Registration Dossier

Administrative data

Description of key information

The acute oral LD50 toxicity of 4-Hydroxy-TEMPO was tested in a standard OECD 401 guideline study. Classification: H302, Harmful if swallowed. An LD50 of 1053 mg/kg bw was determined. The acute dermal LD50 toxicity of 4-Hydroxy-TEMPO was tested in a standard OECD 402 guideline study. A limit test with rats at 2000 mg/kg bw dose was performed. A LD50 of >2000 mg/kg was determined. Thus, no classification in regard of dermal toxicity is necessary.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 053 mg/kg bw
Quality of whole database:
Study according to guideline

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
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP and guideline conform study

Additional information

Oral:

In an acute oral toxicity study (83-0232 -FGT), rats (5/sex) were given a single oral dose of 4-Hydroxy-TEMPO in distilled water at doses of 0, 500, 1000, 2000 or 5000 mg / kg bw. Animals were then observed for 14 days. The following treatment related clinical signs were noted: Dyspnoea, exophthalmus, ruffled fur and curved body position. In addition: Ventral and lateral body position, tonic-clonic convulsions and sedation (in all dose groups: dyspnoea and convulsions, the latter for up to 5 hrs past dose, incl. non-moribund animals). Oral LD50 combined: 1053 mg/kg bw (males: 953, females 1155 mg/kg bw).The study was QA-monitored (GLP was not compulsory in 1983) and it satisfies the requirements of OECD test guideline 401. The study is considered acceptable (key study).

Inhalation:

In accordance with column 2 of REACH Annex VIII, the test acute toxicity after inhalation (required in section 8.5) does not need to be conducted as acute toxicity studies for oral and dermal application are available. Inhalation exposure is regarded negligible as the substance has a very low vapour pressure. In addition the solid substance consists of flakes which are very unlikely to be inhaled due to their big particle size. Thus, no test on acute inhalation toxicity has to be conducted.

Dermal:

A limit-dose study (2012-0068-DGT) was conducted according to OECD TG 402, Regulation (EC) No 440/2008 method B.3 and OPPTS 870.1200. A dose of 2000 mg/kg bw of 4-Hydroxy-TEMPO in distilled water was applied on rats (5/sex) once for 24 hours on the shaved intact dorsal skin.The test patch was occlusive. This treatment was followed by an observation period of 2 weeks. No influence on animal behaviour or premature death was noted. The body weight gain was not influenced by the test item administration. No skin reactions were observed at the application site. The macroscopic examination did not reveal any changes. The LD50 could not be calculated due to lack of death at the applied dose level. Thus, the Dermal LD50 was determined to be: >2000 mg/kg bw.



Justification for selection of acute toxicity – oral endpoint
Adequate assay to address endpoint

Justification for selection of acute toxicity – dermal endpoint
Only one GLP and guideline study available.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study, the test substance should be classified as Xn, R22 (Harmful, Harmful if swallowed) according to the criteria of EU Directive 67/548/EEC and as Cat. 4, H302 (Harmful if swallowed) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.

Based on the results obtained from acute dermal toxicity study, the substance was not classified and labeled in respect to dermal toxicity according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).