Objectives: During the preparation (manufacture), storage and environmental lifetime, organophosphorus (OP) insecticides become chemically altered. Many of these """"""""contaminants"""""""" have been shown to have insidious toxicity to mammals. One of the most common alteration reactions is the alkoxy thiophosphoryl to thioalky phosphoryl. This subtle transformation is hazardous to public health owing to an enhancement of both acute and chronic toxicity. This research plan is directed towards studying the formation, characterization, composition and toxicological profile of thioalkyl organosphosphorus esters. Since most commercial insecticides are O,O-dialkly thiophosphoryl linkages, we are directly concerned with the corresponding O,S-dialkyl phosphorothioate alteration products. Further, this conversion results in the generation of enantiomers at phosphorus. The steroselectively of intoxication by OP esters is a rapidly emerging field and these compounds must be included to determine their toxic profile with respect to stereochemistry. Chiral thioalkyl OP esters are structural hybrids between anticholinesterases and delayed toxins. Therefore, their mode of action cannot be readily predicted. As these compounds are somewhat ubiquitous owing to their presence in commercial insecticides, the primary focus is to determine the level of toxic exposure to mammals and the public health risk assessed. Methods: The title compounds will be synthesized in racemic and optically active form. These standards will be used to determine the levels and composition of isomerides in technical material. They will also be used to determine the in vitro potency against acetylcholinesterase and neurotoxic esterase (NTE).

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29ES004434-05
Application #
3465220
Study Section
Safety and Occupational Health Study Section (SOH)
Project Start
1987-08-01
Project End
1992-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Loyola University Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60660