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Description of key information

The acute oral toxicity of the substance was assessed using:
-2 acute oral toxicity limit tests performed in rats according to OECD 423 and 401 guidelines and Good Laboratory Practices (Longobardi, 2002a and Daamen, 1991a).
The substance is of low acute toxicity following oral exposure:
The oral LD0 was found to be greater than 2000 mg/kg bw in both sexes.
The acute dermal toxicity of the substance was assessed using:
- An acute dermal toxicity test performed in rats according to OECD 402 guideline and Good Laboratory Practices (Queudot, 2010).
The substance is of low acute toxicity following dermal exposure:
The oral LD0 was found to be greater than 2000 mg/kg bw.
No information regarding the acute inhalation toxicity of the substance were available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute Oral Toxicity:

Two reliable without restrictions studies were reported for the acute oral toxicity endpoint. The Longobardi (2002a) and the Daamen (1991) studies reached the same conclusions about the toxicity of the substance and were therefore identified as key studies.

The study of Longobardi (2002a) was designed to evaluate the toxicity of the test material following a single oral administration in rats according to the OECD guideline 423 and to the EU Method B.1 tris. The study was conducted in compliance with the principles of Good Laboratory Practice regulations.

As the oral toxicity was expected to be low, a limit test at one dose level of 2000 mg/kg bw was carried out with 6 animals,3 males in the first step and 3 females in the second step.The test material was prepared in aqueous solution containing 0.5%(w/v) carboxymethylcellulose and was administered by gavage under a dosage-volume of 10 ml/kg.

Clinical signs, mortality and body weight were checked for a period of 14 days following the single administration of the test item. All animals were subjected to necropsy.

No mortalities occurred in both the male and females. In males, clinical signs were limited to hunched posture and reduced activity but a full recovery was noted by Day 7. In females, no clinical signs were noted up to Day 7 of the observation period but therafter, difficulty in breathing, cold to touch, hunched posture, piloerection and rales were noted in a single animal. Changes in bodyweight observed in treated animals were in general not remarkable and no abnormalities were observed at necropsy.

Under these experimental conditions, the oral LD0 of the test material was equal or higher than 2000 mg/kg bw in rats.

The purpose of the study of Daamen (1991a) was to assess the toxicity of the test material when administered to rats as a single oral dose. The study was carried out in accordance with OECD Guideline No. 401, 'Acute Oral Toxicity and EEC Directlve 84/449/EEC, Part 8.1, "Acute Toxicity-Oral". The test material was administered by oral gavage, to five rats of each sex, at 2000 mg / kg bw.

Clinical signs, mortality and body weight were checked for a period of 14 days following the single administration of the test item. All animals were subjected to necropsy.

At the dose-level of 2000 mg/kg, no mortality, no clinical signs and no effects on body weight gain were observed. There were no apparent abnormalities at necropsy.

Under these experimental conditions, the oral LD0 of the test material was equal or higher than 2000 mg/kg bw in rats.

Acute dermal Toxicity:

One study is recorded for this endpoint.The study of Queudot (2010) was reliable without restrictions and selected as a key study.

The study of Queudot (2010) was conducted to evaluate the potential acute dermal toxicity of the substance in rats.

The study was conducted according to OECD guideline 402 and EU method B.3 in compliance with the principles of Good Laboratory practices.

The test item in its original form was applied to the skin of Sprague-Dawley rats. The treated area was then covered by a semi-occlusive dressing for 24 hours. In first instance, the test item was administered sequentially at dose-levels of 200, 1000 then 2000 mg/kg to one female per dose-level, in order to evaluate the potential toxicity and local tolerance of the test item. According to the results obtained at each dose-level, a highest dose-level was tested or the dose-level was confirmed in four other females and tested in five males.

Mortality and clinical signs were checked daily for a period of 14 days following the single application of the test item. Body weight was recorded on days 1, 8 and 15. At the end of the 14-day observation period all animals were sacrificed and subjected to necropsy.

In the first step, at the dose-level of 200 and 1000 mg/kg, no mortality and systemic clinical signs were noted. The local reactions, as erythema (well-defined to severe), scabs, dryness and discoloration area (greenish, brownish or blackish) and/or oedema were observed with a similar severity.

According to these results, a highest dose-level of 2000 mg/kg was tested in one other female and then confirmed in four additionnal females and five males.No deaths and no relevant systemic clinical signs were observed during the study at the dose-level of 2000 mg/kg. Local reactions (erythema, dryness, edema, discoloration area and scabs) observed at 2000 mg/kg were similar in severity to those recorded at 1000 mg/kg. The body weight was not affected by the test item treatment. No abnormalities were observed at macroscopic examination.

Under these experimental conditions, the dermal LD0 of the substance was higher than or equal to 2000 mg/kg in rats.

Justification for classification or non-classification

According to the criteria laid down in EU regulation (EC) n° 1272/2008/EC (CLP) and EU directive67/548/EEC, the substance is not classified for acute oral and dermal toxicities.