Data collection, hazard characterisation and establishment of cumulative assessment groups in view of the cumulative risk assessment of pesticides for liver

The aim of the present report is to collect data on toxic effects in the liver and gallbladder from various pesticides and their metabolites and, subsequently, to establish cumulative assessment groups (CAGs), in view of performing cumulative risk assessment (CRA) of pesticide residues for liver. For this purpose, a list of previously defined indicators of the specific effects was consulted to retrieve the relevant data from toxicological assessment reports. Toxicological data from 62 prioritised pesticide active substances and 20 identified metabolites were collected from regulatory documents. For each substance, a LOAEL was derived for the most sensitive indicator(s) of the specific effect. From originally defined ten specific effects and the respective CAGs, seven were populated by active substances and metabolites: 1) hypertrophy due to enzymatic induction, liver; 2) fatty change and/or phospholipidosis, hepatocellular; 3) degeneration/cell death, hepatocellular; 4) porphyria, hepatocellular, biliary duct; 5) cholestasis, hepatocellular, biliary duct; 6) preneoplastic and neoplastic changes, hepatocellular; 7) neoplastic changes, biliary duct. No compounds were identified to populate three previously defined specific effects on gallbladder: 1) erosion/ulceration, gallbladder; 2) calculi, gallbladder; 3) neoplastic changes, gallbladder. The identified uncertainties in the allocation of the substances in the different CAGs were highlighted. Overall, this project utilises the methodology previously developed and described in the report dealing with the identification of specific effects on liver and it provides a comprehensive hazard characterisation of substances.