Background: Over the past 10–15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment.Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas.Data sources: To better understand and manage the risks of PPCPs in the environment, we used the “key question” approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance.Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f ) antibiotic resistance, and g) risk management.Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.

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Investigations into the environmental fate and effects of microplastics have been gaining momentum. Small, insoluble polymeric particles are implicated by scientists in a wide variety of studies that are used to suggest a potential for widespread impacts in freshwater and marine pelagic and sediment environments. An exponential growth in scientific publications and an increase in regulatory attention have occurred. However, despite these efforts, the environmental hazard of these particles is still unknown. To evaluate the hazard of microplastics within a risk assessment context, we need a way to evaluate the quality of experimental studies. We performed a thorough review of the quality and focus of environmental microplastic research, to understand the methodologies employed and how this may assist or distract from the ability of environmental risk assessors to evaluate microplastics. We provide guidance to improve the reliability and relevance of ecotoxicological studies for regulatory and broader environmental assessments. Nine areas of needed improvement are identified and discussed. Important data gaps and experimental limitations are highlighted. Environ Toxicol Chem 2017;36:1697-1703. © 2017 SETAC.

The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had sufficient reproducibility across a range of potencies and modes of action. In the present study, the suitability of the FET as an alternative model is reviewed by relating FET and AFT. In total, 985 FET studies and 1531 AFT studies were summarized. The authors performed FET-AFT regressions to understand potential relationships based on physical-chemical properties, species choices, duration of exposure, chemical classes, chemical functional uses, and modes of action. The FET-AFT relationships are very robust (slopes near 1.0, intercepts near 0) across 9 orders of magnitude in potency. A recommendation for the predictive regression relationship is based on 96-h FET and AFT data: log FET median lethal concentration (LC50) = (0.989 × log fish LC50) - 0.195; n = 72 chemicals, r = 0.95, p < 0.001, LC50 in mg/L. A similar, not statistically different regression was developed for the entire data set (n = 144 chemicals, unreliable studies deleted). The FET-AFT regressions were robust for major chemical classes with suitably large data sets. Furthermore, regressions were similar to those for large groups of functional chemical categories such as pesticides, surfactants, and industrial organics. Pharmaceutical regressions (n = 8 studies only) were directionally correct. The FET-AFT relationships were not quantitatively different from acute fish-acute fish toxicity relationships with the following species: fathead minnow, rainbow trout, bluegill sunfish, Japanese medaka, and zebrafish. The FET is scientifically supportable as a rational animal alternative model for ecotoxicological testing of acute toxicity of chemicals to fish.

The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV<30%) for most chemicals and laboratories. The reproducibility was lower (CV>30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes.

Tests with vertebrates are an integral part of environmental hazard identification and risk assessment of chemicals, plant protection products, pharmaceuticals, biocides, feed additives and effluents. These tests raise ethical and economic concerns and are considered as inappropriate for assessing all of the substances and effluents that require regulatory testing. Hence, there is a strong demand for replacement, reduction and refinement strategies and methods. However, until now alternative approaches have only rarely been used in regulatory settings. This review provides an overview on current regulations of chemicals and the requirements for animal tests in environmental hazard and risk assessment. It aims to highlight the potential areas for alternative approaches in environmental hazard identification and risk assessment. Perspectives and limitations of alternative approaches to animal tests using vertebrates in environmental toxicology, i.e. mainly fish and amphibians, are discussed. Free access to existing (proprietary) animal test data, availability of validated alternative methods and a practical implementation of conceptual approaches such as the Adverse Outcome Pathways and Integrated Testing Strategies were identified as major requirements towards the successful development and implementation of alternative approaches. Although this article focusses on European regulations, its considerations and conclusions are of global relevance.

Environmental risk assessments often use multiple single species toxicity test results and species sensitivity distributions (SSDs) to derive a predicted no-effect concentration in the environment, typically the 5th percentile of the SSD, termed the HC5. The shape and location of the distribution are best known when populated with numerous toxicity values. To help overcome the cost of multiple toxicity tests, we explored the potential of the U.S. EPA's Interspecies Correlation Estimation (ICE) program to predict single species toxicity values from a single known toxicity value. ICE uses the initial toxicity estimate for one species to produce correlation toxicity values for multiple species, which can be used to develop SSD and HC5. To test this approach to deriving HC5, we generated toxicity values based on measured toxicity values for three surrogate species Pimephales promelas (Fathead minnow), Onchorynchus mykiss (Rainbow trout), and Daphnia magna (water flea). Algal taxa were not used due to the paucity of high quality algal-aquatic invertebrate and algal-fish correlations. The compounds used (dodecyl linear alkylbenzenesulfonate (LAS), nonylphenol, fenvalerate, atrazine, and copper) have multiple measured toxicity values and diverse modes of action and toxicities. Distribution parameters and HC5 values from the measured toxicity values were compared with ICE predicted distributions and HC5 values. While distributional parameters (scale and intercept) differed between measured and predicted distributions, in general, the ICE-based SSDs had HC5 values that were within an order of magnitude of the measured HC5 values. Examination of species placements within the SSDs indicated that the most sensitive species were coldwater species (e.g., salmonids and Gammarus pseudolimnaeus). These results raise the potential of using quantitative structure activity models to estimate HC5s.