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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Relevance of findings unclear; source and quality of human liver microsomes cannot be judged.

Data source

Reference
Reference Type:
publication
Title:
Glucuronidation of propofol and its analogs by human and rat liver microsomes
Author:
Shimizu M, Matsumot Y, Tatsuno M, Fukuoka M
Year:
2003
Bibliographic source:
Biol. Pharm. Bull. 26; 216-219 (2003)

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
kinetic parameters for the glucuronidation of 6-tert-butyl-p-cresol and several other phenolderivatives were determined in vitro using pooled human and rat liver microsomes. Km and Vmax values were determined and compared with each other.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
6-tert-butyl-m-cresol
EC Number:
201-842-3
EC Name:
6-tert-butyl-m-cresol
Cas Number:
88-60-8
Molecular formula:
C11H16O
IUPAC Name:
2-tert-butyl-5-methylphenol
Details on test material:
no purity data, purchased from Aldrich Chem Co.
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
male Wistar rats, 7-8 weeks old were anesthetized with ether and then sacrificed by exsanguination

Administration / exposure

Route of administration:
other: not applicable - rat liver microsomes were used for experiment
Vehicle:
other: not applicable
Details on exposure:
not relevant - rat liver microsomes were used for experiment
Duration and frequency of treatment / exposure:
not relevant - rat liver microsomes were used for experiment
Doses / concentrations
Remarks:
Doses / Concentrations:
not relevant - rat liver microsomes were used for experiment
No. of animals per sex per dose / concentration:
not relevant - rat liver microsomes were used for experiment
Control animals:
no

Results and discussion

Preliminary studies:
no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data
Details on distribution in tissues:
no data
Details on excretion:
no data

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
glucoronidation was examined using both rat liver microsomes and pooled human liver microsomes from 15 individuals (8 males and 7 females)

Any other information on results incl. tables

Rat liver microsomes werde much more active (>10 fold) at low  concentrations. 
Maximum activity in rat microsomes was ~ 2.8 nmol/min/mg protein at ~ 0.2  mM substrate, while the activity of human microsomes never exceeded 0.2  nmol/min/mg protein

Human liver microsomes:
Km: 180.7 µM
Vmax: 0.211 nmol/min/mg protein

Rat liver microsomes:
Km: 17.3 µM
Vmax: 3.06 nmol/min/mg protein

Applicant's summary and conclusion

Executive summary:

method: kinetic parameters for the glucuronidation of 6 -tert-butyl-p-cresol and several other phenolderivatives was determined in vitro using pooled human and rat liver microsomes. Km and Vmax values were determined

result: glucuronidation of 6 -tert-butyl-p-cresol is in rat liver microsomes greater than in human pooled liver microsomes

reference: Shimizu, 2003