Hexane, 1,6-diisocyanato, homopolymer, N-butyl-1-butanamine-blocked

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a GLP compliant study according to OECD guideline 429 the possible skin sensitisation potential of Hexane, 1,6-diisocyanato, homopolymer, N-butyl-1-butanamine-blocked was studied (Harlan CCR, 2012). Three groups each of five female mice were treated once daily with the test item at concentrations of 2.5, 5 and 10% (w/w) in dimethylformamide by topical application to the dorsum of each ear for three consecutive days. The test item could be dissolved in the vehicle. The appropriateness of the used concentrations was previously assessed by two pre-experiments. A control group of five mice was treated with the vehicle (dimethylformamide) 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 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 of ³H-methyl thymidine measured in a β-scintillation counter. The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed. From day 2 to day 6, an erythema of the ear skin was observed in the high and the mid dose group (5%: Score 1, 10%: Score 2 on day 2-4, Score 1 on day 5 and 6). In the low dose group, an erythema Score 1 was observed from day 2 to day 4. A statistically significant increase in ear weights was observed in the mid and high dose group in comparison to the vehicle control group (p<0.05). However, the cutoff-value (1.1) of the ear weight index for a positive response regarding ear skin irritation reported for BALB/c mice was not exceeded in any dose group. As the mean value of the groups did not exceed the range of historical vehicle control data for the ear weight, the observed increase in ear weight was considered to be not biologically relevant. 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 of ³HTdR 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 1.40, 1.44, and 1.60 were determined with the test item at concentrations of 2.5, 5, and 10% (w/w) in dimethylformamide, respectively. An EC3 value could not be calculated as none of the determined S.I.s exceeded the threshold value of 3 for a positive response. A statistically significant or biologically relevant increase in DPM value and also in lymph node weight and cell count was not observed in any dose group in comparison to the vehicle control group. Furthermore, the cutoff-value for a positive response regarding the lymph node cell count index of 1.55 reported for BALB/c mice was not exceeded in any dose group. An outlier was identified in the mid dose group (DPM value determined for animal number 15). The corresponding lymph node weight and –cell count values did not confirm the result of the DPM value. The data determined for animal 15 were thus excluded from the calculation of the mean DPM value and the Stimulation Index as well as from the calculation of body weights, ear weights, lymph node weights, and lymph node cell counts of the group. However, exclusion of the outlier did not change the overall test result. The test item Hexane, 1,6-diisocyanato, homopolymer, N-butyl-1-butanamine-blocked was not a skin sensitiserunder the test conditions of this study.

Migrated from Short description of key information:
LLNA (Harlan, 2012): not sensitizing

Justification for classification or non-classification

Based on the available data, the test substance is not classified with regard to skin sensitisation according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP), respectively.