Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, acetates

Endpoint summary

Description of key information

No toxicokinetic studies with the test substance are available. Therefore, a study with DHTDMAC (CAS 61789-80-8) was used as read across to fulfil the data gap for the test substance. The primary component of all substances provide complete coverage of 68334-33-8. 68334-33-8 shares high structural similarity with 61789-80-8, 68783-78-8, 107-64-2, and 112-02-7. As 68334-33-8 is a UVCB its components encapsulate the other substances except for the counter ion (Cl-). In solution, the counter ions will dissociate from the parent structures. Therefore, we are comparing substances of equivalent nature. CAS 107-64-2 represents the C18 boundary of the 61789-80-8. Ignoring the salt component CAS 61789-80-8 is equivalent to CAS 68334-33-8. 68783-78-8 is a worst case of both 68334-33-8 and 61789-80-8 since it is unsaturated and SP2 characterized carbon-carbon bonds are of higher reactivity. The primary component of CAS 112-02-7 is a substructure of all the other substances. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach.

The available in vivo dermal absorption study supported by the physico-chemical properties of the substance and the toxicological data using dermal route provide evidence that the dermal absorption is very low. Therefore, and in accordance with ECHA guidance R7-12, the default value of 10% skin absorption is used for the risk characterization.

Additional information

After dermal administration of 10 mg (˜ 30µCi) 14C-labelled dialkyl (octadecyl) dimethylammonium chloride to the back of each of four rabbits over a 5.8 cm area most of the radioactivity remained at the site of application (88 ± 2.3%). Only traces of administered radioactivity were detected over a 72 h-period in urine (0.15 %), faeces (0.16 %), exhaled carbon dioxide (0.27 %), other skin (0.2%) and cage wash (0.3%). From the data it was concluded that dioctadecyldimethylammonium chloride does not effectively penetrate the skin (Drotman, 1977). The quality of the study was evaluated by an expert panel of the American Chemistry Council who concluded that the endpoint has been adequately characterized (Klimisch 2D, reliable with restrictions). The study of Drotman (1977) predated GLP but followed accepted scientific standards at the time of performance.

In in vitro studies on human abdominal skin, no absorption of Dioctadecyldimethylammonium chloride was detected (no further information was given) (Drotman, 1977). These experimental findings are supported by the physicochemical properties of the test substance being insoluble in water and in an ionic state which limits absorption across the skin. Furthermore, the test substance has a molecular weight of about 650 g/mol, whereas usually only substances with lower molecular weight are absorbed. No signs of systemic toxicity were observed after acute dermal exposure onto the rat skin indicating that dermal absorption if any, is likely to be very low. Moreover, the substance is not a skin sensitizer. Based on the experimental data, the physicochemical properties of the substance, the results of the acute dermal toxicity and the skin sensitization studies, the dermal absorption and the concentration of the test substance in the skin can be assumed to be very low.

 

Discussion on absorption rate:

Experimental study on the dermal absorption with the read-across substance has revealed, that the absorption rate of this quaternary compound is very low. An increase of the concentration in the skin following dermal application was also not observed. For risk characterisation, the default factor of 10% skin absorption is used. This default factor has been selected taking into account the physico-chemical properties of the substance and the other toxicological data using dermal route.