Registration Dossier

Administrative data

Description of key information

Oral subacute and subchronic toxicity studies are available. The studies were conducted according to the OECD TG 407 (1981) and OECD 408 (1998) and were GLP-conform. Sprague-Dawley rats of both sexes were daily treated with the test substance by gavage during 4 weeks. No obvious signs of toxicity were seen. The NOAEL was established at 1000 mg/kg bw/day for subacute and for 300 mg/kg bw for subchronic exposure.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An oral subacute, 28-day repeated dose oral (gavage) toxicity study was conducted according to the OECD TG 407 (1981) and was GLP-conform, followed by a 2 -week recovery period (Huntingdon Life Sciences Ltd 964059).

Based on a 7-day range-finding study (Huntingdon Life Sciences Ltd 964058), the dose levels were selected as 0, 15, 150 and 1000 mg/kg bw/day.

Each of the groups comprised 5 animals per sex 5 animals per sex and group. Following the 4-week treatment period, another five males and five females of the control and the high dose group were allowed a 2 -week period without treatment.

No obvious signs of toxicity were observed. Since all findings reported were incidental and/or within the range of background no treatment-related effects could be derived. The highest tested dose level of 1000 mg/kg bw/day was established as the NO(A)EL.

For the OECD 408 study, the substance was administered by gavage to groups of 10 male and 10 female Wistar rats at dose levels of 0 mg/kg body weight/day (drinking water with 1% carboxymethyl cellulose served as vehicle control; test group 0), 100 mg/kg bw/d (test group 1), 300 mg/kg bw/d (test group 2) and 1000 mg/kg bw/d (test group 3) over a period of 92 days (male animals) / 93 days (female animals) (BASF 2014).

Food consumption and body weights were determined weekly. The rats were examined for signs of toxicity or mortality at least once a day. In addition, the rats were daily examined for any clinically abnormal signs. Detailed clinical examinations in an open field were conducted prior to the start of the administration period and weekly thereafter. Ophthalmological examinations were performed before the beginning and at the end of the administration period. A functional observational battery (FOB) and measurement of motor activity (MA)were carried out on study days 86 and 90 in males and on study days 87 and 91 in females.

Clinicochemical and hematological examinations as well as urinalyses were performed towards the end of the administration period. After the administration period all rats were sacrificed and assessed by gross pathology, followed by histopathological examinations.

No treatment-related, adverse clinical effects were observed. No adverse findings were observed for histopathology, gross necropsy, urinalyis, functional observation battery and opthalmoscopy. At the highest dose group of 1000 mg/kg bw, increased hemoglobin and hematocrit values in both sexes were found. In males only, increased red blood cell counts and decreased total protein and albumin values were detected.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. No serious irreversible effects were observed at dose levels of less than 50 mg/kg bw upon subchronic exposure. As a result the substance is not considered to be classified for repeated dose toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EG.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. There were no significant toxic effects at doses of less than 100 mg/kg bw upon subchronic oral exposure in rats. As a result the substance is not classified for repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended for the fifth time in Directive EC 944/2013.