Biotransformation of acrolein in rat: excretion of mercapturic acids after inhalation and intraperitoneal injection.
Biotransformation of acrolein (ACR) was studied in vivo in the rat following inhalation and ip administration. The major and minor urinary metabolites were 3-hydroxypropylmercapturic acid (HPMA) and 2-carboxyethylmercapturic acid (CEMA), respectively. Male Wistar rats were exposed to ACR, 23, 42, 77 and 126 mg/m3, for 1 hr. The sum of mercapturic acids HPMA and CEMA excreted within 24 hr after the exposure amounted to 0.87 +/- 0.12, 1.34 +/- 0.5, 2.81 +/- 1.15, and 7.13 +/- 1.56 mumol/kg, i.e., 10.9 +/- 1.5, 13.3 +/- 5.0, 16.7 +/- 6.9, and 21.5 +/- 4.8% of the estimated absorbed dose, respectively. The dose estimate was based on reported values of minute respiratory volume and respiratory tract retention and was corrected for the ACR-induced changes in minute respiratory volume. In the relevant dose range (8.9 to 35.7 mumol/kg) the portion of mercapturic acids excreted was nearly constant for ip exposed rats. The sum of HPMA and CEMA amounted to 29.1 +/- 6.5% of the dose. These results indicate that the deficiency in rat lung metabolism of ACR to acrylic acid previously observed is not compensated by the other detoxication pathway in vivo, mercapturic acid formation. The health hazard arising from inhalation of ACR is likely to be higher than that from other routes of exposure.
Linhart
I
I
Centre of Industrial Hygiene and Occupational Diseases, National Institute of Public Health, Prague, Czech Republic.
Frantík
E
E
Vodicková
L
L
Vosmanská
M
M
Smejkal
J
J
Mitera
J
J
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000652:urine; D000171:Acrolein / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D000280:Administration, Inhalation; D000818:Animals; D001711:Biotransformation; D015824:Blood-Air Barrier / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000032:analysis / Q000097:blood; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
D004987:Ethers; D000171:Acrolein; C001423:S-(3-hydroxypropyl)cysteine N-acetate; C011779:diisopropyl ether; C073258:S-(2-carboxyethyl)-N-acetylcysteine; D000111:Acetylcysteine