methyl (2Z)-2-(2-nitrobenzylidene)-3-oxobutanoate

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: This study had been performed in accordance with OECD Guideline No.:429.

Data source

Reference

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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:

methyl (2Z)-2-(2-nitrobenzylidene)-3-oxobutanoate

EC Number:

810-021-4

Cas Number:

111304-31-5

Molecular formula:

C12H11NO5

IUPAC Name:

methyl (2Z)-2-(2-nitrobenzylidene)-3-oxobutanoate

Test material form:

solid: crystalline

Details on test material:

Name: Niliden (Nifedipine Intermediate 11)
CAS: 111304-31-5
Batch No.: ND-78
Description: A white to pale yellow crystalline substance
Date of analysis: 10 2014
Storage: in well closed vial, up to 25 °C

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Number of animals: 24 animals / main test (4 animals/treatment group)
Sex: Female, nulliparous, non-pregnant
Age of animals: 8-9 weeks old (at start of the main test)
Body weight range at starting: 17,2 - 22,0 g
Acclimatization time: 7 days
Light: 12 hours daily, from 6:00 a.m. to 6:00 p.m.
Temperature: 22± 3 °C
Relative humidity: 30-70 %

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

25 %

No. of animals per dose:

Dose range finding animals: 4 female animals
Main test animals: 24 female animals

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The positive control group animals were treated with 25 % (w/v) HCA solution (dissolved in AOO) concurrent to the test item treated groups. No mortality, cutaneous reactions or sign of toxicity were observed in the positive control group. Significant lymphoproliferative response (SI≥3) was noted for HCA (SI=7.3) The results of the positive control item demonstrated appropriate performance of the test in accordance with the relevant guidelines and confirmed validity of the assay.

In vivo (LLNA)

Results

Parameter:

SI

Remarks on result:

other: The observed stimulation index values were 14.4, 13.5 or 12.2 at concentrations of 10 %, 5 %, and 2.5 % (w/v), respectively.

Any other information on results incl. tables

The maximum dose selection was performed according to the relevant guidelines and based on results of a formulation evaluation and also results of the preliminary irritation/toxicity test. Since the test was valid and no signs systemic toxicity or significant irritation were observed the proliferation values obtained are considered to reflect the real potential of the test item to cause lymphoproliferation in the Local Lymph Node Assay.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present assay, niliden tested at the maximum feasible (non-toxic, non-irritant) concentration of 10 % and at concentrations of 5 % and 2.5 % (w/v) as formulations in a suitable vehicle (DMF) was shown to have skin sensitization potential (skin-sensitizer) in the Local Lymph Node Assay (LLNA).