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Administrative data

Description of key information

The acute oral and dermal toxicity of the test substance was evaluated in three different studies in rats. One male animal died by day 9 of the dermal toxicity study. The death is  not considered as treatment-releated mortality. Gross pathology was without any findings. Diarrhoea was observed in oneoral toxicity study and is considered as high dose phenomenom. LD50 in acute oral and dermal test was estimated to be greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
5 000 mg/kg bw

Acute toxicity: via dermal route

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

Additional information

Procedure and observations

 

The acute oral toxicity of the test substance was evaluated in two studies. In the key study, a limit test was performed in which one group of five male and five female Sprague-Dawley rats received a single oral administration of the test article at a dose of 2000 mg/kg body weight. Following dosing, the limit test rats were observed at 1, 2, 4, 8 and 24 hours post-dose and daily thereafter and weighed weekly. No mortality occurred during the limit test. The most notable clinical abnormalities observed during the study included faecal/urine stain, mucoid/soft stools, diarrhoea, congested breathing and dark material around the nose/eyes. No gross internal findings were observed at necropsy on study day 14.

In a second, supporting study, acute oral toxicity was evaluated in male and female rats when administered as a single gavage dose at a level of 2000 mg/kg of body weight. No mortality was observed during the study. All animals appeared normal and exhibited body weight gain during the study. The macroscopic necropsy examinations conducted at termination did not reveal any visible lesions.

Dermal toxicity of the test substance was evaluated on Sprague-Dawley rats. A limit test was performed in which one group of five male and five female rats received a single dermal administration of the test article at a dose of 2000 mg/kg body weight. Mortality during the limit test occurred at 2000 mg/kg bw in one male rat by study day 9. In the animal that died, gross internal findings included abnormal contents in the small intestine, mottled lungs, enlarged spleen, distended urinary bladder and fluid contents in the thoracic cavity. No gross internal findings were observed at necropsy on study day 14. The most notable clinical abnormalities observed during the study included dark material around the facial area, urine stain and ocular discharge. No dermal irritation was noted at the site of test article application.

 

Discussion

The observations of the first oral toxicity test revealed staining of urine and faeces which might implicate that the substance is not absorbed but eliminated without metabolizing. The test material caused mucoid/soft stools and diarrhoea. Thus, the substance might influence the texture of faeces or, maybe, water resumption in colon leading to diarrhoea. However, in the second acute oral toxicity study and in the repeated dose study, no findings or abnormalities of digestion and excretion were observed. Gross pathology was also without any findings. Therefore, the observations of the first oral toxicity study might be high dose phenomena.

At the dermal toxicity study, no irritations were observed but one male animal died by day 9. The gross internal findings included abnormal contents in the small intestine, mottled lungs, enlarged spleen, distended urinary bladder and fluid contents in the thoracic cavity. However, neither in skin irritation study nor in sensitisation test animals died or showed any other symptoms. Thus, mortality is not considered as treatment-related death but as a single, individual death. Moreover, dark material around faecal area was found in all animals. There was no explanation of material origin or composition mentioned in the study report but also this symptom did not occur in irritation or sensitisation study and is therefore considered as single high dose phenomenon.

 

 

 

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute toxicity under Directive 67/548/EEC, as amended for the 30th time in Directive 2008/58/EC.

                               

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).