Toxicity Summary
Acute oral toxicity:
In a recent study (2010), performed according to actual guidelines, an LD50 of >5000 mg/kg bw was determined. The test substance was administered in deionised water. All animals showed signs of reduced well-being fromuntilp. a. This term encompasses unspecific alterations, like sedation, apathy, piloerection, hunched posture or closed eyes, in single or multiple occurrence. There were no other adverse effects noted in the animals.
Acute dermal toxicity:
In a recent study (2010), performed according to actual guidelines, the LD50 was >2000 mg/kg bw and no adverse effects were noted in the animals. No indication for a dermal absorption was obtained from this study.
Repeated dose toxicity:
Results of a Combined Repeated Dose / Reproduction /Developmental Toxicity Screening Study give some indication for an absorption of the test substance in the gastrointestinal tract and a distribution in the body:
In the livers of high dosed males a slight centrolobular hepatocyte cytoplasmatic basophilia was noted. This is interpreted as an indicator of enzyme induction, and is taken as an adaptive response, although not supported by clinical chemistry parameters. A slight proliferation of the limiting ridge of the stomach without signs of inflammation in almost all high dosed males is interpreted as a slight local irritation by the test substance.
All test substance related findings were present only in a low grade of severity and never became life-threatening.
The No-observed-effect-level (NOEL) of the test substance was at 316 mg per kg body weight and day for males and at 870 mg per kg body weight and day for females, based on the effects described above. No severe toxic effects were noted even at a dose of 870 mg/kg.
In a Combined Repeated Dose / Reproduction /Developmental Toxicity Screening Study (see also above) no effects on reproduction parameters and on the offspring were noted at doses up to 870 mg per kg body weight and day.
The test item gave positive results in one bacterial gene mutation test (positive for three out of five Salmonella strains) and in one in one mammalian cytogenetic study, regardless whether tested without or with the addition of metabolizing enzymes. Both studies were performed under GLP and according to current guidelines. The test item was mutagenic and clastogenic in the two in vitro tests.
Toxicokinetic summary
Absorption / distribution
Absorption of the test substance in the gastrointestinal tract and a distribution in the body was demonstrated by a Combined Repeated Dose / Reproduction /Developmental Toxicity Screening Study with the test item. Indications for systemic effects were also seen after single oral administration (acute oral toxicity).
No systemic effects were noted after single dermal exposure to the test substance (acute dermal toxicity study). The low partition coefficient n-octanol/water (1.67) and the high water solubility (>100 g/L) do not favour a penetration of the test item through biological membranes. The potential for bioaccumulation is considered to be low, based on the low partition coefficient and the ready biodegradability.
No relevant differences occurred in the two mutagenicity studies with and without the addition of a metabolising system. Therefore no indication of the importance of the metabolism of the test item was obtained from these studies.
No information is available on excretion of the test item.