Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non guideline, no GLP

Data source

Reference
Reference Type:
publication
Title:
The Metabolism of Cyclo-octene, 1, 3-cyclo-octadiene and 1, 5-cyclo-octadiene in the Rat and Rabbit, and the Reaction of these Compounds with Glutathione in vivo in the Rat
Author:
Waring, R.H.
Year:
1971
Bibliographic source:
Xenobiotica 1, 303-308

Materials and methods

GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): cyclooctene

Test animals

Species:
other: rats and rabbits
Strain:
not specified
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
2.0 mmol/kg bw
No. of animals per sex per dose:
6
Control animals:
no

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Two sulfur containing metabolites were detected in urine of both female rats and rabbits following a single dose of cyclooctene.
These were identified as 2-hydroxycyclo-octyl mercapturic acid and 3-hydoxycyclo-octyl mercapturic acid by co-chromatography with synthetic standards and mass spectrometry.
Cis/trans isomers were present in 1:1 ratio.

Any other information on results incl. tables

Sulfur containing metabolites in urine (24h)

 

Dose (mmol/kg bw)

Female Rabbit (n=6)

Female Rat (n=6)

Glucuronide (% of dose)

Ethereal sulphate
(% of dose)

Mercapturic acids
(% of dose)

Mercapturic acids
(% of dose)

2-Hydroxy-

3-Hydroxy-

2-Hydroxy-

3-Hydroxy-

Cyclooctene

2.0

51.2

20.3

2.3

8.3

4.9

7.2

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
More than 80% of an oral dose of 2 mmol cyclooctene (220mg)/kg bw was excreted within 24h as sulfur containing metabolites indicating extensive absorption and extensive metabolism including hydroxylation as well as rapid excretion.
Executive summary:

In a published study the formation of sulfur containing metabolites in female rabbits and rats was investigated.

Animals received a single dose of 2 mmol (220mg) per kg bw, 24h urine was collected and analysed. More than 80% of the dose was recovered as sulfur containing metabolites of which 2-hydroxy and 3-hydroxy-mercapturic acids were identified.