The disposition of acrylic acid in the male Sprague-Dawley rat following oral or topical administration.
The disposition of [1-14C] acrylic acid (AA) was characterized in the male Sprague-Dawley rat following oral administration, by gavage in water, at 400 mg/kg and topical application, in acetone, at 501 micrograms/cm2. The oral dose was well absorbed, rapidly and extensively metabolized, and excreted primarily (approx. 80%) as 14CO2 within 24 hr of administration. The rate and extent of 14CO2 evolution from [14C]AA was greater for [1-14CAA] while a significantly lower proportion of the dosed radioactivity remained in the tissue of animals than that reported for [2,3-14C]AA (Winter et al., Drug Metabolism and Disposition 1992, 20, 665). This is consistent with incorporation of AA into a minor beta-oxidation pathway of mitochondrial propionate metabolism by which AA may be metabolized to CO2 or incorporated into cellular constituents. Approximately 5% of the dosed radioactivity was excreted in the urine. The disposition of [1-14C]AA following dermal application was studied using charcoal-containing traps attached to the back of the rats to trap volatilized AA from the dosing sites. Following application of 100 microliters AA [4% (v/v) in acetone] to an area of 8.4 cm2 of the skin of a rat (501 micrograms/cm2), the majority (about 73%) of the dose volatilized and was recovered in the charcoal trap. Percutaneous absorption of AA that did not volatilize was rapid and appeared to have the same metabolic fate as AA administered orally with about 75% of the absorbed dose excreted as 14CO2 within 24 hr.
Winter
S M
SM
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson.
Sipes
I G
IG
D000179:Acrylates / Q000008:administration & dosage / Q000378:metabolism*; D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D002250:Carbon Radioisotopes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000179:Acrylates; D002250:Carbon Radioisotopes; C036658:acrylic acid