Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In this GLP conform study the test item Oxooel 13 dissolved in methyl ethyl ketone was assessed for its skin sensitizing potential using the Local Lymph Node Assay (LLNA) in mice according to the OECD Guideline 429 (BASF SE, 2010). The basic principle underlying the LLNA is that sensitisers induce a primary proliferation of lymphocytes in the lymph node draining the application site. The ratio of proliferation in test item treated groups compared to that in vehicle controls is termed the Stimulation Index (S.I.). Radioactive labelling is used to measure cell proliferation. A test item is regarded as a sensitiser in the LLNA if exposure to one or more test item concentration results in a 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.). The estimated test item concentration required to produce a S.I. of 3 is referred to as the EC3 value.

In this study, three groups each of five female mice were treated with 25, 50 or 100 % test item (purity: 99.7 weight-%) concentration by topical application at the dorsum of each ear on three consecutive days. The appropriateness of these concentrations was previously confirmed in a pre-experiment.

An additional group of five mice was treated with the positive control item at 25 % and two negative control groups (methyl ethyl ketone for the test item or acetone:olive oil (4+1) for the positive control) were treated with the respective vehicles only. Five days after the first topical application, the mice were intravenously injected into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed and the draining auricular lymph nodes were excised and pooled per animal. Furthermore, both ears of the mice were punched at the apical area using a biopsy punch and were immediately weighed pooled per animal.

Single cell suspensions of lymph node cells were prepared and lymphocyte proliferation was quantified by measuring the incorporation of radiolabelled thymidine into the lymph node cells by β-scintillation counting.

Results of the formulation analysis showed that all measured concentrations of Oxooel 13 were within the acceptable range set at 100 ± 15 % of the nominal concentration. The obtained results ranged between 87.6 – 94.6 % of the nominal values.

The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed. Signs of local irritation (e.g. reddening of the ear skin, ear swelling) were also not observed during the study period. A statistically significant increase in ear weights was observed in the groups treated with 50 and 100% test item concentration in comparison to the vehicle control group (p=0.012). However, the individual results of the low dose and mid dose group are very similar and the increase in ear weight in comparison to the vehicle control is just about 13%. Thus, this is not considered as biologically relevant.

Here, Stimulation Indices (S.I.) of 2.98, 4.86 and 9.92 were determined with the test item at concentrations of 25, 50, and 100% in methyl ethyl ketone, respectively. A statistically significant increase in DPM/animal values was observed in all test item treated groups in comparison to the vehicle control group (p<0.001). A clear dose response was observed.

Although in the high dose group, an influence of the potential irritation on Lympho-proliferation cannot be excluded, the threshold value of 3 was also exceeded in the mid dose group, where no biologically relevant increase in ear weight was found. The S.I. of the positive control group was 8.24. Although the results were somewhat ambiguous, the test item Oxooel 13 was found to be a skin sensitiser in this assay under the conditions of this study and an EC3 value of 25.3 % (w/v) was derived.

Remark:

The LLNA is known to overestimate a few structural classes, e.g. aldehydes. As Oxooil 13 consists of various aldehydes the LLNA is not the appropriate test system for this structural class, and for this test item. However, preliminary no other data (e.g. a GPMT) is available. Therefore, Oxooel 13 is considered to be a sensitiser.


Migrated from Short description of key information:
Local Lypmh Node Assay (LLNA), mice: sensitising (BASF SE, 2010)

Respiratory sensitisation

Endpoint conclusion
Additional information:
Migrated from Short description of key information:
No information available

Justification for classification or non-classification

skin sensitisation

Dangerous Substance Directive (67/548/EEC):

The available study is considered as limited suitable for classification purposes under 67/548/EEC. However, since no other data are available, the test item is considered to be classified for skin sensitisation under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008:

The available experimental test data is considered as limited suitable for classification purposes under Regulation 1272/2008. However, since no other data are available, the test item is considered to be classified for skin sensitisation under Regulation (EC) No. 1272/2008.

 

respiratory sensitisation

no data available