Registration Dossier

Administrative data

Description of key information

ORAL

LD50 550 mg/kg bw, Sprague-Dawley rat, OECD 425

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
550 mg/kg bw
Quality of whole database:
There are two studies available to address this endpoint. Both are guideline studies conducted under GLP conditions and awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997). The quality of the database is therefore considered to be high.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are two studies available; one was conducted on commercially purchased material and the other was conducted using material manufactured by the registrant to confirm the parity of the two materials. On this basis, the study performed using the material manufactured by the registrant was selected as key.

The key study was performed to assess the acute oral toxicity of the test material manufactured by the registrant in the Sprague-Dawley strain rat using the up and down procedure. It was conducted in accordance with the standardised guideline OECD 425 under GLP conditions.

A total of six female animals were dosed individually in sequence with sufficient time (at least 48 hours) between each animal, at dose levels ranging from 175 mg/kg body weight to 2000 mg/kg body weight.

The test material was administered orally by gavage as a solution in distilled water. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

The animal treated at a dose level of 2000 mg/kg and one animal treated at a dose level of 550 mg/kg were found dead on the day of dosing. One other animal treated at a dose level of 550 mg/kg was killed in extremis four hours after dosing. There were no deaths at a dose level of 175 mg/kg.

Signs of systemic toxicity noted in the animal treated at a dose level of 2000 mg/kg were hunched posture, ataxia, ptosis, occasional body tremors and cyanosis. Signs of systemic toxicity noted at a dose level of 550 mg/kg were hunched posture, lethargy, ataxia, ptosis, pilo-erection, decreased respiratory rate, laboured and noisy respiration, occasional body tremors, pallor of the extremities, emaciation, fasciculations and red/brown staining around the snout. There were no signs of systemic toxicity noted in one animal treated at 550 mg/kg and in the animals treated at the dose level of 175 mg/kg. Surviving animals showed expected gains in body weight.

At necropsy, abnormalities noted in animals that died or were humanely killed during the study were dark liver, gaseous stomach, clear liquid present in the stomach and haemorrhagic gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Under the conditions of this study, the acute oral LD50 of the test material was determined to be 550 mg/kg bodyweight (95 % confidence limits 88.94 to 2430 mg/kg bodyweight). In accordance with EU criteria, the test material requires classification for Acute Toxicity as Category 4.

The acute oral toxicity of the commercially purchased test material was assessed in a supporting study conducted under conditions of GLP and in accordance with the standardised guideline OECD 425.

A single oral dose of the test material in corn oil was administered by gavage to a total of six female Sprague-Dawley CD rats. The animals were dosed individually in sequence with sufficient time (at least 48 hours) between each animal, at dose levels ranging from 175 mg/kg bodyweight to 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

The single animal treated at a dose level of 2000 mg/kg and two of the three animals treated at a dose level of 550 mg/kg were found dead during the day of dosing. Both animals treated with 175 mg/kg survived.

Signs of systemic toxicity noted in the two animals treated at a dose level of 550 mg/kg that died were hunched posture, lethargy and decreased respiratory rate with ataxia and occasional body tremors. Furthermore, ptosis was noted in one animal. There were no signs of systemic toxicity noted in the surviving animal treated at a dose level of 550 mg/kg and animals treated at a dose level of 175 mg/kg.

Abnormalities noted at necropsy of the animals treated at a dose level of 550 mg/kg that died during the study were haemorrhagic lungs, dark liver, dark kidneys and haemorrhagic gastric mucosa. No abnormalities were noted at necropsy of the animal treated at a dose level of 2000 mg/kg that died during the study or animals that were killed at the end of the study.

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

Under the conditions of this study, the acute oral LD50 of the test material was determined to be 550 mg/kg bodyweight, based on an assumed sigma of 0.5 (95 % confidence limits 89 to 2430 mg/kg bodyweight). In accordance with the EU CLP criteria, the test material requires classification as Acute Toxicity, Category 4.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance requires classification with respect to acute toxicity as Category 4 (H302 Harmful if swallowed).

In accordance with the criteria for classification as defined in Annex VI, Directive 67/548/EEC (DSD), the substance requires classification with respect to acute toxicity as R22 Harmful if swallowed (Xn).