Citation:

Parrott, J., P. Bjerregaard, C. Bogert, K. Brugger, E. Gray, T. Iguchi, s. Kadlec, L. Weltje, AND J. Wheeler. Uncertainties in biological responses that influence hazard or risk approaches to the regulation of endocrine active substances. SETAC Nantes, Nantes, FRANCE, May 22 - 26, 2016.

Impact/Purpose:

The presentation will present scientific evidence on the potential for EDCs to induce transgenerational effects and to induce non-monotonic dose response relationships. These issues are highly controversial in the EDC field. This group of experts from government, industry and academia report that the evidence for transgenerational and NMDR effects that would impact risk assessment as a general issue is limited. A proposal of how to evaluate NMDRs in the context of endocrine hazard and risk assessment procedures is presented. If careful consideration of delayed, transgenerational and NMDR effects is made, it is feasible to assess environmental endocrine hazards and derive robust endpoints for risk assessment procedures ensuring a high level of environmental protection.

Description:

Endocrine Disrupting Chemicals (EDCs) may have delayed or transgenerational effects and display non-monotonic dose response relationships (NMDRs) that require careful consideration when determining environmental hazards. The case studies evaluated for the SETAC Pellston Workshop™: Environmental Hazard and Risk Assessment Approaches for Endocrine-Active Chemicals and other key examples from the literature are discussed. EDCs can have specific and profound effects when exposure occurs over sensitive windows of the lifecycle (developmental, reproductive). This may induce delayed effects where the adverse effect is manifest at different lifestage(s). This underscores the need for testing in appropriate (sensitive) lifestages and full lifecycle designs that capture adverse effects wherever they occur in the lifecycle. Such tests are available in the tool box and should be employed to derive endpoints that cover all life stage sensitivities. Similarly, the potential for effects to become manifest in subsequent generations (transgenerational) has also been raised as a potential issue in the derivation of appropriate endpoints for EDCs. However, the evidence for such effects as a general issue is limited. Indeed this is reflected in the design of new higher tier tests to assess EDCs developed under the auspices of the OECD and US-EPA by the move to extended one-generation designs away from multi-generational studies for fish and mammals. The occurrence of non-monotonic dose or concentration response relationships is also considered a limiting factor for reliable risk assessment of EDCs. Substantial data reviews are underway to inform on their occurrence and relevance. However, evidence to date indicates they are more prevalent in in vitro and in vivo mechanistic data, not often translating to adverse apical endpoints that would be employed in risk assessment. A proposal of how to evaluate NMDRs in the context of endocrine hazard and risk assessment procedures is presented. If careful consideration of delayed, transgenerational and NMDR effects is made, it is feasible to assess environmental endocrine hazards and derive robust endpoints for risk assessment procedures ensuring a high level of environmental protection.

Record Details: