Applicability of kinetically-based maximum dose studies for hazard and risk assessments of the fungicide fluoxapiprolin.

Fluoxapiprolin is a new fungicide developed for the control of oomycetes that damage crops such as tomato, potato, grapes and leafy vegetables. Human safety studies have shown no toxicity clearly attributable to fluoxapiprolin, highlighting its favourable toxicological profile compared to many other fungicides. It meets all human health risk assessment criteria without difficulty. However, fluoxapiprolin was tested up to a Kinetically-Derived Maximum Dose (KMD) rather than the conventional limit dose, making it necessary to justify this approach in the context of regulatory hazard assessment. Official guidance documents encourage the application of KMD approaches under specific conditions. In the case of fluoxapiprolin, oral absorption was shown to become saturated as doses increased, supporting the selection of the high dose in long-term studies based on a KMD rather than using a fixed limit dose. Even if a limit dose had been used, systemic exposure would have been only about twice as high as that observed at the KMD. Given the absence of treatment-related toxicity in any study and the relatively small difference in systemic exposure, the toxicological database is considered sufficient to identify relevant hazards and to support a robust human health risk assessment.