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Description of key information

No information is available on the toxicokinetics of LAS TEA. The endpoint of toxicokinetics was addressed with data for LAS Na and TEA (see read-across statement). Overall the substance is notexpected to have a bioaccumulation potential.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - dermal (%):
22

Additional information

No information is available on the toxicokinetics of LAS TEA. The endpoint of toxicokinetics was addressed with data for LAS Na and TEA (see read-across statement).

TEA:

Studies with experimental animals suggest 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 are 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.

LAS Na:

The absorption, distribution, metabolism and elimination of LAS (radioactively labeled with 35S) were studied in male Charles River rats. LAS was readily absorbed by the gastrointestinal tract(80-90% of the dose)and rapidly metabolized and excreted in the urine. Most of the absorbed 35S was eliminated within 72 hours and 60-65% of the absorbed dose was eliminated in the urine, 35% of the absorbed 35S was excreted in the bile and was reabsorbed completely from the gastrointestinal tract. Retention of radioactivity was not observed in any organ (Michael, 1968).

The disposition of radioactivity was studied in single and repeated oral or subcutaneous doses of [14C]LAS to rhesus monkeys. Results show that LAS is rapidly absorbed, then rapidly metabolized and excreted, primarily in the urine but also in the bile and feces. No accumulation or localization of radioactivity or change in elimination was observed. LAS does not bioaccumulate in the tissues (Cresswel et al., 1978).

Radiolabelled test substance (3 mM solution) was applied to the shaved skin of female rats. The exposure lasted 15 min, after which is was rinsed off. After a 24 hr observation period during feces, urine, and expired air was collected, the animals were sacrificed and the excised skin was examined by autoradiography. Results show that the test substance, which is of low solubility, did not penetrate through the skin to any significant degree. The amount of test substance penetrating the skin was below the detection limit. The penetration through rat skin was < 0.3% (Howes, 1975).

Radiolabelled LAS was applied (0.1 ml of a 3 mM solution) to samples of human abdominal skin from four female cadavars. Exposure time was 48 hrs. Analysis by liquid scintillation counting was done at 0.5, 1, 2, 3, 4, 6, 7, 8, 24, and 48 hrs. Penetration through human skin was negligible, with < 0.07% absorbed in 48 hrs (Howes, 1975).