Recommended approaches to the scientific evaluation of ecotoxicological hazards and risks of endocrine-active substances.

A SETAC Pellston Workshop® "Environmental Hazard and Risk Assessment Approaches for Endocrine-Active Substances (EHRA)" was held in February 2016 in Pensacola, Florida, USA. The primary objective of the workshop was to provide advice, based on current scientific understanding, to regulators and policy makers; the aim being to make considered, informed decisions on whether to select an ecotoxicological hazard- or a risk-based approach for regulating a given endocrine-disrupting substance (EDS) under review. The workshop additionally considered recent developments in the identification of EDS. Case studies were undertaken on 6 endocrine-active substances (EAS-not necessarily proven EDS, but substances known to interact directly with the endocrine system) that are representative of a range of perturbations of the endocrine system and considered to be data rich in relevant information at multiple biological levels of organization for 1 or more ecologically relevant taxa. The substances selected were 17α-ethinylestradiol, perchlorate, propiconazole, 17ß-trenbolone, tributyltin, and vinclozolin. The 6 case studies were not comprehensive safety evaluations but provided foundations for clarifying key issues and procedures that should be considered when assessing the ecotoxicological hazards and risks of EAS and EDS. The workshop also highlighted areas of scientific uncertainty, and made specific recommendations for research and methods-development to resolve some of the identified issues. The present paper provides broad guidance for scientists in regulatory authorities, industry, and academia on issues likely to arise during the ecotoxicological hazard and risk assessment of EAS and EDS. The primary conclusion of this paper, and of the SETAC Pellston Workshop on which it is based, is that if data on environmental exposure, effects on sensitive species and life-stages, delayed effects, and effects at low concentrations are robust, initiating environmental risk assessment of EDS is scientifically sound and sufficiently reliable and protective of the environment. In the absence of such data, assessment on the basis of hazard is scientifically justified until such time as relevant new information is available. Integr Environ Assess Manag 2017;13:267-279. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances.

In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high-throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid signaling. Integr Environ Assess Manag 2017;13:302-316. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

ICON rice seed treatment toxicity to crayfish (Procambarus clarkii) in experimental rice paddies.

Outdoor pools (2.3 x 2.3 m) were used to simulate typical rice agricultural practices in Louisiana, USA, to evaluate the toxicity of ICON (active ingredient [a.i.] fipronil) and its degradates to crayfish (Procambarus clarkii). Six paddies were planted with seed treated with ICON 6.2 FS at an exaggerated application rate of 0.05 kg a.i./ha (recommended rate, 0.042 kg a.i./ha), simulating three rice-planting scenarios. Two reference paddies were planted with untreated seed. Crayfish were exposed to tail water within 24 to 48 h after seeding, simulating standard Louisiana agricultural and water management practices. At 50 d after planting, a separate group of crayfish was caged in situ for 14 d to evaluate toxicity. An additional 50 crayfish were added to two paddies approximately 100 d after rice planting and held for 29 weeks to evaluate bioaccumulation. Residues of fipronil and its degradates in water and soil were similar to residue concentrations measured from rice fields in Louisiana. Tail water from the treated paddies was not toxic to crayfish. The fipronil 96-h median lethal concentration (LC50) for adult crayfish was 180 microg/L, which would provide at least a sixfold safety factor between the maximum fipronil concentration in tail water and the crayfish LC50. In situ exposures of crayfish also were not toxic. Concentrations of fipronil and its degradates after 29 weeks of exposure were less than 5 microg/kg in crayfish tail muscle tissue. These results demonstrate that label instructions adequately protect crayfish in a rice-crayfish cropping scenario when ICON is applied at maximum application rates as a seed treatment.