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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
August 6, 1992-February 28, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study.

Data source

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

Materials and methods

Objective of study:
other: distribution, metabolism and excretion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A single intravenous dose of test substance was given to 5 male and 5 female rats. Samples of urine and feces were taken at pre-dose, 0.5, 4, 8, 24, 72, and 96 hrs post-dose. Whole body autoradiography was done for 1 animal of each sex at 0.5, 4, 8, 24, and 96 hrs after dosing.
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
other: Crl: CD(SD)BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd.
- Age at study initiation: 8 weeks of age
- Weight at study initiation: males 201-265 g, females 178-220 g
- Fasting period before study:
- Housing: individual all-glass cages suitable for collecting urine and feces, identified with ear notching
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): SQC Rat and Mouse Maintenance Diet No. 1, Expanded, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: August 6, 1992 To: February 28, 1993

Administration / exposure

Route of administration:
intravenous
Vehicle:
other: ethanol: polyethylene glycol 400 (5:95 v/v)
Details on exposure:
HOMOGENEITY AND STABILITY OF TEST MATERIAL: test material was tested for stability for 24 hrs using TLC
Duration and frequency of treatment / exposure:
1 intravenous injection
Doses / concentrations
Remarks:
Doses / Concentrations:
1 mg/kg bw (10 uCi)
No. of animals per sex per dose:
5 of each sex per dose
Control animals:
no
Details on dosing and sampling:
- Tissues and body fluids sampled: Urine and faeces were collected using suitable vessels surrounded by solid CO2. Cage washings and cage debris were also collected. Whole-body autoradiography was done for 1 animal of each sex at 0.5, 4, 8, 24, and 96 hrs after dosing. Sections obtained include the exorbital lachrymal gland or ovaries, intra-orbital lachrymal gland, Harderian gland, adrenal gland, thyroid, and brain and spinal cord.
- Time and frequency of sampling: Urine and feces: pre-dose, 0.5, 4, 8, 24, 72, and 96 hrs post-dose
- Method type(s) for identification: Liquid scintillation counting and TLC, urine and feces were pooled by time point and sex
- Limits of detection and quantification: for LSC the limit of detection was twice the background disintegration rate obtained from the measurement of the pre-dose samples.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
Highest levels were observed early in the liver and kidneys. The radioactivity was widely distributed early in the experiment, but was largely gone by 24 hrs after dosing. The Steno's gland, however, still contained radioactivity. Tissues with high lipid content and those with oily secretions still showed low but persistent radioactivity. No radioactivity was noted in the blood after 4 hrs in males, and 8 hrs in females.
Details on excretion:
79.88% of the test substance was excreted by male rats, and 85.87% by the female rats within 96 hrs. The main route of excretion was the urine (75.97% female, 57.94% males) and mostly within the first 24 hrs (72.15% female, and 53.19% males). The amount excreted in the feces was 8.865% for males and 5.285% in females.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
Parent compound was a major component of radiation in the feces. The test compound appeared to be rapidly eliminated from the body via the urine. Up to 9 different metabolites were resolved by TLC. A volatile fraction that was most likely parent compound was noted at the first time point. This was no longer evident at later time points.

Any other information on results incl. tables

No clinical signs were observed during the experiment.

Applicant's summary and conclusion

Conclusions:
The test substance was rapidly eliminated from the majority of tissues, though some remained in fatty tissues. Metabolism of the test substance was rapid, and it was eliminated mostly through the urine.
Executive summary:

A single intravenous dose of test substance was given to 5 male and 5 female rats. Samples of urine and feces were taken at pre-dose, 0.5, 4, 8, 24, 72, and 96 hrs post-dose. Whole body autoradiography was done for 1 animal of each sex at 0.5, 4, 8, 24, and 96 hrs after dosing. No clinical signs were observed during the study. The test substance was rapidly eliminated from the majority of tissues, though some remained in fatty tissues. Metabolism of the test substance was rapid, and it was eliminated mostly through the urine.