Using existing knowledge for the risk evaluation of crop protection products in order to guide exposure driven data generation strategies and minimise unnecessary animal testing.

ABSTRACT

Traditionally, human health risk assessment focuses on defining the hazard through mammalian toxicity studies followed by exposure estimation. We have explored ways of predicting exposure based primarily on the use scenario and comparing the exposure to reference dose values derived by various regulatory agencies (US EPA, JMPR, and EU Commission) in order to identify mammalian toxicity studies that are relevant to human health risk assessment. Human dietary exposure was based on existing residue data for substances with comparable use on the same or similar crops. Human occupational exposures were based on the use scenarios and application methods. To provide a point of comparison for the exposure predictions, data were collated for acute, chronic and occupational reference dose values derived by various regulatory agencies (US EPA, JMPR, and EU Commission). The exposure predictions and range of hazard endpoints were compared using the ILSI HESI Risk21 risk matrix plots in order to visualise and contextualise the level of potential concern for the exposure prediction. In addition, an approach is proposed to categorise the likelihood of acceptability of risk based on where the exposure sits relative to the distribution of reference dose values. The approaches proposed in this study allow for exposure prediction based on the Good Agricultural Practice (GAP) in conjunction with the use of existing hazard data for crop protection products in order to make an initial determination on acceptability of risk and to identify key studies that are required for human health risk assessment and also opportunities for study waivers.