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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics 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

Objective of study:
other: ADME
Principles of method if other than guideline:
Study to investigate the pharmacokinetics of MDEA following acute intravenous 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
Radiolabelling:
yes

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

Route of administration:
intravenous
Vehicle:
not specified
Duration and frequency of treatment / exposure:
single application
Doses / concentrations
Remarks:
Doses / Concentrations:
50 or 500 mg/kg bw;
No. of animals per sex per dose:
4 male
Control animals:
not specified
Details on study design:
The pharmacokinetics and tissue distribution of N-methyldiethanolamine were study in Fischer 344 rats after a single intravenous dose (50 or 500 mg/kg bw).
 
One day prior to dosing, animals had an indwelling jugular vein cannula implanted by a modification of the method of Harms and Ojeda and then acclimated to individual Roth-type glass metabolism cages. For the intravenous dosing study four male rats per group were given 50 or 500 mg/kg bw [14C] MDEA (10 μCi ) via the cannula at a dose volume of 2 ml/kg, and held for 72 h in metabolism cages.
 
Urine, feces, and expired 14CO2 were collected at various intervals up to 72 h postdosing from animals held in individual metabolism cages. Blood was collected via the jugular cannula, except for the last sample, which was by cardiac puncture.

The amounts of radioactivity in various samples were measured by liquid scintillation spectrometry. Unchanged MDEA concentrations in the plasma and urine were determined by high-performance liquid chromatography in conjunction with an in-line radioactivity monitor.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
Distribution of MDEA was relatively uniform throughout the major organs, with the highest concentrations being in the liver and kidney.
Details on excretion:
The predominant excretion route for MDEA was in the urine. Urinary excretion of MDEA was slow. Metabolites constituted the major fraction in urine, indicating that metabolism plays an important role in MDEA elimination.

Metabolite characterisation studies

Details on metabolites:
MDEA was substantially metabolised. Metabolism could be saturated at high dosages since nonlinear kinetic behavior was observed in rats dosed i.v. with 500 mg/kg bw.

Applicant's summary and conclusion