Registration Dossier

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1966
Report Date:
1966
Reference Type:
study report
Title:
Unnamed
Year:
1965
Report Date:
1965

Materials and methods

Objective of study:
absorption
Principles of method if other than guideline:
The absorption of the compound was evaluated by the Levine technique, using C-labeled materials as described in the Journal of Pharmacology and Experimental Therapeutics, 114:78 (1955), 121019 (1961).
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): RA 565
Radiolabelling:
yes
Remarks:
C14

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Fasting period before study: Yes

Administration / exposure

Route of administration:
other: injected into gut lumen
Vehicle:
CMC (carboxymethyl cellulose)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Suspension in 1% carboxymethylcellulose solution was made by sonication.
Duration and frequency of treatment / exposure:
single introduction
Doses / concentrations
Remarks:
Doses / Concentrations:
891, 865, and 907 µg
No. of animals per sex per dose:
1
Control animals:
no
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption)
A small abdominal opening was made in a lightly etherized, fasted rat and the upper end of the small intestine was exposed and ligated about 6 inches below the pylorus. A second ligature was placed loosely 5 inches below the first. The test material (as a solution 1 % carboxymethylcellulose) was introduced with a hypodermic syringe as follows: the needle was inserted into the gut lumen from a point beyond the second tie, the ligature was pulled tight around the barrel of the needle, the sample was injected and, as the needle was withdrawn, the ligature was secured. The abdominal incision was closed and the animal recovered.
The intestinal vasculature remained essentially intact, allowing absorbed material to be removed to the general circulation in the normal manner. After a suitable period of time, generally 3 hours, the rat was again etherized and the ligated intestinal segment was removed for determination of the amount of compound still present.

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
The test substance is poorly absorbed.
Type:
distribution
Results:
No data
Type:
metabolism
Results:
No data
Type:
excretion
Results:
No data

Any other information on results incl. tables

Tab. 1: Absorption of the test substance 3 hours after injection (1st series, 1965).

Dose (µg)

Amount recovered (µg)

Absorption (%)

891

879

1.3

865

835

3.5

907

812

10.5

Tab. 2: Absorption of the test material in the Levine Procedure (1st and 2nd series, 1965 and 1966)

 

1stseries

10.5 %

3.5 %

1.3 %

 

2ndseries

12.3 %

2.5 %

0.2 %

Average 1stseries

5.1 %

Average 2ndseries

5.0 %

Mean (all vaues)

5.0 ± 5.1 %

95% Confidence Limits

- 0.3 to 10.4 %

Applicant's summary and conclusion