2,3-epoxypropyl phenyl ether

Basic toxicokinetics

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: Acceptable study which meets basic scientific principles

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Dosimetry of glycidyl ethers in mice by quantification of haemoglobin adducts

Author:

Perez HL, Plna K, Ostermann-Golkar S

Year:

1997

Bibliographic source:

Chemico-Biological Interactions 103, 1-16

Reference 2

Reference Type:

secondary source

Title:

Epoxy Compounds

Author:

Waechter JM et al.

Year:

2001

Bibliographic source:

Patty´s Toxicology, fifth edition, vol. 6, 1063-1085

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

N-alkyl Edman method (not further specified)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Phenyl glycidyl ether

IUPAC Name:

Phenyl glycidyl ether

Details on test material:

- Name of test material (as cited in study report): Phenyl glycidyl ether
- Purity: 99 %

Test animals

Species:

mouse

Strain:

other: C3H/Hej mice

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 30 g
- Diet (e.g. ad libitum): standard pellet diet ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: Tricaprylin

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The glycidyl ethers were dissolved in tricaprylin to give 40 mg/ml.

Duration and frequency of treatment / exposure:

once in 24 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
4 mg/mouse

No. of animals per sex per dose / concentration:

3

Control animals:

yes, concurrent vehicle

Details on study design:

- Control animals were administered 0.1 ml tricaprylin. The animals of the test and control group were sacrificed 24 h after injection and blood was collected in heparinsed tubes. The control animals were killed at the same time.
- Isolation of globin
- Derivatisation of globin samples
- Calibration
- Analysis of PFPTHs with GC/MS and GC/MS-MS

Results and discussion

Any other information on results incl. tables

- Characterisation of the pentafluorophenylthiohydantoin derivatives of the glycidyl ether-valine adducts by GC-MS: adduct formation mainly occurs through reaction of valine with the chiral beta-carbon of the glycidyl ethers.

- Haemoglobin adduct levels in glycidyl ether-treated mice: The HBI (haemoglobin binding index)-values were used to calculate the dose in erythrocytes resulting from 1 mmol/kg body weight of the various glycidyl ethers. The doses calculated for the glycidyl ethers are somewhat lower than that of other substances like propylene oxide suggesting a rapid detoxification of the compounds in the mouse. Therefore the test substance appears to be more rapidly detoxified.

- HBI of the test substance = 1.3 pmol/g globin.

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