A proposed NAM-based tiered phototoxicity testing and human risk assessment framework for agrochemicals

Abstract

Phototoxicity testing is required by European regulations for agrochemicals with UV/visible molar extinction/absorption coefficient (MEC) higher than 10 L x mol^-1 x cm^-1 in the 290-700 nm wavelength range. Furthermore, regulations identify a need of considering human exposure in case of positive results. While in vitro OECD test guidelines are available for hazard characterisation, there is no guidance on how to utilise positive results in human exposure risk assessments. Our goal was to take a first step towards developing a NAM based tiered testing approach and a framework for non-dietary acute human dermal risk assessment for phototoxicity to agrochemicals. The proposed framework can be divided into a few steps: 1) use the OECD updated MEC values of 1000 L x mol^-1 x cm^-1 as trigger for phototoxicity testing; 2) establish a reference concentration (RfC) from in vitro phototoxicity studies using BMC approach, 3) estimate potential exposure to skin, target organ for phototoxicity, using EFSA exposure models, product specific labels and skin penetration values, and 4) phototoxicity risk assessment; 5) refinement to RfC and/or exposure estimates can be considered. Finally, case studies of a nematicide and an herbicide active substance are provided to illustrate the proposed framework.

Keywords: Agrochemicals; In vitro assays; New approach methodologies (NAM); OECD TG 432; OECD TG 498; Phototoxicity risk assessment framework; Phototoxicity testing; Reference concentration (RfC); Regulation (EC) no. 1107/2009; Tiered testing strategy.