In Vivo Investigation of Dietary Exposure to 5

In Vivo Investigation of Dietary Exposure to 5 Pesticides

8 Perspectives

From a regulatory point of view the CNS symptoms seen in the initial study still gives reason to concern, and there is a need to explain the findings. Which of the pesticides in the combination gave the CNS symptoms alphacypermethrin, chlorpyrifos or a combination? Since the level of mancozeb in the diet in combined exposure study was only 18-26% of the intended it cannot be excluded that the toxicity was caused by mancozeb in combination with chlorpyrifos and/or alphacypermethrin.

There is furthermore a need to perform some toxicokinetic studies of the single compounds and compounds in combination. Toxicokinetic studies might elucidate possible modes of action, since there might be changes in absorption, distribution, metabolism and elimination of a single compound in the combinations.

To support the toxicokinetic studies, further investigation on which of the cytochrome P450 enzymes that are important in activation and detoxification of chlorpyrifos or the other pesticides in the rat is needed.

This emphasizes the complexity of combination studies. In the ideal combination toxicity study there are dose-response and toxicokinetic studies of each compound and of all possible combinations of the compounds. This might make it possible to predict which of the compounds are responsible for the changes seen in the combination. However, from an ethical point of view this is unacceptable, since it would require a large number of animal experiments.