Allyl 2,3-epoxypropyl ether

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Biotransformation of the double bond in allyl glycidyl ether to an epoxide ring. Evidence from hemoglobin adducts in mice.

Author:

Pérez HL and Osterman-Golkar S

Year:

2000

Bibliographic source:

Chemico-biological interactions 125: 17-28. Cited in OECD SIDS (SIAM 25, October 2007, Helsinki)

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

Nine male mice (C3H/Hej) were administered the test substance dissolved in tricaprylin, 4 mg/mouse, by intraperitoneal (i.p.) injection. Adducts to N-terminal valine in hemoglobin were analyzed using a modified Edman method for derivatization and using gas chromatography/tandem mass spectrometry for detection.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Allyl 2,3-epoxypropyl ether

EC Number:

203-442-4

EC Name:

Allyl 2,3-epoxypropyl ether

Cas Number:

106-92-3

Molecular formula:

C6H10O2

IUPAC Name:

2-[(prop-2-en-1-yloxy)methyl]oxirane

Details on test material:

- Name of test material (as cited in study report): Allyl glycidyl ether (AGE)
- Analytical purity: 99%

Test animals

Species:

mouse

Strain:

C3H

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld, Germany or bred at the Arrhenius Laboratories for Natural Sciences, Stockholm, Sweden
- Average weight at study initiation: 28 g
- Diet (e.g. ad libitum): standard pellet diet
- Water (e.g. ad libitum): tap water

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: tricaprylin

Details on exposure:

VEHICLE
- Concentration in vehicle: 4 mg/100 µl

Duration and frequency of treatment / exposure:

single injection

Doses / concentrations

Remarks:

Doses / Concentrations:
4 mg/mouse

No. of animals per sex per dose / concentration:

9

Control animals:

yes

Details on dosing and sampling:

- The animals were sacrificed 5 or 24 h after treatment and blood was collected in heparinized tubes. The control animals were killed 5 h after exposure.
- Adducts to N-terminal valine in hemoglobin were analyzed using a modified Edman method for derivatization and using gas chromatography/tandem mass spectrometry for detection.

Results and discussion

Any other information on results incl. tables

Adducts of diglycidyl ether (I) or 2,3-dihydroxypropyl glycidyl ether (III) with N-terminal valine, N-(2-hydroxy-3-(2,3-dihydroxy)propyloxy) propylvaline (diOHPrGEVal) were demonstrated in mice administered the test substance by i.p. injection. The levels were in the 1600-5600 pmol/g globin.

Table: Hemoglobin adducts formed from AGE and its metabolites 2,3-dihydroxypropyl glycidyl ether or diglycidyl ether in mice treated with AGE.

Time after treatment (h)	AGEVal (pmol/g globin)	diOHPrGEVal (pmol/g globin) Mean (±)
5	n.d (a)	2.3 (±0.7) x 10E3 (n =3) (b)
24	1.6 x 10E3 (n =4)	n.d
24	n.d	5.0 (±0.7) x 10E3 (n =3)
24	n.d	2.2 (±0.7) x 10E3 (n =3)
5 *	n.d	<20 (n =4)

* control group; (a) not determined; (b) n denotes the number of mice;

AGE may directly, without metabolic activation, react with N-terminal valine (AGEVal). Metabolism of AGE may lead to formation of diglycidyl ether (I) by P450-catalysed epoxidation or to 1-allyloxy-2,3-dihydroxypropane (II) by epoxide hydrolase-catalysed hydrolysis. 2,3-Dihydroxypropyl glycidyl ether (III) may be formed either by hydrolysis of I or epoxydation of II. Both I and III may give the N-(2-hydroxy-3-(2,3-dihydroxy)propyloxy)propylvaline adduct. AGEVal was not detected in control mice (n =6; detection limit 2 pmol/g globin).