Oral absorption, metabolism and excretion of 1-phenoxy-2-propanol in rats.
1. This study was designed to determine the absorption, metabolism and excretion of 1-phenoxy-2-propanol in Fischer 344 rats following oral administration in an effort to bridge data with other propylene glycol ethers. 2. Rats were administered a single oral dose of 10 or 100 mg kg(-1) 14C-1-phenoxy-2-propanol as a suspension in 0.5% methyl cellulose ether in water (w/w). Urine was collected at 0-12, 12-24 and 24-48 h and faeces at 0-24 and 24-48 h post-dosing and the radioactivity was determined. Urine samples were pooled by time point and dose level and analysed for metabolites using LC/ESI/MS and LC/ESI/MS/MS. 3. The administered doses were rapidly absorbed from the gastrointestinal tract and excreted. The major route of excretion was via the urine, accounting for 93 +/- 5% of the low and 96 +/- 3% of the high dose. Most of the urinary excretion of radioactivity occurred within 12 h after dosing; 85 +/- 2% of the low and 90 +/- 1% of the high dose. Total faecal excretion remained < 10%. Rats eliminated the entire administered dose within 48 h after dosing; recovery of the administered dose ranged from 100 to 106%. Metabolites tentatively identified in urine were conjugates of phenol (sulphate, glutathione) with very low levels (< 2%) of hydroquinone (glucuronide), conjugates of parent compound (glucuronide, sulphate) and a ring-hydroxylated metabolite of parent. There was no free parent compound or phenol in non-acid-hydrolysed urine. In acid-hydrolysed urine, 61% of the dose was identified as phenol and 13% as 1-phenoxy-2-propanol. Although the parent compound was stable to acid hydrolysis, some of the phenol in acid hydrolysed urine may have arisen from degradation of acid-labile metabolite(s) as well as hydrolysis of phenol conjugates. 4. Rapid oral absorption, metabolism and urinary excretion of 1-phenoxy-2-propanol in rats were similar to other propylene glycol ethers.
Saghir
S A
SA
Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI 48674, USA. ssaghir@dow.com
Brzak
K A
KA
Bartels
M J
MJ
D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D007477:Ions; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D008956:Models, Chemical; D011409:Propylene Glycols / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors; D014466:Ultraviolet Rays
D002250:Carbon Radioisotopes; D007477:Ions; D011409:Propylene Glycols; C012917:1,2-dihydroxy-1-phenylpropane