Carbamic acid, N-[[5-[[[2-[2-(dimethylamino)ethoxy]ethoxy]carbonyl]amino]-1,3,3-trimethylcyclohexyl]methyl]-, 2-[2-(dimethylamino)ethoxy]ethyl ester

Endpoint summary

Additional information

There is no available study for toxicokinetics, metabolism and distribution of UAX-1179. However, based on the available data of the substance an expert judgement of the toxicokinetic behaviour of UAX-1179 was conducted.

The substance is a viscous liquid (molecular weight 488.67 g/mol) with a high water solubility (> 525 g/L at 20 °C) and a log Pow of 1.4. The substance shows no significant hydrolytic degradation at pH 4, 7, and 9. The vapour pressure of UAX-1179 is 0.0014 Pa at 20 °C.

The acute oral toxicity of the substance is moderate (200 < LD50 < 2000 mg/kg). At 2000 mg/kg bw, two out of three animals died within two hours of treatment, indicating bioavailablility of the substance via the oral route. The early onset of toxic effects indicates a rapid absorption of the substance in the stomach.

The molecular weight (488.67 g/mol) and the log Pow of the substance (1.4) indicates a facilitated passive diffusion through the lipophilic phase of the gastric mucous membrane. It also has to be considered that ionisation of the substance at low pH (e.g. protonization of amine groups) may take place and influence the location of resorption in the gastrointestinal duct.

In an acute dermal toxicity study, dose levels of up to 2000 mg/kg bw UAX-1179 were administered to rats. The LD50 level was not attained even with these very high doses, indicating primarily a low dermal toxicity. In contrast, acute toxicity/mortality occured after ingestion of UAX-1179; therefore is is assumed, that the bioavailability of UAX-1179 by the dermal route is much lesser than the bioavailablilty by the oral route.

Since it is generally accepted that substances with a log Pow ranging from 0.1 to 6 and a molecular weight below 500 g/mol are able to penetrate the skin, it is to be expected that the substance will be absorbed to some extent through the skin. This assumption is corroborated by the skin sensitising effect observed.

UAX-1179 has a low vapour pressure of 0.0014 Pa at 20°C indicating that inhalation as a vapour will be negligible. Also, aerosol exposure can be excluded, as spray application is not given for the substance. Therefore, inhalation is not a relevant route of exposure.

Since the substance is highly water soluble, though slightly lipophilic (log Pow 1.4), an accumulation in fatty tissues is not probable.

E.g. oxidative dealkylation of the amino- and ether-groups may occur. The formed metabolites of the substance might lead to toxic effects as indicated by a dose-related increase in LDH and AST activity in hepatocytes and dose- related decrease of reticulocytes in the blood. Thus, the substance is anticipated to be distributed from the portal vein blood into the liver, and further into the blood plasma, bone marrow and other organs. The generated metabolites are expected to be excreted mainly in the urine.