N,N-dimethyl-alkyl-1-amines, reaction products with alkali hydroxide and chloroacetic acid

Endpoint summary

Description of key information

Human irritation: irritating (human patch test) 
Human sensitisation: not sensitising (human patch test, medical monitoring) 
Human dermal absorption (0.4% of applied dose within 30 minutes)

Additional information

There is no data available on the skin irritation, skin sensitisation and dermal absorption of N,N-dimethyl-alkyl-1-amines, reaction products with alkali hydroxide and chloroacetic acid in humans. However, there is reliable data for the structural related substance CAS 683-10-3. The target substance and the source substances show pronounced structural and physico-chemical similarities. Therefore, read-across was performed based on an analogue approach. For a detailed justification of the analogue approach, please refer to section 13 of the technical dossier.

 

Several sources revealing data on skin irritation, skin sensitisation and dermal absorption in humans are available for CAS 683-10-3, the C12-betaine, which is the most frequently used betaine and which is representative for the category due to its occurrence in all substances in the category in varying amounts. Therefore, read-across of exposure-related observations in humans from CAS 683-10-3 is justified. Data from several human closed patch tests (Basketter et al., 1997; Haskell Laboratory, 1963) demonstrate skin irritations in humans ranging from mild to strong under occlusive conditions even with concentrations as low as 1%. In contrast, exposure to 0.1% under open conditions did not induce any positive skin reactions (Haskell Laboratory, 1963).

Information on skin sensitisation in humans is available from a closed human patch test with CAS 683-10-3 (Haskell Laboratory, 1963). After an induction period of 6 days with 0.1% of active ingredient, followed by a treatment-free period of 10 days, the volunteers were challenged under occlusive conditions for 24 hours. No reactions were observed immediately after challenge; during the next 4 days only irritation reactions were observed.

This finding was further supported by industrial medical monitoring data (InfraServ GmbH & Co. Gendorf KG, 2009). Workers involved in the production of CAS 683-10-3 are routinely checked every 3 years for signs of skin sensitisation, respiratory irritation, skin irritation and eye irritation. The last check had been carried out in 2009; during these examinations no signs of the aforementioned disorders have been observed which were related to the test substance.

Moreover, a study focusing on dermal uptake of C12BET (i.e. CAS 683-10-3) into human skin and the effects of surfactants on skin barrier function (Bucks et al., 1993) demonstrated that only up to 0.4% of the applied dose was absorbed within 30 minutes of exposure, with absorbance being dependent on the concentration applied. Tape stripping of the skin revealed that the administered test substance was primarily located in the outer stratum corneum layer.