diethyl pyridine-2,4-dicarboxylate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, according to guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

draft

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: EEC Methods for the determination of toxicity, Annex to Directive 96/54/EC (OJ n° L248 of 30.9.96), Part B, Method B.6. Skin sensitization

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Mexoryl SBU

Cas Number:

41438-38-4

Molecular formula:

C11H13N04

IUPAC Name:

Mexoryl SBU

Constituent 2

Reference substance name:

diethyl pyridine-2,4-dicarboxylate

EC Number:

680-341-5

Cas Number:

41438-38-4

Molecular formula:

C11H13N04

IUPAC Name:

diethyl pyridine-2,4-dicarboxylate

Details on test material:

- Name of test material: MEXORYL SBU- The test material is the same than the one mentioned in section 7.2.1

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/J

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS- Source: Janvier, Le Genest-Saint-Isle, France- Age at study initiation: 9 weeks old- Weight at study initiation: mean±SD 19.8±1.4 g- Housing: individually in disposable crystal polystsrene cages (22cmx8.5cmx8cm)- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: at least 5 days before the beginning of the studyENVIRONMENTAL CONDITIONS- Temperature (°C): 22±2- Humidity (%): 30 to 70- Air changes (per hr): 12 cycles of filtered, non-recycled air- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

0.5, 5 and 50% (w/v)

No. of animals per dose:

4

Details on study design:

RANGE FINDING TESTS:- Compound solubility: the test item was freely soluble in vehicle, acetone/olive oil (4/1, v/v)MAIN STUDYANIMAL ASSIGNMENT AND TREATMENT- Name of test method: LLNA- Criteria used to consider a positive response: stimulation index ≥3TREATMENT PREPARATION AND ADMINISTRATION: On days 1, 2 and 3, a dose-volume of 25 µL of the control or dosage form preparations was applied to the dorsal surface of both ears, using an adjustable pipette fitted with a plastic tip.

Positive control substance(s):

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

Statistics:

no data

Results and discussion

Positive control results:

In the positive control group given HCA at the concentration of 25 %, an increase in cellularity and a stimulation index exceeding the threshold value of 3 (SI=11.32) were noted.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: 2 (0.5%): 1.37, 3 (5%): 1.08, 4 (50%): 1.99, 5 (control positive): 11.32

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: 1 (control): 1226.59, 2 (0.5%): 1686.53, 3 (5%): 1328.39, 4 (50%): 2443.20, 5 (control positive): 13886.44

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Under experimental conditions, the test item Mexoryl SBU does not induce delayed contact hypersensitivity in the murine Local Lymph Node Assay.

Executive summary:

The aim of this study was to evaluate the potential of the test item Mexoryl SBU to induce delayed contact hypersensitivity using the murine LLNA. The study was conducted in compliance with the principes of GLP Regulations and according to OECD guidelines 406 and 429 (draft). Five groups of four animals received 0.5, 5 and 50 % of test item, vehicle (negative control group, receiving a mixture acetone/olive oil (4/1, v/v)) and reference item α-hexylcinnamaldehyde (HCA)at the concentration of 25 % (v/v) (positive control group).

No mortality and no clinical signs were observed. No cutaneous reactions and no increase in ear thickness were observed in the animals of the treated groups. No lymphoproliferation was noted at any tested concentration, while significant lymphoproliferation was observed with the reference item.

In conclusion, the test item did not induce delayed contact hypersensitivity in the murine Local Lymph Node Assay.