1-Butanamine, N-[3-(trimethoxysilyl)propyl]-, reaction products with (trimethoxysilyl)-N-[(trimethoxysilyl)propyl]-1-propanamine and 1,6-diisocyanatohexane homopolymer

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In a GLP compliant study according to OECD guideline 429 the possible skin sensitization potential of iGloss Crosslinker (ZQ54-2211) was studied (Harlan CCR, 2012). Three groups each of five female mice were treated daily with the test item at concentrations of 2.5, 5, and 10% (w/w) in acetone:olive oil (4+1 v/v) by topical application to the dorsum of each ear once daily for three consecutive days. The test item could be dissolved in the vehicle. The appropriateness of the used concentrations was previously assessed by three pre-experiments. Two further groups each of five mice were treated with the vehicle only or with the positive control at 25% (w/v). 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 were excised, pooled per animal and immediately weighed. Furthermore, after excision of the lymph nodes, both ears of the mice were punched at the apical area using a biopsy punch and were immediately weighed pooled per animal using an analytical balance. Afterwards, single cell suspensions of lymph node cells were prepared from lymph nodes pooled per animal. An aliquot of each cell suspension was used for determination of lymph node cell count. Subsequently the suspensions were washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of³H-methyl thymidine measured in a ß-scintillation counter. All treated animals survived the scheduled study period and no signs of systemic toxicity were observed. On day 2, an erythema of the ear skin (Score 1) was observed in all animals treated with 10% test item concentration. A statistically significant increase in ear weights was observed in the low and the high dose group in comparison to the vehicle control group (p<0.05). Furthermore, for BALB/c mice, a cutoff-value of 1.1 was reported for a positive response of the ear weight index regarding ear skin irritation. The indices determined for the low and high dose group exceeded this threshold (indices of 1.2). A test item is regarded as a sensitiser in the LLNA if exposure to one or more test item concentration results in a 3-fold or greater increase in incorporation of³HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.). The estimated test item concentration required to produce a S.I. of 3 is referred to as the EC3 value.

In this study Stimulation Indices (S.I.) of 2.81, 5.96, and 10.36 were determined with the test item at concentrations of 2.5, 5, and 10% (w/w) in acetone:olive oil (4+1 v/v) and an EC3 value of 2.7% (w/w) was calculated. A statistically significant increase in mean DPM value, lymph node weight, and lymph node cell count was observed in all test item treated groups in comparison to the vehicle control group (p<0.05). A clear dose response was observed in all parameters. For BALB/c mice, a cutoff-value for the lymph node cell count index of 1.55 was reported for a positive response. The indices determined for the lymph node cell count were exceed in the mid and high dose group (index of 2.1 and 2.8, respectively) and therefore considered to be biologically relevant. The S.I. determined with the positive control item at 25% was 10.77, demonstrating the validity of the study. Furthermore, a statistically significant increase in DPM value and also in lymph node weight and -cell count (p<0.05) was observed here in comparison to the acetone:olive oil (4+1 v/v) vehicle control group, corroborating this result. Also, the cutoff value for a positive response of the lymph node cell count index of 1.55 was exceeded in this group (index: 3.44). Although a certain amount of skin irritation was observed (see above mentioned results for the ear weight determination and ear weight index), it was unlikely that irritation had an influence on lymphocyte proliferation, as a Stimulation Index above the threshold value of 3 was also obtained in the mid dose, where no statistically significant or biologically relevant amount of irritation had been noted. The test item iGloss Crosslinker (ZQ54-2211) was a skin sensitizer under the test conditions of this study.

Migrated from Short description of key information:
LLNA (OECD 429): sensitizing (Harlan, 2012)

Justification for classification or non-classification

According to the findings of the available studies, the test substance has to be classified R43 (Directive 67/548/EEC) and Skin sensitisation Cat. 1B (CLP).