Toxicity and pharmacokinetics of 2-(2-dimethylaminoethoxy)ethanol following cutaneous dosing.
A 9-day repeated cutaneous toxicity study in the New Zealand White rabbit was conducted using 6-h occluded contact with 0 (water control), 50, 250 and 500 mg dimethylaminoethoxyethanol (DMEE)/kg. There were no clinical signs, and no effects on body weight, food consumption or serum chemistry. Hematological effects were limted to increased leukocyte count due to heterophil leukocytosis, increased platelet count, and decreased hemoglobin and hematocrit at the high dose. These findings are typical of the response of cutaneous inflammation. Histopathological findings were limited to the DMEE-treated skin, and consisted of acanthosis and ulcerative/necrotizing dermatitis. Thus, there was no evidence for cumulative percutaneous systemic toxicity for DMEE. The pharmacokinetics of DMEE was investigated in the Fischer 344 rats. Rats were given an intravenous dose of 15 or 150 mg/kg, or an occluded cutaneous dose of 150 mg/kg [14C]DMEE, and its fate was followed for 48-72 h. DMEE was readily absorbed through the skin (bioavailability=72-80%). Concentration in plasma rose steadily to a maximum at about 3.5 h after dosing, and then declined in a biphasic manner. 14C-DMEE-derived radioactivity was distributed throughout the body, with no apparent sequestration in any particular organ. The highest concentrations were observed in the kidney, liver and lung, and the lowest concentrations were found in the brain and fat. Urine was the major route of excretion, with minor amounts eliminated in the feces and as expired CO(2). The rate of excretion was moderate, with about 30% of the applied dose eliminated in the first 12 h, and by 72 h after dosing, less than 4% of the dose remained in the carcass. Unchanged DMEE was the principal component detected in the urine. This observation, together with the less than 1% of the dose excreted as CO(2), showed that metabolism was not an important process in the elimination of DMEE in the rat.
Leung
H W
HW
Applied Toxicology Group, Union Carbide Corporation, 39 Old Ridgebury Road, Danbury, CT 06817, USA. hleung18@comcast.net
Frantz
S W
SW
Ballantyne
B
B
D000287:Administration, Topical; D000818:Animals; D001682:Biological Availability; D004123:Dimethylamines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D000431:Ethanol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344
D004123:Dimethylamines; C462122:2-(2-dimethylaminoethoxy)ethanol; D000431:Ethanol