Acute oral toxicity assessment of pesticides

LENZE, MARIELA; PINA, JUAN IGNACIO; BENEDETTI, MARTINA; ROCO, JULIETA; GUTIÉRREZ, MARÍA LAURA

Niagara Falls

Congreso; 12th World Congress on Alternatives and Animal Use in the Life Sciences; 2023

Alternative Congress Trust

Agencies worldwide have attempted to develop nonanimal approaches to predict acute systemic toxicity, but it remains a challenge yet. In Argentina, the rodent acute oral lethal dose (LD50) is demanded for products registration. However, local regulatory organisms and industries are willing to replace the in vivo assay. Our goal is to develop an integrated approach for acute oral toxicity assessment of pesticides. The BALB/3T3 Neutral-Red Uptake Cytotoxicity Assay (OECD 129) was used to estimate the in vitro LD50 values of 19 pesticides, which were provided by ATANOR S.C.A and GLEBA S.C.A along with their in vivo LD50 doses. In vitro/in vivo datasets were classified as Extremely Hazardous (EH:2000mg/Kg). None of the pesticides was classified as EH for both datasets. With the in vivo data 84,2% were classified as UH while 15.8% as MH. In the in vitro assay 10.5% were classified as UH while and 89.5% as MH. The concordance was 26%, none of the in vitro LD50 values were underestimated, 74% were overestimated. In vitro results were integrated with the oral bioavailability of the active ingredients predicted by SwissADME and the overestimations decreased to 57.1%. In vitro classification is more conservative than in vivo one, most of the pesticides were categorized as UH with the in vivo data unlike the in vitro data that fell into the MH level. Integration of the in vitro assay and in silico tools represents a first step for the replacement of the in vivo assay.