) surfactants indicate that structures with greater than 20 ethoxylate (EO) units per molecule or with multibranched alkyl chains may not pass a ready biodegradability test. This could have important consequences for complying with regional regulatory requirements and for the potential risks these chemicals could present to the environment. We investigated the influence of chemical structure on the biodegradability of AEs with different alkyl chain branching and EO content. The AEs investigated were a multibranched AE (average, 18 EO), an oxo-AE (monobranched; average, 23 EO), and a linear AE of oleochemical origin (average, 40 EO). The aims of the present study were to assess the ready biodegradability of AEs with high EO content and to establish the mechanism or pathway by which biodegradation occurs for the oxo-AE. Biodegradation studies were conducted using standard test conditions (International Standards Organization 14593). Solid-phase extraction and liquid chromatography with electrospray mass spectrometry were used to detect profiles in both derivatized and underivatized extracts of samples. Derivatization with phthalic anhydride was used to improve ionization of the lower-ethoxylated AEs and free alcohol that were key indicators in the present study. All AEs were rapidly biodegraded, achieving more than 60% mineralization of parent material. Central fission was the predominant mechanism for the oxo-AE, as confirmed by identification of the oligomeric distribution and quantification of polyethylene glycol released during biodegradation.

Aquatic toxicity of ethoxylated and propoxylated alcohols to daphnia magna.

Ethoxylated alcohols, which are used as nonionic surfactants, are known to act as general narcotics in acute aquatic toxicity; that is, they behave in the same way as nonsurfactant unreactive organic chemicals. The toxicity of such chemicals is well predicted by quantitative structure-activity relationships based solely on the logarithm of the octanol/water partition coefficient (log P), which can be calculated from structure. In the present study, we have shown, using experimental results, that a similar approach can be used to determine the toxicity of ethoxylate/propoxylate alcohols (i.e., containing propoxy [PO] and ethoxy [EO] units). Our calculations indicate that use of the Roberts position-dependent branching factor in calculating the PO group contribution is more appropriate than the Leo and Hansch branch factor. The resulting log P value for a PO group is 0.01; that is, the overall contribution to the final log P value is close to zero. On this basis, it is predicted that nonionic surfactants containing both EO and PO groups should have the same molar toxicity as surfactants based on the same parent alcohol and with the same number of EO groups but with no PO groups. This prediction has been confirmed in Daphnia acute toxicity tests. Furthermore, both EO/PO and EO-only nonionics are found to fit the same linear relationship between log P and toxicity.

Prospective mixture risk assessment and management prioritizations for river catchments with diverse land uses

Abstract Ecological risk assessment increasingly focuses on risks from chemical mixtures and multiple stressors because ecosystems are commonly exposed to a plethora of contaminants and nonchemical stressors. To simplify the task of assessing potential mixture effects, we explored 3 land use–related chemical emission scenarios. We applied a tiered methodology to judge the implications of the emissions of chemicals from agricultural practices, domestic discharges, and urban runoff in a quantitative model. The results showed land use–dependent mixture exposures, clearly discriminating downstream effects of land uses, with unique chemical “signatures” regarding composition, concentration, and temporal patterns. Associated risks were characterized in relation to the land‐use scenarios. Comparisons to measured environmental concentrations and predicted impacts showed relatively good similarity. The results suggest that the land uses imply exceedances of regulatory protective environmental quality standards, varying over time in relation to rain events and associated flow and dilution variation. Higher‐tier analyses using ecotoxicological effect criteria confirmed that species assemblages may be affected by exposures exceeding no‐effect levels and that mixture exposure could be associated with predicted species loss under certain situations. The model outcomes can inform various types of prioritization to support risk management, including a ranking across land uses as a whole, a ranking on characteristics of exposure times and frequencies, and various rankings of the relative role of individual chemicals. Though all results are based on in silico assessments, the prospective land use–based approach applied in the present study yields useful insights for simplifying and assessing potential ecological risks of chemical mixtures and can therefore be useful for catchment‐management decisions. Environ Toxicol Chem 2018;37:715–728.

Ecotoxicological thresholds—practical application to an industrial inventory

The concept of thresholds of toxicological concern as a potentially useful tool in environmental risk assessment has been applied to the inventory of a home and personal care products company to derive a series of chemical class-based ecotoxicological threshold of concern (ecoTTC) values. Cationic chemicals of various types show notably higher toxicity than other classes and should be treated separately. Despite this, the ecoTTC for the full data set in the present study is only slightly lower than that derived previously for chemicals causing toxicity via Verhaar modes of action (MoAs) 1 to 3. Exclusion of cationic chemicals resulted in an ecoTTC value slightly higher than the MoA 1 to 3 value. These observations indicate that such data sets contain few specifically acting chemicals. The applicability of threshold approaches in environmental risk assessment has been extended to include a limited number of inorganic/organometallic chemicals, polymers, and all classes of surfactants. The use of such ecoTTC values in conjunction with mode of action-based quantitative structure-activity relationships will allow the efficient screening and prioritization of large inventories of heterogeneous chemicals, focusing resources on those chemicals that require additional information to better understand any potential risk.

Priorities and opportunities in the application of the ecosystem services concept in risk assessment for chemicals in the environment

The ecosystem services approach has gained broad interest in regulatory and policy circles for use in ecological risk assessment. Whilst identifying several challenges, scientific experts from European regulatory authorities, the chemical industry and academia considered the approach applicable to all chemical sectors and potentially contributing to greater ecological relevance for setting and assessing environmental protection goals compared to current European regulatory frameworks for chemicals. These challenges were addressed in workshops to develop a common understanding across stakeholders on how the ecosystem services concept might be used in chemical risk assessment and what would need to be done to implement it. This paper describes the consensus outcome of those discussions. Knowledge gaps and research needs were identified and prioritised, exploring the use of novel approaches from ecology, ecotoxicology and ecological modelling. Where applicable, distinction is made between prospective and retrospective ecological risk assessment. For prospective risk assessment the development of environmental scenarios accounting for chemical exposure and ecological conditions was designated as a top priority. For retrospective risk assessment the top priority research need was development of reference conditions for key ecosystem services and guidance for their derivation. Both prospective and retrospective risk assessment would benefit from guidance on the taxa and measurement endpoints relevant to specific ecosystem services and from improved understanding of the relationships between measurement endpoints from standard toxicity tests and the ecosystem services of interest (i.e. assessment endpoints). The development of mechanistic models, which could serve as ecological production functions, was identified as a priority. A conceptual framework for future chemical risk assessment based on an ecosystem services approach is presented.