Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(hydroxyethyl) derivs.

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Evaluation of dermal sensitisation of Tris (2-hydroxyethyl) tallow diaminopropane, CAS 90367-27-4 (recently redefined as Amines, N-(C16-18 (even numbered) and C18-unsatd. alkyl) trimethylenedi-, ethoxylated (NLP), CAS 1290049-56-7), also referred to as Tallow-diamine3EO:

 

Tallow-diamine3EO has been tested for skin sensitisation in a Guinea pig Maximisation Test according to OECD 406 guidelines and in compliance to GLP using 20 test and 10 control animals.

Two phases were involved in the main study; an induction of a response by intradermal injection and topical application and a topical challenge of that response. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as:

Intradermal Induction    0.1% v/v in corn oil

Topical Induction          5% v/v in ethanol/water (80/20) 

Topical Challenge         5% in acetone.

Possibly the induction concentration were too high as marked local reactions at the intradermal injection sites were noted in a few animals of the treated group, between days 10 and 23. Therefore, one of these animals had actually to be sacrificed on day 21 for ethical reasons.

Upon challenge, no cutaneous reactions were observed in the animals of the control group.

In the treated group, at the 24-hour reading, a discrete erythema was noted in 5/19 animals. At the 48-hour reading, a discrete or moderate erythema was recorded in 3/19 and 2/19 animals, respectively. Dryness of the skin, which masked the evaluation of the erythema in one animal, was also observed in 5/19 animals at the 48-hour reading.

The cutaneous reactions observed at the 48-hour reading in 5/19 animals of the treated group were attributed to delayed contact hypersensitivity.

Although borderline for classification, the reactions were very mild, especially considering that 2 animals that showed erythema at 24 hours showed no erythema at 48 hours, and two orther animals that did not show erythema before, showed additionally erythema at 48 hours. Additionally, the reactions following induction were very severe in some animals, requiring even the sacrifice of one animal.

 

There are additional old maximisation studies on a substance called TL 455 / TL 455 oil that is supposed to be or contain Tallow-diamine3EO. So far no confirmation for this was obtained and therefore the validity of these studies is uncertain. Besides, the applied scoring methods deviate from current guidelines and a control group is lacking. These studies show the following rates of positive reacting animals:

Rate of positive reaction	Conclusion for classification
- 5/10 (50%)	positive
- 4/10 (40%)	positive
- 0/10 (0%)	negative
- 9/20 (45%)	positive

 

Support for non-sensitising properties comes from a recent study that evaluated skin sensitising properties ofOleyl-diamine3EO. Oleyl-diamine3EO is comparable to Tallow-diamine3EO, except that the level of unsaturation in the alkyl chain is higher. These study results are therefore fully applicable to Tallow-diamine3EO .

The study was performed in Guinea pigs according to OECD 406 Maximisation test method, and in compliance to GLP, using ten test and five control animals. Two phases were involved in the main study; an induction of a response by intradermal injection and topical application and a topical challenge of that response. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as:

Intradermal Induction    0.1% v/v in arachis oil

Topical Induction          5% v/v in arachis oil 

Topical Challenge         2% and 1% v/v in arachis oil

Under the conditions of the test, the test material produced a 0% (0/10) sensitisation rate.

Consequently, Oleyl-diamine3EO is considered not to possess sensitising properties.

 

 

Further information that should be considered:

- These substances are corrosive to skin. - Very possible that the corrosive/irritant properties are causing marginal positive results in sensitisation studies (increased irritation reaction following repeated irritation)

- The profiling of these substances do not indicate reactivity to protein; No alerts for sensitisation are given by QSARs on these structures (DEREK v.3.01)

- No concerns from structural analogues; specifically Oleyl-diamine3EO

- No concerns have been raised from the use/application of these products with respect to the occurrence of sensitisation (or contact dermatitis).

 

Migrated from Short description of key information:

A recent GLP Guinea pig study following the Magnusson and Kligman Maximisation Method according to OECD guidelines indicated that Tallow-diamine3EO was mildly sensitising to skin, but does not need classification. An additional also recent GLP Maximisation has shown Oleyl-diamine3EO not to be sensitising to skin.

Justification for selection of skin sensitisation endpoint:

Most relevant study of high quality.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

There is no information on respiratory sensitisation. However, no concerns are expected.

As chemical respiratory sensitisers also elicit positive results in predictive tests for contact sensitisation, a negative outcome for dermal sensitisation is also predictive for non respiratory sensitisation of the substance.

Additionally, the likelihood for exposure via inhalation and thus becoming sensitised to Oleyl-diamine3EO, is very low, based on the high boiling point (> 300 °C) and very low vapour pressure (< 0.0015 Pa at 20°C) and use that is limited to industrial and professional users and which does not involve the forming of aerosols, particles or droplets of an inhalable size.

Migrated from Short description of key information:

As suggested in REACH guidance R7a. (R.7.3.5 Information and its sources on respiratory sensitisation), the negative results on skin sensitisation from an adequately performed appropriate test can also be regarded as lacking the potential to cause allergic sensitisation of the respiratory tract.

Justification for classification or non-classification

Tallow-diamine3EO was mildly sensitising to skin in an Guinea pig Maximisation Test, but did just not trigger the criteria for classification.

Oleyl-diamine3EO has shown to be non-sensitising in a similar adequately performed Guinea pig study, indicating that the structure does not need to be classified for sensitisation.

 

In conclusion:

- Available data from animal studies shows possible borderline sensitisation results, although (just) not resulting to need for classification.

- These substances are corrosive to skin. Very possible that the corrosive/irritant properties are causing the marginal positive results in sensitisation studies (increased irritation reaction following repeated irritation)

- The profiling of these substance do not indicate reactivity to protein

- No concerns from structural analogues, specifically Oleyl-diamine3EO

- So far we have no concerns from the use/application of these products with respect to sensitisation

- Corrosive substances do not need (in vivo) testing for REACH

Following the WoE, Tallow-dieamine3EO does not need to be classified for sensitisation.

 

Negative results for skin sensitisation can also be regarded as indicating the lack of the potential to cause allergic sensitisation of the respiratory tract.