Identification of urinary mercapturic acids formed from acrylate, methacrylate and crotonate in the rat

Abstract

1. After administration to rats of methyl acrylate (I), methyl methacrylate (II) and methyl crotonate (III), urinary mercapturic acids were isolated and identified as the dicarboxylic acids N-acetyl-S-(2-carboxyethyl)cysteine (IV, R = H), N-acetyl-S-(2-carboxypropyl)cysteine (V, R = H) and N-acetyl-S-(1-methyl-2-carboxyethyl)cysteine (VI, R = H) and for a minor part as their monomethyl esters IV (R = CH3) and VI (R = CH3). 2. After a single dose of the acrylates (I), (II) and (III) (0.14 mmol/kg), the excretion of the thioethers amounted to 6.6 +/- 0.6, 0.0, and 2.0 +/- 0.6% dose respectively. 3. After 18 h previous administration of the carboxylesterase inhibitor tri-o-tolyl phosphate (0.34 mmol/kg) the excretion of the thioethers amounted to 40.6 +/- 2.1, 11.0 +/- 3.3, and 16.0 +/- 2.0% dose. 4. For methyl acrylate (I) the ratio of the excreted dicarboxylic acid and monomethyl ester was 20:1. After previous administration of tri-o-tolyl phosphate this ratio was 1:2.

Methyl acrylate [MAK Value Documentation, 1993]

“…In other studies, mercapturic acids were found in the urine of rats given methyl acrylate by intraperitoneal injection. Pretreatment of the rats with TOTP resulted in increased levels of thioethers in the urine [31]. These results indicate that degradation via the unspecific carboxylesterase and SH conjugation are alternative pathways of methyl acrylate metabolism.…”

“…After occlusive application to the skin, methyl acrylate was absorbed only slowly and so weak radioactivity was detected in the urinary bladder and in other organs only after 16 and 28 hours (after local irritation and corrosion and local retention of radioactivity). During this time metabolism of the substance took place mostly in the skin where a large part of the radioactive material was also retained [20,21].…”

Inhalation anesthetics, anticancer drugs and sterilants as chemical hazards in hospitals.

“…The most prominent effects of occupational chemical exposures detected so far have been dermatologic problems and spontaneous abortions among operating room personnel. In addition to the chemical risks dealt with in this review, there are many other potential chemical hazards related to, eg, the use of plastic biomaterials (19,39,62,74). While the well-established infection diseases must not be forgotten, more emphasis should be placed in the future on the possible chemical hazards in hospitals.…”

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to Flavouring Group Evaluation 5 (FGE.05); Esters of 23 branched- and straight-chain aliphatic saturated primary alcohols and

“…After administration of the esterase inhibitor, TOTP 7 (0.34 mmol/kg in arachis oil 18 hours before injection with methyl crotonate), there was a significant increase in urinary thioether excretion as compared to the controls (increasing from 2 to 16% of the dose), indicating that hydrolysis by carboxylesterase influences conjugation with glutathione in that the ester (methyl crotonate) reacts more readily in a Michael-type reaction with glutathione than the unesterified crotonic acid (Delbressine et al, 1981a).…”

“…This reaction may lead to glutathione depletion after i.p administration. When ester hydrolysis is inhibited by pre-treatment with TOTP 7 , the urinary excretion of these conjugates is strongly increased, indicating that only the ester but not the free unsaturated acid is subject to this conjugation reaction (Delbressine et al, 1981a). This conjugation has been observed after intraperitoneal injection of the esters, and it is questionable whether it is very relevant after oral exposure, due to presystemic ester hydrolysis.…”