Registration Dossier

Administrative data

Description of key information

LLNA: Not sensitising, (mouse, GLP study according to OECD 429, Harlan-CCR 2010)

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitization potential of the main constituent 3-methylbut-3 -en-1-ol (CAS 763-32-6).

In the key study for skin sensitization according to OECD 429 and GLP, i.e. a Local Lymph Node Assay according to OECD 429 and GLP, 3 -methylbut-3 -en-1 -ol was assessed for its possible contact allergenic potential (Harlan CCR 2010). 3 -methylbut-3 -en-1 –ol was dissolved in acetone:olive oil (4+1) and female mice were treated with the test item concentrations of 25, 50, and 100%. The animals did not show any signs of systemic toxicity or local irritation during the course of the study and no cases of mortality were observed. Stimulation Indices (S.I.) of 1.48, 1.67, and 2.28 were determined with the test item at concentrations of 25, 50, and 100% in acetone:olive oil (4+1), respectively. A relevant increase in ear weights was not observed. A statistically significant increase in lymph node weights was observed in the groups treated with 50 and 100% test item concentration in comparison to the vehicle control group (p=0.027). However, none of the S.I.s determined for these concentrations exceeded the threshold of 3.

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-3 -en-1-ol or Isoprenol).

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.

 

Conclusion:

Overall, the skins sensitization data for the impurity formaldehyde trigger a classification for the registered substance (3-methylbut-3-en-1-ol or Isoprenol) as a skin sensitizer Cat 1 (H317: May cause an allergic skin reaction).

In contrast, Isoprenol, was not a skin sensitiser under the test conditions of the performed Local Lymph Node Assay. Accordingly, 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, however, no clear substance related effects were seen in the acute inhalation toxicity assay.

Justification for classification or non-classification

The present data on dermal sensitization for the main constituent 3-methylbut-3 -en-1-ol (Isoprenol) 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).