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Studies in experimental animals indicated that TEA is absorbed through the skin. No data on oral and inhalation exposure is available. Besides data regarding the dermal route, data on the i.v. route is also available. Differences in the rate of absorption between rats and mice have been described regarding dermal exposure. In mice, most of the topically applied14C-TEA is absorbed, and only 2% to 11% is detected at the site of application after 48 hours (Dow 1988,1989; Stott, 2000).The dermal absorption of TEA in rats was less extensive and much slower than in mice (Dow, 1988,1989).An absorption, distribution, metabolism, and excretion study by the NTP (2004) found that after 72 hours of exposure, only 20% to 30% of the applied dermal dose of TEA (68 or 276 mg/kg) was absorbed in rats and 60% to 80% was absorbed in mice (79 or 1120 mg/kg). These differences in absorption have been attributed either to the different doses used in comparative studies or to species-specific factors. No differences in tissue distribution were noted after i.v. or dermal exposure (NTP, 2004).

The elimination of14C-TEA-derived radioactivity from the blood of mice after a 1 mg/kg intravenous injection displays two-phase elimination kinetics with an initial rapid distribution phase (0.3-0.6 hour half-life) followed by a slower elimination phase (10-hour half-life) (Dow, 1988,1989; Stott, 2000).Radioactivity in blood after dermal application of 2000 mg/kg neat TEA declined in a bi-exponential manner through 3-hour post-dosing with a rapid initial phase (half-life of 1.9 hr) followed by a slower terminal phase (half-life of 31 hr)(Stott, 2000).Both rats and mice rapidly excreted the absorbed dose, primarily in urine (followed by faeces) after i.v. and dermal exposure. Regarding dermal exposure, in rats, less than 1% of the dose was present in the tissue samples (except the dose site) 72 hours after treatment; the heart, kidney, liver, lung, and spleen contained elevated concentrations of radiolabel relative to blood (NTP, 2004).

 

In addition to animal studies, human skin penetration of TEA was tested in vitro using diffusion cell techniques (Kraeling, 2003). Oil-in-water emulsions containing 1% or 5%14C-TEA were added to the stratum corneum side of 200-300 µm thick human skin sections and penetration of radioactivity into and through the skin (into a receptor fluid, sampled up to 24 hours after application) was determined. At pH 8.0, 1.1 and 1.2% of the dose was absorbed into the receptor fluid with a total penetration of 22.0 and 16.5% for 1 and 5% TEA, respectively. At pH 7.0, 0.43 and 0.28% was absorbed into the receptor fluid with a total penetration of 9.8 and 5.8% after 24 hours for 1 and 5% TEA, respectively. After 48 hours at pH 7.0, 0.68 and 0.60% was absorbed into the receptor fluid with a total penetration of 9.6 and 6.9%, for 1 and 5% TEA respectively. This pH-related difference reflects the higher percentage of unionised test material pH 8.0.

For diethanolamine dermal administration (in vivo) resulted in the following absorption figures: 3-16% in rats; 25-60% in mice. When applied dermally, DEA appears to facilitate its own absorption, as higher doses were more completely absorbed than lower doses.

DEA (20 mg/cm²) applied to skin preparations in vitro showed penetration rates of 6.7% (mouse), > 2.8 % (rabbit), >0.56% (rat) and > 0.23% (human).

DEA is well absorbed following oral administration in rats (57%).Distribution to the tissues was similar via all routes examined. DEA is cleared from the tissues with a half-life of approximately 6 days. The highest concentrations are observed in liver and kidney.

Metabolism after oral administration revealed non-metabolized DEA and smaller proportions of N-methyl-DEA (N-MDEA), N,N-dimethyl-DEA (N’N-DMDEA) and DEA-phosphates co-eluting with phosphatidyl ethanolamine and phosphatidyl choline. After digestion 30% of the phospholipids were identified as ceramides and the remaining 70% as phosphoglycerides.

DEA is excreted primarily in urine as the parent molecule (25-36%), with lesser amounts of O-phosphorylated and N-methylated metabolites.

Accumulation of DEA at high levels in liver and kidney is assumed by a mechanism that normally conserves ethanolamine, a normal constituent of phospholipids. DEA is incorporated as the head group to form aberrant phospholipids, presumably via the same enzymatic pathways that normally utilize ethanolamine.