Vanillin

Endpoint summary

Description of key information

In a subchronic study by oral route (Monsanto, 1955, reliability 2) selected as a key study, no effect related to vanillin was observed. Based on this study, the NOAEL determined was 650 mg/kg/day. 
Other studies by dermal and inhalation route were poorly described and were not taken into account for assessment.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

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.

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

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

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

Dose / conc.:

0 ppm

Dose / conc.:

1 000 ppm

Remarks:

Nominal in diet. Corresponds to 0.1%.

Dose / conc.:

5 000 ppm

Remarks:

Nominal in diet. Corresponds to 0.5%.

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

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

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

Dose descriptor:

NOAEL

Effect level:

10 000 ppm

Sex:

male

Basis for effect level:

other: no effect observed

Critical effects observed:

not specified

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

650 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

8 studies by oral route on rats and mice were available from 16 weeks to 2 years of treatment. Only one of them (Monsanto, 1955) was selected as key study and was with validity 2.

Other available studies were with validity from 2 to 4.

All studies described by Hagan, 1967 (validity 2), in which the time of treatment varied from 16 weeks to 2 years, were selected for a weight of evidence approach. Hagans' studies were summarised in WHO technical report 909 published in 2002.

In most of these studies, no effects were observed (body weight, clinical signs, organ weight, histopathology. . .).

The key study has the following summary:

In a subchronic toxicity study (Mosanto, 1955) vanillin (purity unknown) was administered to male Carworth Farms rats, 10/dose, in diet at dose levels of 0, 1000, 5000,10000ppm.No effect related to vanillin was observed.

The NOEL is 10000 ppm (equivalent to ca. 650 mg/kg bw/d).

One study by dermal route and two studies by inhalation route were available. They were of validity 4, poorly described and were not taken into account for assessment.

Justification for classification or non-classification

All the results available indicated that Vanillin had no effect in oral subchronic toxicity studies. According to classification criteria of EC regulation 1272/2008 Vanillin should not be classified for repeated exposure.