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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic information available, no information on distribution in tissue

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Metabolism of derivatives of toluene: cresols.
Author:
Bray HG , WV Thorpe, K White
Year:
1950
Bibliographic source:
Biochem. J. 46, 275-278
Reference Type:
review article or handbook
Title:
EHC (Environmental Health Criteria) No. 168: Cresols
Author:
WHO
Year:
1995
Bibliographic source:
IPCS (International Programme on Chemical Safety) WHO, Geneva

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
Method: Single oral application by gavage, test substance dissolved in bicarbonate, urinary excretion was collected over a period of 24 hours and levels of free and conjugated cresols was estimated by the method of Folin O and Ciocalteu V (1927): J. biol Chem. 73, 627
Metabolites were measured with the method described in Bray et al 1947 Biochem j 41, 212 and Bray et al (1948) Biochem J 43, 561
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
IUCLID4 Test substance: o-cresol: no data on purity
Radiolabelling:
no

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMAL
- Weight at study initiation: 2-3 kg
-diet: rabbit pellets ad libitum
-water: ad libitum
no further data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: solution of sodium bicarbonate
Details on exposure:
single oral application by gavage,solvent sodium bicarbonate
Duration and frequency of treatment / exposure:
once
Doses / concentrations
Remarks:
Doses / Concentrations:
200 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
not specified
Positive control:
no data
Details on study design:
no further data other than described under 'Principles of test method'
Details on dosing and sampling:
no further data other than described under 'Principles of test method'
Statistics:
no data

Results and discussion

Preliminary studies:
no data
Main ADME resultsopen allclose all
Type:
absorption
Results:
Within 24 hours 80% of the o-cresol doses was excreted in the urine indicating that at least this amount was absorbed through the gastrointestinal tract.
Type:
excretion
Results:
Urinary excretion was the maine route of elemination: Within 24 hours ca 80% of the o-cresol doses was excreted in the urine

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Within 24 hours 80% of the o-cresol doses was excreted in the urine indicating that at least this amount was absorbed through the gastrointestinal tract.
Details on distribution in tissues:
no data
Transfer into organs
Observation:
not determined
Details on excretion:
urinary excretion was the maine route of elemination:
Within 24 hours ca 80% of the o-cresol doses was excreted in the urine
excreted products: ca 15 % as ethereal sulphate, ca 72 % as ether glucuronide and ca 1% as free cresol

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
see section 'remarks on results'

Any other information on results incl. tables

RS-Freetext:
o-Cresol was excreted by the rabbit
55-91 % as ether glucuronides and
13-19 % as ethereal sulphates.
0-2 % as free cresol

75-83 % total cresol

Applicant's summary and conclusion

Executive summary:

Single oral application by gavage of o-cresol dissolved in bicarbonate and collection of urinary excretion over a period of 24 hours showed that o-cresol was excreted mainly in the urine : 55 -91 % as ether glucuronides, 13 -19 % as ethereal sulphates and 0 -2 % as free cresol