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

The test article was not sensitizing in guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982-06-07 - 1982-08-05

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

no

Type of study:

Maurer optimisation test

Justification for non-LLNA method:

Valid guinea pig data are available, no further LLNA is necessary

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: in house bred
- Age at study initiation: ca. 10 weeks
- Weight at study initiation: 283 - 377 g
- Housing: individually in Macrolon cages
- Diet: ad libitum, standard guinea pig pellets (NAFAG No. 830, Gossau SG)
- Water: ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1
- Humidity (%): 50±10
- Photoperiod (hrs dark / hrs light): 10/14

Route:

epicutaneous, open

Vehicle:

physiological saline

Remarks:

during 2nd and 3rd week the test substance was solved in a 1:1 mixture of normal vehicle and Freund complete adjuvant

Concentration / amount:

0.1 %

No.:

#1

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

0.1 %

No.:

#2

Route:

intradermal

Vehicle:

other: Vaseline

Concentration / amount:

30 %

No. of animals per dose:

20 (10/sex)

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Test groups: 2
- Control group: 1
- Site: right flank and the back
- Frequency of applications: every second day (except weekends)
- Duration: 3 weeks
- Concentrations: 0.1 %

B. CHALLENGE EXPOSURE (INTRADERMAL)
- No. of exposures: 1
- Day(s) of challenge: 10 days
- Test groups: 2
- Control group: 1
- Site: right flank and the back
- Concentrations: 0.1 %
- Evaluation (hr after challenge): 24 hours

C. CHALLENGE EXPOSURE (EPICUTANEOUS, OCCLUSIVE)
- No. of exposures: 1
- Day of challenge: 24 hours
- Test groups: 2
- Control group: 1
- Site: right flank and the back
- Concentrations: 30 %
- Evaluation (hr after challenge): 24 hours

Challenge controls:

Not available

Positive control substance(s):

not specified

Reading:

other: Reading after intradermal exposure

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Reading:

other: Reading after intradermal exposure

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 %

No. with + reactions:

0

Total no. in group:

20

Reading:

other: Reading after epicutaneous occlusive exposure

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

17

Reading:

other: Reading after epicutaneous occlusive exposure

Hours after challenge:

24

Group:

test chemical

Dose level:

30% in vaseline

No. with + reactions:

0

Total no. in group:

20

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

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.

CAS 80584-92-5:

In a dermal sensitisation study equivalent or similar to OECD guideline 406, guinea pigs (10/sex) were tested in a Freund´s complete adjuvant test. During the induction period, the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1% solution of the test substance in physiological saline. One control group was treated with the vehicle alone ("negative control"). On the first day, injections of 0.1 mL were administered onto the shaved skin of the right flank and the back, while on the following days a single intracutaneous injection was given into the back. During the second and third week of the induction period the test material was incorporated in a mixture of the normal vehicle with complete Bacto Adjuvant (vehicle : adjuvant = 1:1). Fourteen days after the last sensitizing injection, a challenge injection of 0.1 mL of a freshly prepared 0.1% solution of the test substance in physiological saline was administered onto the skin of the left flank. Twenty-four hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded. Intradermal injections of the vehicle alone failed to induce sensitization. Three animals of the control group died during the rest period between challenge I and II. The death of all three animals must be considered to be unrelated to the treatment. No positive reactions were observed after the intradermal challenge injection or the occlusive epicutaneous application. The test substance is not considered as skin sensitising according to the results of this study.

CAS 80584-91-4:

The triazine compound's potential to cause sensitization after dermal exposure was assessed in a GLP-compliant maximization test with Dunkin Hartley guinea pigs according to OECD guideline 406. In this study, the test group animals received 15 % of the test item by intradermal induction as well as 40 % of the test item for epicutaneous induction one week later for 48 hours. 0.5 % carboxy methylcelluose served as vehicle. For intradermal induction, three pairs of injections (50% FCA; test item in vehicle; test item in vehicle plus 50% FCA) were given. In the absence of irritation at dose ranging, the animals were treated with 0.5 ml of 10% sodium lauryl sulphate (SLS) one day prior to epidermal induction treatment. Epidermal challenge was performed by occlusive application for 24 h two weeks later (40% in CMC). A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period, the group was treated with the test compound. Following challenge reaction, no positive responses were noted in any animal of the test or control group. In conclusion, based on the result of this study, the test article is not considered to cause skin sensitization in guinea pigs.

CAS 102-71-6

The sensitising potential of TEA was investigated in a Guinea Pig Maximisation Test according to OECD TG 406 under GLP conditions. Based on the results of a pre-test, animals were dermally injected twice with 0.1 mL 2% TEA on day 1, followed by an epicutaneous induction (occlusive) with 0.5 mL undiluted TEA for 48 hours starting on day 9, and a dermal challenge (occlusive) with 0.5 mL 10% TEA for 24 hours on day 22. Dermal reactions were evaluated according to Draize 48 and 72 hours after the start of the dermal challenge. No clinical signs were noticed and all readings were negative.

Regarding the available human data, the positive reactions interpreted as allergic seem to be caused by exposure to TEA in cosmetics and/or topical therapeutic preparations possibly on damaged skin. The diagnosis of TEA contact sensitisation should therefore not be based on a positive patch test reaction alone but on a combination of history and – preferably – validation tests.

The negative experimental findings in animals and the level of exposure to TEA in the population, together with the low frequency of positive reactions to low TEA concentrations in patch-tested patients indicate a very low sensitisation potential in humans, and the risk of sensitisation to TEA on uncompromised skin seems to be very low.

Conclusion

The test article itself and its individual components, the triazine part and the amine, were not sensitizing in animal studies, therefore the test article is considered to be not sensitizing.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

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 under Regulation (EC) No 1272/2008.