RESEARCH Review Ecological Risk Assessment of Endocrine Disruptors Thomas H

RESEARCH Review Ecological Risk Assessment of Endocrine Disruptors Thomas H. Hutchinson,1 Rick Brown,2 Kristin E. Brugger,3 Pamela M. Campbell,4 Martin Holt,5 Reinhard Länge,6 Peter McCahon,7 Lisa J. Tattersfield,8 and Roger van Egmond 9 1AstraZeneca, Brixham Environmental Laboratory, Brixham, Devon, United Kingdom; 2Exxon Biomedical Sciences Inc., East Millstone, New Jersey, USA; 3Du Pont, Wilmington, Delaware, USA; 4Procter & Gamble, Toronto, Ontario, Canada; 5ECETOC, Van Nieuwenhuyse, Brussels, Belgium; 6Schering AG, Berlin, Germany; 7Aventis, Research Triangle Park, North Carolina, USA; 8ZENECA Agrochemicals, Jealott’s Hill Research Station, Bracknell, United Kingdom; 9Unilever Research, Port Sunlight Laboratory, Bebington, United Kingdom characterize the ecological risk of selected The European Centre for Ecotoxicology and Toxicology of Chemicals proposes a tiered approach endocrine-active substances. For example, for the ecological risk assessment of endocrine disruptors, integrating exposure and hazard recent progress toward this goal is illustrated (effects) characterization. Exposure assessment for endocrine disruptors should direct specific tests by tributyltin (9). In general, however, further for wildlife species, placing hazard data into a risk assessment context. Supplementing the suite of work is needed to evaluate potential mammalian screens now under Organization for Economic Cooperation and Development endocrine disruptors within the established (OECD) validation, high priority should be given to developing a fish screening assay for detect- ecological risk assessment concept (2,10,11) ing endocrine activity in oviparous species. Taking into account both exposure characterization (Figure 1). Although much will be learned and alerts from endocrine screening, higher tier tests are also a priority for defining adverse through the on-going application of the eco- effects. We propose that in vivo mammalian and fish assays provide a comprehensive screening logical risk assessment paradigm to both nat- battery for diverse hormonal functions (including androgen, estrogen, and thyroid hormone), ural and synthetic endocrine disruptors, we whereas Amphibia should be considered at higher tiers if there are exposure concerns. Higher tier support the views of Kendall et al. (4) in that endocrine-disruptor testing should include fish development and fish reproduction tests, whereas “There is no need to develop a new frame- a full life-cycle test could be subsequently used to refine aquatic risk assessments when necessary. work for ecological risk assessment of For avian risk assessment, the new OECD Japanese quail reproduction test guideline provides a endocrine disrupters.” What is needed, how- valuable basis for developing a test to detecting endocrine-mediated reproductive effects; this ever, is a scientifically and ethically justifiable species could be used, where necessary, for an avian life-cycle test. For aquatic and terrestrial approach to prioritizing endocrine-disruptor invertebrates, data from existing developmental and reproductive tests remain of high value for screening and testing that effectively protects ecological risk assessment. High priority should be given to research into comparative endocrine the diversity of wildlife. physiology of invertebrates to support data extrapolation to this diverse fauna. Key words: ecologi- The established risk assessment frame- cal risk assessment, endocrine disruptor, environment, hormone mimic, screening, testing. work provides a robust tool with which to Environ Health Perspect 108:1007–1014 (2000). [Online 4 October 2000] evaluate the impacts of natural and synthetic http://ehpnet1.niehs.nih.gov/docs/2000/108p1007-1014hutchinson/abstract.html toxicants, endocrine disruptors, and other stressors on ecosystems. This framework bal- ances exposure characterization versus effects Given many reports of contaminant-associ- disruptors and supports the establishment of characterization, taking into account the ated reproductive and developmental new wildlife screening and testing protocols. need for test validation, data acquisition, and impacts in wildlife, often considered to be Our strategy for ecotoxicity screening and field monitoring. caused by endocrine disruption, there is now testing is discussed versus the proposed EDSP Exposure assessment for potential a major global effort to develop ecotoxicity (2), based on the earlier report from the endocrine disruptors is important in directing test guidelines for the hazard assessment of EDSTAC (1). Specifically, our critical review specific-effects testing, such that risk assess- endocrine disruptors. The Endocrine of the EDSTAC considers both the scientific ment and risk management can proceed. Disruptor Screening and Testing Advisory rationale and ethical use of animals for eco- Exposure assessment may be defined as the Committee (EDSTAC) (1) and the U.S. toxicity hazard assessment (5). Throughout contact between the bioavailable fraction of Environmental Protection Agency’s (U.S. this exercise, we support the internationally the compound of interest and the organisms EPA’s) proposed Endocrine Disruptor agreed definition from the 1996 Weybridge of concern. A tiered approach to exposure Screening Program (EDSP) (2) have made workshop, whereby an endocrine disruptor is assessment whereby conservative assumptions key initiatives for hazard assessment per se. “an exogenous substance which causes adverse Critically, however, the strategy for ecologi- effects in an organism, or its progeny, subse- Address correspondence to T. Hutchinson, cal effects characterization of endocrine dis- quent to changes in the endocrine system.” AstraZeneca, Brixham Environmental Laboratory, ruptors also needs to be integrated into the (6). In vitro test systems are not addressed in Freshwater Quarry, Brixham, Devon TQ5 8BA, UK. exposure characterization component of a our present discussion because it has been Telephone: 44-1803-882882. Fax: 44-1803-882974. risk-based laboratory and field approach widely agreed at several international work- E-mail: [email protected] (3,4). shops that endocrine-disruptor assessments in The members of the European Centre for Ecotoxicology and Toxicology of Chemicals Wildlife The European Centre for Ecotoxicology wildlife should primarily focus on in vivo Working Group are R. Länge, R. Brown, K. Brugger, and Toxicology of Chemicals (ECETOC) studies (7,8). P.M. Campbell, S. Einarson, M. Holt, T.H. established the Environmental Oestrogens Hutchinson, P. McCahon, O. Oppen-Berntsen, L.J. Task Force to identify the best ways to eval- The Ecological Risk Tattersfield, R. van Egmond, and S. Zok. uate potential endocrine-disrupting sub- Assessment Context We thank our colleagues in the Chemical stances for human and ecological risk Although evaluation of endocrine disruptors Manufacturers Association and the European Crop Protection Association for their helpful comments assessment. From these efforts, our ECE- is a relatively new area, both field and labora- on this paper. TOC working group argues for an ecologi- tory studies have been conducted to define Received 13 December 1999; accepted 16 June cal risk assessment framework for endocrine ecological effects, determine sources, and 2000. Environmental Health Perspectives • VOLUME 108 | NUMBER 11 | November 2000 1007 Review • Hutchinson et al. in the estimate are progressively refined is In comparing the degree of toxicity with Key elements of our approach are, first, likewise appropriate for endocrine disruptors the level of exposure, the risk of the com- to focus testing needs through a greater con- as well as compounds that may be active via pound may then be characterized and any sideration of exposure characterization data other mechanisms. necessary risk management can be conducted when deciding which types of chronic tests Potential for exposure should drive the (Figure 1). Ultimately, potential impacts (e.g., avian, fish, or invertebrate) may be selection of appropriate test organisms in from synthetic substances should be consid- required at the higher tiers (15). Second, our hazard assessment. For example, where a ered in the context of natural stressors to scheme offers a pragmatic alternative to the pesticide is sprayed directly onto crops, it is help define what is an acceptable ecological technical and ethical concerns raised by the reasonable to expect potential exposure to impact. The concept of acceptability under- EDSTAC recommendation to move to aquatic organisms and birds via spray drift. pins the regulatory programs for pesticides extensive multispecies testing directly after The expected environmental concentrations in many countries. For example, the U.S. the Tier 1 screening, without first recogniz- should then be compared with the toxic EPA characterizes “unacceptable” as “wide- ing the value of partial life-cycle (PLC) tests, concentration to aquatic organisms and spread and repeated mortality in the face of which use fewer animals. The following con- birds to determine the potential ecological minor economic benefits to society” cepts have proved useful in consideration risk. For natural or synthetic substances dis- (11,13). Finally, it is essential that new test of new wildlife protocols for endocrine-disrup- charged via wastewater into rivers, aquatic methods should provide data that can be tor screening and testing: a) conceptual organisms are expected to be exposed if the related directly to the field monitoring protocol, which refers

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