Registration Dossier

Administrative data

Description of key information

Oral (OECD 423), rat (f): LD50 > 5000 mg/kg bw (limit test)
Dermal (OECD 402), rat (m/f): LD50 > 2000 mg/kg bw (limit test)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Oral

The acute oral toxicity of the test substance was investigated in a limit test in female Sprague Dawley rats according to OECD guideline 423 and GLP (Colas, 2011). In the first step, 3 animals received 2000 mg/kg bw of the test material in vehicle (olive oil) by gavage. Since no mortality occurred, the treatment procedure of the first step was repeated in a second step using 3 further animals. No clinical signs of toxicity and no mortality were seen up to the end of the 14-day observation in all 3 animals of both treatment procedures. No effects on body weights were observed and necropsy revealed no substance-related findings. Based on the results of the stepwise treatment procedure, the oral LD50 value for female rats was greater than 2000 mg/kg bw. In accordance with OECD guideline 423, the oral LD50 cut-off of the test substance may be considered to be higher than 5000 mg/kg bw.

A second acute oral toxicity test according to OECD 425 (Up-and-Down Procedure) was conducted in female Wistar rats to determine the potential for the test substance to produce toxicity from a single dose via the oral route (Ravi, 2011). In a stepwise procedure, the test item suspended in corn oil was administered as a single oral dose to 5 rats at a dose level of 2000 mg/kg bw. After each treatment step, no mortalities and no clinical signs of toxicity were observed up to the end of the 14-day observation period. At necropsy, no abnormalities were detected in any of the rats. Based on the present study results, the acute oral LD50 of the test substance is greater than 2000 mg/kg bw in female rats.

Dermal

The acute dermal toxicity of the test substance was studied in accordance with OECD guideline 402 and in compliance with GLP (Colas, 2011). The experiment was performed as a limit test in Sprague Dawley rats (5 males and 5 females) at a dose of 2000 mg/kg bw. The test substance was applied in olive oil as vehicle on the shaved skin of the test animals for 24 h under semiocclusive conditions. After removal of the test substance, animals were observed for 14 days and sacrificed thereafter for gross pathological examinations. No treatment-related mortalities occurred and no signs of systemic toxicity were observed. No cutaneous reactions were seen in the animals. The body weight evolution in all animals was not affected by treatment. No test substance-related abnormalities were found at macroscopic post mortem examination of the animals. Therefore, the dermal LD50 value for male and female rats was considered to be greater than 2000 mg/kg bw.

In a further GLP-compliant acute dermal toxicity according to OECD guideline 402, 5 Wistar rats per sex were exposed to the test substance at a limit dose of 2000 mg/kg bw for 24 h (Mohan Kumar, 2012). The test substance was moistened with water and applied to the clipped dorsolateral thoracic surface skin of the test animals under semiocclusive conditions. After 24-h exposure, residual test substance was removed by wiping with water and animals were observed for a period of 14 days. No treatment-related mortalities occurred, no signs of systemic toxicity and no local skin reactions were observed. All animals showed the expected gain in body weight. No test substance-related abnormalities were found at macroscopic post-mortem examination of the animals. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute toxicity of the substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.