Registration Dossier

Administrative data

Description of key information

Oral: Discriminating dose=500 mg/kg bw, male/female, rat, OECD 420, Johnson 1999
Dermal: LD50=612 mg/kg bw (C.I. 500 - 750 mg/kg bw), male, rat, OECD 402, Johnson 2000
Dermal: LD50=709 mg/kg bw (C.I. 606 - 828 mg/kg bw), female, rat, OECD 402, Johnson 2000

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
500 mg/kg bw
Quality of whole database:
GLP compliant guideline study, Klimisch 1

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
612 mg/kg bw
Quality of whole database:
GLP compliant guideline study, Klimisch 1

Additional information

Acute oral toxicity:

In this GLP compliant fixed dose oral toxicity study, performed according to OECD guideline 420, Alpk:APrSD (Wistar-derived) rats were administered the test substance by oral gavage followed by a 14 -day observation period. In a sighting phase, single female animals received a single oral dose of 2000 or 500 mg/kg of test substance and were assessed daily for 6 days for any signs of systemic toxicity. Following a dose of 2000 mg/kg, the animal was killed in extremis on day 1. Following a dose of 500 mg/kg, the animal showed signs of evident toxicity, with complete recovery by day 6. From the results of the sighting phase of the study, a single fixed dose level of 500 mg/kg was selected for the main phase of the study. A group of five male and five female rats was dosed once and assessed daily for 14 days for any signs of systemic toxicity. Their body weights were recorded at intervals throughout the study. At the end of the study all the animals were killed and subjected to a macroscopic examination. Following a dose of 500 mg/kg, none of the animals died. There were signs of evident toxicity in all animals, with complete recovery by day 4. All the males and two of the females showed an overall body weight gain during the study. Three females showed a slight overall weight loss. There were no treatment-related abnormalities at examination post mortem. In conclusion, the highest fixed dose of the test substance administered in this test without causing any lethality (i.e. the discriminating dose-level), was 500 mg/kg to male and female rats.

Acute dermal toxicity:

In this acute dermal toxicity study in rats, according to OECD guideline 402, and GLP, groups of five male and five female Alpk:APrSD (Wistar-derived) rats received a single dermal application of 500, 750 or 1000 mg/kg of test substance. Test substance was moistened to a dry paste with a small amount of water and applied to shaved skin and kept in contact with skin using an occlusive dressing for approximately 24 hours after which the skin was cleansed free of test substance. Surviving animals were assessed daily for the following 14 days for any signs of systemic toxicity and their body weights were recorded at intervals of 1 week throughout the study. Animals in extremis and those surviving to the end of the study were killed and, together with those found dead, were subjected to a macroscopic examination. Following a dose of 500 mg/kg, none of the animals died. Signs of slight systemic toxicity were seen in all animals, with complete recovery by day 4. All animals showed an overall body weight gain during the study. There were no macroscopic abnormalities. Slight skin irritation was seen in three males and all the females, but had completely resolved by day 13. Following a dose of 750 mg/kg, all the males were killed in extremis on days 1 or 2 and three of the females were found dead on day 2. The surviving females showed signs of slight systemic toxicity, with complete recovery by day 3; both showed an overall body weight gain during the study. At examination postmortem, treatment-related abnormalities were seen in one male and the three females killed in extremis and comprised eye discharge, staining of the nares, and discolouration of the thymus. There were no macroscopic abnormalities in the surviving females. Slight skin irritation was seen on day 2 in one male. Following a dose of 1000 mg/kg, all the animals were killed in extremis on day 1. At examination postmortem one male had a discoloured thymus. In conclusion, the acute dermal median lethal dose of the test substance is estimated to be 612 mg/kg (95% confidence limits 500, 750) to male rats and 709 mg/kg (95% confidence limits 606, 828) to female rats.

Acute inhalation toxicity

No study available.


Justification for selection of acute toxicity – oral endpoint
Only study available. GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Justification for selection of acute toxicity – dermal endpoint
Only study available. GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Justification for classification or non-classification

Based on the observed discriminating dose level of 500 mg/kg in the acute oral toxicity study and the observed LD50 <2000 mg/kg in the acute dermal toxicity study, the test substance is classified as Xn R21/22 harmful in contact with skin and if swallowed according to Directive 67/548/EEC.

Based on the observed discriminating dose level of 500 mg/kg in the acute oral toxicity study and the observed LD50 <2000 mg/kg in the acute dermal toxicity study, the test substance is classified as H302: harmful if swallowed and H312: harmful in contact with skin, according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.