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

Endpoint summary

Description of key information

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

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin 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 analytical purity of the test substance was given. The animals were treated on intact and abraded skin for 24 h under occlusive conditions, and no reading was performed after 48 h.

Qualifier:

according to guideline

Guideline:

other: "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(adopted 2002)

Deviations:

yes

Remarks:

Six animals were used (intact and abraded skin); 24 h treatment under occlusive conditions; No reading after 48 hours

GLP compliance:

no

Species:

rabbit

Strain:

Californian

Details on test animals or test system 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.

Type of coverage:

occlusive

Preparation of test site:

other: shaved, intact and abraded skin

Vehicle:

other: Polyethylene glycol (50% aqueous solution)

Controls:

not specified

Amount / concentration applied:

1 mL (corresponding to 500 mg test substance)

Duration of treatment / exposure:

24 hours

Observation period:

14 days intended, however study was terminated after 72 h because of negative results

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: back, 2.5 cm x 2.5 cm
- % coverage: 10%
- Type of wrap if used: gauze pad covered with aluminum foil (covered by "COBAN" self adhesive bandage)

REMOVAL OF TEST SUBSTANCE
- Washing: no
- Time after start of exposure: 24 h

SCORING SYSTEM:
Draize scheme

SCORING TIME POINTS:
24 h: directly after patch removal
72 h: 48 h after patch removal

Irritation parameter:

erythema score

Basis:

mean

Remarks:

intact skin

Time point:

24 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

intact skin

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

intact skin

Time point:

24 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

intact skin

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

abraded skin

Time point:

24 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

abraded skin

Time point:

72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

abraded skin

Time point:

24 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

abraded skin

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No dermal reactions were recorded when tested on intact skin, all scores for erythema and edema were zero in all six animals. One animal showed minimal redness after 24 hours (score = 1) when treated on abraded skin, reversible within 72 hours.

Interpretation of results:

not irritating

Remarks:

Migrated information

Conclusions:

The test article did not cause any signs of irritation when applied occlusively for 4 hours to the intact rabbit skin.

Executive summary:

The test article's potential to cause dermal irritation was assessed with an in vivo irritation study performed with six Californian rabbits. All animals were treated occlusively with 500 mg test material for 24 hours on either intact or abraded skin. The dermal reactions were recorded after 24 and 72 hours. All scores for erythema and edema were zero in all animals at all time points when treated on intact skin. Similar results were observed on abraded skin, only one animal showed minimal erythema formation at the 24 hour time point reversible within 72 hours. Therefore, based on the result of this study, the test article is not considered to be a skin irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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.

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

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

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.

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.

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

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Remarks on result:

other: unwashed eyes

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

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

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

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Remarks on result:

other: washed eyes

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

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.

 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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
key study

Justification for selection of eye irritation endpoint:
key study
Conclusion: The test article caused slight ocular reactions below the level of regulatory significance and is therefore considered as not irritating.

Justification for classification or non-classification

According to the criteria of Regulation (EC) No.: 1272/2008, the substance is not classified with regard to Skin corrosion/Irritation and Serious damage to eyes/eye irritation. Also, according to the criteria specified by Directive 67/548/EEC the substance is not classified with regard to these hazard classes.