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Uncertainties in biological responses that influence hazard and risk approaches to the regulation of endocrine active substances
Citation:
Parrott, J., P. Bjerregaard, K. Brugger, E. Gray, T. Iguchi, S. Kadlec, L. Weltje, AND J. Wheeler. Uncertainties in biological responses that influence hazard and risk approaches to the regulation of endocrine active substances. Integrated Environmental Assessment and Management. Allen Press, Inc., Lawrence, KS, 13(2):293-301, (2016).
Impact/Purpose:
Endocrine Disrupting Substances (EDSs) may have certain biological effects including delayed effects, multigenerational effects, and 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. A proposal of how to evaluate NMDRs in the context of endocrine hazard and risk assessment procedures is presented. If careful consideration of delayed, multigenerational and NMDR effects are made, it is feasible to assess environmental endocrine hazards and derive robust apical endpoints for risk assessment procedures ensuring a high level of environmental protection.
Description:
Endocrine Disrupting Substances (EDSs) may have certain biological effects including delayed effects, multigenerational effects, and 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. EDSs can have specific and profound effects when exposure occurs during sensitive windows of the lifecycle (development, reproductive). This creates the potential for delayed effects where the adverse effect becomes manifest when exposure has ceased, possibly in a different lifestage. 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 can be considered protective of all life stages. Similarly, the potential for effects to be manifest in subsequent generations (multigenerational effects) has also been raised as a potential issue in the derivation of appropriate endpoints for EDSs. 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 endocrine active substances (EASs) developed by the OECD and US-EPA that 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 EDSs. Substantial data reviews are underway to inform on their occurrence. However, evidence to date indicates they are more prevalent in in vitro and 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, multigenerational and NMDR effects are made, it is feasible to assess environmental endocrine hazards and derive robust apical endpoints for risk assessment procedures ensuring a high level of environmental protection.
