6,6',6''-(1,3,5-triazine-2,4,6-triyltriimino)trihexanoic acid, compound with 2,2',2''-nitrilotriethanol (1:3)

Endpoint summary

Description of key information

Minimal irritation was observed in both skin and eyes, well below the level of significance. The test article is considered to be not irritating to skin and eye.

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:

1982-09-06 - 1982-09-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other: EPA guideline: Paragraph 163.81-5 "Primary dermal irritation study". Federal Register, Vol 43 No. 163, August 22, 1978

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, 4414 Fuellinsdorf, Switzerland
- Weight at study initiation: 2 - 3 kg
- Housing: individually in metal cages
- Diet: ad libitum (NAFAG, No. 814 Tox, NAFAG AG, Gossau, Switzerland)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated skin site served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: entire back and the flank
- Type of wrap if used: impermeable patches fastened with adhesive tape

SCORING SYSTEM:
Erythyma and eschar formation
No erythema 0
Very slight erythema (barely perceptible 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4
Total possible erythema score 4

Edema formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised more than 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond area of exposure 4
Total possible edema score 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.77

Max. score:

4

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.94

Max. score:

4

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: abraded skin

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.39

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: abraded skin

Irritant / corrosive response data:

The test substance caused slight irritation to the intact and abraded skin (please refer to the table at "Any other information on results incl. tables" showing the single results of the intact skin).

Irritation parameter	Basis	Time point	Score	Max. score	Reversibility	Remarks
Erythema score	Animal #1	24, 48, 72 hours	0.66	4	Fully reversible after 48 hours	Intact skin
Edema score	Animal #1	24, 48, 72 hours	0	4	-	Intact skin
Erythema score	Animal #2	24, 48, 72 hours	0.33	4	Fully reversible after 48 hours	Intact skin
Edema score	Animal #2	24, 48, 72 hours	0	4	-	Intact skin
Erythema score	Animal #3	24, 48, 72 hours	0.66	4	Fully reversible after 48 hours	Intact skin
Edema score	Animal #3	24, 48, 72 hours	0.66	4	Fully reversible after 48 hours	Intact skin
Erythema score	Animal #4	24, 48, 72 hours	1	4	Fully reversible after 72 hours	Intact skin
Edema score	Animal #4	24, 48, 72 hours	1	4	Fully reversible after 72 hours	Intact skin
Erythema score	Animal #5	24, 48, 72 hours	1.33	4	Fully reversible after 72 hours	Intact skin
Edema score	Animal #5	24, 48, 72 hours	0.33	4	Fully reversible after 48 hours	Intact skin
Erythema score	Animal #6	24, 48, 72 hours	1.33	4	Fully reversible after 72 hours	Intact skin
Edema score	Animal #6	24, 48, 72 hours	0.33	4	Fully reversible after 48 hours	Intact skin

Interpretation of results:

GHS criteria not met

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:

1982-09-06 - 1982-09-17

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other: Environmental Protection Agency (EPA) Paragraph 163. 81-5 "Primary eye irritation study". Federal Register, Vol. 43 No. 163, August 22, 1978

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, 4414 Fuellinsdorf, Switzerland
- Weight at study initiation: 2-3 kg
- Housing: individually in metal cages
- Diet: ad libitum (Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, Switzerland)
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent eye served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:

In 3 of 6 rabbits approx. 30 sec after the treatment the treated eye was rinsed. The other three rabbits stayed treated until the end of the observation period.

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: 3 out of 6 rabbits were rinsed with 10 mL physiological saline.
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 , 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: Eye was not rinsed.

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: Eye was not rinsed.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 , 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: Eye was rinsed.

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 , 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: Eye was rinsed.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48 , 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Eye was not rinsed.

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48 , 72 hours

Score:

0.66

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Eye was not rinsed.

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48 , 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Eye was not rinsed.

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

other: 24, 48 , 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Eye was rinsed.

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

other: 24, 48 , 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Eye was rinsed.

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

other: 24, 48 , 72 hours

Score:

0.66

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Eye was rinsed.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48 , 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Eye was not rinsed.

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48 , 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Eye was not rinsed.

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48 , 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Eye was not rinsed.

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

other: 24, 48 , 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Eye was rinsed.

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

other: 24, 48 , 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Eye was rinsed.

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

other: 24, 48 , 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: Eye was rinsed.

Irritant / corrosive response data:

Minimal irritation was observed in the unrinsed eye.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The substance is a salt which is a reaction product of an acid (triazine compound, CAS 80584-91-2) and a base (triethaonoleamine, TEA, CAS 102-71-6) that retain their ionic character. Under aqueous conditions it is expected to be present in its dissociated form. Therefore, the individual components of the salt are assessed separately. Data on the salt itself are also provided.

Skin irriation

CAS 80584-92-5:

Following the experimental design according to EPA Paragraph 163.81-5 "Primary dermal irritation study", Federal Register, Vol 43 No. 163, August 22, 1978, 0.5 mL of the test substance were applied to the back of six New Zealand White rabbits. The skin sites were occlusively covered and the dressings were removed after 24 hours. The test animals were observed for a total of 7 days. Irritation reactions were scored by the method of Draize. Very slight to slight erythema was observed in all six animals after 24 hours. In three animals, the irritation lasted up to 48 hours. Very slight to slight edema was observed in four animals after 24 hours. In one animal, very slight edema was still observed after 48 hours. Irritation signs had resolved after 72 hours in all animals.

CAS 80584-91-4:

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. No reading was performed after 48 hours. The observation period of the study was shortened to 72 hours, probably due to the negative findings observed after the reading at 72 hours. Nevertheless, the study was considered suitable for classification. 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.

CAS 102-71-6

In a skin irritation test performed according to OECD guideline 404 (not GLP-compliant), three rabbits were exposed to TEA using an occlusive application for 4 hours. Erythema and edema were scored at 4, 24, 48, and 72 hours and the mean score was 0. The test substance was not a skin irritant under the conditions of this study. Several other studies, in which rabbits were exposed for up to 20 hours, yielded similar results.

Eye irritation

CAS 80584-92-5:

Following the experimental design according to EPA Paragraph 163. 81-5 "Primary eye irritation study". Federal Register, Vol. 43 No. 163, August 22, 1978, 0.1 mL of the test substance was instilled in the conjunctival sac of six rabbits. The eyes were not washed in three out of six animals. The treated eye of the other three animals was rinsed after approximately 30 seconds of treatment. Animals were observed for 8 days. Irritation was scored by the method of Draize et al.. The application to the intact eye resulted in redness in all animals after 24 hours (rinsed and unrinsed eye). Chemosis was observed in five out of six animals after 24 hours. Redness persisted until 72 hours after exposure, but had resolved by the end of the study period. Chemosis was resolved after 48 hours. No corneal opacity or iritis was observed in any of the six animals. According to the reversible results, the test substance is considered to cause minimal irritation in the intact eye, but is not considered for classification.

CAS 80584-91-4:

The test article's potential to induce ocular irritation was investigated in six Californian rabbits. 100 mg of the test material was instilled unchanged 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 right eyes served as control. 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. The observation period of the study was shortened to 72 hours, probably due to the negative findings observed after the reading at 72 hours (conform to guideline). 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.

CAS 102-71-6:

In an eye irritation test equivalent to OECD guideline 405 (non GLP-compliant), 6 rabbits/dose were exposed to undiluted TEA at dose volumes of 0.01, 0.03, and 0.1 ml. The eyes were not irrigated. Eyes were examined and scored according to Draize et al. (1944) 1, 3, 7, 14, and 21 days after dosing. TEA was not an eye irritant under the conditions of this study. The same conclusion was reached in an eye irritation test (non GLP-compliant, according to internal BASF standards), in which 50 µl of the test substance was instilled into the eyes of 2 rabbits, and irritation was scored 10 min, 1 and 24 hours and 8 days after administration. In addition, no eye irritation was observed in response to the application of 0.5 mL 20% TEA in water at pH 10 and pH 8. Two other studies (performed according to internal BASF standards) demonstrated some mild irritation due to the application of 50 µl undiluted TEA to the rabbit eye, which was not fully reversible within 8 days in one animal. Overall, TEA is judged not to be irritating to the eyes.

Conclusion

The test article itself and its individual components, the triazine part and the amine, were not irritating to both skin and eyes. Slight irritating effects well below the level of significance were observed with the salt, however similar slight reactions were also reported for the individual components in some reports. Based on the results of the available studies, the test article is considered to be not irritating to both skin and eyes.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled as eye or skin irritating under Regulation (EC) No 1272/2008.