Registration Dossier

Administrative data

Description of key information

28 d (+14 d recovery), rat, gavage: NOAEL/NOEL >= 1000 mg/kg bw/d (GLP, OECD 407)

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:
subacute
Species:
rat

Additional information

There is a reliable study available to assess the potential of the substance for repeated dose toxicity after oral dosing.

 

The subacute oral toxicity in the rat was investigated in a GLP conform study according to OECD guideline 407 (1983) with a daily gavage application in the rat for 28 consecutive days, followed by a 14 day recovery period (NOTOX 1993f). The study design did not include a functional observation battery. This is considered be a non critical deviation as the substance did not cause any adverse effects and toxicokinetic data on a related pigment shows absence of systemic availability after ingestion.

The test substance was administered daily for 28 days by oral gavage to SPF-bred Wistar rats.

Based on the results of a 5-day range finding study, the dose levels for the 28-day toxicity study were selected to be 0, 50, 200 and 1000 mg/kg/day. One control group and three treated groups were tested, each consisting of 5 males and 5 females. An extra 5 animals per sex in the control and high dose group were allowed 14 days of recovery.

The following parameters were evaluated: clinical signs daily; body weight and food consumption weekly; ophthalmoscopy at week 4; clinical pathology and macroscopy at termination; organ weights and histopathology on a selection of tissues.

In none of the treatment groups, treatment related findings were observed.

From the results presented in this report a definitive No Observed Adverse Effect Level (NOAEL) and No Observed Effect Level (NOEL) of 1000 mg/kg/day was established.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC):

The available study is considered reliable and suitable for classification purposes under 67/548/EEC. As a result the test item is not considered to be classified for its potential for repeated dose toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the test item is not considered to be classified for its potential for repeated dose toxitity under Regulation (EC) No. 1272/2008.