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

Abstract

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 (BMD 10 , 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 BMD 10. BMD 10 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 BMD 10 levels were about half of the BMD 10 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.

UPLC-MS/MS Analysis of Naturally Derived Apis mellifera Products and Their Promising Effects against Cadmium-Induced Adverse Effects in Female Rats

“…The remarkable weight loss in rats pretreated with RJ for one week and then treated simultaneously with RJ and Cd for 30 days is likely related to the effective role of RJ in initiating the female defense (including immunologic) response against the adverse effects of the nesting Cd. Our findings for body mass are consistent with previous reports [ 58 ].…”

Crassocephalum rubens (Juss Ex Jacq) leaf diets ameliorate systemic oxidative stress and tissue damage in a Wistar rat model

“…The statistically significant lower weights observed in the MNU control compared to the normal and dietary control group (Figure 1a,b) may be linked to the effect of MNU exposure and the associated lower appetite resulting therefrom (Belhadj Benziane et al, 2019). Similar observations, including a dose‐dependent decrease in weight have been made in several studies where animals have been exposed to an array of compounds (Hadrup et al, 2016; Wang et al, 2019). However, the similarity in terminal weights between all MNU‐treated groups fed C. rubens ‐included diets suggests that the included plant eliminated changes in body weights of experimental animals as a possible confounding factor in the experiment.…”

Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring

“…The influence of environmental xenobiotics on the body weight is usually assessed at the end of toxicological studies [ 35 ]. Thus, to evaluate the potential toxic effects of TiO 2 NPs during pregnancy exposure, the body weight was firstly measured.…”