Registration Dossier

Administrative data

Description of key information

According to an OECD 423 and GLP compliant study the median lethal dose of the test item waterfree after oral administration was found to be greater than 2000 mg/kg bw in rats.

According to an OECD 402 and GLP compliant study the median lethal dose (LD50) of the test item, waterfree after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
GLP and guideline study.

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:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Guideline and GLP study.

Additional information

Acute oral toxicity

In an acute oral toxicity study performed according to the Acute Toxic Class Method, 2000 mg/kg of the test item, waterfree (preparations in 0.5% CMC-solution) were administered by gavage to two test groups of three fasted Wistar rats each (6 females). The following test substance-related clinical observations were recorded, clinical signs occurred within 10 days after administration:

 

2000 mg/kg (first test group):

- No mortality occurred

- Impaired general state in all animals

- Dyspnoea in all animals

- Piloerection in all animals

- Diarrhea in all animals

- Exsiccosis in all animals

- Cowering position in all animals

- Reduced defecation in all animals

- Non defecation in two animals

- Fur contaminated with feces in one animal

- Reduced body weight in all animals

- Chromodacryorrhea in one animal

 

2000 mg/kg (second test group):

 

- Mortality in one animal

- Impaired general state in all animals

- Poor general state in one animal

- Dyspnoea in all animals

- Piloerection in all animals

- Diarrhea in all animal

- Exsiccosis in all animals

- Cowering position in one animal

- Twitching in one animal

 - Tremor in one animal

- Reduced defecation in all animals

- Macroscopic pathological findings in the animal that died:

Due to the advanced putrefaction no macroscopic pathological findings could be determined.

 

 

The body weight of the animals in the first 2000 mg/kg bw test group decreased within the first 2 or 3 days after administration. Thereafter, the body weight slightly increased until the end of the first observation week. In the second week, the body weight increased within the normal range in these animals. The body weight of the surviving animals in the second 2000 mg/kg bw test group increased within the normal range throughout the study period. There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period (5 females).

The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw.

Acute dermal toxicity

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test item, waterfree (as suspension in 0.5 % CMC-solution). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

-      No mortality occurred.

-      Neither signs of systemic toxicity nor skin effects were observed

-      The body weight of all animals increased within the normal range throughout the study period.

-      No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study (5 males and 5 females).

 

Accordingly, the acute dermal median lethal dose (LD50) was determined to beLD50, dermal, rat > 2000 mg/kg bw

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The LD50 was greater than 2000 mg/kg bw for the oral and dermal route, respectively. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.