Registration Dossier

Administrative data

Description of key information

In a GLP-study according to OECD test guideline 408 (90-days rat study, oral gavage), the NOEL of the registered substance was determined as 1000 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Mode of Action Analysis / Human Relevance Framework

Additional information

For the registered substance, one repeated dose study was available. As this study was conducted under GLP-conditions according to an OECD test guideline, it was considered as reliable, i.e. Klimisch 1.

The systemic toxicity of the registered substance was examined in a 90 -day oral gavage study in rats according to OECD test guideline 408 and to GLP. The rats were treated daily with 100, 300 or 1000 mg/kg bw/day. No mortality occured. No influence on the behaviour or external appearance was observed. Body weight and body weight gain, food and drinking water consumption, haematological and biochemical parameters were comparable to control. No effect on the eyes, the oestrus cycle and the spermatogenesis was observed. Histopathology did not reveal any test substance related changes.

The male and female animals treated with 300 or 1000 mg/kg bw/day revealed a dose dependent decrease of urinary pH value by up to 11 % (statistically significant at p ≤ 0.01 for males of both dose levels and for the female at the high dose). This effect is considered to potentially caused by the low pH of the registered substance or by a metabolite eliminated at large doses via the urine.

Treatment with 1000 mg/kg bw/day caused an increase in the absolute and relative liver weights (both sexes). The increase is considered to be a non-specific adaptive change to the high work load of the liver caused by a dose level of 1000 mg/kg b.w./day.

Therefore, the NOEL for systemic changes of the registered substance was determined as 1000 mg/kg bw/day (LPT, 2006).

Justification for classification or non-classification

The test item did not induce adverse effects indicative of serious damage at dose levels relevant for classification and labelling when tested for oral repeated dose toxicity. Thus, the test item is not subjected to classification and labelling for repeated dose toxicity according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (GHS, CLP).