Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

Assessment of the Toxicokinetic Behaviour

 

2-ethyl-N,N-bis(2-ethylhexyl)hexylamine (CAS-No.1860-26-0)

 

There were no studies available in which the toxicokinetic properties of 2-ethyl-N,N-bis(2-ethylhexyl)hexylamine were investigated.

 

2-ethyl-N,N-bis(2-ethylhexyl)hexylamine (molecular weight of 353.7 g/mol) is a colourless to yellow liquid with low water solubility(calculated water solubility for the uncharged molecule: 0.00013 mg/L at 25 °C ; and for the charged molecule: 0.1031 mg/L at 25 °C (EPISUITE, see chapter “water solubility”).The log Po/w for the uncharged molecule was calculated to be 10.13 at 25 °C (EPISUITE, see chapter “partition coefficient”), indicating that accumulation of the substance is possible.

 

 

Absorption

In an acute oral toxicity study, rats were administered the substance by gavage at a limit dose of 8170 mg/kg bw. No mortality, clinical signs and pathologic abnormalities were reported; therefore no conclusions concerning bioavailability of the substance after oral administration can be drawn from this study (BASF AG 1975, see chapter “acute oral toxicity”).

No acute dermal toxicity study is available. Based on a water solubility below 1 mg/L, dermal uptake is likely to be low.

For highly lipophilic substances (log P greater than 6) that come into contact with the skin, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow. Dermal uptake for such substances is expected to be low (ECHA GD 7c, 2008).

 

2-ethyl-N,N-bis(2-ethylhexyl)hexylamine has a very low measured vapour pressure of 0.00078 Pa at 20 °C (BASF AG 1986, see chapter “vapour pressure”); accordingly, in an inhalation hazard test of the dissolved substance with saturated vapour atmosphere, none of the 12 tested rats showed clinical signs indicative for systemic availability after inhalative exposure.

In addition, a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD TG 422 and a subchronic repeated dose toxicity study according to OECD TG 408 was performed with the substance in Wistar rats (BASF SE 2010 + 2014, see chapter “repeated dose toxicity”). In these studies the substance was administered in the diet and no NOAEL for general, systemic toxicity of the test substance could be determined for the F0 parental animals based on clinical-pathological and histopathological findings in all treated groups, predominantly dose-related histiocytic/mixed cell infiltrates in multiple organs which lead to secondary multiple local inflammatory reactions. Thus, bioavailability of the substance after oral administration is indicated.

 

 

 

Metabolism

Using the OECD toolbox vs.2.0, the (improved) liver metabolism simulator provided 50, and the skin simulator 19 potential metabolites (OECD toolbox vs.2.0, 2011).

Most of the predicted metabolites were hydroxylated aliphatic tertiary amines. Two of the liver metabolites and five of the skin metabolites were predicted by OASIS to be direct acting mutagens. These metabolites were aldehydes which may possibly act as direct acting Schiff Base formers. This prediction is not supported by various experimental studies on genetic toxicity. Studies on genotoxicity, i.e. ames assay, gene mutation in mammalian cells in-vitro, chromosome aberration assay in-vitro, gave no indications of a reactivity of the substance or its metabolites under the test conditions (i.e. no increased mutagenicity or cytotoxicity in treatments with or without metabolic activation).

 

 

Excretion

The potential hydroxylated metabolites as well as the parent chemical have a molecular weight lower than 500 g/mol. The potential metabolites are expected to be soluble in water and therefore are likely to be excreted predominantly via the urine (ECHA GD 7c, 2008).

 

 

 

ECHA (2008). GD 7c. Endpoint specific Guidance.