m-cresol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: experiments with a m/p-cresol mixture and not with a single isomer

Data source

Reference

Reference Type:

publication

Title:

Quantitative analysis of cresol and ists metabolites in biological materials and distribution in rats after orál administration

Author:

Morinaga Y, Fuke Ch, Arao T, Miyazaki T

Year:

2004

Bibliographic source:

Legal Med 6, 32-40

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

Oral application of a cresol soap solution to male rats via gastric tube and examination of cresol content in various tissues at various time points as well as the analysis of the respective glucuronides and sulfates.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

cresol soap solution containing 200 mg/ml p-cresol and 320 mg/ml m-cresol

Radiolabelling:

not specified

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: average weight 410 g
- Fasting period before study: 24 hours
- Diet : . ad libitum
- Water :ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
the with water diluted cresol soap solution of which amounts were 2.5 ml/kg (100 mg p-cresol and 160 mg m-cresol)

Duration and frequency of treatment / exposure:

once

Doses / concentrations

Remarks:

Doses / Concentrations:
see above

No. of animals per sex per dose / concentration:

no data on number of male rats

Control animals:

not specified

Positive control reference chemical:

no data

Details on study design:

see section " additional information on matereial and method"

Details on dosing and sampling:

see section " additional information on matereial and method"

Statistics:

see section " additional information on matereial and method"

Results and discussion

Preliminary studies:

see section "remarks on results"

Toxicokinetic / pharmacokinetic studies

Details on absorption:

see section "remarks on results"

Details on distribution in tissues:

see section "remarks on results"

Details on excretion:

see section "remarks on results"

Metabolite characterisation studies

Details on metabolites:

see section "remarks on results"

Any other information on results incl. tables

It was found that cresol administered via the stomach tube diffused directly through the gastric and small intestinal walls because the conjugate cresol concentration were extremely high not only in the liver, but also in the spleen. The unconjugates of cresol in the liver, spleen and kidney were detected in high concentrations even when the unconjugates were not detedcted in the blood. m-Cresol was easily metabolized to sulfate and the p-cresol to glucuronide in rats.The concentration ratios of m-cresol to p-cresol in blood and organs were different from the rate of the cresol soap solution that was administered. The pharmacokinetics was different between p-cresol and m-cresol in rats.

Applicant's summary and conclusion

Executive summary:

It was found that cresol adinistered via the stomach tube to rats diffused directly through the gastric and small intestinal walls.