Registration Dossier

Administrative data

Description of key information

Not sensitising

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The aim of this study was to evaluate the skin sensitization potential of test item following dermal exposure in the Local Lymph Node Assay on Similar substance 01.

No mortality was observed during the main test. No significant, treatment related effect on body weights or any other sign of systemic toxicity were observed in any treatment group. No signs of irritation (monitored by erythema scoring) or any other local effect were observed at the treatment site (ears) in any treatment group.

No significant lymphoproliferation (SI ≥ 3) compared to the relevant control (DMF) was observed for the test item at the tested concentrations. The corresponding stimulation index values were 0.5, 0.9, 0.9 and 2.1 at test item concentrations of 25 %, 10 %, 5 % and 2.5 % (w/v), respectively. No significant, biologically relevant dose-response relationship was observed (p = 0.26, r = 0.74; evaluated by linear regression using the calculated SI values).

The lack of a significantly increased lymphoproliferation up to the maximum attainable concentration of 25 % (w/v, based on solubility) and also the lack of a significant, biologically relevant dose-response relationship are considered evidence that the substance is not a skin sensitizer.

Under the conditions of the assay, substance tested at the maximum feasible concentration of 25 % (w/v, based on solubility) and also at concentrations of 10 %, 5 % or 2.5 % (w/v) as formulations (apparently solutions) in a suitable vehicle (DMF) was shown to have no skin sensitization potential in the Local Lymph Node Assay.

Similar substance 01 is not a skin sensitizer.

Based on the read-across principle, the results can be considered for the assessment of the registered substance.

Justification for read-across is detailed in the report attached to the IUCLID section 13.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitisation

According to the CLP Regulation n. 1272/2008, substances shall be classified as skin sensitisers (Category 1) where data are not sufficient for sub- categorisation (1A and 1B) in accordance with the following criteria:

(a) if there is evidence in humans that the substance can lead to sensitisation by skin contact in a substantial number of persons; or

(b) if there are positive results from an appropriate animal test (according to 3.4.2.2.4.1).

Specific criteria of animal test:

when an adjuvant type test method for skin sensitisation is used, a response of at least 30 % of the animals is considered as positive.

For a non-adjuvant Guinea pig test method a response of at least 15 % of the animals is considered positive.

Furthermore, stimulation index of three or more is considered a positive response in the local lymph node assay.

Sub-category 1A

Substances showing a high frequency of occurrence in humans and/or a high potency in animals can be presumed to have the potential to produce significant sensitisation in humans. Severity of reaction may also be considered.

Specific criteria:

Local lymph node assay-EC3 value ≤ 2 %

Guinea pig maximisation test- ≥ 30 % responding at ≤ 0,1 % intradermal induction dose or ≥ 60 % responding at > 0,1 % to ≤ 1 % intradermal induction dose

Buehler assay - ≥ 15 % responding at ≤ 0,2 % topical induction dose or ≥ 60 % responding at > 0,2 % to ≤ 20 % topical induction dose

Sub-category 1B

Substances showing a low to moderate frequency of occurrence in humans and/or a low to moderate potency in animals can be presumed to have the potential to produce sensitisation in humans. Severity of reaction may also be considered.

Local lymph node assay - EC3 value > 2 %

Guinea pig maximisation test- ≥ 30 % to < 60 % responding at > 0,1 % to ≤ 1 % intradermal induction dose or ≥ 30 % responding at > 1 % intradermal induction dose

Buehler assay - ≥ 15 % to < 60 % responding at > 0,2 % to ≤ 20 % topical induction dose or ≥ 15 % responding at > 20 % topical induction dose.

The LLNA assay failed to calculate an EC value higher than 2 %; Stimulation Index resulted to be lower than 3 for all of the tested concentrations.

As conclusion, according to the paragraph 3.4 of the CLP Regulation n. 1272/2008, the registered substance is not classified as skin sensitizer.