Amides, vegetable-oil, N,N-bis(hydroxyethyl)

Endpoint summary

Additional information

Oral

Simulators of molecular transformations imitating liver and gastro-intestinal metabolism of amides, C8 -18 unsatd., N, N-bis(hydroxyethyl) CAS 68155-07-7 were modelled using OECD (Q)SAR APPLICATION TOOL BOX V.1.1.02.

The simulator indicates that it is predominantly metabolised by dealkylation, hydroxylation and oxidation transformation reactions. Further, the generation of acetic acid, may be indicative of being involved in Kreb's cycle metabolic pathway, to generate usable energy.¹

The disposition of carbon-14-labeled lauramide diethanolamine (LDEA), CAS 120-40-1 was determined in rats after iv, dermal, and oral administration, and in mice after iv and dermal administration.

High oral doses of LDEA (100 mg/kg) in rats were well absorbed and mostly excreted in the urine as two very polar metabolites. The metabolites were isolated and characterized as the half-acid amides of succinic and of adipic acid, presumably arising from omega-hydroxylation and eventual beta-oxidation to give the chain-shortened products.. LDEA concentrated to the highest levels in the adipose tissue, and was only very slowly cleared from that tissue. Residues were also observed in liver and kidney, but clearance from those tissues paralleled the decreases in blood concentrations. Incubations of LDEA with liver slices from rats and humans showed that the compound is well absorbed by hepatic tissue from both species. LDEA was readily converted to metabolites found in vivo in rats, as well as other metabolites that are potentially intermediate products formed after omega- and/or omega-1 to 4 hydroxylation. Treatment with diethylhexylphthalate, an inducer of cytochrome P4504A1, which catalyzes the omega-hydroxylation of lauric and other fatty acids, demonstrated the involvement of that isozyme in the hydroxylation of LDEA. This metabolism does not release free diethanolamine in rats or mice.^{1 2 3 4}

Dermal

The disposition of carbon-14-labeled lauramide diethanolamine (LDEA), CAS 120-40-1 was determined in rats after iv, dermal, and oral administration, and in mice after iv and dermal administration.

Dermally applied LDEA, at doses of 25 and 400 mg/kg to rats, was moderately (25-30%) well absorbed. Repeat administration (25 mg/kg/day for 3 weeks) did not change the rate of LDEA absorption.⁴

Absorption of diethanolamine, present at 2 -5%, was much slower through the skin than by the i.v. or oral route.

Liver, kidney, heart, spleen and brain represent the major target organs for DEA accumulation. DEA was accumulated particularly to high concentrations compared to the levels observed in blood. DEA had a particularly high affinity for liver and kidney.⁵

 

It can be supposed that the PRODUCT L6143 has a similar oral and dermal metabolism and similar pathways of transformations in tissues and organs.

Reference:

¹ECHA Registration Dossier Amides, C8-18 (even numbered) and C18-unsatd., N,N-bis(hydroxyethyl), CAS 68155-07-7

²ECHA Registration Dossier Amides, C12-18 (even-numbered) and C18 (unsatd.), N,N-bis(hydroxyethyl), CAS 90622-74-5

³ECHA Registration Dossier Amides, C16-18 and C18-unsatd., N,N-bis(hydroxyethyl), CAS 68603-38-3

⁴Mathews JM, deCosta K, Thomas BF, Lauramide diethanolamine absorption, metabolism, and disposition in rats and mice after oral, intravenous, and dermal administration (abstract); IARC monographs n.101

⁵ECHA Registration Dossier 2,2'-iminodiethanol CAS 111-42 -2