Registration Dossier

Administrative data

Description of key information

ORAL: LD50 =  > 5000 mg/kg male/female rat, OECD 401, EU Method B.1, Korenaga et al. (1983) & Bullock et al. (1982)
DERMAL: LD50 = > 5000 mg/kg male/female rat, OECD 402, EU Method B.3, Korenaga et al. (1983) & Bullock et al. (1982)

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 was performed under GLP conditions and followed methods equivalent to those in standardised guidelines. Both studies were therefore assigned a reliability score of 1 according to the criteria of Klimisch (1997).

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
Quality of whole database:
Both studies were was performed under GLP conditions and followed methods equivalent to those in standardised guidelines. Both studies were therefore assigned a reliability score of 1 according to the criteria of Klimisch (1997).

Additional information

ORAL

Two studies assessing the acute oral toxicity of the test material are available. Both studies followed a methodology equivalent to that in the standardised guidelines OECD 401 and EU Method B.1. During the studies, 5 male and 5 female rats were treated with 5000 mg/kg test material and another group of 5 male and 5 female rats served as controls. In the study reported by Korenaga et al., none of the animals died, no clinical signs were reported and the bodyweights of the treated animals were comparable to those of the controls. No gross pathological changes attributable to treatment with the test material were observed in any of the animals at necropsy. The acute oral LD50 of the test material was subsequently determined to be in excess of 5000 mg/kg. In the study reported by Bullock et al., none of the animals died, no clinical signs were reported and the bodyweights of the treated animals were comparable to those of the controls. No gross pathological changes attributable to treatment with the test material were observed in any of the animals, at necropsy. The acute oral LD50 of the test material was subsequently determined to be in excess of 5000 mg/kg.

 

DERMAL

Two studies are available assessing the dermal toxicity of the test material. Both studies followed a methodology equivalent to that in the standardised guidelines OECD 402 and EU Method B.3. During the studies, five male and female rabbits received a single dermal application of 5000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. An additional group of 5 males and 5 females served as the controls. In the study reported by Korenaga et al., none of the animals died and no signs of toxicity attributable to treatment with the test material were observed. The mean bodyweight of treated male animals was significantly less than that of the controls at 14 days after dosing. At necropsy, some treated animals showed dry and flakey skin but no other gross pathological changes, which could be related to treatment with the test material, were observed. Histopathological evaluation of treated skin sections revealed mild diffuse hyperkeratosis, however, this was thought to be related to experimental manipulation of the skin rather than due to treatment with the test material. Furthermore, the changes in the skin from these animals was easily reversible. No permanent alterations in the structure of the skin would be anticipated in these animals. The acute dermal LD50 of the test material was subsequently estimated to be in excess of 5000 mg/kg. In the study reported by Bullock et al., none of the animals died and no signs of toxicity attributable to treatment with the test material were observed. There were no significant differences between bodyweights of the treated and control groups. No gross pathological changes related to treatment with the test material were observed at necropsy. Histopathological examination of skin sections from the treated rabbits revealed hyperkeratosis, a mild proliferative response of the epidermis which suggests a very mild cutaneous injury. A liver section from a treated female rabbit revealed diffuse chronic cholangiohepatitis that was probably not related to treatment with the test material. The acute dermal LD50 of the test material was subsequently estimated to be in excess of 5000 mg/kg.

 

INHALATION

The generation of inhalable forms of the test material is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed.


Justification for selection of acute toxicity – oral endpoint
Two studies were available and both were considered as key studies.

Justification for selection of acute toxicity – dermal endpoint
Two studies were available and both were considered as key studies.

Justification for classification or non-classification

ORAL

In accordance with with criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute oral toxicity as no signs of toxicity were noted in the available studies.

DERMAL

In accordance with with criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute dermal toxicity as no signs of toxicity were noted in the available studies.