glyoxal … %; ethandial … %

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

Version / remarks:

(2004)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.7600 (Dermal Penetration)

Version / remarks:

(1998)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Glyoxal

EC Number:

203-474-9

EC Name:

Glyoxal

Cas Number:

107-22-2

Molecular formula:

C2H2O2

IUPAC Name:

oxalaldehyde

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 954-1012

RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity: 96.1%
- Specific activity: 69.2 MBq/mg
- Locations of the label: 1,2-14C

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at low temperatures and the dark

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain as described in the report: Crl:WI(Han)
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld
- Age at start of acclimatization: 6 to 12 weeks
- Weight at study initiation: 250 - 350 g
- Housing: prior test initiation, in groups in Macrolon cages; during experiment, individually in all-glass metabolism cages type Metabowl (Jencons Leighton Buzzard, U.K.) labeled with the project number, animal number, dose and time of first application
- Diet (e.g. ad libitum): Kliba mouse/rat maintenance diet “GLP” (Provimi Kliba SA, Kaiseraugst, Switzerland), ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: planned, duration not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): air-conditioned room
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h
- Any deviations will be documented

ANALYSIS OF FOOD, WATER, BEDDING
- The food used in the study will be assayed for chemical and microbial contaminants according to the Fed. Reg. Vol. 44, No. 91 of May. 09, 1979, p 27354 (EPA);
- The drinking water is regularly assayed for chemical contaminants both by the municipal authorities of Frankenthal and by the Environmental Analytics Water/Steam Monitoring of BASF SE as well as for bacteria by a contract laboratory. The Drinking Water Regulation will serve as the guideline for maximum tolerable contaminants;
- The bedding (Type Lingocel FS 14 fibres, dustfree bedding, supplied by SSNIFF, Soest, Germany) is regularly assayed for contaminants (chlorinated hydrocarbons and heavy metals). The values given in Lab Animal, Nov.–Dec. 1979, pp 24–33, will serve as the guideline for maximum tolerable contaminants.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Duration of exposure:

The complete exposure period was 8 hours.

Doses:

Nominal doses: 20 µg/cm2
The intended amount of radioactivity per animal was about 0.5 - 2 MBq/animal.

No. of animals per group:

Four animals/group

Control animals:

no

Details on study design:

DOSE PREPARATION
In order to achieve the intended activity in the solution, an appropriate amount of stock solution of the radiolabeled test substance will be evaporated to dryness. The dried residue will be mixed with an appropriate amount of Glyoxal solved in water. The final concentration of Glyoxal in water should be 0.2 % (w/w). The preparation will be stirred and sonicated in order to produce homogeneous preparation.

APPLICATION OF DOSE:
24 hours before treatment, the animal will be thoroughly clipped and then cleaned with acetone. Animals showing skin damage at the time of dosing will not be used. On the day of dosing, a spacer will be glued to the skin with tissue glue. The test item preparation will be administered to the application site (dosing volume: 10 μl/cm²; treated area: about 10 cm²). The treated skin area will be covered with a permeable (gauze) dressing and the whole further protected beneath a semi occlusive adhesive bandage.

REMOVAL OF TEST SUBSTANCE
After exposure, the gauze and bandage will be removed from the animals. The skin of the animals will be washed with a mild soap solution and rinsed with warm water. For animals with a post-observation period, a new gauze and bandage will be applied and an additional skin wash will be done before sacrifice.

SAMPLING
Excreta (urine, feces), blood (blood cells and plasma), application site, skin surrounding the application site, remaining carcass, and skin wash(es) will be sampled. For balance estimates the cage wash, the gauze with bandage and the glas ring also will be assayed for radioactivity.

ANALYSIS
Radioactivity in all samples of biological material will be counted in a liquid scintillation counter. The samples will be prepared for analysis using conventional methods described in standard operating procedures, any additional measures/deviations from standard practice will be detailed in the raw data and the study report. Unless stated otherwise in this protocol or in the study raw data, total radioactivity is measured.

Results and discussion

Total recovery:

Following a single dermal administration [14C]-glyoxal, the mean recovery of radioaetivity in the different groups was between 102% and 107% of the applied radioactivity.

Percutaneous absorption

Percutaneous absorption 1

Dose:

0.68 mg/kg bw

Parameter:

percentage

Absorption:

ca. 4.6 %

Remarks on result:

other: 8 h

Percutaneous absorption 2

Dose:

0.68 mg/kg bw

Parameter:

percentage

Absorption:

ca. 6.4 %

Remarks on result:

other: 24 h

Percutaneous absorption 3

Dose:

0.68 mg/kg bw

Parameter:

percentage

Absorption:

ca. 5.4 %

Remarks on result:

other: 120 h