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Morphological alterations of rat lung bronchiolar epithelium produced by various trialkyl phosphorothioates
Abstract:
A single oral administration of O, O, S-trimethyl phosphorothioate (OOS-Me), an impurity in widely used organophosphorus insecticides, causes delayed toxicity (delayed death) which is accompanied by morphological changes in the bronchiolar epithelium of rat lungs. A series of simple O,O-dimethyl and O,O-diethyl S-alkyl phosphorothioate esters, which induce delayed toxicity, were examined for their effect on rat bronchiolar epithelium. The structural analogues synthesized and tested include O, O-dimethyl S-ethyl phosphorothioate, O,O-dimethyl S-isopropyl phosphorothioate, O,O,S-triethyl phosphorothioate, and O,O-diethyl S-methyl phosphorothioate. The present investigation demonstrated that these analogues of OOS-Me which cause delayed toxicity produce body weight loss, accompanied by morphological alterations of terminal bronchiolar epithelium, i.e. loss of the apical bulge of non-ciliated Clara cells. Another impurity which produces delayed toxicity, O,S,S-trimethyl phosphorodithioate, was also capable of producing similar effects at near the LD50 level.
Insights
Organophosphorus insecticide impurities like O, O, S-trimethyl phosphorothioate (OOS-Me) cause delayed toxicity and lung damage. Structural analogues also induced similar effects, impacting bronchiolar epithelium and Clara cells.
Area of Science:
- Toxicology
- Pulmonary Pathology
- Environmental Health
Background:
- Organophosphorus insecticides are widely used globally.
- Impurities in these insecticides can exhibit significant toxicity.
- O, O, S-trimethyl phosphorothioate (OOS-Me) is a known impurity causing delayed toxicity.
Purpose of the Study:
- To investigate the effects of OOS-Me analogues on rat bronchiolar epithelium.
- To determine the relationship between chemical structure and delayed toxicity.
- To understand the morphological changes associated with OOS-Me induced toxicity.
Main Methods:
- Synthesis and oral administration of O,O-dimethyl and O,O-diethyl S-alkyl phosphorothioate esters.
- Morphological examination of rat lung bronchiolar epithelium.
- Assessment of body weight changes and toxicity near LD50 levels.
Main Results:
- Structural analogues of OOS-Me induced delayed toxicity and body weight loss in rats.
- Morphological alterations, including loss of Clara cell apical bulge, were observed in the terminal bronchiolar epithelium.
- O,S,S-trimethyl phosphorodithioate also caused similar effects.
Conclusions:
- OOS-Me and its structural analogues exhibiting delayed toxicity induce specific morphological changes in rat bronchiolar epithelium.
- Clara cell alterations are a key feature of this toxicity.
- Understanding these effects is crucial for assessing the risks of organophosphorus insecticide impurities.