Reaction mass of 3,5,6,6-tetramethyl-4-methyleneheptan-2-one and (E)-3,4,5,6,6-pentamethylhept-3-en-2-one

Endpoint summary

Description of key information

Skin sensitisation: Skin sensitiser 1B based on testing in OECD TG 429

Respiratory sensitisation: The substance is not a respiratory sensitiser in absence of human data.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

LLNA

In a study, performed according to OECD TG 429 (Local Lymph Node Assay in mice) and in compliance with GLP, four groups of four female mice were treated by topical application to the dorsal surface of each ear lobe with 0% (vehicle control), 25%, 50% and 100% solutions of the substance in acetone/olive oil (4:1 v/v) for three consecutive days. A positive control group of four female mice was treated with hexyl cinnamic aldehyde (25% v/v in the same vehicle). Five days after the first topical application, the mice were injected intravenously (tail vein) with3H-thymidine. Five hours thereafter, the draining auricular lymph nodes were excised, pooled per animal, processed in physiologically-buffered saline, and analysed for lymphocyte proliferation by measuring the incorporation of 3H-thymidine in a scintillation counter. The stimulation index (SI) was 2.31, 2.80 and 3.60 for the 25%, 50% and 100% solution of the substance, respectively. The SI for the positive control was 4.3 and in agreement with a previous reliability check. An EC3 value of 64% (v/v) was calculated based on the study results. Based on the results of this study, the substance is considered to give a positive result in the LLNA test.

An EC3 value of 64% (v/v) was calculated based on the study results. This value can be converted to an EC3 figure expressed as μg/cm² based on an application volume of 25 μL, an application area of 1 cm² and the relative density of the substance (0.867 g/mL) as follows: EC3 (μg/cm²) = 64/100 x 25 μL/cm² x 0.867 g/mL x1000 = 13872 μg/cm². Instead of the EC3 also a NOAEL can be used because at 50% the EC3 was < 3. This NOAEL of 50% (v/v) can be similarly converted and results to 10838 μg/cm2.

HRIPT

The skin sensitising potential of the substance was evaluated in the repeated insult patch test with 54 human volunteers. The substance, tested as 15% solution (v/v) in 0.2 mL was applied to 7.62 cm² for 24 hours on Monday, Wednesday and Friday for 3 consecutive weeks for a total of 9 applications. This resulted in 200 mg * 0.15 / 7.62 = 3.94 mg/cm². Skin reactions were scored after 24 hours exposure. After 2 weeks rest period, the subjects were rechallenged at a virgin site for 24 hours and the reactions were scored over a period of 3 days. Two cases of mild erythema (score 1) were reported after the 7th and the 8th exposure in the induction phase. No further skin reactions were noted. The substance was found incapable to elicit any visible consistent irritation in any of the panellists.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The substance is not a respiratory sensitiser in absence of human data indicating such effects. In addition, the respiratory sensitisation is assessed using the integrated evaluation strategy for respiratory sensitisation data in the ECHA guidance (R7A, Fig. 7.3-4, 2017).

1) The substance is a skin sensitiser;

2) The substance does not belong to the di-isocyanates;

3) The substance has no structural alerts or is structurally related to chemicals causing respiratory sensitisation as presented in Table R.7.3-1 in the ECHA guidance of 2008 or those provided in the following document: http://ec.europa.eu/health/scientific_committees/docs/annex6_respiratory.pdf. Therefore, the substance is not considered to be a respiratory sensitiser.

Justification for classification or non-classification

Based on the positive results in the LLNA study, the substance has to be classified for skin sensitisation, Category 1B, H317: 'May cause an allergic skin reaction' according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Based on the absence of structural alerts indicating a respiratory sensitisation potential, the substance does not need to be classified as respiratory sensitiser.