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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is sufficiently documented and is acceptable for the assessment. Performed before GLP establishment.

Data source

Reference
Reference Type:
publication
Title:
The metabolism of vanillin and isovanillin in the rat
Author:
Strand LP and Scheline RR
Year:
1975
Bibliographic source:
Xenobiotica, 5(1), 49-63

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
Metabolism by oral route
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Test material identity: vanillin from commercial source (no other information are available)

Test animals

Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS:
- Species: rat
- Strain: no data
- Sex: male
- Weight at study initiation: 200-350 g (qualitative experiments), approx. 250 g (quantitative experiments)
- Diet: purified diet, ad libitum
- Water: ad libitum
- Source, age at study initiation, fasting period before study, housing, individual metabolism cages, 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:
other: water (qualitative experiments) or propylene glycol-water 1:1 (quantitative experiments)
Details on exposure:
no data
Duration and frequency of treatment / exposure:
single administration
Doses / concentrations
Remarks:
Doses / Concentrations:
100 mg/kg or 300 mg/kg
No. of animals per sex per dose:
6 males per dose
Control animals:
not specified
Positive control:
no
Details on study design:
no data
Details on dosing and sampling:
- Tissues and body fluids sampled: urine, faeces, bile
- Time and frequency of sampling: 24, 48 and 96 hrs after dosing
- From how many animals: data not available
- Method type(s) for identification: GC and GC-MS
- Limits of detection and quantification: data not available
Statistics:
no data

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Vanillic acid, Vanilliyl alcohol . . .

Any other information on results incl. tables

QUALITATIVE EXPERIMENT:
Table 1: Urinary metabolites of vanillin after oral administration to rats
-------------------------------------------------------------------------- --
Metabolite detected                Free fraction                Conjugated fraction
-------------------------------------------------------------------------- --
Vanillin                         
      0/6                         6/6
Vanillyl alcohol                 
    6/6                         6/6
Vanillic acid                         
   6/6                         6/6
Protocatechuic acid                  0/6                         4/6
Vanilloylglycine                 
   6/6                         6/6 (trace)
Catechol                         
    3/6                         6/6
4-Methylcatechol                  0/6                         6/6
Guaiacol                         
    0/6                          5/6
4-Methylguaiacol                 0/6                          5/6

QUANTITATIVE EXPERIMENT:
Table 2: Urinary excretion of vanillin and metabolites in rats (urine collected for 48 h after oral administration of approx. 100 mg/kg  vanillin)
-------------------------------------------------------------------------- --
Metabolite                Approximate mean excretion values (%)
-------------------------------------------------------------------------- --
Vanillin                  7
Vanillyl alcohol          19
Vanillic acid                47
Vanilloylglycine         10
Catechol                  8
4-Methylcatechol        2
Guaiacol                  0.5
4-Methylguaiacol       0.6

Vanillin undergo two primary pathways of transformation, oxidation and  reduction.
However, the quantitative results show that oxidative metabolism  dominates.

Applicant's summary and conclusion