Vanillin

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Even if all the detail are not given, the test condition described are reliable for the assessment. Test performed before GLP establishment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1955

Report date:

1955

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

only male rats were used, exposure of 26 weeks instead of 13 weeks, no detailed information about the observations

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Vanillin

EC Number:

204-465-2

EC Name:

Vanillin

Cas Number:

121-33-5

Molecular formula:

C8H8O3

IUPAC Name:

1-butoxypropan-2-ol

Details on test material:

Vanillin from Monsanto Chemical Company (USA), received on 18-JAN-1955
* Physical state: solid
* Analytical purity, impurities, purity test date, lot/batch No, expiration date of the lot/batch, stability under test conditions, storage condition of test material: data not available

Test animals

Species:

rat

Strain:

other: Carworth Farms

Sex:

male

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 57 to 74 g
- Housing: individually in wire meash cages elevated above the droppings
- Diet: ad libitum
- Water: ad libitum
- Source, age at study initiation, fasting period before study, acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data
IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on oral exposure:

* DIET PREPARATION:
Rate of preparation of diet: weekly
Storage temperature of food: no data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

26 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 ppm

Doses / concentrations 2

Dose / conc.:

1 000 ppm

Remarks:

Nominal in diet. Corresponds to 0.1%.

Doses / concentrations 3

Dose / conc.:

5 000 ppm

Remarks:

Nominal in diet. Corresponds to 0.5%.

Doses / concentrations 4

Dose / conc.:

10 000 ppm

Remarks:

Nominal in diet. Corresponds to 1%.

No. of animals per sex per dose:

10 animals per dose group

Control animals:

yes, plain diet

Details on study design:

Post-exposure period: none

Positive control:

no

Examinations

Observations and examinations performed and frequency:

* CAGE SIDE OBSERVATIONS: No data
* DETAILED CLINICAL OBSERVATIONS: No data
* BODY WEIGHT: Yes (weekly)
* FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
* FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
* OPHTHALMOSCOPIC EXAMINATION: No data
* HAEMATOLOGY: No data
* CLINICAL CHEMISTRY: No data
* URINALYSIS: No data
* NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

* SACRIFICE AND PATHOLOGY:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see table)

Statistics:

statistical analysis of body weight was by means of the Fisher Student "t" test

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEL

Effect level:

10 000 ppm

Sex:

male

Basis for effect level:

other: no effect observed

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No effect related to vanillin was observed.

Executive summary:

In a subchronic toxicity study (Anon., 1955) vanillin (purity unknown) was administered to male Carworth Farms rats, 10/dose, in diet at dose levels of 0, 1000, 5000, 10000 ppm.
No effect related to vanillin was observed.
The NOEL is 10000 ppm (equivalent to ca. 650 mg/kg bw/d).