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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:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no guideline study,no single isomer examined but a m/p-mixture

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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
no data on number of male rats
Control animals:
not specified
Positive control:
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

p-cresol administered by gavage to male Wistar rats were detected in blood and distributed to the brain, kidney, liver, lung, muscle, and spleen. The unconjugated p-cresol as well as the glucuronide and sulfate metabolites were eliminated from blood, brain, lung, muscle, liver, spleen, and kidneys for the most part within several hours.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Executive summary:

Oral application of a cresol soap solution containing m- and p-cresol to Wistar rats was readily absorbed, distributed in liver, spleen and kidney and excreted as sulfate or glucuronide.

p-cresol administered by gavage to male Wistar rats were detected in blood and distributed to the brain, kidney, liver, lung, muscle, and spleen. The unconjugated p-cresol as well as the glucuronide and sulfate metabolites were eliminated from blood, brain, lung, muscle, liver, spleen, and kidneys for the most part within several hours.