2-methyl-p-phenylenediamine sulfate

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, not enough details to warrant Klimisch rating 1

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: The Code of Federal Regulations, Title 16, Section 1500.42 (Test for eye irritants)

Deviations:

yes

Remarks:

only three rabbits were used against six as recommended by guideline. Eyes were washed 10 sec after instillation of test substance (eyes can be washed after 24 h reading as per the guideline)

GLP compliance:

no

Remarks:

(pre-dates GLP)

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl-p-phenylenediamine

EC Number:

202-442-1

EC Name:

2-methyl-p-phenylenediamine

Cas Number:

95-70-5

Molecular formula:

C7H10N2

IUPAC Name:

2-methylbenzene-1,4-diamine

Constituent 2

Reference substance name:

2-methyl-1,4-benzenediamine

IUPAC Name:

2-methyl-1,4-benzenediamine

Details on test material:

- Name of test material: Toulene-2, 5 -diamine
- Molecular formula (if other than submission substance): Not reported
- Molecular weight (if other than submission substance): Not reported
- Substance type: Pure active substance
- Physical state: Not reported - Stability under test conditions: Not reported
- Storage condition of test material: Not reported

Test animals / tissue source

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Details on test animals & environmental conditions are not provided in the report.

Test system

Vehicle:

water

Remarks:

(containing 0.05% sodium sulphite (pH 7.0))

Controls:

other: Additional control animals are not required. Eye which did not receive any test substance served as control

Amount / concentration applied:

- Concentration: 2.5 % w/v

VEHICLE
- Amount(s) applied (volume or weight with unit): Not reported
- Concentration (if solution): Not reported
- Lot/batch no. (if required): Not reported
- Purity: Not reported

Duration of treatment / exposure:

10 sec

Observation period (in vivo):

1 h and once daily for Day 1, 2, 3, 4 and Day 7

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Eyes were washed with 50 mL of lukewarm (37°C) water 10 seconds after instillation of the test substance.
- Time after start of exposure: 10 Sec.

SCORING SYSTEM:
U.S. Department of Health, Education and Welfare. Food and Drug Administration Washington. D.C. 20204. “The illustrated Guide for Grading Eye Irritation by Hazardous Substances"

CorneaNo 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 those or combination of any thereof), iris still reacting to light (sluggish reaction is positive): -----------------------------------------------------------------------------1*
No reaction to light, haemorrhage, gross destruction (any or all of these): ------------------------------------------2

Conjunctivae

Redness: (Refers to palpobral 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 figure indicate lowest grades s considered positive under Title 16, Section 15100.42 of the Code of federal Regulations.

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: Not reported

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible

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:

0.3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

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

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 13

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 14

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 15

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 16

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Any other information on results incl. tables

Table 1: Numerical scores awarded to the ocular reactions elicited by toluene-2,5-diamine (study # 71168)

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

- None of the animals gave a "positive" reaction.

- Mild conjunctival inflammation only was observed in two animals on days one and three respectively.

- The third animal did not show any observable response to treatment.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: US CPSC / US FDA

Conclusions:

Under the conditions of this test, a 2.5% toluene-2,5-diamine solution caused slight irritation to rabbit eyes.

Executive summary:

The acute eye irritation of Toulene-1,5-Diamine on rabbit eye was determined following procedure described by The Consumer Product Safety Commission of the U.S.A. in The Code of Federal Regulations, Title 16, Section 1500.42

The study was designed to evaluate the irritant effect of 2.5% w/v solution of Toulene-2,5-diamine (prepared as aqueous solution containing 0.05% sodium sulphite (pH 7.0)) to the rabbit eye

3 rabbits were instilled with 2.5% w/v solution of test substance (containing 0.05% sodium sulphite (pH - 7.0) into one eye. The untreated eye served as control. The eyes were washed with 50 mL lukewarm water (37°C) 10 sec after instillation of the test substance. Animals were examined for ocular reaction at 1 h, Day 1, 2, 3, 4 and 7.

None of the animals gave positive reaction. Mild conjunctival inflammation was observed in 2 animals (score 1) on Days 1 and 3 respectively.

Under the conditions of this test, a 2.5% toluene-2,5-diamine solution caused slight irritation to rabbit eyes.