Butanone oxime

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics 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

Objective of study:

other: Disposition

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 intravenous (i.v.) 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

Route of administration:

intravenous

Vehicle:

other: isotonic saline

Details on exposure:

Isotonic was used for iv doses, which were administered via the lateral tail vein at a volume of 0.8 mL/kg body weight.

Duration and frequency of treatment / exposure:

Single intravenous (iv) exposure

Doses / concentrations

Dose / conc.:

2.7 mg/kg bw/day (nominal)

Remarks:

A single dose level of 2.7 mg C14-MEKO/kg bw

No. of animals per sex per dose / concentration:

3 male rats per dose

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Adipose, blood, kidney, liver, muscle, skin, testis, urine, faeces, and volatiles.
- Time and frequency of sampling: 2, 8, 24 and 72 hours after iv administration

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: 0 and 8 hours after iv administration
- From how many animals: (samples pooled): 3
- Method type(s) for identification: HPLC

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

About 7% of the administered radioactivity remained in the tissues after 72 hours.

Details on excretion:

The i.v. dose of 2.7 mg/kg was principally excreted as CO2 (48.8%) with excretion in urine, and as expired volatiles, accounting for 21.4 and 11.4%, respectively.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles.

Applicant's summary and conclusion

Conclusions:

An intravenous dose of C-14 methyl ethyl ketoxime at 2.7 mg/kg body weight was primarily excreted as CO2 (48.8%) with excretion in urine, and as expired volatiles, accounting for 21.4 and 11.4%, respectively. About 7% of the administered radioactivity remained in the tissues after 72 hours. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles.