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1. Physical-chemical properties

TEA (MW 149.2 g/mol) is a liquid with a measured melting point of 20.5°C, a measured boiling point of 336.1°C at 1013.25 hPa, a measured vapour pressure of 0.00029 hPa at 21°C, and a dissociation constant (pKa) of 7.86 at 25°C. The octanol-water partition coefficient (log Pow) is -2.3 at 25°C, and the substance is fully miscible with water.

2. Data from acute and repeated dose toxicity studies

Acute toxicity data indicate low toxicity: in rats the oral LD50 was 6400 mg/kg bw, no mortality was observed at or below 5000 mg/kg bw. Clinical signs (elevated respiration, anancasm to chew, apathy, reduced grooming) disappeared 2 days after dosing, and gross pathology at necropsy revealed no abnormalities (BASF AG, 1966). In an acute dermal toxicity study in rabbits, no mortality was observed up to the limit concentration and the LD50 was established to be > 2000 mg/kg bw (TSCATS, 1989). Due to its extremely low vapour pressure, exposure to TEA vapour is very unlikely. One report stated that whole-body exposure of rats to an atmosphere saturated with TEA vapour (concentration not given) at 20°C for 8 hours failed to cause any deaths, therefore no LC50 value was established (BASF AG, 1966).

In an oral repeated dose study, rats were administered 0 - 1000 mg/kg bw/day in the diet for 91 days. Since no adverse effects were observed, the NOAEL was established to be 1000 mg/kg bw/day (TSCATS, 1989). In a sub-chronic dermal toxicity study, rats were treated with 0 - 2000 mg/kg bw/day on the skin for 90 days (Battelle Columbus Laboratories, 1987a). At the highest doses, decreases in body weight, irritation and inflammation at the site of application were observed - ranging from minimal acanthosis at the lower doses to chronic active inflammation, erosion and ulceration in higher dose groups - accompanied by haematologic changes. NOAELs for local effects were determined to be 125 and 250 mg/kg bw/day for males and females, respectively. The NOAEL for systemic effects was established at 125 mg/kg bw/day, based on renal effects (i.e. increased kidney weight). Similar effects were observed in a sub-chronic dermal toxicity study in mice, receiving 0 - 4000 mg/kg bw/day TEA on the skin for 90 days (Battelle Columbus Laboratories, 1987b). The kidneys were identified as the target organ at lower doses, accompanied by increased liver weights at the top dose level. Dermal irritation and inflammation was noted at the site of application. In an 28 -day inhalation toxicity study in rats, exposed to 0 - 0.5 mg/L TEA for 6 hours/day and 5 hours/week, the NOAEC for systemic effects was established at 0.5 mg/L since no adverse systemic effects were observed. The NOAEC for local effects (laryngeal inflammation) was determined to be 0.02 mg/L for females; since slight inflammation was still observed in males, this concentration was designated the LOAEC for local effects in males (BASF AG, 1993).

3. Absorption, distribution, metabolism, excretion

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.