Agriculture pesticides as risk factor: toxicologic pathology, immunology, and molecular and analytical evaluations in experimental models of single or combined exposures

Abstract

This research proposal aims to explore the problem of agriculture pesticides toxicity and its potential relevance to human health. Rats and mice orally (diet) exposed to pesticides will be used as models. This proposal will focus on two general topics and comprises seven (07) different studies. The first topic deals with the effects of extended exposure to five pesticides mixed at low concentrations. Residues of these pesticides were found by the Brazilian Agência Nacional de Vigilância Sanitária (ANVISA) in tomatoes regularly available for the Brazilian population. This mixture of pesticides will be verified regarding: 1) its potential for induction of the liver CYP450 enzyme system; 2) its promoting potential in a medium-term liver bioassay for carcinogenesis and 3) its potential for endocrine disruption in the young adult male rat. The other topic refers to Diuron, a widely used herbicide for sugar cane and soy cultures in Brazil. This herbicide has been shown to induce urinary bladder cancer in rats and has been considered a likely human carcinogen by the U.S. Environrnental Protection Agency (EPA). Under this topic, it will be verified: 1) the carcinogenic mode of action (MOA) of Diuron on the urothelial mucosa of rats, 2) its potential immunotoxicity to rats and 3) its initiating and promoting potentials in a mouse initiation promotion skin cancer model. The procedures to be developed encompass routine optical microscopy, immunohistochernistry, Westem-blot, real time PCR, serum hormones determination and assays for spermatic morph-functional integrity, and scanning electron rnicroscopy. Studies for improvement and validation of chemical analytical methods for the pesticides studied will also fie developed under each topic. (AU)