Registration Dossier

Administrative data

Endpoint:
dermal absorption 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

Principles of method if other than guideline:
Eleven male mice (C3H/Hej) were administered 4 mg/mouse of the test substance dissolved in acetone, by skin application. 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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Allyl glycidyl ether (AGE)
- Analytical purity: 99%
Radiolabelling:
no

Test animals

Species:
mouse
Strain:
C3H
Sex:
male
Details on test animals 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

Type of coverage:
open
Vehicle:
acetone
Duration of exposure:
5 or 24 h
Doses:
4 mg/mouse

No. of animals per group:
6
Control animals:
yes

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) was below the detection limit of the analytical method, 20 pmol/g globin (n=5). The level of AGEVal (AGE reacted with N-terminal valine) in mice administered AGE by skin application (n=6) was about 20 pmol/g globin. Neither AGEVal nor diOHPrGEVal were detected in control animals.

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

Supplier of mice

Time after treatment (h)

AGEVal (pmol/g globin)

diOHPrGEVal (pmol/g globin) Mean (±)

Charles River

5

18; 27 (a)

n.d (b)

Charles River

24

23; 99 (a)

n.d

Stockholm

24

9; 15 (a)

n.d

Stockholm and  

Charles River

24

n.d

<20 (n =5) (c)

 Charles River

5*

n.d

<20 (n =3)

Stockholm and  

Charles River

5*

<2 (n =6)

n.d

(a) data for individual animals; (b) not determined; (c) n denotes the number of mice; * control groups

Applicant's summary and conclusion