Next generation risk assessment of organophosphate pesticides

Due to the use of organophosphate pesticides in agricultural practice, the public is exposed to these compounds via their diet. Traditional risk assessment of such chemicals determines safe dose levels for humans based on animal experiments. Recently, ethical concerns and concerns about species differences between humans and experimental animals have been raised, stimulating research into animal-free methods supporting chemical risk assessment. In this thesis, animal-free approaches to predict safe exposure levels to organophosphate pesticides are investigated. Computer models are used to simulate how these pesticides behave inside the body, and lab experiments for determining the neurotoxic effects of organophosphate pesticides. The computer models are used to determine when the neurotoxic effects, found in lab experiments, occur in living humans or rats. This research shows that for organophosphate pesticides, animal-free risk assessment approaches are similar in accuracy to animal experiments. These findings support the transition of risk assessments based on animal experiments to animal-free and human centric risk assessments.