IDENTIFYING TARGET ORGANS AND CANDIDATE CONTAMINANTS BASED ON ADVERSE OUTCOMES FOLLOWING SUB-CHRONIC EXPOSURE IN RATS TO CONTAMINATED SOIL EXTRACTS FROM A PESTICIDE MANUFACTURING SITE.
Date
2020-01-15
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Thesis
Degree Level
Masters
Abstract
Soil sample extracts from a legacy contaminated manufacturing site were examined using an effects-directed approach. This study was aimed to identify target organ toxicities following twice-weekly oral gavage of three different soil extracts (vehicle control and 0.1% of each extract in polyethylene glycol) in male Sprague Dawley rats (n=10 rats/group). After 28 days of oral exposure, there were no mortalities and no significant differences in body or organ weights relative to control. Blood biochemistry and cell counts were unchanged except for exposure to soil extract A, where significant increases in neutrophils and lymphocytes were observed. In contrast, all three soil extracts resulted in significant increases in plasma alpha-2 macroglobulin compared to control, indicating increased, low-level inflammation. In support of this, splenic tissues in rats exposed to all soil extracts showed evidence of mild to moderate lymphocytic proliferation. Some evidence oforganophosphate/carbamate contamination was found with a significant reduction in plasma cholinesterase compared to the control in rats exposed to extract A, but not in the brain. Organochlorine or petroleum contamination was suggested by increased hepatic ethoxyresorufin-o-deethylase activity (30- and 10-fold after exposure to soil extracts A and B, respectively). Lipid peroxidation was detected via significantly increased malondialdehyde concentration in the brain and kidney tissues after exposure to soil extracts B and C, respectively. Kidney histopathology included acute tubular necrosis in rats exposed to all three soil extracts, with extract C being the most severe. Finally, electrocardiographic analyses showed significantly prolonged QTc interval in rats exposed to extract C. Candidate contaminants include organochlorine, organophosphate/carbamate insecticides or their breakdown products. Kidney damage and systemic inflammation are major targets, but some risk may arise from brain oxidative stress and potential cardiotoxicity. Actual human health risk after oral exposure to the soil from the study site must be determined in future risk assessments.
Description
Keywords
Contaminants, Target organs, Health risk
Citation
Degree
Master of Science (M.Sc.)
Department
Toxicology Centre
Program
Toxicology