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Description of key information

The subacute oral toxicity of 4-Hydroxy TEMPO was tested in a standard OECD 407 guideline study. Liver and spleen were identified as the target organs. The NOAEL was set to 40 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
40 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Study according to guideline

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral:

In a repeated dose toxicity study according to GLP and OECD Guideline 407 (92-0574-FGT), the test item was administered orally by gavage to 6 SD-rats per dose group and gender at 0, 8, 40, 200 or 1000 mg/kg bw/day for 28 days. Additional recovery groups of the same size, comprising vehicle and high dose animals, were monitored for an additional 14 days. There were no fatalities; body weight food consumption, serum chemistry and urinalysis remained unaffected. Apart from salivation, which was mainly observed in all high dose animals, no abnormal clinical signs occurred. The most prominent effects in the high dose groups were a decreased red blood cell count, haemoglobin and haematocrit and an increase of reticulocytes. Low corpuscular haemoglobin concentrations and high counts of segmental neutrophils were found in high dose females only. The decrease of red blood cell counts and haemoglobin concentration persisted throughout the recovery phase. Absolute and relative spleen and liver weights were increased in high dose animals of both sexes at the end of the dosing period, spleen weight reduction persisted throughout the recovery phase. High dose animals showed a reversible blackening of spleen hue. Histopathology revealed congestion and hemosiderin accumulation in the spleen of all high dose animals and the females of the 200 mg/kg bw/d group. In addition swelling of hepatocytes was noted in all high dose animals. All histopathological effects were detectable until the end of the recovery phase. Based on these findings, the liver and spleen were identified as the target organs. The NOAEL was set to 40 mg/kg bw/day.

Inhalation:

In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after inhalation (required in section 8.6) does not need to be conducted as repeated dose toxicity studies for oral application are available or will be proposed. 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 repeated dose inhalation toxicity has to be conducted.

Dermal:

In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after dermal application (required in section 8.6) does not need to be conducted as a repeat dose toxicity study for oral application is available. The substance is not irritating and not sensitizing to the skin. No dermal effects are expected for repeated dose application to the skin and a low dermal absorption is expected due to the physico-chemical properties of the substance. Thus, no test on repeated dose dermal toxicity has to be conducted.



Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Adequate assay to address endpoint.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after inhalation does not need to be conducted as repeated dose toxicity studies for oral application are available.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after inhalation does not need to be conducted as repeated dose toxicity studies for oral application are available.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after dermal application does not need to be conducted as repeated dose toxicity studies for oral application are available.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
In accordance with column 2 of REACH Annex IX, the test repeated dose toxicity after dermal application does not need to be conducted as repeated dose toxicity studies for oral application are available.

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: spleen; digestive: liver

Justification for classification or non-classification

Based on the results of the subacute oral toxicity study, the test substance was classified as STOT RE cat 2 with H373 (May cause damage to organs through prolonged or repeated exposure) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.