Environmental effect assessment for sexual endocrine‐disrupting chemicals: Fish testing strategy

Abstract

Current standard testing and assessment tools are not designed to identify specific and biologically highly sensitive modes of action of chemicals, such as endocrine disruption. This information, however, can be important to define the relevant endpoints for an assessment and to characterize thresholds of their sublethal, population-relevant effects. Starting a decade ago, compound-specific risk assessment procedures were amended by specifically addressing endocrine-disrupting properties of substances. In 2002, the Conceptual Framework, agreed upon by OECD's Task Force on Endocrine Disrupters Testing and Assessment, did not propose specific testing strategies, and appropriate testing methods had not yet been developed and approved. In the meantime, the OECD Test Guidelines Programme has undertaken important steps to revise established and to develop new test methods, which can be used to identify and quantify effects of endocrine-disrupting chemicals on mammals, birds, amphibians, fish, and invertebrates. For fish testing of endocrine-disrupting chemicals, the first Test Guidelines have recently been adopted by the OECD and validation of further test systems is under progress. Based on these test systems and the experience gained during their validation procedures, we propose a 3-step fish testing strategy: 1) Weight-of-evidence approach for identifying potential sexual endocrine-disrupting chemicals; even after advanced specification of systematic criteria, this step of establishing initial suspicion will still require expert judgment; 2) in vivo evaluation of sexual endocrine-disrupting activity in fish by applying in vivo fish screening assays; sufficient data are available to diagnose the aromatase-inhibition and estrogen-receptor agonist mechanisms of action by indicative endpoints (biomarkers), whereas the ability of the respective biomarkers in the screening assay to identify the estrogen-receptor antagonists and androgen-receptor agonists and antagonists requires further validation; 3) characterization of sexual endocrine-mediated adverse effects including threshold concentrations; in cases when the most sensitive population-relevant endpoints and the most sensitive time window for exposure are known for the mechanisms of action, the fish full life-cycle or 2-generation test, which are the normal definitive tests, might be abbreviated to, e.g., the fish sexual development test. In the European Union, the measurement of indicative endpoints in the definitive test might be crucial for the authorization procedure under REACH and plant-protection products. The results of the definitive tests can be used in existing schemes of compound-specific environmental risk assessments.

Endocrine disruption: Where are we now: Tier 2 testing

“…While the study provides data on adults, data on sexual development from earlier stages of development are missing. Knacker et al (2010) demonstrates that for most modes of action for endocrine disruption in zebrafish, sexual development is the most sensitive stage to look for effects. Such data gaps demonstrate the need for pilot studies that are smaller and more focused experiments that provide additional information for designing a higher tiered test.…”

A farewell to Dr Thomas Knacker (* 29.04.1951 – † 30.10.2011): scientific contributions and personal memories

“…Although Thomas was formally responsible for aquatic ecotoxicology at ECT GmbH, his research interests were much broader [4][5][6][7]. His influence was probably most visible in the environmental risk assessment of chemicals [8][9][10], such as their regulation in the marine environment (OSPAR process), the effects of endocrine disruptors [11,12] or their testing in higher-tier studies, especially Terrestrial Model Ecosystems (TMEs) [13][14][15].…”

Endocrine disruptor screening: regulatory perspectives and needs

“…Similarly, many in vitro but also some in vivo assays make decisions based on effects that are measured at the sub-organismal (molecular, sub-cellular or cellular) level. What is often lacking, though, is the ability to link these endpoints with biological relevant responses [59]. Thus, one of the key future challenges is to align the primary mechanistic data obtained by means of genomic or other sub-organismal studies with outcomes of demographic relevance such as survival and reproduction.…”