Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

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

For this endpoint, 4 studies are available.

1/Local Lymph Node Assay (LLNA) with heptanol (batch No.1103007)

The objective of this study was to evaluate the potential of the test item, N-HEPTANOL, to induce delayed contact hypersensitivity using the murine Local Lymph Node Assay (LLNA). Evaluation of local irritation was also carried out in parallel. This study was conducted in compliance with the principles of Good Laboratory Practice. Following the solubility assay, acetone/olive oil (4/1, v/v) was chosen as vehicle. A solution was obtained at the maximum tested concentration of 50%. Consequently, the concentrations selected for the preliminary test were 10%, 25%, 50% and 100%. Since the test item was non-irritant in the preliminary test, the highest concentration retained for the main test was the maximal practicable concentration (100%).No treatment-related mortality and no clinical signs were observed during the observation period.
The EC3value was equal to 38%.
Conclusion The test item, N-HEPTANOL, induced delayed contact hypersensitivity in the murine Local Lymph Node Assay. According to the EC3value obtained, the test item should be considered as a weak sensitizer.

2/Magnusson and Kligman study (OECD 406) with heptanol (batch No. 1103007)

The objective of this study was to evaluate the potential of the test item, n-HEPTANOL (batch No. 1103007), to induce delayed contact hypersensitivity in guinea pigs. This study was conducted in compliance with the principles of Good Laboratory Practice and OECD 406 guideline.

After the challenge application, no erythema was observed at left flank treated with vehicle and at right flank treated with test item of control animals. Only dryness of the skin was noted at right flank of 1/10 animals at the 48-hour reading.

 In the test item-treated group, at the 24-hour reading, a discrete or moderate erythema was noted at right flank treated with test item of 3/20 animals. At the 48-hour reading, a discrete erythema was observed at left flank treated with vehicle of 1/20 animals and at right flank treated with test item of 2/20 animals. In addition, dryness of the skin was noted at right flank of 3/20 animals.

As the cutaneous reactions were similar at right flank treated with test item and at left flank treated with vehicle, they were considered not to be attributed to delayed contact hypersensitivity.

Conclusion

The test item did not induce delayed contact hypersensitivity in guinea pigs. Therefore, the test item should not be considered as sensitizing.

3/Magnusson and Kligman (OECD 406) with heptanol (batch No.1103016)

The objective of this study was to evaluate the potential of the test item, n-HEPTANOL (batch No. 1103016), to induce delayed contact hypersensitivity in guinea pigs. This study was conducted in compliance with the principles of Good Laboratory Practice.

After the challenge application, in the control group, at the 24-hour reading, a discrete erythema was observed at right flank treated with test item of 1/10 animals. At the 48-hour reading, a discrete erythema was observed at left flank treated with vehicle of 1/10 animals.

In the test item-treated group, at the 24-hour reading, a discrete erythema was noted at right flank treated with test item of 1/20 animals.

At the 48-hour reading, a discrete erythema was observed at left flank treated with vehicle of 1/20 animals and at right flank treated with test item of 4/20 animals. In addition, dryness of the skin was noted at right flank of 1/20 animals.

As the cutaneous reactions were similar at right flank treated with test item and at left flank treated with vehicle, they were considered not to be attributed to delayed contact hypersensitivity.

Conclusion

The test item did not induce delayed contact hypersensitivity in guinea pigs.  Therefore, the test item should not be considered as sensitizing.

4/ Human patch test

A maximization test was carried out on 20 volunteers. The material was tested at a concentration of 1% in petrolatum and produced no sensitization reactions.




Migrated from Short description of key information:
There are 4 studies:
-1 GLP reliable LLNA study performed with heptanol showing that heptanol is a week sensitizer
-2 GLP reliable magnusson and kligman studies perfomed with two different batches of heptanol showing negative results.
-1 Human patch study perfomed on 210 volunteers with a relaibility of 4 showing negative results.

Respiratory sensitisation

Endpoint conclusion
Additional information:
Migrated from Short description of key information:
There is no information available on the potential for Heptanol to produce respiratory sensitisation in animals.

Justification for classification or non-classification

No classification is warranted based on the two negative Magnusson and Kligman studies performed with two different batches of Heptanol and the negative Human patch test performed on 20 volonteers.

The positive results obtained in the LLNA study was considered to be a false positive results : Indeed, the major issue of debate for the LLNA is the degree to which the assay is associated with false positive and false negative outcomes especially when the tested item is an irritant as it is the case with heptanol. In conclusion, considering the weight of evidence assessment from data generated from the two Magnusson ans Kligman studies and the Human patch test, no classification is warranted for the sensitization endpoint.