Propanoic acid, 2-cyano-2-methyl-, methyl ester

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study conducted according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

2-cyano-2-methyl-propanoic acid methyl ester

EC Number:

615-749-4

Cas Number:

72291-30-6

Molecular formula:

C6 H9 N O2

IUPAC Name:

2-cyano-2-methyl-propanoic acid methyl ester

Details on test material:

Identity: 2-cyano-2-methyl-propanoic acid-methyl ester
Appearance: Colourless, clear, liquid
Batch No.: 11-0068
BASF Substance No.: 04/0567-2
Purity: 99.924 area-%
Homogeneity: The test substance appeared to be homogeneous.
Stability in Solvent: Not indicated by the sponsor
Storage: At room temperature
Expiration Date: September 09, 2012

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

control, 25, 50, 100%

No. of animals per dose:

5

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: control: 1.0 25%: 1.0 50%: 0.88 100%: 0.63

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Mean DPM control: 850.1 25%: 852.5 50%: 747.9 100%: 532.1

Applicant's summary and conclusion

Conclusions:

The test item 2-cyano-2-methyl-propanoic acid-methyl ester was not a skin sensitiser under the test conditions of the LLNA.

Executive summary:

The test item 2-cyano-2-methyl-propanoic acid-methyl ester was assessed for its skin sensitising potential using the Local Lymph Node Assay (LLNA) in mice. Test item solution at different concentrations was prepared in the vehicle acetone:olive oil (4+1 v/v). 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. For this purpose a local lymph node assay was performed using test item concentrations of 25, 50% (w/w), and 100% (undiluted test item). The animals did not show any signs of systemic toxicity or local skin irritation during the course of the study and no cases of mortality were observed. A statistically significant increase in ear weights was not observed in in any test item group in comparison to the vehicle group. The cutoff-value for a positive response regarding the ear weight index of 1.1 reported for BALB/c mice was also not exceeded in any dose group. 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 Stimulation Indices (S.I.) of 1.00, 0.88, and 0.63 were determined with the test item at concentrations of 25, 50% (w/w) and 100% in acetone:olive oil (4+1 v/v), respectively. A statistically significant or biologically relevant increase in DPM value or in lymph node weight and cell count was not observed in any of the tested dose groups in comparison to the vehicle control group. The cutoff-value for a positive response regarding the lymph node cell count index of 1.55 reported for BALB/c mice was also not exceeded in any dose group. The test item 2-cyano-2-methyl-propanoic acid-methyl ester was thus not a skin sensitiser under the test conditions of this study.