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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
See Specific explanation in addition to field 'Justification for data waiving' in the attached document (see field 'Attached justification' below).
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
data waiving: supporting information
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).

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Few details are available.
Principles of method if other than guideline:
no data
GLP compliance:
no
Limit test:
yes
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Age at study initiation: weanling rats
- Housing: individually in wire cages
- Diet: ad libitum
- Water: ad libitum
- Source, weight at study initiation, fasting period before study, acclimation period: no data

ENVIRONMENTAL CONDITIONS (Temperature, humidity, air changes, photoperiod): no data

IN-LIFE DATES: no data
Route of administration:
oral: feed
Vehicle:
not specified
Details on oral exposure:
- Vehicle: no data
- Diet preparation: fresh diets were made and distributed weekly
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
16 weeks
Frequency of treatment:
daily
Dose / conc.:
0 ppm
Dose / conc.:
10 000 ppm
Remarks:
Nominal in diet
No. of animals per sex per dose:
5 females and 5 males
Control animals:
yes
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: Yes (weekly)
* FOOD EFFICIENCY: No data
* OPHTHALMOSCOPIC EXAMINATION: No data
* HAEMATOLOGY: Yes
> Time schedule for collection of blood: at termination of the study
> Anaesthetic used for blood collection: No data
> Animals fasted: No data
> How many animals: data not available
> Parameters: white cell counts, red cell counts, haematocrit
* CLINICAL CHEMISTRY: No data
* URINALYSIS: No data
* NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
* SACRIFICE AND PATHOLOGY (see Table 2 in attached document):
> GROSS PATHOLOGY: Yes (see table)
> HISTOPATHOLOGY: Yes (see table)
Statistics:
no data
Clinical signs:
not specified
Mortality:
not specified
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:
no effects observed
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:
not specified
Dose descriptor:
NOAEL
Effect level:
10 000 ppm
Sex:
male/female
Basis for effect level:
other: body weight; haematology; gross pathology; histopathology;
Remarks on result:
other: No effect observed.
Critical effects observed:
not specified
Conclusions:
No effects observed at 10000 ppm of vanillin.
Executive summary:

In a repeated sub-chronic study, males and females rats were exposed daily to 0 or 10 000 ppm of vanillin by feed during 16 weeks. At 10 000 ppm, compared to the control group, there is no effect on body weight, haematological parameters and on gross pathology and histopathological findings.

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Few details are available
Principles of method if other than guideline:
no data
GLP compliance:
no
Limit test:
yes
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Age at study initiation: weanling rats
- Housing: individually in wire cages
- Diet: ad libitum
- Water: ad libitum
- Source, weight at study initiation, fasting period before study, acclimation period: no data

ENVIRONMENTAL CONDITIONS (Temperature, humidity, air changes, photoperiod): no data

IN-LIFE DATES: no data
Route of administration:
oral: feed
Vehicle:
not specified
Details on oral exposure:
- Diet preparation: fresh diets were made and distributed weekly
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
27-28 weeks
Frequency of treatment:
no data
Dose / conc.:
0 ppm
Dose / conc.:
1 000 ppm
Remarks:
Nominal in diet
No. of animals per sex per dose:
5 females and 5 males
Control animals:
yes
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: Yes (weekly)
* FOOD EFFICIENCY: No data
* OPHTHALMOSCOPIC EXAMINATION: No data
* HAEMATOLOGY: Yes
> Time schedule for collection of blood: at termination of the study
> Anaesthetic used for blood collection: No data
> Animals fasted: No data
> How many animals: data not available
> Parameters: white cell counts, red cell counts, haematocrit
* CLINICAL CHEMISTRY: No data
* URINALYSIS: No data
* NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
* SACRIFICE AND PATHOLOGY (see Table 2 in attached document):
> GROSS PATHOLOGY: Yes (see table)
> HISTOPATHOLOGY: Yes (see table)
Statistics:
no data
Clinical signs:
not specified
Mortality:
not specified
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:
no effects observed
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
Dose descriptor:
NOAEL
Effect level:
>= 1 000 ppm
Sex:
male/female
Basis for effect level:
other: body weight, haematology, gross pathology, histopathology
Remarks on result:
other: No effect observed.
Critical effects observed:
not specified
Conclusions:
No effect observed at 1000 ppm of vanillin.
Executive summary:

Males and females rats were exposed by feed to vanillin during 27-28 weeks at 0 and 1000 ppm. Compared to the control group, there is no effect on body weight, haematological parameters, gross pathology and histopathological findings at 1000 ppm of vanillin.

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Few details are available
Principles of method if other than guideline:
no data
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Age at study initiation: weanling rats
- Housing: individually in wire cages
- Diet: ad libitum
- Water: ad libitum
- Source, weight at study initiation, fasting period before study, acclimation period: no data

ENVIRONMENTAL CONDITIONS (Temperature, humidity, air changes, photoperiod): no data

IN-LIFE DATES: no data
Route of administration:
oral: feed
Vehicle:
propylene glycol
Details on oral exposure:
- Vehicle: propylene glycol (3 % w/w added to control and test diets)
- Diet preparation: fresh diets were made and distributed weekly
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2 years
Frequency of treatment:
no data
Dose / conc.:
0 ppm
Dose / conc.:
5 000 ppm
Remarks:
Nominal in diet.
Dose / conc.:
10 000 ppm
Remarks:
Nominal in diet.
Dose / conc.:
20 000 ppm
Remarks:
Nominal in diet.
No. of animals per sex per dose:
12 females and 12 males
Control animals:
yes, concurrent vehicle
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: Yes (weekly)
* FOOD EFFICIENCY: No data
* OPHTHALMOSCOPIC EXAMINATION: No data
* HAEMATOLOGY: Yes
> Time schedule for collection of blood: 3, 6, 12 and 22 months
> Anaesthetic used for blood collection: No data
> Animals fasted: No data
> How many animals: data not available
> Parameters: white cell counts, red cell counts, haematocrit
* CLINICAL CHEMISTRY: No data
* URINALYSIS: No data
* NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
> GROSS PATHOLOGY: Yes (see table)
> HISTOPATHOLOGY: Yes (see table)

Statistics:
no data
Clinical signs:
not specified
Mortality:
not specified
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:
no effects observed
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
Dose descriptor:
NOAEL
Effect level:
>= 20 000 ppm
Sex:
male/female
Basis for effect level:
other: body weight, haematology, gross pathology, histopathology
Remarks on result:
other: No effect observed up to 20 000 ppm of vanillin.
Critical effects observed:
not specified
Conclusions:
No effect observed up to 20 000 ppm of vanillin.
Executive summary:

Males dans females rats (12 animals/sex/dose) received 0, 5000, 20 000 or 50 000 ppm of vanillin by feed during 2 years. No effect were observed on body weight, haematological parameters, gross pathology and histological findings up to 20 000 ppm and compared to the control group.

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Few details are available
Principles of method if other than guideline:
no data
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Osborne-Mendel
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Age at study initiation: weanling rats
- Housing: individually in wire cages
- Diet: ad libitum
- Water: ad libitum
- Source, weight at study initiation, fasting period before study, acclimation period: no data

ENVIRONMENTAL CONDITIONS (Temperature, humidity, air changes, photoperiod): no data

IN-LIFE DATES: no data
Route of administration:
oral: feed
Vehicle:
corn oil
Details on oral exposure:
- Vehicle: corn oil (3 % w/w added to control and test diet)
- Diet preparation: fresh diets were made and distributed weekly
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
1 year
Frequency of treatment:
no data
Dose / conc.:
0 ppm
Dose / conc.:
20 000 ppm
Remarks:
Nominal in diet.
Dose / conc.:
50 000 ppm
Remarks:
Nominal in diet.
No. of animals per sex per dose:
5 males per dose
Control animals:
yes, concurrent vehicle
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: Yes (weekly)
* FOOD EFFICIENCY: No data
* OPHTHALMOSCOPIC EXAMINATION: No data
* HAEMATOLOGY: Yes
> Time schedule for collection of blood: at termination of the study
> Anaesthetic used for blood collection: No data
> Animals fasted: No data
> How many animals: data not available
> Parameters: white cell counts, red cell counts, haematocrit
* CLINICAL CHEMISTRY: No data
* URINALYSIS: No data
* NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
> GROSS PATHOLOGY: Yes (see table)
> HISTOPATHOLOGY: Yes (see table)
Statistics:
no data
Clinical signs:
not specified
Mortality:
not specified
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:
no effects observed
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
Dose descriptor:
NOAEL
Effect level:
>= 50 000 ppm
Sex:
male
Basis for effect level:
other: body weight, haematology, gross pathology, histopathology
Remarks on result:
other: No effect observed up to 50 000 ppm of vanillin.
Critical effects observed:
not specified
Conclusions:
No effects observed up to 50 000 ppm of vanillin.
Executive summary:

Male rats were exposed by feed to vanillin (0, 20 000 and 50 000 ppm) during 1 year. Compared to the control group, there is no effect on body weight, haematological parameters, gross pathology and histophatological findings up to 50 000 ppm of vanillin.

Data source

Materials and methods

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion