Acute Oral Toxicity Assessment of Pesticides

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

Montevideo

Congreso; SETAC Latin America 15th Biennial Meeting; 2023

SETAC

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 20 pesticide formulations, which were provided by ATANOR S.C.A and GLEBA S.C.A companies 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, 80% was classified as UH while 20% as MH. In the in vitro assay 10% was classified as UH while 90% as MH. The concordance was 30%, none of the in vitro LD50 values were underestimated and 70% was overestimated. 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. In addition, I am currently working with differentsoftwares such as SwissADME, ICE (Integrated Chemical Environment) and QSAR toolbox to predict the physicochemical descriptors as well as the ADME parameters of the pesticide active ingredients. We expect to integrate the in vitro results with the in silico data in order to develop an acute oral toxicity prediction model for pesticides, which would represent a first step to replace the in vivo assay