Methyl nicotinate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication .

Data source

Reference

Reference Type:

publication

Title:

An Animal Model for Non immunologic Contact Urticaria

Author:

ARTO LAHTI' AND HOWARD I. MAIBACH

Year:

1984

Bibliographic source:

Toxicology and applied pharmacology 76, 219-224 (1984)

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

The skin sensitizing potential of Methyl nicotinate was evaluated in guinea pig by guinea pig ear swelling test.

GLP compliance:

not specified

Type of study:

other: guinea pig ear swelling test.

Justification for non-LLNA method:

Not specified.

Test material

Test material information

Constituent 1

Reference substance name:

Methyl nicotinate

EC Number:

202-261-8

EC Name:

Methyl nicotinate

Cas Number:

93-60-7

Molecular formula:

C7H7NO2

IUPAC Name:

methyl pyridine-3-carboxylate

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Methyl nicotinate
- Molecular formula (if other than submission substance): C7H7NO2
- Molecular weight (if other than submission substance): 137.137 g/mol
- Substance type: Organic
- Physical state: white solid powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): Methyl nicotinate
- Molecular formula: C7H7NO2
- Molecular weight: 137.137 g/mol
- Substance type: Organic

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Mass.
- Age at study initiation: No data available.
- Weight at study initiation: 350 to 500 g
- Housing: Housed, five per cage.
- Diet (e.g. ad libitum): Guinea Pig Diet, Wayne Laboratory Animal Diets, Chicago, Ill. Were supplied ad libitum.
- Water (e.g. ad libitum): Water was supplied ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23+/-1 C
- Humidity (%): No data available.
- Air changes (per hr): No data available.
- Photoperiod (hrs dark / hrs light): In artificially illuminated ( 12 hr/day)

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, open

Vehicle:

other: ethyl alcohol

Concentration / amount:

50µl at the concentration of 0.2, 0.05, and 0.01%

Day(s)/duration:

3 hour

Adequacy of induction:

other: Concentrations of the teat substances were selected so that the highest concentration was near the solubility of the substance in absolute ethyl alcohol, and so that those concentrations known to produce NICU in humans were included.

Challenge

Route:

epicutaneous, open

Vehicle:

other: Ethyl alcohol

Concentration / amount:

50µl at the concentration of 0.2, 0.05, and 0.01%

Day(s)/duration:

3 hour

Adequacy of challenge:

other: Concentrations of the teat substances were selected so that the highest concentration was near the solubility of the substance in absolute ethyl alcohol, and so that those concentrations known to produce NICU in humans were included.

No. of animals per dose:

5 animals

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: First
- Exposure period: 3 hour
- Test groups: 5 animals
- Control group: Animals treated with absolute ethyl alcohol. The ear treated with absolute ethyl alcohol was served as control.
- Site: Fifty micro liters of the test substances was applied with a micropipette to both sides of the earlobe. The mean area ± SD of one side of the ear of 10 guinea pigs, weighing 370 to 500 g, was 597 ±39 mm2 .
- Frequency of applications: once
- Duration: No data available.
- Concentrations: 50µl at the concentration of 0.2, 0.05, and 0.01%

B. CHALLENGE EXPOSURE
- No. of exposures: Once
- Day(s) of challenge: No data available.
- Exposure period: 3 hour
- Test groups: 5
- Control group: Animals treated with absolute ethyl alcohol. The ear treated with absolute ethyl alcohol was served as control.
- Site :The mean area ± SD of one side of the ear of 10 guinea pigs 8.4µl/cm2.
- Concentrations: 50µl at the concentration of 0.2, 0.05, and 0.01%
- Evaluation (hr after challenge): 5 min after
the application, and then every 10 min during the 1hour, every 15 min during the second, and every 30 min during the third hour.

Other; Six groups of five guinea pigs were used Hair on the back, abdomen, and flank was shaved with an electric razor; remaining short
hair was removed with a depilatory cream
applied to the shaved areas for 15 min and washed away with a soft sponge and lukewarm water. These procedures did not cause any visible changes in guinea pig skin.
The test sites were marked with a plastic ring stamp,17 mm in diameter. The following sites were selected: upper back, lower back, upper abdomen, lower abdomen and flank. Twenty micro liters of the following test substances
was applied to the marked sits 0.2% MN in absolute ethyl alcohol, and 100% DMSO. The test sites were examined for 3 hr at the same intervals as mentioned before.

Histology ; For histologic studies, 0.2% MN, and was applied to the right earlobes and the vehide, absolute ethyl alcohol, to the left ones; each substance to two guinea pigs. After 40
min (maximal swelling), the animals were killed, the earlobes were excised, and 6-mm punch biopsies were taken from the measurement sites. The specimens were fixed with 10% formaldehyde and stained with hematoxylin and eosin.

Challenge controls:

Animals treated with absolute ethyl alcohol. The ear treated with absolute ethyl alcohol was served as control.

Positive control substance(s):

yes

Remarks:

Benzoic acid

Study design: in vivo (LLNA)

Statistics:

The mean of these 12 measurements was recorded as the preapplication thickness, and was 0.85 f 0.1 I mm (SD) in 100 guinea pigs. All measurements after the
application of the test substance.

Results and discussion

In vivo (non-LLNA)

Results

Key result

Reading:

other: challenge

Hours after challenge:

3

Group:

test chemical

Dose level:

0.2, 0.05, and 0.01%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

The substance tested caused immediate erythema and swelling in the guinea pig earlobe ,maximal swelling was seen within 30 to 40 min after the application of the test substances.The edema tended to disappear within the observation period of 3 hr.

Remarks on result:

no indication of skin sensitisation

In vivo (LLNA)

Cellular proliferation data / Observations:

CLINICAL OBSERVATIONS:The substance tested caused immediate erythema and swelling in the guinea pig earlobe ,maximal swelling was seen within 30 to 40 min after the application of the test substances.The edema tended to disappear within the observation period of 3 hr.

Any other information on results incl. tables

The thickness of the ear (0.85 + 0.11 mm, X + SD, 100 animals) was measured with a string micrometer before application and at 5- to 30-min intervals thereafter.

Maximal increase in ear thickness was produced within 30 to 40 min by 0.2% MN (0.80 ± 0.03 mm). All responses were dose Dependent.

 

Control- The thickness of the ear (0.85 + 0.11 mm, X + SD, 100 animals)

 Test group- The thickness of the ear by 0.2% MN (0.80 ± 0.03 mm)

Applicant's summary and conclusion

Interpretation of results:

other: not sensitizing

Conclusions:

Skin sensitization for Methyl nicotinate was observed in female Hartley strain guinea pigs .Methyl nicotinate was considered to be non sensitizing in female Hartley strain guinea pigs.

Executive summary:

Skin sensitization forMethyl nicotinate was observed infemale Hartley strain guinea pigs byGuinea pig Ear swelling test.Fifty microliters of the test substances was applied with a micropipette to both sidesof the earlobe. The mean area ± SD of one side of the ear of 10 guinea pigs, weighing 370 to 500 g, was 597 ±39 mm²

the average challenge dose thus being 8.44µl/cm2.One ear of an animal was challenged with the test material , and the other ear served as a control with absolute ethyl alcohol. Ear thickness measurementswere started 5 min after the application and then every 10 min during the 1hour, every 15 min during the second, and every 30 min during the third hour. The thickness of the ear (0.85 + 0.11 mm, X + SD, 100 animals) was measured with a string micrometer before application and at 5- to 30-min intervals thereafter.

Maximal increase in ear thickness was produced within 30 to 40 min by 0.2% MN (0.80 ± 0.03 mm).

Control- The thickness of the ear (0.85 + 0.11 mm, X + SD, 100 animals)

 Test group- The thickness of the ear by 0.2% MN (0.80 ± 0.03 mm)

Guinea pig Ear swelling test result was found to be negative based on the result given above.Therefore Methyl nicotinate was considered to be non sensitizing in female Hartley strain guinea pigs.