Cyclopentanone

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The purity of the test substances was unknown. However, the study was well conducted and the results were quite detailed.

Data source

Reference

Reference Type:

publication

Title:

the metabolism of alicyclic ketones in the rabbit and rat.|- Bibliographic source

Author:

James SP, Waring RH

Year:

1971

Bibliographic source:

Xenobiotica, 1(6), 573-580

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Modified naphtharesorcinol method described by Bray et al. (1952), method of Folin, mass spectrometry and gas-liquid chromatography

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cyclopentanone

EC Number:

204-435-9

EC Name:

Cyclopentanone

Cas Number:

120-92-3

Molecular formula:

C5H8O

IUPAC Name:

cyclopentanone

Details on test material:

Cyclopentanone purchased from Koch-Light Ltd. No more data

Radiolabelling:

no

Test animals

Species:

other: rats and rabbits

Strain:

other: WISTAR and NEW ZEALAND

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Species: rat and rabbit
- Strain: Wistar (rat) and White New Zealand (rabbit)
- Sex: female
- Source, Age at study initiation, Weight at study initiation, Fasting period before study, Housing, Individual metabolism cages, Diet, Water,
Acclimation period: data not available

ENVIRONMENTAL CONDITIONS (temperature, humidity , air changes, photoperiod: data not available

IN-LIFE DATES: data not available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Duration and frequency of treatment / exposure:

single exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
Rats and rabbits received by gavage a dose of:
- cyclopentanone at 203 mg/kg bw and 193 mg/kg bw respectively,
- cyclohexanone at 245 mg/kg bw and 186 mg/kg bw respectively.

No. of animals per sex per dose / concentration:

no data available

Control animals:

no

Details on study design:

no data available

Details on dosing and sampling:

- Tissues and body fluids sampled: urine
- Time and frequency of sampling: data not available
Urine samples were collected and metabolites excreted in urine were analysed by:
- gas-liquid chromatography to determine sulphur-containing metabolites and 2-hydroxycycloalkylmercapturic acids.
- mass spectrometry to determine the methyl esters of the metabolites.
- the method of Folin to determine sulphate.
- the modified naphtharesorcinol method described by Bray et al. (1952) to determine glucuronic acid.

Liver extracted from undosed and dosed rats were prepared for the determination of total glutathione by the method of Martin & McIlwain (1959).

Statistics:

no data available

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Sulphur containing metabolites were detected at 2.5% and 3% of the cyclopentanone administered dose, in rabbit and rat urine respectively:
- rabbits and rats excreted traces of the corresponding 2-hydroxycyclopentylmercapturic acids. Both cis and trans isomers of the
2-hydroxycyclopentylmercapturic acids were detected by gas-liquid chromatography.
- mass spectroscopic analysis suggested that further sulfur containing metabolite was the sulphate ester of 2-hydroxycyclopentylmercapturic acid.
It was excreted both in urine of rabbits (at 2% of the dose administered) and rats.

Glucuronic acid conjugate was the major metabolite in rabbits and found in urine at 47% of the dose administered.
Cyclopentanone gave a slight reduction in the level of total glutathione in the rat liver, presumably because glutathione was involved in the
metabolism of the cyclopentanone to the corresponding mercapturic acid.

After cyclohexanone administration, only cis 2-hydroxy- cyclohexylmercapturic acid was detected in rabbits and rats. Further sulphur-containing
metabolites excreted by both rabbits and rats were detected: it is also postulated that these metabolites were sulphate esters of hydroxymercapturic
acids.
In rabbits, the major metabolite of cyclohexanone was a glucuronide (66% of the dose).

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The major metabolite of cyclopentanone in rabbit after oral route (gavage) exposure is glucosiduronic acid (ca. 47%). Other metabolites were
excreted in rabbit urine such as ethereal sulphate (ca. 2%), sulphur-containing metabolite (ca. 2.5) and traces of 2-hydroxycycloalkylmercapturic
acids.
In rats, traces of the corresponding 2-hydroxycycloalkylmercapturic acids and small amounts of a second sulphur-containing metabolite are
excreted.

Executive summary:

In this study, rats and rabbits were treated (gavage, single exposure) with cyclopentanone (193 and 203 mg/kg bw) and cyclohexanone (186 and 245 mg/kg bw). Rabbits and rats dosed with cyclopentanone or cyclohexanone excrete traces of the corresponding 2 -hydroxycycloalkylmercapturic acids. In each case small amounts of a second sulphur-containing metabolite are excreted. In rabbits the major metabolite of cyclopentanone and cyclohexanone is glucosiduronic acid. In both species, the metabolism of cyclopentanone resembles that of cyclohexanone.