5-amino-o-cresol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data provided, followed scientific principles standards.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 1500.42, Test for eye irritants.

Deviations:

yes

Remarks:

only 3 animals were included in the study while guideline recommends 6 animals. The eyes were washed 10 sec. after instillation of the test material while guideline recommends no wash.

GLP compliance:

no

Remarks:

pre-GLP

Test material

Test material information

Constituent 1

Reference substance name:

5-amino-o-cresol

EC Number:

220-618-6

EC Name:

5-amino-o-cresol

Cas Number:

2835-95-2

Molecular formula:

C7H9NO

IUPAC Name:

5-amino-2-methylphenol

Constituent 2

Reference substance name:

4-amino-2-hydroxytoluene

IUPAC Name:

4-amino-2-hydroxytoluene

Test material form:

not specified

Details on test material:

- Name of test material: 4-amino-2-hydroxytoluene
No other information on ‘details of test material’ were provided in the study report.

Test animals / tissue source

Species:

rabbit

Strain:

other: albino

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- No information on the details on ‘test animals and environmental conditions’ were provided in the study report.

Test system

Vehicle:

other: 0.5% aqueous gum tragacanth containing 0.05 % sodium sulphite (pH: 7.0)

Controls:

other: additional control animals are not required. untreated eye, served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: 2.5% w/v solution

VEHICLE
- Concentration: 0.5% aqueous gum tragacanth containing 0.05 % sodium sulphite (pH: 7.0)
- Lot/batch no. (if required): Not reported
- Purity: Not reported

Duration of treatment / exposure:

10 seconds

Observation period (in vivo):

Eyes were examined at 1 hour, and at Day 1, 2, 3, 4, and 7 post application

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Yes; post exposure, the eyes were washed with 50 mL lukewarm (37°C) water.
- Time after start of exposure:10 Seconds

SCORING SYSTEM: The eye irritation were scored according to the following scale:

CORNEA
- No ulceration or opacity = 0
- Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible = (1)*
- Easily discernible translucent areas, details of iris slightly obscured = 2
- Nacreous areas, no details of iris visible, size of pupil barely discernible = 3
- Complete corneal opacity, iris not discernible = 4

IRIS
- Normal = 0
- Markedly deepened folds, congestion, swelling, moderate circumcorneal injection (any of these or combination of any thereof). Iris still reacting to light (sluggish reaction is positive) = (1)*
- No reaction to light, hemorrhage, gross destruction (any or all of these) = 2

CONJUNCTIVAE
Redness (Refers to palpebral and bulbar conjunctivae excluding cornea and iris)
- Vessels normal = 0
- Some vessels definitely injected = 1
- Diffuse, crimson red, individual vessels not easily discernible (2)*
- Diffuse beefy red = 3

Chemosis
- No swelling = 0
- Any swelling above normal (including nictating membrane) = 1
- Obvious swelling with partial eversion of lids = (2)*
- Swelling with lids about half closed = 3
- Swelling with lids more than half closed = 4

*Bracketed figures indicate lowest grades considered positive under Title 16, Section 1500.42 of the Code of Federal Regulations.

-TOOL USED TO ASSESS SCORE: Not reported

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 1, 2 and 3

Time point:

other: all

Score:

0

Max. score:

4

Remarks on result:

other: All animals with grade 0 cornea score

Results 2

Irritation parameter:

iris score

Basis:

animal: 1, 2 and 3

Time point:

other: all

Score:

0

Max. score:

2

Remarks on result:

other: All animals with grade 0 iris score

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: 1, 2 and 3

Time point:

other: 1 hour

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 1 day

Remarks on result:

other: All animals exhibited grade 1 conjunctivae (redness) score at 1 hour observation point.

Results 4

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

animal: 1, 2 and 3

Time point:

other: all

Score:

0

Max. score:

4

Remarks on result:

other: All animals with grade 0 conjunctivae (chemosis) score

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 13

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 14

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 15

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 16

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

- No effects on the cornea or iris were noted at any reading. In all animals, a slight conjunctival redness (score 1) was noted 1 hour after instillation but this redness had gone within 24 hours after application in all animals.

Other effects:

None

Any other information on results incl. tables

Table 1: Numerical scores awarded to the ocular reaction (Study# 71152)

Animal No.	Region of eye		Observation point						Positive (+) or Negative (-)
			1 hour	Day 1	Day 2	Day 3	Day 4	Day 7
1	Cornea		0	0	0	0	0	0	Negative (-)
	Iris		0	0	0	0	0	0
	Conjunctiva	Redness	1	0	0	0	0	0
		Chemosis	0	0	0	0	0	0
2	Cornea		0	0	0	0	0	0	Negative (-)
	Iris		0	0	0	0	0	0
	Conjunctiva	Redness	1	0	0	0	0	0
		Chemosis	0	0	0	0	0	0
3	Cornea		0	0	0	0	0	0	Negative (-)
	Iris		0	0	0	0	0	0
	Conjunctiva	Redness	1	0	0	0	0	0
		Chemosis	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

other: Test substance produced transient irritation to the conjunctivae at 2.5% dilution

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

A 2.5% aqueous solution of 4-amino-2-hydroxy toluene showed transient irritation to rabbit conjunctivae under the test conditions, based on the slight and reversible effects noted 1 hour post instillation in this study.

Although the test procedure did not follow currently accepted guidelines and the purity of the test substance is unknown, the results can be accepted as being indicative of the irritant potential of a 2.5% dilution of the test substance.

Executive summary:

The acute eye irritation potential of toxicity of 4-amino-2-hydroxy toluene was determined following Code of Federal Regulations, Title 16, Section 1500.42, test for eye irritants.

0.1 mL of a 2.5% solution of 4-amino-2-hydroxy toluene in 0.5% aqueous gum tragacanth containing 0.05% sodium sulphite, was introduced into the conjunctival sac of one eye each of 3 albino rabbits: the untreated eyes served as controls. 10 seconds after instillation of the test material, the eyes were washed with 50 mL (37°C) water. Both eyes were examined at 1 hour, and at Day 1, 2, 3, 4 and 7 post application and effects were scored according to the Draize scheme.

No effects on the cornea or iris were noted at any reading. In all animals, a slight conjunctival redness (score 1) was noted 1 hour after instillation but this redness was gone within 24 hours after application in all animals.

Based on the slight and reversible effects noted 1 hour post instillation in this rabbit study, a 2.5% aqueous solution of 4-amino-2-hydroxy toluene showed transient irritation to rabbit conjunctivae under the test conditions. Although the test procedure did not follow currently accepted guidelines and the purity of the test substance is unknown, the results can be accepted as being indicative of the irritant potential of a 2.5% dilution of the test substance.