Registration Dossier

Diss Factsheets

Administrative data

Description of key information

An acute oral toxicity study and an acute dermal toxicity study have been conducted on the test item. 
Acute oral toxicity: The acute oral median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight.
Acute dermal toxicity: The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 500 mg/kg bw

Acute toxicity: via dermal route

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

Additional information

Acute oral toxicity:

Introduction:

A study was performed to assess the acute oral toxicity of the test material following a single oral administration to the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 22 March 1996) and Method B1 tris of Commission Directive 96/54/EC (which constitutes Annex V of Council Directive 67/548/EEC).

Method:

Using all available information, 2000 mg/kg bodyweight was selected as the starting dose.

A group of three fasted females was treated with the starting dose. This was followed by a group of three fasted males at the same dose level.

The test material was administered orally as a solution in distilled water. The animals were observed 30 minutes,1, 2 and 4 hours after dosing and then once daily for up to fourteen days. Bodyweights were recorded on Day a (day of dosing) and on Days 7 and 14, or at death. At the end of the observation period the surviving animals were killed by cervical dislocation and all animals were subjected to gross necropsy.

Results:

One female was found dead two days after dosing.

Clinical signs of toxicity commonly noted were diarrhoea, hunched posture, lethargy, pilo-erection and ptosis with additional incidents of ataxia, decreased respiratory rate, laboured respiration and staining around eyes, mouth and snout.

The surviving animals showed expected gains in bodyweight over the study period.

Abnormalities noted at necropsy of the female that died during the study were haemorrhagic lungs, dark liver, dark kidneys and sloughing of the gastric mucosa and non-glandular epithelium of the stomach. White foci in one area of the non-glandular epithelium of the stomach were noted in one male that was killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

Conclusion:

The acute oral median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight.

Acute Dermal Toxicity:

Introduction.The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted24 February 1987)

- Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008

United States Environmental Protection Agency Health Effects Test Guidelines OPPTS 870.1200 Acute Dermal Toxicity August 1998

 -Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended26 June 2001

 -Japanese Ministry of Health and Welfare, 1992

Method. 

Initially, two animals (one male and one female) were given a single, 24-Hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations. 

There were no signs of systemic toxicity.

Dermal Irritation. 

Signs of dermal irritation noted were light brown discolouration of the epidermis, scabbing, scab lifting to reveal glossy skin or dried blood, scab cracking, scab undulating, loss of skin elasticity and flexibility and glossy skin. Adverse reactions prevented accurate evaluation of erythema and oedema at the test sites of nine animals.

Bodyweight. 

Animals showed expected gains in bodyweight over the study period, except for three animals which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Acute Inhalation Toxicity:

Inhalation is not considered a significant route of exposure and a study has therefore not been conducted.

Justification for classification or non-classification

The substance does not meet the criteria for classification (under CLP or DSD) for acute toxicity via the oral or dermal routes based on the results of an acute oral toxicity study and an acute dermal toxicity study, which gave LD50 results of greater than 2500 mg/kg bodyweight and greater than 2000 mg/kg bodyweight respectively.

Categories Display