5H-Cyclopenta[h]quinazoline, 6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-

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

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

LLNA

The substance was tested in an LLNA test (OECD TG 429) at concentrations of 10%, 25% and 50%. Positive and negative controls were included to confirm the validity of the test. In a range finding test, no signs of systemic toxicity or excessive irritation indicated by an equal to or greater than 25% increase in mean ear thickness were noted. Very slight erythema was noted on both ears on days 3 and 4. Based on this information the dose levels for the main test were selected (10%, 25% and 50% w/w in acetone/olive oil 4:1). In the main test, no mortality occurred and no signs of systemic toxicity were noted in the test animals during the test. SI values were 1.66, 5.34 and 7.56 for the 10%, 25% and 50% test group, respectively. An EC3 value of 15% was calculated. The NOEC is considered to be 10%. Based on these results, the substance is a skin sensitiser (1B).

HRIPT

In addition to the LLNA test two HRIPT studies with the substance were performed. The substance was tested in 104 and 106 subjects, using concentrations of 5% and 10%, respectively. No dermal reactions were seen. This information is not used for further assessment.

HRIPT (5%)

The induction phase took place on Monday, Wednesday and Friday till 9 applications had been made in approximately 3 weeks. The amount of volume applied was 0.2 ml, test concentration used was 5% and the applied surface was 3.63 cm^2.

During the induction patches were placed at the upper side of the back. Technicians removed the patches 24 hours after application, except for Saturdays on which the patients removed the patches themselves. After removal, 24 hours the skin was not treated, except for the 48 hours treatment free period after the Friday application. Two weeks after the final induction treatment, a challenge patch was applied to untreated sites of the back and removed after 24 hours. Reactions to the challenge were assessed after 24, 48, 72 and 96 hours. None of the 104 subjects tested was sensitised by the sample. It was therefore concluded that the test substance is not sensitising at the concentration used. This result can be compared to LLNA results as the application equals 200 mg*0.05/3.63 = 2.75mg (2750 µg)/cm^2.

HRIPT (10%)

The induction phase took place on Monday, Wednesday and Friday till 9 applications had been made in approximately 3 weeks. The amount of volume applied was 0.2 ml, test concentration used was 10% and the applied surface was 3.63 cm^2.

During the induction patches were placed at the upper side of the back. Technicians removed the patches 24 hours after application, except for Saturdays on which the patients removed the patches themselves. After removal, 24 hours the skin was not treated, except for the 48 hours treatment free period after the Friday application. Two weeks after the final induction treatment, a challenge patch was applied to untreated sites of the back and removed after 24 hours. Reactions to the challenge were assessed after 24, 48, 72 and 96 hours. None of the 106 subjects tested was sensitised by the sample. It was therefore concluded that the test substance is not sensitising at the concentration used. This result can be compared to LLNA results as the application equals 200 mg*0.1/3.63 = 5.5mg (5500 µg)/cm^2.

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

The substance has to be classified as skin sensitisation category 1B and shall be labelled with H317: May cause an allergic skin reaction according to EU CLP (EC no. 1272/2008 and its amendments).