3-methylbut-2-en-1-ol

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Additional information:

Skin sensitization potential of the main constituent 3-methylbut-2-en-1-ol (CAS 556 -82 -1).

In the key study for skin sensitization acc. to OECD TG 429 and GLP, 3-methylbut-2-en-1-ol (Prenol) was assessed using the radioactive Murine Local Lymph Node Assay (BASF 2018, 58V0013/18A007). Groups of 5 female CBA/CaOlaHsd mice each were treated with the undiluted test substance, 50% and 25% w/w preparations of the test substance in Methyl Ethyl Ketone (MEK) or with the vehicle, respectively. Each test animal was treated with 25μL per ear of the appropriate test-substance preparation or undiluted test substance, applied to the dorsal surface of both ears for three consecutive days. Lymph node response was evaluated measuring 3H-thymidine incorporation. Cell counts and weights of each animal’s pooled lymph nodes were also determined. In addition, the weight of the pooled ear punches was determined to obtain an indication of possible skin irritation.

No signs of systemic toxicity were noticed in all animals during general observation. When applied undiluted or as 50% and 25% solution in MEK, the Prenol did not induce a biologically relevant (no increase to 3-fold or above of control value) increase of 3H-thymidine incorporation into the cells from the auricular lymph nodes. Concomitantly no biologically relevant (no increase to 1.5-fold or above of control value) increase in lymph node cell counts was observed at all tested concentrations. However, statistically significant increases in 3H-thymidine incorporation and lymph node cell counts were noted at the 50% concentration. No relevant increase in lymph node weights was observed at all concentrations. The test-substance concentrations did not cause relevant increases in ear weights demonstrating the absence of ear skin irritation under the chosen testing conditions.

Overall, it is concluded that Prenol does not exhibit a skin sensitizing potential in the Murine Local Lymph Node Assay under the test conditions chosen.

 

The skin sensitizing potential of Prenol was further evaluated in a human volunteer study: 

In a human maximization test, 3-methylbut-2-en-1-ol at a concentration of 10 % in petrolatum did not produce skin sensitization in 26 volunteers (Epstein 1977). Application was under occlusion to the same site on the forearms for five alternate-day 48 hour periods (pretreated for 24 hours with 5% aqueous sodium lauryl sulfate). Following a ten to fourteen day rest period, challenge patches were applied under occlusion to fresh sites for 48 hours.

 

 

Skin sensitization potential of the impurity formaldehyde (CAS 50-00-0).

The impurity formaldehyde is found to be present at concentrations up to 0.999% in the substance to be registered (3-methylbut-2-en-1-ol; Prenol).

There is sufficient evidence for skin sensitizing properties of formaldehyde in guinea pig maximization tests (GPMT), in a Buehler test in guinea pigs and in mouse local lymph node assays (LLNA). Furthermore, formaldehyde is also identified as a dermal allergen in humans. Accordingly, formaldehyde is listed Annex VI to the CLP Regulation with the harmonized classification as a skin sensitizer Cat.1. Various skin sensitization data in the GPMT (see. e.g. Kimber 1991), Bühler test (see e.g. Hilton 1996), or LLNA (see e.g Hilton 1998) provide evidence of a strong skin sensitizing potential of formaldehyde. Quantitative estimates such as the EC3 values of the LLNA ranged between 0.33% and 0.96% formaldehyde.

According to current knowledge and application of the criteria given in Annex I of Regulation (EC) No. 1272/2008, the classification Skin Sens 1A, exceeding the classification given in Regulation (EC) No. 1272/2008, Annex VI, Table 3.1 is required.

- Kimber et. al. 1991. The murine local lymph node assay: results of an inter-laboratory trial. Toxicol Lett 55: 203-213.

- Hilton et. al. 1996. Experimental assessment of the sensitizing properties of formaldehyde. Fd Chem Toxicol 34: 571-578.

- Hilton et. al. 1998. Estimation of relative skin sensitizing potency using the local lymph node assay: a comparison of formaldehyde with glutaraldehyde. Am J Contact Dermat 9(1):29-33.

Overall, the skin sensitization data for the impurity formaldehyde trigger a classification for the registered substance (3-methylbut-2-en-1-ol or Prenol) as a skin sensitizer Cat 1 (H317: May cause an allergic skin reaction). In contrast, the alternative grade is not to be classified as a skin sensitizer Cat.1, due to its intrinsic properties and the absence of relevant levels of the impurity formaldehyde.

Respiratory sensitisation

Endpoint conclusion

Additional information:

No data available.

Justification for classification or non-classification

The present data on dermal sensitization for the main constituent 3-methylbut-2-en-1-ol (Prenol) do not fulfill the criteria laid down in 1272/2008/EEC, and therefore, a non-classification is warranted. However, the skin sensitization data for the impurity formaldehyde (up to 0.999%) trigger a classification for the registered substance as a skin sensitizer Cat 1 (H317: May cause an allergic skin reaction).