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:

Skin sensitisation

One animal study described in Haferkorn (2008) (EU method B.6; GLP compliant) is considered to be reliable without restrictions for this kind of substance. According to the results of this test, the substance does not have a sensitising potential. Furthermore, one animal study described in Rudolph (2009)(OECD 429; GLP compliant) is considered to be reliable with restrictions and again shows that the substance does not have a sensitising potential. However, a third reference (Bradshaw (2009))(OECD 429; GLP compliant) reliable with restrictions stated results, which indicated that the test substance is considered to be a skin sensitiser.

Given that the substance lacks any significant capacity to cause skin irritation (please refer to Section 7.3.1 Skin irritation / corrosion: k_Bradshaw_2008 and Section 7.10. 2: s_Eisenberg_2009), skin reactions seen in sensitisation testing ought, most probably, to indicate the presence of allergenic hazard. However, two well conducted predictive assays which used high purity test samples (98% or greater), a GPMT (reference Haferkorn (2008)) and a LLNA (reference Rudolph (2009)), were both convincingly negative. This conclusion was supported by a predictive human sensitisation test (please refer to Section 7.10.4 Sensitisation data (humans): s_Eisenberg_2009). Furthermore, the chemical structure of the test substance, is not one likely to be associated with the reactive chemistry of skin sensitisation (Roberts et al. (2007))*.

Set against this, the other LLNA (reference Bradshaw (2009)), conducted with a less pure sample and in a different vehicle, gave a weakly positive result. Added to this was the (unconfirmed) identification of a pre-sensitised individual in the HRIPT (please refer to Section 7.10.4 Sensitisation data (humans: s_Eisenberg_2009). It is possible that this individual was already sensitised to one of a number of related chemicals, eg p-tertbutylphenol, p-tert-butylcatechol etc., but it must be borne in mind that the chemistry of benzene and cyclohexane differs and that the understanding of cross reaction chemistry remains somewhat limited.

Search of the clinical literature does not yield any evidence of skin sensitisation to SymSitive® 1609 pur (eg Rietschel and Fowler (2008)**; Johansen et al. (2011)*** ), neither does a search of the internet via Google for “tertiary butyl cyclohexanol allergy”. Although the search is therefore consistent with a lack of skin sensitising activity associated with the test item, it must be recognised that this only represents an absence of evidence.

Based on the weight of available evidence, the test substance should not be classified as a skin sensitiser. This conclusion could be further substantiated by an active programme of diagnostic patch testing in dermatology clinics to confirm the absence of evidence. However deployment of as yet unvalidated in vitro assays seems premature.

For more information please refer to the expert statement attached.

* (Roberts et al. (2007) Electrophilic chemistry related to skin sensitisation. Reaction mechanistic applicability domain classification for a published data set of 106 chemicals tested in the mouse local lymph node assay. Chemical . Research. Toxicology. 20, 44-60)

** Rietschel and Fowler (2008) Fisher’s Contact Dermatitis, 6th edition. BC Decker, Hamilton.

*** Johansen et al. (2011) Contact Dermatitis, 5th edition. Springer, Heidelberg


Migrated from Short description of key information:
Skin sensitisation: not sensitising (EU method B.6; OECD 429; GLP compliant)

Justification for classification or non-classification

Skin sensitisation

The test item should not be classified as a skin sensitiser.

Respiratory sensitisation

During long-year industrial practice no cases of hypersensitivity were observed till now by workers exposed exclusively to the test item. Thus, no classification as respiratory sensitiser according to regulation (EC) 1272/2008 is required up to now.