1-isoctyloxycarbonyl ethylated 2,4,6 tris (2,4- hydroxyphenyl) -1,3,5 triazine derivatives

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Performance and Observation

To evaluate the allergenic potential of the test substance, different studies according OECD guideline 429 (CIBA 2003, 2002) and 406 (CIBA 2002b) were performed.

The first study was a lymph node assay, GLP-conform and performed according OECD guideline 429. Three groups each of four female mice were treated daily with the test item at concentrations of 5%, 10% and 25% (w/w) in acetone:olive oil, 4:1 (v/v) by topical application to the dorsum of each ear lobe (left and right) for three consecutive days. A control group of four mice was treated with the vehicle only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a scintillation counter.

No test item-related clinical signs were observed. All treated animals survived the scheduled study period. A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of radio-labelled thymidine compared with concurrent controls, as indicated by the STIMULATION INDEX (S.I.). S.I. after exposure to 5, 10 and 25% concentration of the test item was 1.1, 0.8 and 2.0, respectively.

 

The second and third study were also lymph node assays, performed according the same protocol as given for the first test. For the second study, the test animals were exposed to 5 %, 10 % and 15 % in acetone:olive oil, 4:1. In the third study, concentrations of 10 %, 25 % and 50 % in acetone:olive oil were used. Determined S.I. were 1.9, 1.2 and 0.9 and 1.4, 1.5 and 2.8, respectively.

 

In the last study, a Maximization-Test was performed in 15 (10 test and 5 control) male albino guinea pigs, in accordance with OECD Guideline 406. The intradermal induction of sensitization in the test group was performed in the nuchal region with a 5 % dilution of the test item in PEG 300 and in an emulsion of Freund's Complete Adjuvant (FCA) / physiological saline. The epidermal induction of sensitization was conducted for 48 hours under occlusion with the undiluted test item one week after the intradermal induction. Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the test item at 10% in PEG 300 and PEG 300 alone under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.

Eight out of 10 test animals showed discrete to moderate erythema at the 24-hour reading. Seven out of 10 animals were observed with discrete erythema at the 48-hour reading. No skin effect was observed in the control group.

Discussion

Three local lymph node assays in mice were performed with different concentrations of the test item. None of the test revealed a positive reaction to the test substance. However, in Maximization assay a positive reaction of the test substance to skin was determined. In the study report of this assay, no purity of the test substance was given. Therefore, it is possible that impurities caused the allergic reaction. Additionally, the substance consists of different isomeres with different molecular weights. The major part of the test article (99.6 %) has a molecular weight between 744 and 1142 g/mol and is therefore not membrane permeable.

The local lymph node assay (LLNA) is considered as a reliable and modern test system to determine the allergic potential of a substance. Three independent LLNA of the test item showed negative results. Thus, the substance is considered to be a non-skin sensitizer.

Migrated from Short description of key information:
The allergenic potential of the test item was evaluated in three local lymph node assays (LLNA) and a maximization test. All studies were GLP-conform and performed according OECD guideline 429 and 406. In the course of the LLNAs, mice were exposed to the test substance at concentrations of 5-50% dissolved in acetone:olice oil. None of the three test revealed a positive reaction to the test article. The maximization test was performed according guidelines but with a batch of unknown purity. Positive reactions to the test article on skin were determined in this assay.

Respiratory sensitisation

Endpoint conclusion

Additional information:

Migrated from Short description of key information:
The test item is a viscous liquid and therefore not inhalable. During formulation, the substance is not exposed to high temperatures whereby development of vapour can be excluded.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin sensitization under Directive 67/548/EEC,as amended for the 30th time in Directive 2008/58/EC.

                               

Classification, Labeling, 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 is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).