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Description of key information

Oral: LD50 =  > 5000 mg/kg bw male/female rat, mouse, OECD 401, EU Method B.1, EPA OPP 81-1, Gillis 1997a
Dermal: LD50 = > 2000 mg/kg bw male/female rat, OECD 402, EU Method B.3, EPA OPP 81-2 - Gillis 1997c
Inhalation: LC50 = > 5.03 mg/L air male/female rat, OECD 403, EU Method B.2, EPA OTS 798.1150, Decker & Biedermann 1997

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Both studies were performed in line with GLP and accepted standardised guidelines with a high standard of reporting. Both studies were assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test material. The overall quality of the database is therefore high.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was performed in line with GLP and accepted standardised guidelines with a high standard of reporting. The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and was considered suitable for assessment as an accurate reflection of the test material. The overall quality of the database is therefore high.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was performed in line with GLP and accepted standardised guidelines with a high standard of reporting. The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and was considered suitable for assessment as an accurate reflection of the test material. The overall quality of the database is therefore high.

Additional information

Oral

The acute oral toxicity of the test material was determined in two studies, each conducted in accordance with standardised guidelines OECD 401, EU Method B.1 and EPA OPP 81 -1. In the first study, five male and female rats received a single oral dose of 5000 mg/kg of the test material, by gavage, and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died. Piloerection and hunched posture were seen in all high dose animals from 1 hour through day 1 post dose; all animals appeared normal by day 2. Body weights were not affected by treatment. Necropsy examinations revealed haemorrhage of the lung in all 5000 mg/kg females and two 5000 mg/kg males. A mottled lung was seen in one 5000 mg/kg male. The acute oral median lethal dose of the test material was estimated to be in excess of 5000 mg/kg to both male and female rats.

In the second study, groups of 5 mice were administered a single dose of test material by gavage at dose levels of 0 (vehicle control, males and females), 2000 mg/kg (females only) or 5000 mg/kg (males and females), followed by a 14 -day post-treatment observation period. Two females in the 5000 mg/kg dose group were found dead, one on day 1 and one on day 5. Hunched posture, piloerection, hypoactivity, and dyspnoea were observed in all animals at 5000 mg/kg at 1, 3 and 4 -5 hours after treatment. All surviving animals appeared normal by day 1. There were no remarkable clinical observations among the animals in the 0 or 2000 mg/kg dose groups. Slight body weight losses were recorded for one female in the 5000 mg/kg dose group and one female dosed at 2000 mg/kg; other body weights were not affected by treatment. Necropsy examinations revealed no observable abnormalities. Under the conditions of the study, the LD50 of the test material was determined to be greater than 5000 mg/kg to male and female mice.

 

Dermal

The acute dermal toxicity of the test material was determined in accordance with standardised guidelines OECD 402, EU Method B.3 and EPA OPP 81 -2. During the study, five male and female rats received a single dermal application of 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died and there were no signs of systemic toxicity. All animals gained weight during the study. There were no macroscopic abnormalities at examination post mortem. The acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to both male and female rats.

 

Inhalation

The acute inhalation toxicity of the test material was determined in accordance with standardised guidelines OECD 403, EU Method B.2 and EPA OTS. During the study, groups of five male and five female rats were exposed by nose only, flow-past inhalation to the test material at a mean concentration of 5.03 mg/L air. All animals were observed for clinical signs and mortality during exposure and over the course of the 14 day post treatment observation period. On study day 15, all animals underwent necropsy and all gross macroscopical changes were recorded.

During the exposure period, the ranges of temperature, humidity, oxygen content, particle size and airflow were found to be satisfactory. Under the conditions of the study, no animals died. Clinical observations were confined to salivation during the latter half of exposure in addition to deep respiration in one animals. Following exposure, restless behaviour was seen in all animals until test day 5 (i.e. 4 days after exposure); ruffed fur in all animals until test day 2, and in six animals until test day 3; and hunched posture in all animals until test day 2. As from test day 6, until termination of the study, all animals were free from clinical signs.

After a minimal retardation in bodyweight gain in males and a slight retardation in females during the first week following the exposure, all male and female animals gained weight normal until scheduled necropsy. The only macroscopical finding was bilateral dilation in the cerebrum of male no 4. This may have been incidental since this finding occasionally occurs in untreated control rats.

In consideration of the presented results, the LC50 of the test material was estimated to be greater than 5.03 mg/L air.

 

All four studies presented to assess the acute toxicity of the test material were performed in line with GLP and accepted standardised guidelines with a high standard of reporting. All studies were assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test material.

 

The available data is considered to be complete and the results determined, oral LD50   5000 mg/kg; dermal LD50 2000 mg/kg inhalation LC50 5.03 mg/L were taken forward for risk assessment.


Justification for selection of acute toxicity – oral endpoint
The key study was selected on the basis that the rat is the preferred model, the supporting study was performed using mice.

Justification for selection of acute toxicity – inhalation endpoint
Only one high quality study was available.

Justification for selection of acute toxicity – dermal endpoint
Only one high quality study was available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Part 3.1, Regulation 1272/2008, the test material does not require classification for acute oral, acute dermal and acute inhalation toxicity.

In accordance with criteria for classification as defined by Directive 2001/59/EC, Annex VI, Point 3.2, the test material does not require classification for acute oral, acute dermal and acute inhalation toxicity.

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