Methyl isonicotinate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

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, 2, 19-224, (1984)

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

A study was performed to assess irritation potential of methyl nicotinate on guinea pigs

GLP compliance:

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:

3-Pyridinecarboxylic acid methyl ester

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Methyl nicotinate
- Molecular formula: C7H7NO2
- Molecular weight: 137.137 g/mol
- Smiles notation: c1(C(OC)=O)cccnc1
- InChI: 1S/C7H7NO2/c1-10-7(9)6-3-2-4-8-5-6/h2-5H,1H3
- Substance type: Organic
- Physical state: Solid

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
- Smiles notation: c1(C(OC)=O)cccnc1
- InChI: 1S/C7H7NO2/c1-10-7(9)6-3-2-4-8-5-6/h2-5H,1H3
- Substance type: Organic
- Physical state: Solid
- obtained from Sigma Aldrich (St. Louis, Mo., USA)

Test animals

Species:

guinea pig

Strain:

Hartley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: female
- Source: Charles River Breeding Laboratories, Wilmington, Mass, USA
- Age at study initiation: no data
- Weight at study initiation: weighing 350 to 500 g
- Fasting period before study: no data
- Housing: five per cage
- Diet (e.g. ad libitum): Guinea Pig Diet, Wayne Laboratory
Animal Diets, Chicago; ad libitum
- Water (e.g. ad libitum): water; ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature-controlled (23±1 “C) rooms.
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): artificially illuminated ( 12 hr/day)

Test system

Type of coverage:

open

Preparation of test site:

shaved

Vehicle:

other: Absolute ethyl alcohol

Controls:

yes, concurrent vehicle

Amount / concentration applied:

0.2% methyl nicotinate in absolute ethyl alcohol, 20µl to each test site

Duration of treatment / exposure:

15 minutes

Observation period:

The thickness of the ear was measured 5 min after the application, and then every 10 min during the first hour, every 15 min during the second, and every 30 min during the third hour.

Number of animals:

Five guinea pigs, each animal with five test sites

Details on study design:

TEST SITE
- Area of exposure: The following sites were selected:
upper back, lower back, upper abdomen, lower abdomen, and flank.
- % coverage: The test sites were marked with a plastic ring stamp, 17 mm in diameter.
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done):yes
- Time after start of exposure: after 15 minutes of exposure, the test chemical was washed away with a soft sponge and lukewarm water.

Results and discussion

In vitro

Other effects / acceptance of results:

no data available

In vivo

Results

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 5 minutes after application

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The reactivity in different test sites varied greatly, the upper back being the most sensitive part of the guinea pig body. The strength of the reactions varied from slight to intensive erythema without edema.

Any other information on results incl. tables

Table 1: ERYTHEMA REACTIONS TO METHYL NICOTINATE^aON DIFFERENT SITES OF GUINEA PIGS^b BODY SKIN

 

Test substance	Upper back	Lower back	Upper abdomen	Lower abdomen	Flank
Methyl nicotinate	4^c	4	1	0	0

 

a-     0.2% in absolute ethyl alcohol, 20µl to each test site

b-     Five guinea pigs, each animal with 5 test sites

c-      Number of animals with erythema reactions

 

 

 

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Erythema reactions from methyl nicotinate appeared within 5 minutes of application.The reactivity in different test sites varied greatly, the upper back being the most sensitive part of the guinea pig body. The strength of the reactions varied from slight to intensive erythema without edema.
Hence, methyl nicotinate can be considered to be irritating to guinea pig skin.

Executive summary:

A study was performed to assess irritation potential of methyl nicotinate on guinea pigs. Six groups of 5 Hartley 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. 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. 20µl of 0.2% methyl nicotinate in absolute ethyl alcohol was applied to the shaved test sites for 15 minutes. After 15 minutes of exposure, the test chemical was washed away with a soft sponge and lukewarm water. The thickness of the ear was measured 5 min after the application, and then every 10 min during the first hour, every 15 min during the second, and every 30 min during the third hour.

Erythema reactions from methyl nicotinate appeared within 5 minutes of application. The reactivity in different test sites varied greatly, the upper back being the most sensitive part of the guinea pig body. The strength of the reactions varied from slight to intensive erythema without edema.

Hence, methyl nicotinate can be considered to be irritating to guinea pig skin.