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Diss Factsheets

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:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
publication
Title:
Disposition of methyl ethyl ketoxime in the rat after oral, intravenous and dermal administration
Author:
Burka, L.T. et al.
Year:
1998
Bibliographic source:
Xenobiotica 28(10): 1005-1015, 1998

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The disposition of 14C-MEKO was determined in the male F344 rat following dermal administration.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Butanone oxime
EC Number:
202-496-6
EC Name:
Butanone oxime
Cas Number:
96-29-7
Molecular formula:
C4H9NO
IUPAC Name:
butan-2-one oxime
Test material form:
liquid
Radiolabelling:
yes
Remarks:
14C-methyl ethyl ketoxime

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Age at study initiation: 11-13 weeks old
- Weight at study initiation: 210-265 g
- Fasting period before study: no data
- Housing: During experiments, rats were housed individually in glass metabolism cages which provided for the separate collection of urine, feces, CO2 and other volatiles.
- Diet (e.g. ad libitum): Purina Rodent Chow #5002, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2 +/- 1.6
- Humidity (%): 50 +/- 20
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
open
Vehicle:
acetone
Duration of exposure:
Single dermal exposure
Doses:
Dose levels evaluated: 2.7 and 270 mg C14-MEKO/kg body weight
No. of animals per group:
3 male rats per dose
Control animals:
no
Details on study design:
Dermal dose formulations were prepared in acetone to deliver ~20 uCi in a single dose volume of 200 uL and were applied to a 12 square cm area from which the hair had been clipped the previous day. Dose site areas were inspected for damage prior to dosing and any animals with damage in the clipped area were excluded from the study. Dose sites were protected from grooming by a nonocclusive foam appliance with a cloth cover and metal shield.

Results and discussion

Percutaneous absorptionopen allclose all
Dose:
2.7 mg/kg
Parameter:
percentage
Absorption:
ca. 26 %
Remarks on result:
other: 72 hours
Remarks:
Volatilisation from the dose site prior to placement in the metabolism cage may account for the low absorption.
Dose:
270 mg/kg
Parameter:
percentage
Absorption:
ca. 13 %
Remarks on result:
other: 72 hours
Remarks:
Volatilisation from the dose site prior to placement in the metabolism cage may account for the low absorption.

Applicant's summary and conclusion

Conclusions:
Following dermal application of C14-methyl ethyl ketoxime at 2.7 and 270 mg/kg body weight, approximately 26 and 13% of the 2.7 and 270 mg C14 MEKO/kg doses, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption.