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Relationship between magnitude of body weight effects and exposure duration in mammalian toxicology studies and implications for ecotoxicological risk assessment

Wang, Magnus, Guckland, Anja, Murfitt, Roger, Ebeling, Markus, Sprenger, Dennis, Foudoulakis, Manousos, Koutsaftis, Apostolos
Environmental sciences Europe 2019 v.31 no.1 pp. 38
European Union, active ingredients, body weight, chronic toxicity, diet, ecotoxicology, exposure duration, females, fungicides, herbicides, insecticides, long term effects, plant protection, rats, risk assessment, toxicity testing
BACKGROUND: For regulatory approval of pesticides in the EU, an ecotoxicological risk assessment has to be conducted including an assessment of long-term effects on mammals. For this assessment, toxicity studies are considered which are conducted with rodents which are continuously exposed via diet over a long period. A typical observation in these studies is a reduction of body weight. Such reductions are generally more pronounced at the end of a study and are often used to derive an endpoint for the wild mammal long-term risk assessment. However, exposure in the field is rather short for most modern pesticides. Therefore, the change of the magnitude of effects over exposure time may be relevant to obtain a realistic view of effects expected in the field. RESULTS: Time dependence of effects observed in toxicity studies conducted with rats was evaluated, focusing on effects on female body weight. Benchmark doses (BMD₁₀, i.e., 10% effect) were calculated for a total of 37 long-term toxicity studies conducted with 13 different active substances used as pesticides. Female body weights after 14, 21, 28, 42 and 70 days of dosing were used for BMD analysis per active substance to evaluate time-dependent changes of BMD₁₀. BMD₁₀ values declined continuously with exposure duration, indicating that the longer the duration of exposure, the greater are the effects on body weights. This continuous decline was observed for all pesticide classes (i.e. herbicides, insecticides and fungicides) from the studies analyzed. After 70 days, the BMD₁₀ levels were about half of the BMD₁₀ at day 14. CONCLUSION: The results indicate that animals respond to pesticide exposure in an exposure-time-dependent way, i.e. effects on body weight of the animals are less pronounced when the duration of exposure is short. The greatest body weight effects were observed at the end of toxicity studies (after longest exposure). The realism of the current wild mammal risk assessment for plant protection products is discussed and how it could be improved by considering an appropriate time period for the selection of endpoints in chronic toxicity studies, which reflects the exposure time of free ranging animals in the field.