Absorption, distribution, metabolism and excretion of intravenously and dermally administered triethanolamine in mice.
Triethanolamine (TEA) is an amino alcohol having widespread applications in consumer goods and as an industrial chemical. A number of relatively high-dose dermal toxicity studies have been conducted in rats and mice reflecting the principal route of human exposure to TEA. The absorption, distribution, metabolism and excretion (ADME) of (14)C-TEA derived radioactivity were determined in male C3H/HeJ mice following dermal application of 2000 mg/kg (neat) or, to characterize blood kinetics, intravenous (iv) injection of 1 mg/kg (14)C-TEA. Balance and excretion data were also collected in mice utilizing several dermal dosing scenarios (1000 mg/kg in acetone, 2000 mg/kg neat, 2000 mg/kg in water) and, for comparative purposes, in male Fischer 344 rats dosed dermally with 1000 mg/kg neat (14)C-TEA. Urine, feces, expired CO(2) (iv) and, where appropriate, blood were collected over a 24- or 48-hour period post-dosing. The half-life for dermal absorption of radioactivity was estimated to be 1.3 hours. Intravenously administered radioactivity was eliminated in a biphasic manner with a prominent initial phase (half-life of 0.3 hr) followed by a slower terminal phase (half-life of 10 hr). Radioactivity was excreted primarily via the urine (49-69%) as unmetabolized TEA, regardless of dosage, route or vehicle used. Fecal excretion of radioactivity comprised 16-28% of dose administered. The body burden at sacrifice (sum of liver, kidney, carcass and non-application site skin) ranged from 3 to 6% of the dose. It was concluded that TEA is absorbed extensively following dermal application to mice at dosages relevant to toxicity testing and that acetone or water vehicles do not appear to significantly alter total uptake. Significantly, the blood kinetics and ADME of TEA in mice and/or rats differs from that of a related chemical, diethanolamine, which appears to be more toxic to rodents than TEA.
Stott
W T
WT
Toxicology & Environmental Research, Bldg 1803, The Dow Chemical Company, Midland, MI 48674, USA. wstott@dow.com
Waechter
J M
JM
Rick
D L
DL
Mendrala
A L
AL
D000279:Administration, Cutaneous; D000818:Animals; D002250:Carbon Radioisotopes; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D004983:Ethanolamines; C009546:triethanolamine