N,N-bis(trimethylsilyl)aminopropylmethyldiethoxysilane

Endpoint summary

Description of key information

In the key skin sensitisation study, conducted according to OECD TG 429 and in compliance with GLP, the test material, N,N-bistrimethylsilyl)aminopropylmethyldiethoxysilane, was reported to be a skin sensitiser (Huntingdon, 2003).

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In the key skin sensitisation study, conducted according to OECD TG 429 and in compliance with GLP, the test material, N,N-bis(trimethylsilyl)aminopropylmethyldiethoxysilane, was reported to be a skin sensitiser (Huntingdon, 2003).

Based on results from a preliminary study, the chosen concentrations for the main study were 25, 50 and 100% of test substance in dimethylformamide. In each phase of the study the mice were treated by daily application of 25 µl of each concentration, or vehicle control, to the dorsal surface of both ears for three consecutive days. No deaths occurred during the study period. No clinical signs of toxicity were noted in any of the animals. Five days following the first topical application of the test substance (day 6) all mice were injected via the tail vein with 250 µl of phosphate buffered saline containing ³H-methyl thymidine giving a normal 20 µCi to each mouse. The proliferative response of the lymph node cells (LNC) from the draining auricular lymph nodes was assessed five days following the initial application by measurement of the incorporation of ³H-methyl thymidine by β-scintillation counting of LNC suspensions. The response was expressed as radioactive disintegrations per minute per lumph node and as the ratio of ³H-methyl Thymidine incorporation into LNC of test nodes relative to that recorded for control ratios (SI = 27.1; EC3 = 10.96).

The guideline (OECD TG 429) acknowledges the limits of the LLNA, and states that there are instances where ‘test substance classes or substances containing functional groups shown to act as potential confounders’ make the use of guinea pig tests more appropriate. It is concluded that the LLNA is not applicable where the properties of the test material cause interference in the accuracy of the LLNA (OECD 2010). The statement in the OECD TG 429 is given with reference to the findings of Basketter et al. (2009a), who demonstrated false positives in silicon based substances which had previously been demonstrated to be non-sensitisers in the guinea pig maximisation test (GPMT). 

The importance of available evidence from guinea pig results, consideration of chemical reactivity, epidermal bioavailability and clinical and experimental human data are emphasised as central to reaching appropriate regulatory decisions for substances which have been shown to fall outside the specificity of the LLNA (Basketter et al., 2009b). The non-applicability of the LLNA for silicone based substances has also been demonstrated by Petry et al. (2012). 

The sensitisation potential of polyfunctional silicone materials was tested in a comparative study investigating the GPMT and the LLNA assays, which found the five tested substances to be negative in the GPMT whereas they were concluded to be weak to moderate skin sensitisers in the LLNA (Petry et al., 2012).

In addition, research conducted by Petry et al. (2017) shows that in vitro skin sensitisation tests with validated OECD test guidelines are not suitable for aminofunctional silicone substances as they only have limited predictability for this type of substance.

Therefore, there is a concern that the LLNA is not an appropriate test for silicon based substances. However, in the interest of animal welfare, the current positive result is accepted for the registered substance.

References:

Basketter D, Ball N, Cagen S, Carillo JC, Certa H, Eigler D, Garcia C, Esch H, Graham C, Haux C, Kreiling R, Mehling A (2009a). Application of weight of evidence approach to assessing discordant sensitisation datasets: implication for REACH. Reg. Toxicol. Pharmacol., 55, 90-96.

Basketter D, McFadden JF, Gerberick F, Cockshott A, Kimber I (2009b) Nothing is perfect, not even the local lymph node assay: a commentary and the implications for REACH.Contact Dermatitis, 60, 65-69.

Petry, T., Bosch, A., Coste, X., Dupuis, V., Eigler, D., Germain, P. (2012). An assessment of the skin sensitisation hazard of a group of polyfunctional silicones using a weight of evidence approach. Regulatory Toxicology and Pharmacology, 64, 305-314.

Petry, T., Bosch, A., Coste, X., Eigler, D., Germain, P., Seidel, S. and Jean, P. A. Evaluation of in vitro assays for the assessment of the skin sensitization hazard of functional polysiloxanes and silanes (Regulatory Toxicology and Pharmacology, 2017, 84, 64-76)

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data for N,N-bis(trimethylsilyl)aminopropylmethyldiethoxysilane, classfication for skin sensitisation Category 1B, H317: "May cause an allergic skin reaction" is required according to Regulation (EC) No. 1282/2008.