1,2,3,4,4a,5,6,7-octahydro-2,5,5-trimethyl-2-naphthol

Endpoint summary

Description of key information

DPRA: Positive in an OECD TG 442C test.

KeratinoSens: Negative in an OECD TG 442D test.

U-SENS: Positive in an OECD TG 442E test

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

DPRA

In an in chemico (DPRA) study, performed according to OECD guideline 442C and in accordance with GLP principles, the reactivity of the test substance towards model synthetic peptides containing either cysteine (SPCC) or lysine (SPCL) was determined. Following incubation of the test substance with either SPCC or SPCL, the relative peptide concentration was determined by High-Performance Liquid Chromatography (HPLC) with gradient elution and spectrophotometric detection at 220 nm and 258 nm. SPCC and SPCL Percent Depletion Values were calculated and used in the prediction model. ACN was found to be an appropriate solvent to dissolve the test substance and was therefore used in this DPRA study. Cinnamic aldehyde was used as a positive control. All acceptability criteria were met and therefore, the study was considered to be valid. No precipitate or phase separation was observed in the SPCC samples before and after the incubation. Upon preparation as well as after incubation of the SPCL test item samples, a precipitate was observed. In the cysteine reactivity assay the test item showed 74.1% SPCC depletion and in the lysine reactivity assay the test item showed 0.0% SPCL depletion. The mean of the SPCC and SPCL depletion was 37.1% and as a result the substance was considered to be positive in the DPRA and classified in the “moderate reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model.

 

KeratinoSens

A KeratinoSensTM assay was performed with the substance according to OECD 442D and in accordance with GLP principles. Two valid independent experiments were performed. The cells in these experiments were incubated with the test item in a concentration range of 0.98 – 2000 µM (2-fold dilution steps) for 48 ± 1 hours. Positive controls and vehicle controls were included. All acceptability criteria were met and therefore the study was considered to be valid. The test item showed no precipitation. The test item showed cytotoxicity (IC30 values of 303 μM and 356 μM and IC50 values of 359 μM and 440 μM in experiment 1 and 2, respectively). No biologically relevant induction of the luciferase activity (no EC1.5 value) were measured at any of the test concentrations in both experiments. The maximum luciferase activity induction (Imax) was 1.21-fold and 0.99-fold in experiment 1 and 2, respectively. The substance is classified as negative in the KeratinoSensTM assay since negative results (<1.5-fold induction) were observed at test concentrations up to and including 2000 μM.

 

U-SENS

A U-Sens assay was performed with the substance according to OECD 442E and in accordance with GLP principles. Two valid independent experiments were performed. The cells (U937 cell line) in these experiments were incubated with the test item at six test concentrations (1, 10, 20, 50, 100 and 200 μg/mL) for 45 ± 3 hours. Positive controls, negative and vehicle controls were included. All acceptability criteria were met and therefore the study was considered to be valid. The test item showed no precipitation or color interference. The test item showed no toxicity (No CV70 value). A biologically relevant, induction of the CD86 activity (EC150 values of 37 μg/mL and 34 μg/mL in experiment 1 and 2, respectively) was measured in both experiments. The test item is classified as Positive in the U-Sens assay since positive results (> 150% increase) were observed at test concentrations with a cell viability of >70% compared to the vehicle control.

 

DEREK NEXUS

Derek Nexus 6.1.0 identified the structural alert 712: Terpinoid. Terpenoids have been reported as moderate to weak or non sensitisers. Derek uses the nearest neighbour approach comparing EC3 values, derived from LLNAs (OECD 429), of structural similar substances. 31 compounds were identified of which 10 were used in the calculation. The potential mode of actions are: Prehapten producing a free radical generator and/or Prehapten producing an electrophilic Michael acceptor. Derek predicts the EC3 to be 18%. As this EC3 value is well above the Skin Sensitisation 1A classification cut-off of 2%, any uncertainty in the prediction is taken into account for classification purposes.

Justification for classification or non-classification

The substance has to be classified as Skin Sens 1B and shall be labelled with H317: May cause an allergic reaction according to EU CLP (EC No. 1272/2008 and its amendments).