Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vitro
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
Assessment of skin sensitization potential of the substance DOPO-HQ is required to meet the data requirements of Annex VII, Point 8.3 of the REACH regulation. Consideration has been given to testing the substance using in chemico and in vitro test methods to address key events 1, 2 and 3 of the skin sensitization adverse outcome pathway (AOP). Initially, solubility tests were conducted to determine if suitable concentrations of DOPO-HQ could be obtained to conduct an In Chemico Direct Peptide Reactivity Assay (DPRA) according to OECD Test Guideline 442C (key event 1) and an In Vitro human Cell Line Activation Test (h-CLAT) test according to OECD Test Guideline 442E (key event 3). The solubility of DOPO-HQ in the recommended solvents was found to be limited, such that if negative results were obtained in DPRA and h-CLAT studies it would not be possible to make a firm conclusion on lack of skin sensitization potential. It was considered that whilst conduct of an in vitro ARE-Nrf2 Luciferase (KeratinoSens™) test (or an in vitro ARE-Nrf2 LuSens test) according to OECD Test Guideline 442D (key event 2) might be technically possible, this would only be at low test concentrations of substance and again it would not be possible to reach a firm conclusion on lack of skin sensitization potential. Meanwhile, positive results in the in chemico and in vitro tests, either in isolation or in combination, would not satisfy the EU REACH requirement for concluding whether the substance has the potential to produce significant sensitization in humans (i.e. Category 1A according to EU CLP). Hence, in vivo testing to generate skin sensitization data in accordance with point 8.3.2 of Annex VI to allow hazard and risk assessment is considered justified, the preferred test method being the OECD 429 Local Lymph Node Assay.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

Conclusions:
Owing to low solubility of the substance DOPO-HQ, the use of in chemico and in vitro test methods to address key events 1, 2 and 3 of the AOP for skin sensitization initiated by covalent binding to proteins is not possible. Hence, in vivo testing in accordance with point 8.3.2 of Annex VII, to generate skin sensitization data suitable for hazard and risk assessment, is considered justified. According to EU REACH, the preferred in vivo test method is the OECD 429 Local Lymph Node Assay. Scientific justification should be provided for use of a different in vivo test method.