Registration Dossier

Administrative data

Description of key information

Skin irritation (Kligman AM and Wooding WM): not irritant

Additional information

Justification for read-across

There are no data for skin irriation available for Thermomycolin (CAS 52233-31-5). To fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.1, read-across from appropriate substances is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. According to Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met”. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across) “to avoid the need to test every substance for every endpoint”.

For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substances are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

As no experimental/ measured data are available on skin irriation of Thermomycolin (CAS 52233-31-5), read-across to reliable data on the analogue substance Subtilisin (CAS 9014-01-1) was conducted.

Skin Irritation (in vivo) (human)

Supporting data is available on an in vivo human skin irritation test in order to assess cumulative skin irritation. The study was performed according to the procedure of Kligman AM and Wooding WM: A method for the measurement and evaluation of irritants of human skin, Journal of Investigative Dermatology, 1967; 49 : 78-94. The study was conducted before GLP or GCP was implemented but the state of the art of the time of the study was followed (Kligman, 1978). Under a square patch, 0.5 mL of the test substance (1% subtilisin solution in water, 0.14% expressed as active enzyme protein) was applied to the intact skin of the volar forearms of 10 volunteers. The patches were secured in place by occlusive tape. 24 hours after patch application, the test site was clinically evaluated and a new patch applied. The test was repeated for 10 days with daily reading. As no primary skin irritation occurred it is unlikely that subtilisin would present a risk of primary skin irritation for humans under normal use conditions.