[S(R*,R*)]-2,3-bis[(4-methylbenzoyl)oxy]succinic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

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:

Studies on eye irritation caused by chemicals in rabbits--II.

Author:

Syoichiroh SUGAI et.al

Year:

1991

Bibliographic source:

The Journal of Toxicological Sciences, 1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Draize test

Principles of method if other than guideline:

The primary eye irritation potential of the test chemical was evaluated according to Draize method

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-p-toluic acid

EC Number:

200-068-3

EC Name:

2-hydroxy-p-toluic acid

Cas Number:

50-85-1

Molecular formula:

C8H8O3

IUPAC Name:

2-hydroxy-p-toluic acid

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): 4-methyl salicylic acid
- Molecular formula : C8H8O3
- Molecular weight : 152.148 g/mol
- Substance type: Organic
- Physical state: Solid
- Purchased from: Tokyo Kasei Kogyo Co. Ltd, Tokyo, Japan

Test animals / tissue source

Species:

rabbit

Strain:

other: Japanese White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: Female
- Source: Takeo Breeder, Shizuoka, Japan
- Age at study initiation: no data available
- Weight at study initiation: 2.0-2.2 kg
- Fasting period before study: no data available
- Housing:metal cages (39*40*44 cm)
- Diet (e.g. ad libitum): RC4 diet (Oriental Yeast Co.Ltd, Tokyo, Japan), ad libitum
- Water (e.g. ad libitum): Water, ad libitum
- Acclimation period: bo data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25±1 deg C
- Humidity (%): 55±5%
- Air changes (per hr): no data available
- Photoperiod (hrs dark hrs light): constant 12 hour light: dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100mg

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

1, 4, 24, 48, 72, 96 hours, 7, 14, 21 days after administration of chemical

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Corneal opacity, erythema, chemosis, secreta and iritis were classified according to the Draize method. The sum of values recorded for cornea, conjunctivae, iris was divided by the number of observations times and the average scores (Draize score) were used as the grade of eye irritation potential of the test chemical. Maximum value of Draize score for cornea, conjunctivae and iris was 80, 20, 5 respectively.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

21 d

Score:

33.9

Max. score:

80

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

7 d

Score:

0.6

Max. score:

5

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

21 d

Score:

5.1

Max. score:

8

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

4-methylsalicylic acid caused moderate eye irritation recovering within 21 days of treatment

Any other information on results incl. tables

Table 1: Physchem Parameters and Primary Irritation Scores

Name of the test chemical	Log P*	Draize Scores
		Cornea	Iris	Conjunctiva
4-methylsalicylic acid	2.82	33.9 (21)	0.6(7)	5.1 (21)

*= Hansch and Leo, 1979, -=not evaluated due to corneal opacity

Figures in parenthesis indicate the days of recovery.

 

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The average Draize scores after 21 days were as follows: CORNEA = 33.9/80, iris = 0.6, conjunctiva = 5.1.
The test chemical caused moderate eye irritation recovering within 21 days of treatment.
Hence, the test chemical can be considered irritating to eyes.

Executive summary:

The primary eye irritation potential of the test chemical was evaluated according to Draize method.

3 female Japanese White rabbits (2.0-2.2 kg) were used for the study. The chemical (if solid= 100 mg, if liquid = 0.1ml) was instilled into the conjunctival sac of the left eye.Right eye (untreated eye) served as blank control.The eyes were examined and the grade of ocular lesions was recorded at 1, 24, 48, 72, 96 hours and 7, 14, 21 days after administration of test chemical.Corneal opacity, erythema, chemosis, secreta and iritis were recorded and classified under Draize method (Draize et.al, 1944)

The sum of values, recorded for cornea, conjunctiva and iris was divided by the number of observation times and the average scores (Draize scores) were used as grades of ocular irritation potential of the chemical.

The maximum value of Draize score are as follows: Cornea =80, Conjunctiva = 20 and Iris = 5

The average Draize scores after 21 days were as follows:CORNEA = 33.9/80, iris = 0.6, conjunctiva = 5.1.

The test chemical caused moderate eye irritation recovering within 21 days of treatment.

Hence,the test chemical can be considered irritating to eyes.