Cumulative risk assessment methodology applied to non-dietary exposures: developmental alterations in professional agricultural settings

The safety assessment of combined exposure to xenobiotics has been an emerging topic for several years. Methodologies and approaches for cumulative risk assessment (CRA) are being developed primarily for the dietary risk assessment of pesticides, thus focusing only on consumer exposure. However, as highlighted in recent years, non-dietary exposures, such as those encountered by professionals in agricultural settings, may pose a significant risk due to their higher levels compared to dietary exposure. Despite this, existing methodologies for cumulative risk assessment (CRA) have not adequately addressed this critical aspect. In the EU, even if several legislations highlight the need to address the non-dietary CRA, no legal requirements are in place yet, therefore, there are no harmonized methodologies and approaches currently available. In a first step to fill this gap, this study is aimed at exploring CRA methodology applied to non-dietary exposure to pesticide in agricultural settings, specifically targeting operators, re-entry workers, and bystanders. The primary objective of the study was to verify the feasibility of an electronic register of plant protection treatments as data source for identifying and characterizing in field mixtures and consequently estimating cumulative non-dietary systemic exposure in real life. The relevant active substances selected for this investigation were those listed in foetal craniofacial alterations cumulative assessment groups (CAGs), established by the European Food Safety Authority (EFSA) for dietary CRA. Exposures to pesticides were estimated using European Union agreed mathematical models. The preliminary findings of this investigation effectively revealed the value of the register of treatments in assessing real-life plant protection products (PPP) usage in professional agricultural settings. In conclusion, the study provides encouraging insights into using the pesticide dietary CRA approach for non-dietary risk assessment in agricultural settings, underlining the necessity for further research and investigation of its feasibility for the evaluation of other acute effects but also for long-term effects related CAGs.