Potentiation by triorthotolyl phosphate of acrylate ester-induced alterations in respiration.
The purpose of this study was to determine whether triorthotolyl phosphate (TOTP), an inhibitor of carboxylesterases, would enhance the inhibitory effects of acrylate esters on respiration. Respiratory frequency was measured and the calculated decreases in respiratory frequency were used as an index of respiratory irritancy due to acrylate compounds. Tidal volume, minute ventilation, and rectal temperature were also measured. Dose-dependent decreases in frequency were found in rats inhaling methyl acrylate, ethyl acrylate and acrylic acid. Tidal volume was also reduced in rats exposed to acrylate compounds and, as a result, the percentage change in minute ventilation was greater than the percentage change in frequency or tidal volume alone. Pretreatment with TOTP (125 mg/kg) enhanced the decreases in frequency and minute ventilation caused by acrylate esters but not those resulting from exposure to acrylic acid. Exposure to ethyl acrylate and acrylic acid also resulted in dose-dependent reductions in rectal temperature. TOTP potentiated ethyl acrylate-induced decreases in rectal temperature but not those caused by acrylic acid. The results suggest that inhibition of carboxylesterases can result in enhanced irritant action of acrylate esters on the upper respiratory tract, and provide support for a local role of carboxylesterases in the detoxification of these irritant esters.
D000179:Acrylates / Q000633:toxicity*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D003408:Cresols / Q000633:toxicity*; D004357:Drug Synergism; D007509:Irritants / Q000633:toxicity*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D014317:Tritolyl Phosphates / Q000633:toxicity*
D000179:Acrylates; D003408:Cresols; D007509:Irritants; D014317:Tritolyl Phosphates; D002265:Carboxylic Ester Hydrolases; C025541:tri-o-cresyl phosphate