[No public or meaningful name is available]

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: toxicokinetics assessment

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The assessment of the toxicokinetics of 'Ester Adipic Acid and Neodecanoic acid, 2-oxiranylmethyl ester' is based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

Principles of method if other than guideline:

assessment on toxicokinetics

The remarks on the toxicokinetics are based on physico-chemical properties of the compound and on toxicological data (Tegethoff, 2019). Experimental toxicokinetic studies were not performed.

 

Additional information

The following remarks on the toxicokinetics of 'Ester Adipic Acid and Neodecanoic acid, 2-oxiranylmethyl ester' are based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

The UVCB substance is a clear, viscous organic liquid with a low vapour pressure under normal ambient conditions (3.08 x 10-15 Pa at 20 °C). No spray applications are intended.  

The physico-chemical characteristics of the substance, as low water solubility (below 1 mg/L), high log Pow of 5.5 and a molecular mass of > 600 g/mol for the main component, are not favourable for intestinal absorption after oral intake via passive diffusion. However, uptake by micellular solubilisation may be of importance for such highly lipophilic compounds.

A single oral dose of 2000 mg/kg bw was tolerated in rats without mortalities, effects on body weight development and gross pathological findings. However, transiently occurring clinical signs point to systemic availability after oral administration. In a study with repeated oral exposure (OECD 422) clinical signs were observed in the pilot phase of the study at high doses. In the main study effects on male kidneys confirmed systemic availability via gastro-intestinal tract.

Because of the high lipophilicity of the substance accumulation of the compound in fatty tissues is not unlikely. The results of the OECD 422 study, in which oral doses up to 500 mg/kg bw were applied for 29 days to male or up to 64 days to female rats, do not reveal indications of a significant accumulation potential of the substance.

Due to the physico-chemical characteristics of the substance no appreciable dermal or mucosal absorption is anticipated. This is confirmed by an acute limit dose study on rats (OECD 402) with occlusive dermal exposure over 24 hours, in which no signs of local or systemic toxicity were observed. In vitro skin and in vitro/ex vivo eye irritation studies did not reveal any signs of local toxicity as well. Additionally, low skin permeability is predicted in the Toolbox (Schlecker, 2019). Therefore, the inconclusive data base for skin sensitization in chemico/in vitro is expected not to be relevant for the in vivo situation.

Results of in vitro genotoxicity tests in bacteria (OECD 471) showed that ‘Ester adipic acid and neodecanoic acid, 2-oxiranylmethyl ester’ contains a minor constituent, i.e. 2,3-epoxypropyl neodecanoate (EC-No. 247-979-2 / CAS-No. 26761-45-5), that exerts mutagenic effects in the Ames test. Reducing the concentration of this constituent to 0.05 % was proven to change the result from positive to negative in the Ames test. No mutagenic effects were observed in mammalian cells in vitro, i.e. the HPRT test (OECD 476) and the micronucleus test (OECD 487). Thus, it is concluded that DNA-reactive metabolites in the course of hepatic biotransformation may occur via 2,3-epoxypropyl neodecanoate.