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Administrative data

Description of key information

NOEL (28 d) = 50 mg/kg bw for male and female rats when administered orally by gavage.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
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

The oral route was considered to be the most relevant way of exposure, therefore a subacute test was performed on rats at 0, 50, 200, 1000 mg/kg bw concentrations. The study was conducted according to internationally accepted guidelines (OECD 407).

The NOEC (28 d) value was determined to be 50 mg/kg bw. Starting from 200 mg/kg bw concentration, adverse effects were determined. The effects evaluated are summarised below.

Mortality

No deaths occurred during the course of this study.

Clinical signs

In 20% of the animals at 1000 mg/kg, ruffled fur was noted in some days during the first part of the treatment period.

In addition passive coloration of the feces by the red test article was noted in all animals at 200 (group 3) and 1000 mg/kg (group 4). This finding was considered to be without any toxicological significance.

Food consumption and body weights

Up to and including the highest dose level of 1000 mg/kg, there were no effects on the food consumption or body weight gain of the animals.

Ophthalmoscopic examinations

No test article related abnormal changes were noted.

Hematology

Slightly decreased haemoglobin concentration in males of group 4, slightly to moderately increased reticulocyte count in both sexes of groups 3 and 4, slightly increased HFR and slightly decreased LFR reticulocyte fluorescence ratio in males of group 4, and slightly to moderately increased methaemoglobin concentration in both sexes of groups 3 and 4.

Clinical biochemistry

Slightly to moderately increased total bilirubin concentration in both sexes of groups 3 and 4 at termination of the treatment.

Urinalysis

Urinalysis data at termination of the treatment indicated no changes of toxicological significance. The only changes noted were a deep yellow urine pigmentation in two females of group 2 (50 mg/kg), in two males of group 3 and in one male and one female of group 4.

Organ weights

At 1000 mg/kg, increased spleen weight was in particular for the female animals. This finding indicate the spleen as a target organ. In addition, at 1000 mg/kg, increased relative liver weight was noted for the female animals. This finding was without any histopathological correlate.

Macroscopic and microscopic findings

At terminal macroscopic examination no test article related abnormal findings were noted.

The inhalation route was not evaluated since exposure by inhalation of the test itemis very unlikely to happen due to its negligible vapour pressure.

The dermal route was not evaluated since exposure by dermal sorption of the test item is very unlikely to happen due to its logKow value (-2.9) and molecular weight (ca. 1470).

Justification for classification or non-classification

A subacute 28 d test is available for rats dosed at 0, 50, 200, 1000 mg/kg bw concentrations.

According to regulation EC 1272/2008 (CLP) section 3.9.2.9.6, the guidance range value to assist in Category 2 classification is between 10 and 100 mg/kg body weight/day (dose/concentration) for a 90-day test, which is multiplied by a factor of 3 in the case of data regarding a 28-day repeated toxicity test.

In the experiment performed, 50 mg/kg bw was determined to be the no observed effect level (NOEL).

A positive dose-response relationship was evident between dose and haematological and biochemical effects observed. The effects observed at 200 mg/kg were not statistically significant and/or toxicologically relevant. For these reasons, a no adverse effect level (NOAEL) of 200 mg/kg bw/day can be assumed.