AOP report: Inhibition of chitin synthase 1 leading to increased mortality in arthropods

Arthropods (including insects, crustaceans, and arachnids) rely on the synthesis of chitin to complete their life cycles (Merzendorfer 2011). The highly conserved chitin synthetic process and the absence of this process in vertebrates make it an exploitable target for pest management and veterinary medicines (Merzendorfer 2013; Junquera et al. 2019). Susceptible, nontarget organisms, such as insects and aquatic invertebrates, exposed to chitin synthesis inhibitors may suffer population declines, which may have a negative impact on ecosystems and associated services. Hence, it is important to properly identify, prioritize, and regulate relevant chemicals posing potential hazards to nontarget arthropods. The need for a more cost-efficient and mechanistic approach in risk assessment has been clearly evident and triggered the development of the adverse outcome pathway (AOP) framework (Ankley et al. 2010). An AOP links a molecular initiating event (MIE) through key events (KEs) to an adverse outcome. The mechanistic understanding of the underlying toxicological processes leading to a regulation-relevant adverse outcome is necessary for the utilization of new approach methodologies (NAMs) and efficient coverage of wider chemical and taxonomic domains. In the last decade, the AOP framework has gained traction and expanded within the (eco)toxicological research community. However, there exists a lack of mature invertebrate AOPs describing molting defect–associated mortality triggered by direct inhibition of relevant enzymes in the chitin biosynthetic pathway (chitin synthesis inhibitors) or interference with associated endocrine systems by environmental chemicals (endocrine disruptors).