2-methylbutan-1-ol

Endpoint summary

Description of key information

No data are available for 2 -methylbutan-1 -ol, but reliable data exist for other category members:

Branched and linear pentanols (cas 94624-12-1) is negative in the Local Lymph Node Assay upto 100% test substance so is therefore not considered a skin sensitizer. 

 

Pentan-1 -ol and 3 -methylbutan-1 -ol are not peptide reactive and do not activate keratinocytes. Therefore, Pentan-1 -ol and 3 -methylbutan-1 -ol are predicted not to be a skin sensitizer.

This is supported by data on 3 -methylbutan-1 -ol, which did not cause sensitization in humans.

 

In summary, 2 -methylbutan-1 -ol is also predicted not to cause skin sensitization.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No study results or publications are available assessing the skin sensitization potential of 2-methylbutan-1-ol but there are results for other members of the category “pentanols”.

The skin sensitising potential of pentanol, branched and linear was investigated in the Local Lymph Node Assay (OECD TG 429) in compliance with GLP regulations.  Following a preliminary screening test in which no clinical signs of toxicity were noted at a concentration of 100% v/v, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay.  Three groups, each of four mice of the CBA/Ca strain, were treated with 50 uL (25uL per ear) of the undiluted test material or the test substance as a solution in acetone/olive oil 4:1 at concentrations of 50% or 25% v/v.  A further group of four animals was treated with acetone/olive oil 4:1 along.  The Stimulation Indes expressed as the mean radioactive incorporation for each treament group divided by the mean readioactive incorporation of the vehicle control group was as follows: 1.16, 0.87, and 1.05 at a concentration of 25, 50 and 100% in the vehicle, respectively.  Thus, the test substance was considered to be a non-sensitizer under the conditions of the study.

 

The skin sensitizing potential of pentanol was evaluated using several in vitro assays that address key events of the adverse outcome pathway of skin sensitization. In the direct peptide reactivity assay, pentanol was incubated for 24h with either cysteine (C-peptide) or lysine reach (K-peptide) synthetic peptides. C-peptide depletion was -1.46%, and K-peptide depletion was 2.88% compared to the vehicle control. Since negative values are considered as "zero", the average peptide depletion was 1.44%. All values below 4.65% are assessed as negative in this assay. Consequently, pentanol shows minimal or no chemical reactivity in this assay.

The ability of pentanol to activate keratinocytes was evaluated in the LuSens assay. Pentanol was incubated with human transgenic HaCat cells for 48h, and activation of the antioxidant response element was measured as luminescence. Concentrations that reduced viability to below 70% were not assessed. As a result, luciferase activity was not increased by at least a factor of 1.5 above control values. From this is has to be concluded that the test substance does not have a keratinocyte activating potential.

Because the results were clearly negative for the first two in vitro assays, pentanol is predicted not to be as skin sensitizier. No additional test for dendritic cell activation is required.

 

The skin sensitizing potential of 3-methyl-1-butanol was evaluated using several in vitro assays that address key events of the adverse outcome pathway of skin sensitization. The reactivity of 3 -methyl-1 -butanol towards synthetic cysteine (C)- or lysine (K)- containing peptides was evaluated in the Direct Peptide Reactivity Assay (DPRA). For this purpose, the test substance was incubated with synthetic peptides for ca. 24 hours at ca. 25°C and the remaining non-depleted peptide concentrations were determined by high performance liquid chromatography (HPLC) with gradient elution and UV-detection at 220nm. The mean C-peptide depletion, caused by the test substance was determined to be 0.48%. The mean K-peptide depletion, caused by the test substance was determined to be -0.14%. Negative depletions were considered to be “zero” for calculation of the mean peptide depletion, which was thus calculated to be 0.24%. Based on the observed results and applying the cysteine 1:10 / lysine 1:50 prediction model it was concluded that 3 -methyl-1 -butanol shows minimal chemical reactivity in the DPRA under the test conditions chosen.

 

The keratinocyte activating potential of test substance 3-methyl-1-butanol was evaluated in the LuSens assay. For this purpose, the test substance was incubated with a luciferase reporter cell line (LuSens cells) for ca. 48 hours at 37°C and antioxidant response element (ARE) dependent luciferase activity was measured in a luminometer. In summary, exposure to test substance 3 -methyl-1 -butanol luciferase activity in LuSens cells was not induced in at least two consecutive concentrations with statistical significance affording at least 70% viability in at least two independent experiments. From this it has to be concluded that test substance 3-Methyl-1-butanol does not have a keratinocyte activating potential. 

 

 3-methyl-1-butanol is not peptide reactive and does not activate keratinocytes. 3-Methyl-1-butanol is predicted not to be a skin sensitizer.

 

A few publications are available assessing the skin sensitization potential of the pentanol or its isomers in humans. The value of the three case reports is fairly limited. The very few reports on positive patch test responses are most likely due to cross-reactivity (proven in 2 cases), and the purity of the test material is questionable. The most reliable study is the human maximisation test with 3 -methylbutan-1 -ol in which no sensitization was caused by the test substance. But also in this case the number of test subjects is far below what would be required for a reliable negative result. Please refer to IUCLID5, section 7.10.4 for details.

 

In the human maximization study (Kligman 1976), 25 human volunteers received an application of 8% 3 -methylbutan-1 -ol in a 2.5 % aqueous sodium lauryl sulfate solution. The substance was applied via an occlusive patch test to the same site on the volar forearm or back of all subjects for five alternate-day 48 hour periods. Evaluation of the skin sites revealed that none of the 25 individuals showed any signs of sensitization. A detailled read across justification is attached in IUCLID chapter 13. 

 

In an epicutaneous patch test (Fregert 1963), one dermatitiis patient reacted to pentan-1 -ol at a concentration of 10 %, but the chromatogram of the test substance showed 11 additional peaks, so the cause for the reaction is unclear. In another publication, four patients also exhibiting dermatitis were tested positive for pentan-1 -ol (Fregert 1969). A further test person who showed positive skin reactions towards hair lotions was exposed to a series of lower aliphatic alcohols did not react to pentan-1 -ol in an epicutaneous patch test (Ludwig 1977). It should be noted that all patients with positive reactions to pentanol also reacted to all other tested lower primary alcohols. From the provided anamnesis data it can be concluded that pentanol was an unlikely inducer of the sensitzisation. Definite cross sensitization was observed in the publication by Stotts (1977). One patient had previously been sensitized against ethanol due to his voluntary participation in a human patch testing procedure. The other person was sensitized against acetaldehyde while undergoing testing for the maximum non-irritant concentration of this substance. During subsequent patch testing, both also reacted to pentanol, but also to all other tested primary alcohols.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data are considered reliable and suitable for classification purposes under Regulation (EC) No 1272/2008 (CLP).

As a result, the substance does not need to be classified for skin sensitisation under Regulation (EC) No 1272/2008.