6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11.3.80 - 14.3.80

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. No data on purity.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(adopted 2002)

Deviations:

yes

Remarks:

Six rabbits were used (in 3 rabbits eyes were washes 30 seconds after instillation of test substance).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid

EC Number:

279-505-5

EC Name:

6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid

Cas Number:

80584-91-4

Molecular formula:

C21H36N6O6

IUPAC Name:

6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid

Details on test material:

- Physical state: White powder

Test animals / tissue source

Species:

rabbit

Strain:

Californian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hylyne Commercial Rabbits Ltd.
- Age at study initiation: 12-16 weeks
- Average weight at study initiation: 2.41 kg (males), 2.21 kg (females)
- Housing: single housing
- Diet: commercial diet (Labsure, Christopher Hill Group); ad libitum
- Water: sterile filtered water; ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 ± 1
- Humidity (%): 50-70
- Photoperiod: Artificial light from 08.00-18.00 hours.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: right untreated eye

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 100 mg

Duration of treatment / exposure:

3 rabbits: single application, washing after 30 seconds with 200 mL warm water.
3 rabbits: single application, no washing was performed

Observation period (in vivo):

72 hours (termination of study because of negative results after 72 h)

Number of animals or in vitro replicates:

6

Details on study design:

PERFORMED OBSERVATIONS:
- 1, 24, 48, and 72 hours after instillation of test substance

REMOVAL OF TEST SUBSTANCE
- Washing:
3 rabbits: single application, washing with 200 mL warm water
3 rabbits: single application, no washing was performed
- Time after start of exposure: 30 seconds

SCORING SYSTEM:
Draize score

TOOL USED TO ASSESS SCORE:
Fluorescein for assessment of corneal damage.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: unwashed eyes

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Remarks on result:

other: unwashed eyes

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.9

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: unwashed eyes

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: unwashed eyes

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Remarks on result:

other: washed eyes

Results 6

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Remarks on result:

other: washed eyes

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.4

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: washed eyes

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Remarks on result:

other: washed eyes

Irritant / corrosive response data:

Very slight conjunctival reactions (redness and chemosis) were seen in 3/3 washed eyes and slight to mild reactions in 3/3 unwashed eyes one hour after compound application, reversible within 72 hours. Slight corneal opacity with damage to the surface epithelium was seen in 3/3 unwashed eyes at one hour, fully reversible within 48 hours the latest. No effects on the iris were observed in the eyes of the animals.

Any other information on results incl. tables

 Table 1: Individual and average irritation scores 1, 24, 48, and 72 hours after instillation of test substance (unwashed eyes)

Rabbit #	Time [h]	conjunctivae		iris	cornea		conjunctivae		iris	cornea
		redness	swelling				redness	swelling
1	1	2	2	0	1
	24	2	1	0	1
	48	1	0	0	0
	72	0	0	0	0
	average	1	0.3	0	0.3	Time to reversion	72 h	48 h	-	48 h
2	1	2	2	0	1
	24	1	0	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	0.7	0	0	0	Time to reversion	72 h	24 h	-	24 h
3	1	2	1	0	0
	24	2	2	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	1	0.7	0	0	Time to reversion	72 h	48 h	-	-
average score	1	2	1.6	0	0
	24	1.6	1	0	0.3
	48	1.0	0	0	0
	72	0	0	0	0
	24+48+72	0.9	0.3	0.0	0.1

 Table 2: Individual and average irritation scores 1, 24, 48, and 72 hours after instillation of test substance (washed eyes)

Rabbit #	Time [h]	conjunctivae		iris	cornea		conjunctivae		iris	cornea
		redness	swelling				redness	swelling
4	1	1	1	0	0
	24	1	0	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	1	0.3	0	0.3	Time to reversion	72 h	24 h	-	48 h
5	1	1	1	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.7	0	0	0	Time to reversion	24 h	24 h	-	-
6	1	1	1	0	0
	24	1	0	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	1	0.7	0	0	Time to reversion	72 h	24 h	-	-
average score	1	1	1.0	0	0
	24	0.7	0	0	0
	48	0.7	0	0	0
	72	0	0	0	0
	24+48+72	0.4	0	0	0

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information

Conclusions:

The test article caused slight ocular reactions below the level of regulatory significance and is therefore considered as not irritating.

Executive summary:

The test article's potential to induce ocular irritation was investigated in six Californian rabbits. 100 mg of the test material was instilled into the left eye of each animal and ocular reactions were assessed according to the Draize scoring scheme after 1, 24, 48 and 72 hours. The eyes of three rabbits were washed 30 seconds after substance application while the other three eyes were not rinsed. The test material caused minimal to slight swelling and reddening of the conjunctiva in all six animals, with slightly increased severity in the unrinsed eyes. These effects were reversible back to normal within 72 hours the latest. Additionally, in the unrinsed eyes minimal effects to the cornea were observed, which was fully reversible within 48 hours in all animals. No other effects were observed. Based on these results, and under the test conditions chosen here, the test article is not considered to be irritating to the rabbit eye and does not require classification.