H112323

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Assessment of the toxicokinetic properties based on the physico-chemical properties of the test substance and the results of toxicity studies.

Adequacy of study:

key study

Study period:

1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Assessment of the toxicokinetic properties based on the physico-chemical properties of the test substance and the results of toxicity studies.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

other: Expert statement

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

no guideline followed

Deviations:

not applicable

Principles of method if other than guideline:

Assessment of the toxicokinetic properties based on the results obtained for the toxicological end-points with simultaneous reference to physico-chemical data such as solubility in various solvents and log Pow

GLP compliance:

no

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): H112323
- Physical state: Dark blue powder

Test animals

Species:

other: Not applicable

Strain:

other: Not applicable

Details on test animals or test system and environmental conditions:

Not applicable

Administration / exposure

Route of administration:

other: Not applicable

Vehicle:

other: Not applicable

Details on exposure:

Not applicable

Duration and frequency of treatment / exposure:

Not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
Not applicable

No. of animals per sex per dose / concentration:

Not applicable

Control animals:

other: Not applicable

Positive control reference chemical:

Not applicable

Details on study design:

Not applicable

Details on dosing and sampling:

Not applicable

Statistics:

Not applicable

Results and discussion

Preliminary studies:

None

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Absorption from the GI tract would be anticipated to be slow. There are indications of a non-absorbed proportion of the dose being passed through the gut, commensurate with the postulated low GI permeability of test substance.

Main ADME results 2

Type:

distribution

Results:

Distributed widely to a number of tissues including skin. At lower doses, distributed only to stomach (site of administration)

Main ADME results 3

Type:

excretion

Results:

via kidneys. No conclusions can be drawn regarding biliary excretion as excreted and unabsorbed compound would both appear in faeces

Main ADME results 4

Type:

metabolism

Results:

No information is available on potential metabolism of test substance.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

No data

Details on distribution in tissues:

No data

Details on excretion:

No data

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

Not applicable

Any other information on results incl. tables

Evaluation and Assessment:

ABSORPTION

Based on the repeat dose oral study it would appear that some test substance was absorbed from rat intestine. Observations of black faeces are indicative of a non-absorbed proportion of the dose being passed through the gut, commensurate with the postulated low GI permeability of the compound. The amount of absorption was apparently dose related in that the level of Hl12323-staining of tissues was greatest with the highest dose level. Based on the repeat dose oral study it would appear that some test substance was absorbed from rat intestine. Observations of black faeces are indicative of a non-absorbed proportion of the dose being passed through the gut, commensurate with the postulated low GI permeability of the compound. The amount of absorption was apparently dose related in that the level of test substance staining of tissues was greatest with the highest dose level.

DISTRIBUTION

Based on appearance of dye in tissues it would appear that the compound was distributed widely to a number of tissues including skin. At lower doses staining was only observed in the stomach (site of administration) and the kidney suggesting that the kidney is involved in excretion of test substance.

METABOLISM

No information is available on potential metabolism of test substance. In the AMES tests the same minor effects were observed both in the presence and absence of 59.

EXCRETION

Following high doses of test substance a coloured compound, presumably parent, was excreted in urine. No conclusions can be drawn regarding biliary excretion as excreted and unabsorbed compound would both appear in faeces.

Compound was eliminated gradually. Nine to 10 d following the final dose no coloration of urine was observed. By Day 43 (15 d post-final dose) in all but 2 rats the skin discoloration had disappeared indicative of compound clearance from the animals.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: does not show any toxicokinetic peculiarity
Test substance is only absorbed to a limited extent following oral dosing. It is distributed to a number of tissues and excreted gradually from the body. Most of the discolouration of tissues has disappeared within 15 d post dose. A coloured compound, presumably parent, is excreted in urine.

Executive summary:

Assessment of the toxicokinetic properties of the test substance was carried out based on the results obtained for the toxicological end-points with simultaneous reference to physico-chemical data.

Test substance is only absorbed to a limited extent following oral dosing. It is distributed to a number of tissues and excreted gradually from the body. Most of the discolouration of tissues has disappeared within 15 d post dose. A coloured compound, presumably parent, is excreted in urine.