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EC number: 225-918-0 | CAS number: 5146-66-7
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:
- 2 013
- 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
- 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
Constituent 1
- 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 resultsopen allclose all
- 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.
- 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
- 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.
- 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
GonadsApplicant'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.
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