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Pure Appl. Chem., 2003, Vol. 75, No. 11-12, pp. 1933-1948

Critical factors in exposure modeling of endocrine active substances

P. de Voogt and B. van Hattum

Environmental and Toxicological Chemistry, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Nieuwe Achtergracht 166, 1018 WV Amsterdam, The Netherlands; 2 Institute for Environmental Studies, Vrije Universiteit, De Boelelaan 1087, 1081 HV, Amsterdam, The Netherlands

Multimedia transport, partitioning, and degradation pathways are key processes in the probability of a substance to interact with target organisms. Biotic factors such as toxicokinetics, biotransformation capacity, and behavioral and life-cycle aspects of the organisms are determinants for final concentrations at target organs. The role of metabolites in endocrine disruption can be quite different from those of the parent compounds, and often this requires separate toxicokinetic evaluation.
The exposure assessment of endocrine active substances (EASs) suffers from a huge lack of reliable data, of both values that are used as input parameters in exposure models, and field data that are needed for validation purposes. In general, for the more classic EASs, such as PCBs, p,p'-DDE, chlorinated dioxins, some pesticides, and organotins, reliable data are sufficiently available, but careful evaluation of the quality of databases is necessary. Several data quality evaluation systems have been proposed. For the "newer" compounds, only few data have been gathered so far. The latter compounds include alkylphenols, bisphenol A, brominated flame retardants, phytoestrogens, and in particular natural and synthetic hormones, which in view of their high estrogenic potency could be the most important compounds in terms of risk.
The suitability of current exposure assessment models for EASs at this moment seems to be restricted to the persistent compounds such as PCBs, PCDDs, and PCDFs. Especially for the compounds subject to biodegradation and biotransformation, the lack of experimental data to derive model-input parameters and perform validation studies at this moment is one of the main obstacles for the further application of generic exposure models to other EASs. Most of the current models do not allow life stage-specific predictions.
Although the mechanisms of endocrine disruption involve different types of action, the principle of additivity, based on the equivalent toxicity approach (using estrogen equivalent potencies relative to 17β-estradiol) seems promising for the design of integrated exposure and effect models for EASs.
Research programs aimed at the endocrine disruption issue must focus on promoting experimental studies for generation of reliable, high-quality parameter data on the one hand, and surveys or monitoring campaigns for collection of representative field data on the other. The non-specificity of possible effects caused through endocrine mechanisms implies that in order to reveal dose-response relationships all potentially active agents, or at least as many as feasible, need be included in the risk assessments. Current regulatory monitoring programs should further be evaluated and harmonized with validation requirements of models used in exposure assessment.