Disposition and metabolism of acrylic acid in C3H mice and Fischer 344 rats after oral or cutaneous administration.
Acrylic acid (AA) is used in large amounts to produce acrylic esters and polymers. Here we report on the disposition and metabolism of [1-14C]AA in male C3H mice and Fischer 344 (F344) rats after oral (40 and 150) mg/kg) or cutaneous (10 and 40 mg/kg) administration. Although these and other strains of rodents have been used frequently in toxicity studies of AA, results of pharmacokinetic studies are available for only the Sprague-Dawley rat. In the current study, C3H mice rapidly absorbed and metabolized orally administered AA, with about 80% of the dose exhaled as 14CO2 within 24 h. Excretion in urine and feces accounted for approximately 3% and 1% of the dose, respectively. Elimination of 14C from plasma, liver, and kidney was rapid but was slower from fat. The disposition of orally administered AA in F344 rats was similar to the results obtained from mice. After cutaneous administration to C3H mice, about 12% of the dose was absorbed, while the remainder apparently evaporated. Approximately 80% of the absorbed fraction of the dose was metabolized to 14CO2 within 24 h. Excretion in urine and feces each accounted for less than 0.5% of the dose. Elimination of radioactivity from plasma, liver, and kidney was rapid; however, levels in fat were higher at 72 h than at 1 or 8 h. After cutaneous administration to F344 rats, 19-26% of the dose was absorbed, and the rest apparently evaporated. Disposition of the absorbed fraction of the dose was similar to results found in mice. Results from an in vitro experiment with rat skin showed that at least 60% of the applied dose evaporated and about 25% was absorbed, confirming the in vivo results. High-performance liquid chromatography (HPLC) analysis of rat urine and rat and mouse tissues indicated that absorbed AA was rapidly metabolized by the beta-oxidation pathway of propionate catabolism. In summary, rapid detoxification of systemically absorbed AA, as observed here in C3H mice and F344 rats, can explain findings that AA causes minimal systemic toxicity despite its causing irritation at portal-of-entry tissues.
Black
K A
KA
Toxicology Department, Rohm and Haas Company, Spring House, Pennsylvania 19477-0904, USA.
Beskitt
J L
JL
Finch
L
L
Tallant
M J
MJ
Udinsky
J R
JR
Frantz
S W
SW
D000179:Acrylates / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption; D014014:Tissue Adhesives / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000179:Acrylates; D014014:Tissue Adhesives; C036658:acrylic acid