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

Endpoint summary

Description of key information

Absorption, Distribution, Metabolism and Excretion

 

In Vitro

 

Dodecanamide, N,N-bis(2-hydroxyethyl)- (CASRN 120-40-1)

 

Human liver slices and liver slices from diethylhexyl phthalate-(DEHP) induced and untreated male F344 rats were incubated with [14C]lauramide DEA.23Lauramide DEA “partitioned well” into the human liver slices and the liver slices from DEHP-induced and untreated rats.Approximately 70% of the radioactivity absorbed into the slices in 4 h. The absorbed radioactivity was present mostly as lauramide DEA. In the media from the human, rat, and DEHP-induced rat liver slice incubations, 32, 18, and 43% of the radioactivity, respectively, was present in the form of metabolites. The analytes present in the incubation media included half-acid amides, parent lauramide DEA, and three other metabolites that are products of ω- and ω-1 to 4 hydroxylation.

The in vitro metabolism of [14C]lauramide DEA, randomly labeled on the diethanolamine moiety, was examined in liver and kidney microsomes from rats and humans to determine the extent of hydroxylation, and to determine the products

formed.24Incubation of lauramide DEA with liver microsomes from control and DEHP-treated rats produced two major high performance liquid chromatography peaks that were identified as 11-hydroxy- and 12-hydroxy-lauramide DEA. Treatment with DEHP increased the 12-hydroxylation rate 5-fold, while the 11-hydroxylase activity was unchanged.

 

Upon comparison of lauramide DEA hydroxylation rates using human liver microsomes from the rates measured using rat liver and kidney microsomes, the lauramide DEA 12-hydroxylase activity in human liver microsomes was similar to the activity in liver microsomes from control rats. The 12-hydroxylase activity in liver microsomes was 3 times greater than that observed in rat kidney microsomes.

 

Oral

 

Non-Human

 

Dodecanamide, N,N-bis(2-hydroxyethyl)- (CASRN 120-40-1)

Three male F344 rats were dosed orally with [14C]lauramide DEA that was randomly labeled on the diethanolamine moiety, 16-18μCi/dose, and that was formulated with an appropriate amount of unlabeled lauramide DEA and water to give delivery of the target dose in a volume of 5 ml/kg bw.23After oral dosing with 1000 mg/kg [14C]lauramide DEA, approximately 10, 60, and 79% of the dose was recovered in the urine after 6, 24, and 72 h, respectively.

 

Approximately 4% of the dose was recovered in the tissues after 72 h, with almost 3% found in adipose tissue and 1.3% in the liver. At 6 h, no diethanolamine, diethanolamine metabolites, or unchanged lauramide DEA were present in the urine; only very polar metabolites were found. The researchers postulated that the metabolites were carboxylic acids, and that the acid function was formed

from the lauryl chain.

 

 

Dermal

 

Non-Human

Dodecanamide, N,N-bis(2-hydroxyethyl)- (CASRN 120-40-1)

 

Groups of four male B6C3F1mice and four F344 rats were dosed dermally with [14C]lauramide DEA that was randomly labeled on the diethanolamine moiety.23The vehicle was ethanol.A non-occlusive application was made to a 0.5 sq. in. area of mouse skin and to a 1 sq. in. area of rat skin. At the end of the study, the excised skin was rinsed with ethanol.

 

Absorption was calculated from the total disposition of radioactivity in the tissues, urine, feces, and dose site. In mice dosed with 5-800 mg/kg [14C]lauramide DEA, 50-70% of the applied radioactivity was absorbed at 72 h, and absorption was similar

for all the doses. Approximately 32-55% of the radioactivity was excreted in the urine. In rats dosed with 25 or 400 mg/kg lauramide DEA, 21-26% of the radioactivity penetrated the skin in 72 h, and 3-5% was recovered at the application site. Approximately

20-24% of the radioactivity was recovered in the urine. The tissue/blood ratio was greatest in the liver and kidney.

 

Lauramide DEA and the half-acid amide metabolites were detected in the plasma, with maximum levels found 24 h after dosing.

 

The researchers also examined the effects of repeated administration lauramide DEA on absorption and excretion. Lauramide DEA, 25 mg/kg/day, was applied to 5 rats, 5 times/wk, for 3 wks. The rate of absorption of lauramide DEA did not vary much at the different collection time points, and the amounts excreted were similar at each collection period.

 

 

Intravenous

 

Non-Human

Dodecanamide, N,N-bis(2-hydroxyethyl)- (CASRN 120-40-1)

 

Three male B6C3F1mice and four F344 rats were dosed intravenously (i.v.) with [14C]lauramide DEA that was randomly labeled on the diethanolamine moiety, 3-5μCi and 16-17μCi, respectively, and that was formulated to deliver a target dose in a volume of 4 ml/kg in mice and 1 ml/kg in rats.23The dose for mice was 50 mg/kg and the dose for rats was 25 mg/kg.In B6C3F1mice, lauramide DEA was quickly metabolized and eliminated. At 24 h after dosing, approximately 95% of the dose was excreted, with 90% found in the urine; the highest concentrations and total amounts of the lauramide DEA were in adipose tissue. In F344 rats, 50% of the dose was excreted in the urine within the first 6 h, and more than 80% was excreted in the urine by 24 h. The rats were killed at 72 h after dosing, and only 3% of the dose was recovered in the tissues; 1% of the dose was in the adipose tissue and 0.67% was found in the liver.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential