o-cresol

Endpoint summary

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.