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Toxicological information

Basic toxicokinetics

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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

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:
(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.