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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:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994

Materials and methods

Objective of study:
absorption
distribution
excretion
Principles of method if other than guideline:
Determination of the tendency of the test substance to adhere to the teeth and oral mucosa and the exrection and distribution of 14C from the compound swallowed and absorbed into the rat. Furthermore, the metabolism of the test material to yield radioactive CO2 was observed.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: applied with a micro-pipette to teeth, oral mucosa and tongue
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The test material was dissolved in water to form a solution having 3.36E6 counts per minute per mL of solution.
Duration and frequency of treatment / exposure:
single treatment
Doses / concentrationsopen allclose all
Dose / conc.:
2.58 other: mg/rat
Remarks:
Experiment A (distribution)
Dose / conc.:
0.3 other: mL/rat
Remarks:
Experiment B (metabolism)
No. of animals per sex per dose:
5 animals at 0, 4 and 24 h after application (distribution)
3 animals (metabolism)
Control animals:
no
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, teeth, oral mucosa, tongue, liver, kidney and bone muscle.
- Time and frequency of sampling: at 0, 4 and 24 h after application

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine, faeces and expired CO2
- Time and frequency of sampling: 48 h
- From how many animals: 3

Results and discussion

Main ADME resultsopen allclose all
Type:
distribution
Results:
1.12% teeth, 2.22% oral mucosa and 2.95% tongue; immediately after application
Type:
distribution
Results:
0.92% teeth, 0.95% oral mucosa, 0.57% tongue, 5.44% liver and 2.78% kidney; 4 h after application
Type:
distribution
Results:
0.79% teeth, 0.92% oral mucosa, 0.57% tongue, 1.62% liver, 0.78% kidney; 24 h after application
Type:
excretion
Results:
0.87% faeces and 33.5% urine; 4 h after application
Type:
excretion
Results:
1.18% faeces and 42.2% urine; 24 h after application
Type:
metabolism
Results:
0.35% were expired as CO2; 48 h after application
Type:
distribution
Results:
1.18% liver, 13.5% bones and 18.7% muscles; 48 h after application
Type:
excretion
Results:
2.1% feces and 49.1% urine; 48 h after application

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Approximately 34% of the activity of the test material was excreted in the urine over a period of 4 h after application, demonstrating rapid absorption and excretion. Some 42% of the activity was excreted during 24 h. The remainder of the activity could be accounted for approximately by estimating the total amount of activity in the blood, muscles, bone and other tissues of the body, such an estimate indicating that very little, if any, of the compound was oxidized to form CO2.
Details on distribution in tissues:
See Table 1 under "Any other information on results incl. tables".
Details on excretion:
The data demonstrated the rapid excretion of 14C from the body and suggested that little of the compound is metabolized and/or held within the tissues.

Any other information on results incl. tables

Table 1. Distribution of 14C (% of the activity administered) 48 h after application.

Organ

Average of 3 rats (%)

Liver

1.18

Bone

13.5

Muscle

18.7

Feces

2.1

Urine

49.1

CO2 expired

0.35

Applicant's summary and conclusion