3,7-dimethylocta-2,6-dienenitrile

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from authoritative source

Data source

Reference

Reference Type:

publication

Title:

Proposal for Harmonised Classification and Labelling Based on Regulation (EC) No 1272/2008 (CLP Regulation), Annex VI, Part 2, Substance Name: 3,7-dimethylocta-2,6-dienenitrile

Author:

Federal Institute for Occupational Safety and Health, Germany

Year:

2013

Bibliographic source:

CLH REPORT FOR [3,7-DIMETHYLOCTA-2,6-DIENENITRILE]

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Principles of method if other than guideline:

Single oral administration toxicokinetics study of 3,7-dimethylocta-2,6-dienenitrile inmice

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

3,7-dimethylocta-2,6-dienenitrile

EC Number:

225-918-0

EC Name:

3,7-dimethylocta-2,6-dienenitrile

Cas Number:

5146-66-7

Molecular formula:

C10H15N

IUPAC Name:

3,7-dimethylocta-2,6-dienenitrile

Test material form:

other: liquid

Details on test material:

Name: 3,7-dimethylocta-2,6-dienenitrile (14C labeled)
Molecular Formula: C10H15N
Molecular Weight: 149.236 g/mole

Radiolabelling:

yes

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

The male and female CD-1 mouse were given single oral administration (gavage) of 300 or 600 mg/kg bw (bw) in corn oil (4-8 ml/kg bw). The actual mean radioactive doses ranged from 15.8 to 30 μCi/mouse

Duration and frequency of treatment / exposure:

48 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
300 or 600 mg/kg bw (bw)

No. of animals per sex per dose / concentration:

Not mentioned

Control animals:

not specified

Positive control reference chemical:

No data

Details on study design:

No data

Details on dosing and sampling:

No data

Statistics:

No data

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

3,7-dimethylocta-2,6-dienenitrile (geranonitrile, GN) undergoes rapid absorption after oral gavage administration. Total mean absorption ranged from 41 to 88% and appeared to be slightly higher in female than male mice.

Main ADME results 2

Type:

distribution

Results:

Peak concentrations of 14C residues in plasma occurred within 0.5 to 1 hour. Clearance from the plasma was also rapid as a result of extensive tissue distribution and biotransformation. It was detected in lung, liver, kidney, adrenals, ovaries and testes

Main ADME results 3

Type:

metabolism

Results:

Three major plasma metabolites were identified as 8- hydroxy-GN, 8-hydroxy-GN-glucuronide, and 8-carboxy-GN. The overall metabolism of GN was characterized by oxidation on the C8- position to form the alcohol, the aldehyde, the acid, and an epoxide.

Main ADME results 4

Type:

excretion

Results:

Material balance indicated minimal excretion of 14C residues by exhalation, with the majority of the dose recovered in urine and feces. Minimum residues (<2% of the dose) were retained in tissues by 48 hours after dose administration.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

3,7-dimethylocta-2,6-dienenitrile was metabolized to the alcohol, the aldehyde, the acid, and an epoxide (6,7-GNO)

Any other information on results incl. tables

Organs exhibiting radioactivity

Liver

Kidney

Ovaries

Gonads

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
3,7-dimethylocta-2,6-dienenitrile is rapidly absorbed and distributed to the tissues. It was detected in lung, liver, kidney, adrenals, ovaries and testes. 3,7-dimethylocta-2,6-dienenitrile is metabolized forming alcohol, the aldehyde, the acid, and an epoxide an and conjugated to glucuronide, glutathione, and amino acids. It is excreted mainly via urine and feces. Since minimum residues (<2% of the dose) were retained in tissues by 48 hours after dose administration, the bio-accumulation potential is expected to be low.

Executive summary:

In an in vivo study conducted on male and female mice (CD-1), which received single oral administration (gavage) of 300 or 600 mg/kg bw (bw) of the chemical in corn oil;3,7-dimethylocta-2,6-dienenitrile was metabolized forming alcohol, the aldehyde, the acid, and an epoxide an and conjugated to glucuronide, glutathione, and amino acids. It was excreted out of the living system mainly via urine and feces. Since minimum residues (<2% of the dose) were retained in tissues by 48 hours after dose administration, the bio-accumulation potential of the chemical is expected to be low.