Registration Dossier

Diss Factsheets

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:

The key study was a Magnusson & Kligman maximisation study (GPMT) performed according to EU Method B.6 (Skin Sensitisation) guideline and in compliance with GLP. Groups (20 males) of Dunkin-Hartley guinea pigs were induced with three pairs of intradermal injections of 0.1 mL of Freund's complete adjuvant 50:50 with water for irrigation (Ph. Eur.), 0.05% w/v DMBA in water for irrigation, 0.05% w/v in a 50:50 mixture of water for irrigation and Freund's complete adjuvant were performed on top, middle and down site of interscapular region, respectively. Control group (10 males) was intradermally induced with three pairs of 0.1 mL of Freund's complete adjuvant 50:50 with water for irrigation (Ph. Eur.), water for irrigation, Freund's complete adjuvant 50:50 with water for irrigation were performed on top, middle and down site of interscapular region, respectively. On Day 8, a 20 x 40 mm patch of Whatman No. 3 paper was saturated with approximately 0.4 mL of test item, 60 % w/v in distilled water and the patch was placed over the intradermal injection sites for 48 h. Control animals received the vehicle (distilled water) only and were treated similarly to the test animals. After 2 weeks of rest period, a challenge application of test item dose formulations i.e., 0.2 mL of DMBA, 60 % w/v in distilled water and 30 % w/v in distilled water was applied to an anterior and posterior site on the flank, respectively and the right flank was treated with 0.2 mL of distilled water alone; the exposure period was 24 h. The test concentrations for the main study were determined from a preliminary toxicity study.

No signs of ill-health or toxicity were observed. Intradermal injections produced necrosis at sites receiving Freund’s Complete Adjuvant in test and control animals. Slight irritation was seen in most test animals at sites receiving DMBA, 0.05 % w/v in water for irrigation and no irritation was observed in most control animals receiving water for irrigation. Well-defined to slight erythema with or without slight oedema was observed in control animals and test animals following topical application of DMBA, 80 % w/v in distilled water. Upon challenge application, there were no dermal reactions seen in 19/20 test animals or in any of the controls, therefore these 19 test animals gave negative responses and the remaining animal gave an inconclusive response. The positive controls (Hexyl cinnamic aldehyde, Benzocaine and Mercaptobenzothiazole) induced sensitization reactions indicating the validity of the study.

Under these test conditions, DMBA is not classified as sensitising to skin according to CLP Regulation (EC) N° (1272-2008).

Justification for classification or non-classification

In a Magnusson and Kligman skin sensitisation study in the Guinea-pig, there were no dermal reactions seen in 19/20 test animals or in any of the controls,and the remaining animal gave an inconclusive response.

DMBA is not classified as sensitising to skin according to CLP Regulation (EC) N° (1272-2008).

Categories Display