Butanone oxime

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:

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

Test material information

Constituent 1

Reference substance name:

Butanone oxime

EC Number:

202-496-6

EC Name:

Butanone oxime

Cas Number:

96-29-7

Molecular formula:

C4H9NO

IUPAC Name:

(NE)-N-butan-2-ylidenehydroxylamine

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 absorption

Percutaneous absorption 1

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.

Percutaneous absorption 2

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.