Assessing the sensitisation hazard of microbial pesticides: potential value of New Approach Methodologies (NAMs) to overcome current challenges

Over the past years, the use of chemical pesticides has increased considerably worldwide, and concerns about human health and the environment have stimulated the development of safer alternatives. Biopesticides, including those with microorganisms as active substances, i.e. microbial pesticides, appear to be specific in action, easily sourced without the need for expensive chemicals, and environmentally sustainable with no residual effects. As such, they are seen as a viable alternative to synthetic pesticides. As with any other plant protection product, microbial pesticides are subjected to regulatory approval before marketing, and sensitisation, either via the dermal and/or inhalation routes, is one of the data requirements that have to be addressed in this process. The biological mechanisms underlying potential concerns related to sensitisation properties of microbial pesticides are reviewed in this article. Mechanistic knowledge was utilised to understand the potential limitations of current testing strategies for assessing sensitisation hazards, primarily defined by chemicals, as well as to demonstrate the potential value of New Approach Methodologies (NAMs) in this process. However, evaluating the sensitisation properties of microbial pesticides requires several protocol adaptations to achieve adequate confidence levels for alternative methods, narrow their applicability domain, and provide potency information on this endpoint. The technical limitations and difficulties in interpreting the results of current testing methods applied to microbial pesticides have long been recognised and are discussed in this article to better drive propositions of NAM-based strategies for microbial pesticides.