2-cyclohexylidene-2-phenylacetonitrile

Basic toxicokinetics

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: Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Chemical models for toxic metabolites of bromobenzene derivatives: Relative toxicity toward isolated hepatocytes.

Author:

DAVID W. G (YrTSCHALL, RAYMOND R. HARDER~,ROBERT A. WILEY and ROBERT P. HANZLIK

Year:

1984

Bibliographic source:

TOXICOLOGY; 31 (3-4). 1984. 251-260.

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

according to guideline

Guideline:

other: refer below principle

Principles of method if other than guideline:

In Vitro metabolism of Cyclohexenecarbonitrile by using Sprague-Dawley rats cell line

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Cyclohexenecarbonitrile

EC Number:

217-454-2

EC Name:

Cyclohexenecarbonitrile

Cas Number:

1855-63-6

IUPAC Name:

cyclohex-1-ene-1-carbonitrile

Test material form:

other: Liquid

Details on test material:

- Name of test material (as cited in study report):Cyclohexenecarbonitrile- Molecular formula (if other than submission substance):C7H9N- Molecular weight (if other than submission substance):107.155- Smiles notation (if other than submission substance):N#CC1=CCCCC1- InChl (if other than submission substance):1S/C7H9N/c8-6-7-4-2-1-3-5-7/h4H,1-3,5H2- Substance type:Organic- Physical state:Liquid

Radiolabelling:

not specified

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

not specified

Administration / exposure

Route of administration:

other: Incubation

Vehicle:

other: 20 μl pentane

Details on exposure:

For lower concentrations of the more volatilecompounds (i.e. ≤ 5 mM; compounds Cyclohexenecarbonitrile) the incubation flask was charged with cells, flushed with O2/CO2 mixture, and the appropriate amount of test compound dissolved in 20 μl pentane was applied to a moist piece of filter paper (1 × 3 cm) adhering inside the neck of the flask just prior to capping the flask.

Duration and frequency of treatment / exposure:

Once

Doses / concentrations

Remarks:

Doses / Concentrations:2-4 mM

No. of animals per sex per dose / concentration:

92-95% of cells

Control animals:

not specified

Statistics:

No data

Results and discussion

Main ADME results

Type:

metabolism

Results:

Cyclohexenecarbonitrile shows lower oder of toxicity to hepatecytes were observed.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

No data available

Details on distribution in tissues:

No data available

Details on excretion:

No data available

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

No data available

Any other information on results incl. tables

EFFECTS OF UNSATURATED COMPOUNDS AND EPOXIDES ON RELEASE OF GPT FROM ISOLATED HEPATOCYTES

Compound	Method ofaddition	Concentration studied (mM)	ECs0 (mM) for GPT release (2 h)
1	A	2	12

^aContained 40-50% benzonitrile impurity

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study resultsCyclohexenecarbonitrile expected to have Low bio-accumulation potential based on study results.

Executive summary:

In a in vivo metabolism study,Sprague-Dawley rats cell line were treated withCyclohexenecarbonitriledissolved in a 20 μl pentane was applied to a moist piece of filter paper (1 × 3 cm) adhering inside the neck of the flask just prior to capping the flask.. Cyclohexenecarbonitrileappears toshows loweer oder of toxicity to hepatecytes by low GPT release with half-maximal release of GPT within 2 h as 12 mM as compared to bromobenzene which show 2.4 mM. Which is much lower than Cyclohexenecarbonitrile. Hance, it is clear that neither the presence of a simple Michael acceptor function (Cyclohexenecarbonitrile) nor the presence of a simple epoxide moiety is sufficient to render the molecule a potent toxin.Therefore,Cyclohexenecarbonitrile considered to haveLow bio-accumulation potential based on study results.