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Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics in vivo
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic information available, no information on distribution in tissue
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
Radiolabelling:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMAL
- Weight at study initiation: 2-3 kg
-diet: rabbit pellets ad libitum
-water: ad libitum
no further data
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
Remarks:
Doses / Concentrations:
200 mg/kg bw
No. of animals per sex per dose / concentration:
10
Control animals:
not specified
Positive control reference chemical:
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
Preliminary studies:
no data
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
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.
Metabolites identified:
yes
Details on metabolites:
see section 'remarks on results'

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

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.

Description of key information

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.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

o-cresol is absorbed across the respiratory and gastrointestinal tract and through the intact skin. The primary metabolic pathway is conjugation with glucuronic acid and inorganic sulfate. Significant amounts of o-cresol are excreted in the bile but most of it is reabsorbed from the intestine. The main route of excretion is renal elimination (WHO 1995).

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.

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