Phenol, 2,4-bis[(dodecylthio)methyl]-6-methyl-

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No data on acute toxicity for the substance (EC 438-600-3) available. Read-across to 4,6-bis(octylthiomethyl)-o-cresol is applied.

The read-across substance differs in the length of the alkyl chain at the thio ether. Specifically, it is a C8 chain in comparison to a C12 chain in the target substance. Due to the shorter chain length, the molecule is smaller and predicted to be of slightly better solubility in water. Therefore, it is considered to be of better systemic availability which might result in a slightly higher toxicity compared to the target substance. As both C8 and C12 chains are metabolized via beta oxidation, both substances are predicted to have the same metabolites. Overall read-across is justified and it was accepted by the Competent Authority for ELINCS registration.

In the key study, the potential of the test article to cause "delayed contact hypersensitivity" after dermal contact was appraised in Dunkin-Hartley Guinea Pigs pursuant to OECD TG 406 (Skin Sensitisation) and GLP guidelines. Intradermal induction and topical induction (occlusive; 48 hours) as well as challenge exposures (epicutaneous occlusive; 24 hours) were performed with the undiluted test article. The control and test groups consisted of 20 animals each. Evaluation of the skin reactions were performed 24 and 48 hours after challenge according to the Draize method in conjunction with histological biopsies for the confirmation of questionable results. After challenge, only 2 out of 20 guinea pigs were positively identified to exhibit evidence of "delayed contact hypersensitivity". All animals of the control group did not show evidence of "delayed contact hypersentisation" (0/19; one animal died). The sensitivity of the assay was ascertained using positive controls which elicited the expected results e.g. Dihydrocoumarin (Hazleton France, 801366).

In support of the findings of the key study are the results of a dermal sensitisation study performed according to OECD Guideline 406 (Skin Sensitisation) and GLP standards, in which Pirbright guinea pigs were used. The control and test groups consisted of 20 animals each. Intradermal inductions were performed with 1% of the test article in Freund's complete adjuvant (FCA) mixed with physiological saline. Topical inductions were carried out under occlusive conditions for 48 hours with 30% of the test article in Vaseline. Challenge exposures were performed epicutaneously (occlusive; 24 hours) with 3% of the test article in Vaseline. Only 10 animals of the control group were challenged with the test article. Evaluation of the skin reactions was performed according to Draize 24 and 48 hours after challenge. Evaluations indicated very slight erythema in 7 animals at the 24 hour examination and in 6 animals at the 48 hour examination. In a re-challenge of the same animals performed 1 week after the standard challenge, only 1 animal had skin irritating reactions. All animals of the control group were negative for being sensitised (0/10). The sensitivity of the assay was ascertained every six months with Paraphenylene-diamine or Potassium-dichromate (Ciba Geigy Ltd., 861247).

Migrated from Short description of key information:
Since there is no data on sensitisation for the substance (EC 438-600-3) available, a read-across to the structural analogon 4,6-bis(octylthiomethyl)-o-cresol has been conducted. In the key study, only 10% (2 out of 20 guinea pigs) of test animals were positive after challenge exposures with the test article. In the supporting study, only 5 % (1 out of 20 guinea pigs) of tested animals produced evidence of skin sensitisation (delayed contact hypersensitivity). Based on the evaluation criteria of Annex VI of the Commission Directive 67/548/EEC, the evaluation "sensitizing" is warranted when at least 30 % of the test animals exhibit positive skin reactions in an adjuvant test. Therefore, in line with the above arguments, the test article is considered not sensitizing after skin contact.

Respiratory sensitisation

Endpoint conclusion

Additional information:

No information is available on respiratory sensitization.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data are considered reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the criteria of Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC, classification as a skin sensitizer is not warranted.

  

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation 1272/2008. Based on the criteria laid down in Regulation (EC) No. 1272/2008, as amended for the second time in Directive EC 286/2011, classification as a skin sensitizer is not warranted.