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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

Toxicological information

Basic toxicokinetics

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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

Constituent 1
Chemical structure
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).

Applicant's summary and conclusion