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The following remarks on toxicokinetics are based on informations and studies performed within the process of notification of a new substance under the Chemicals Act. Experimental studies on toxicokinetics were not performed.

Based on the physico-chemical properties (good water solubility: 4 -6 g/L at 20°C and log Pow of 3.7) a resorption after oral administration and dermal application could be assumed, whereas the relatively high molecular mass of 460 might rather hinder resorption. The results of the available study on acute oral toxicity do not apparently contradict this assumption. After a single oral application the LD50 for Wistar-rats is > 2000 mg/kg bw. There was no evidence for systemic availability of toxicologically relevant amounts or intoxications described (Stropp, 1999a). Due to the slight skin irritation potential (Leuschner, 1999a; Leuschner, 1999b) and the absence of toxicity after acute oral exposure the performance of a study on acute dermal toxicity was waived for reasons of animal welfare.

The results of an oral subacute toxicity study (Temerowski, 1999), in which doses of 40, 200 and 1000 mg/kg bw/day were administered by gavage to Wistar-rats, support the resorption for this route of exposure and indicate renal excretion. The parameters investigated did not reveal evidence of adverse systemic effects up to and including 200 mg/kg bw/day. Only in the highest dose group (1000 mg/kg bw/day) a body weight gain retardation was observed solely in males, which was still detectable at the end of the post observation period. The microscopic findings detectable in the cortical tubulus of the kidney (osmotic nephrosis) at both sexes after 1000 mg/kg bw/day were regarded as indication of an adaptive process. This finding could not be observed anymore at the end of the 2-weeks post observation period. Taken all findings together, no bioaccumulation of the substance could be identified.

After parenteral administration signs of intoxication (e.g. apathy, piloerection, loss of body weight) observed in male mice reveal the systemic availability of the substance. Two i.p. injections of 625, 1250 and 2500 mg/kg bw were given, respectively, separated by 24 hours. No mortality occurred in any dose group (Herbold, 1999b).

Under normal temperature and pressure the substance is a liquid with a very low vapour pressure (< 1E-5hPa at 20°C), therefore inhalation exposure to the vapour is assumed to be low. The calculated saturated vapour concentration is < 0.184 mg/m³ at 20° C. The results of the available study on acute inhalation toxicity in Wistar-rats with exposure to aerosol give no evidence of systemic availability of toxicologic relevant amounts (Pauluhn, 1999). No mortalities occurred up to the the highest tested concentration of 4923 mg/m³. Transiently observed clinical symptoms (reduced motility, piloerection, unkempt fur, bradypnea, hypothermia and decrease in body weight), which were resolved within 3 days after cessation of exposure, indeed, could be interpreted as indication for a mild respiratory tract irritation potential.

The results of in vitro (with and without metabolic activation) and in vivo mutagenicity tests (Herbold, 1999a; Herbold, 1999b) allow the assessment that reactive metabolites will not be generated in appreciable amounts in mammals due to hepatic biotransformation.