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).

Does atrazine affect larval development and sexual differentiation of South African clawed frogs?

The potential impact of atrazine (ATZ) on gonadal malformations in larval Xenopus laevis has been controversially discussed, and a hypothesis has been generated that ATZ might induce the estrogen-synthesizing enzyme aromatase, leading to feminization or demasculinization. Recently, extensive long-term studies clearly indicate that no adverse effect of ATZ on larval development and sexual differentiation could be found. Therefore, to determine potential transient impacts of ATZ on sexual differentiation processes, short-term exposures were conducted using tadpoles treated for 4 days with ATZ at 25 microg/L. The expression levels of the key players for sexual differentiation in amphibians were determined in the brain, assessing aromatase, 5alpha-reductase type 1 (S1) and type 2 (S2), and the gonadotropins luteinizing hormone and follicle-stimulating hormone, and in the gonads, measuring aromatase, S1, and S2, by means of quantitative RT-PCR. No significant changes in any of these parameters have been found, implicating, in accordance with recent long-term exposures, that no aromatase induction by ATZ could be observed, and it seems likely that no further endocrine mechanism of ATZ affecting sexual differentiation in X. laevis exists.