Acetic acid, anhydride, reaction products with 1,5,10-trimethyl-1,5,9-cyclododecatriene

Endpoint summary

Description of key information

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

The substance is not a respiratory sensitiser in absence of human data indicating such effect.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

OECD TG 429

This Local Lymph Node Assay (OECD TG 429) was performed to determine the sensitising potential of the substance in mice. Groups of 4 mice were treated with test concentrations of 10, 25 and 50% v/v acetone/olive oil 4:1, or a vehicle treated control. Hexyl cinnamic aldehyde (HCA), freshly prepared as 10, 25 and 50% v/v dilution in acetone/olive oil 4:1, was used as positive control. Clinical observations and bodyweights were recorded and lymph node proliferation was determined using 3HTdR incorporation. The number of radioactive disintegrations per minute (dpm) reflect the proliferation response of lymph node cells, and were 3181.75, 4635.55, 11376.25, and 21482.15 dpm/animal for the vehicle control, 10%  25%, and 50% concentration groups, respectively. This corresponds with a lymph node proliferation of n.a, 1.5, 3.6 and 6.8, respectively, for the substance-treated groups, calculated as the Stimulation Index (SI). No mortality and no signs of systemic toxicity were observed. Greasy fur was noted for all control and test animals post-dose from Day 1. This was resolved in 6 animals but was still present in all remaining animals at study termination. A loss in bodyweight was recorded for three females dosed at 10% v/v, three females dosed at 25% v/v  and three females dosed at 50% v/v. All remaining animals gained weight during the study. An EC3 value (the concentration of test item expected to cause a 3 -fold increase in 3HTdR incorporation) of 20.71% was calculated. Based on the absence of effects at the lowest concentration tested, a NOEC of 10% could be established.

The dose level was calculated as 0.25 (%)* 980 (density) * 0.025 (ml) * 1000 (conversion from mg to μg) / 1 = 6125 μg/cm2

HRIPT

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 cm2. During the induction patches were placed on the upper back (between the scapulae). The subjects removed the patches 24 hours after application 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 a virgin right of the back and removed after 24 hours. Reactions to the challenge were assessed after 24, 48, 72 and 96 hours. None of the 105 subjects tested was sensitised by the sample. It was therefore concluded that the test substance is not sensitising at the concentration used. Application of 0.2 mL with 10% test substance applied at 3.63 cm2 was not sensitising under the conditions of the test in 105 subjects. This results in 200 mg*0.10/3.63 cm2*0.98 (correction for density) = 5.4 mg (5399 μg)/cm2

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

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 results available, the substance is classified for skin sensitisation (Cat. 1B / H317) in accordance with EU CLP (EC 1272/2008 and its amendments).