Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication, which meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1996

Materials and methods

Principles of method if other than guideline:
Study to investigate the pharmacokinetics of MDEA following acute cutaneous dosing in the rat

GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): N-methyldiethanolamine
- Analytical purity: 99.5%
- Radiochemical purity (if radiolabelling): >99%
- Specific activity (if radiolabelling): 1.95 mCi/mmol

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc . Indianapolis
- Age at study initiation: 8-10 weeks
- Weight at study initiation: males: 216 g; females: 162 g (average)
- Diet: food and water were available ad libitum .
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled temperature and humidity conditions (not further specified)
- Photoperiod 12 hrs dark / 12 hrs light

Administration / exposure

Type of coverage:
occlusive
Vehicle:
not specified
Duration of exposure:
6 h or 72 h contact.

Doses:
500 mg/kg bw
No. of animals per group:
4 male or female
Details on study design:
The pharmacokinetics and tissue distribution of N-methyldiethanolamine were study in Fischer 344 rats after a cutaneous dose (500 mg for 6h or 72 h contact).

For the percutaneous dosing study, the interscapular area of the cannulated animals was first clipped free of fur. [14C] MDEA (500 mg/kg, 25 μCi) was applied to a 2 x 4 cm or a 2 x 3 cm area of four males or four females, respectively. The application site was occluded with polyethylene sheeting held in place with adhesive tape and secured with an elastic wrapping bandage. In one group of rats cutaneous contact with the applied dose was maintained for 72 h, while in the the applied dose was removed after 6 hours of contact.

For the cutaneous dosing portions of liver, kidney, bone marrow, spleen, brain, heart, lung, muscle, fat, uterus, and ovaries/testes were collected. Cages were washed, and the wash was collected.

The amounts of radioactivity in various samples were measured by liquid scintillation spectrometry.

Results and discussion

Absorption in different matrices:
Topically applied substance was well absorbed by both male and female rats (17-21% and 41-50% after 6 and 72 h contact respectively), after apparently being the first sequestered in the skin and later slowly released into the bloodstream. Distribution of MDEA was relatively uniform throughout the major organs, with the highest concentrations being in the liver and kidney. The predominant excretion route for MDEA was in the urine. Urinary excretion of MDEA was slow, with an excretion half-life in excess of 30 h following cutaneous dosing.
Percutaneous absorptionopen allclose all
Dose:
500 mg/kg bw
Parameter:
percentage
Absorption:
>= 17 - <= 21 %
Remarks on result:
other: 6 hours
Dose:
500 mg/kg bw
Parameter:
percentage
Absorption:
>= 41 - <= 50 %
Remarks on result:
other: 72 hours

Applicant's summary and conclusion