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Description of key information

In rabbits, DMEE penetrates skin rapidly and high concentrations of unchanged DMEE in the plasma are quickly cleared and excreted in the urine. When injected intravenously, DMEE is rapidly excreted (in the first 6 hours) in a predominantly unchanged form in the urine in rats.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
71.6
Absorption rate - inhalation (%):
100

Additional information

Two routes of administration were tested in the toxicokinetics study: cutaneous and intravenous. The study followed an internal protocol prepared by Bushy Run Research Center. The study was GLP with well described internal methods and results. The test material was 14C-labeled. Test animals were male and female Fischer 344 rats (10 -12 weeks of age). A determination was made of the LD50 for both male and female rats following intravenous administration in order to allow two choices of doses for the pharamacokinetics assessments. Range finding concentrations were 15 and 150 mg/kg. The final studies were conducted at 150 mg/kg. The sub-cutaneous and intravenous studies each had a duration of 48 hrs.

For the cutaneous study, a total of 72% of the injected dose was recovered for males and 73% for females. Most of the radioactivity was recovered from the urine for both males and females (>50%). The majority of the remaining dose was recovered as unapplied dose from the cutaneous appliances. Skin at the dose site and the carcass contained a combined total of <10% of the applied dose. The majority of the 14C was excreted as unchanged test substance (81 -84% for males and 87.9 -88.2% for females). The apparent radioactivity metabolite(s) in this 6 -12 hr interval amounted to 14 -17% excreted by males and 10 -11% for females. Tmax for male rats was 2.1 hrs and for female rats 2.4 hrs. The 1/2 life for absorption for males was 0.3 -0.7 hrs and 0.4 -0.5 hrs for females. The 1/2 life for elimination was 18.7 hrs for males and 31.8 hrs for females of unchanged test substance.

Overall, cutaneous application of the 14C-test substance penetrated skin rapidly and as a substantial fraction of the applied dose and was excreted primarily as unchanged test substance.

The IV study was conducted using male rats. Metabolic behavior was similar for the intravenous study. A total of 91.5% of the injected dose was recovered. Of this total approximately 88% of the original dose was recovered in urine with another 1.8% recovered from the cage washing. Excretion in the urine was the main route of radioactivity elimination from the body after IV dosing totaling 80.6% excreted in the urine for the 150 mg/kg dose and 86.7% for the 15 mg/kg dose. At equilibrium conditions following the 150 mg/kg IV dose, mean total of 75 -78% of the test material was excreted unchanged. The half life for the rapid initial phase of absorption was 0.82 min for the 150 mg/kg dose. The rate of unchanged test substance appearing in the urine supported the excretion rate estimates by yielding a half life of 5.69 hrs.

Overall, a dose of 14C test substance injected intravenously is rapidly excreted in a predominantly unchanged form in the urine by male Fischer rates. Appearance of 14C in the urine was rapid and substantial in the first 6 hours after IV dosing.