N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Endpoint summary

Description of key information

Animal studies indicate the test substance is rapidly absorbed following dermal, i.v. or inhalation exposure, and eliminated, unchanged, primarily in the urine. Based on the i.v. studies, the elimination half-life for the test substance is ~14 - 18 hours in rats (2 mg/kg and 200 mg/kg administered dose, respectively) and ~26 - 40 hours in the rabbit (1 mg/kg and 100 mg/kg administered dose, respectively).

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - dermal (%):

64.5

Absorption rate - inhalation (%):

60

Additional information

In a vapour inhalation toxicokinetics study in Fischer 344/NHsd rats, the test substance was readily absorbed at a constant rate during exposure and was largely eliminated by urinary excretion following exposure, without significant accumulation in any specific organ. Evaluation of the disposition of the test substance showed that the majority of radioactivity (58% of the recovered dose) was found in the urine. Approximately 3% of the recovered dose was present in the feces and less than 1% of the recovered dose was present in the organs and tissues saved at necropsy; however, 29% was present in the carcass.

 

In a dermal and intravenous toxicokinetics study in CDF Fischer 344 rats, the pharmacokinetic profile was consistent with a two-compartment open model in which elimination is primarily by urine excretion of the unchanged test material. Metabolism was not a major feature of the test substance elimination. 

 

The majority of the radioactivity administered at both intravenous dose levels was eliminated in the urine (high dose: 64.4%; low dose: 60.8%); less than 5% recovery in the feces (high dose: 5.6%; low dose: 4.0%), with total percent dose recovered reported as 75% in the high dose and 69.5% in the low dose. No urinary metabolites were detected in the urine, indicating the test substance is largely eliminated unchanged in the urine. 

 

Following dermal exposure to a 200 mg/kg dose of the test substance, the major fraction of the excreted dose was found in the urine, accounting for 24% of the dose (approximately 95% of the excreted dose). Approximately 1 to 2% of the dose (ca. 5% of the excreted dose) was recovered in the feces of male and female rats.   The cutaneous bioavailability of the test substance was calculated to be 78.2% in males and 50.8% in females (calculated as % Bioavailability = [(AUC₈) cutaneous ÷ (AUC₈) intravenous] x 100), thus the absorption rate constant was significantly greater for males than for females. There was no remarkable tissue specific accumulation in male or female rats.