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EC number: 204-465-2 | CAS number: 121-33-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Endpoint summary
Administrative data
Description of key information
LD50 oral (rat): 3978 mg/kg bw. Vanilline is not harmful by ingestion according to CLP criteria.
LD50 dermal (rat): > 2000 mg/kg bw (no mortality observed at this dose). Vanilline is not harmful by dermal route according to CLP criteria.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- from 12-JUN-1991 to 04-MAR-1992
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted according a recognised guideline and under GLP conditions. Howerer, some deviations occurred and the purity of the test substance is unknown.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 (Acute Toxicity (Oral))
- Version / remarks:
- Cited as Directive 84/449/EEC, B.1
- Deviations:
- yes
- Remarks:
- variation of temperature, variation of humidity beyond the norms
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
- Source: Iffa-Crédo (L'Arbresle, France)
- Age at study initiation: 5 - 7 weeks old
- Weight at study initiation: 132 - 224 g
- Fasting period before study: 16-17 hours
- Housing: by sex and in groups of 5, in polycarbonate cages (365 x 225 x 180 mm)
- Food consumption: complete pelleted rat-mouse maintenance, ad libitum
- Water consumption: softened and filtered mains water, ad libitum
- Acclimation period: at least 9 days before the start of the treatment
ENVIRONMENTAL CONDITIONS:
- Temperature: 19 - 26.5 °C
- Humidity: 30 - 74 %
- Air changes: at least 8 per hour
- Photoperiod: 12 hr light / 12 hr dark
In-life dates: from 06-NOV-1991 to 20-NOV-1991 - Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Details on oral exposure:
- * Vehicle:
- Concentration in vehicle: 20, 25.1, 31.6 and 39.8%
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: data not available
- Lot/batch no.: 85133
- Purity: data not available
* Maximum dose volume applied: 10 mL/kg bw - Doses:
- 0, 2000, 2510, 3160 and 3980 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- mortality: 15 minutes after administration of the treatment, then at 1, 2 and 4 hours, and daily thereafter
- clinical signs: daily
- weighing: on D-1, D1, D8 and D15, and on day of death
- Necropsy of survivors performed: yes - Statistics:
- Bliss' Method (more reliable) and Litchfield & Wilcoxon's Method
- Preliminary study:
- 3 groups each composed of 2 males and 2 females were treated under the same conditions as those employed in the main study, at the dose levels
of 500, 1000 and 2000 mg/kg. Animals were observed for 15 days
No death were seen at a dose level of 2000 mg/kg. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- ca. 3 978 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- > 2 484 - < 6 368
- Remarks on result:
- other: Litchfield & Wilcoxon's method
- Mortality:
- In main study for limit test and principal test, at all doses tested mortality was observed.
Mortality increased with dose level - Clinical signs:
- other: Lethargy, prostration or subdued behaviour were observed in all groups, and sialorrhea was observed in some animals
- Gross pathology:
- Some animals that died during the study presented congestioned lungs at necropsy. No other abnormalities were recorded
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- Based on CLP criteria the substance is not classified. Based on UN GHS criteria the substance is classified Acute Tox. Cat. 5, H303.
- Executive summary:
In an acute oral toxicity study (Lheritier, 1992), groups of fasted, 5-7 weeks old Sprague-Dawley rats (5/sex) were given a single oral dose of crystallised Vanilline (purity unknown) in CMC at doses of 0, 2000, 2510, 3160 and 3980 mg/kg bw and observed for 15 days. Lethargy, prostration or subdued behaviour were observed in all groups, and sialorrhea was observed in some animals. Death occurred in animals tested of main experiment: for limit test 2/10 at 2000 mg/kg bw for principal study : 0/10 at 0 mg/kg bw 1/10 at 2000 mg/kg bw 2/10 at 2510 mg/kg bw 3/10 at 3160 mg/kg bw 5/10 at 3980 mg/kg bw Oral LD50 Combined Males/Females = 3978 mg/kg bw (95% C.I. 2484 - 6368 mg/kg bw) according to Bliss' method
In the preliminary study, 3 groups of 2 males and 2 females/group were treated under the same conditions as those employed in the main study, at the dose levels of 500, 1000 and 2000 mg/kg. Animals were observed for 15 days. No clinical signs nor death were seen at all doses tested up to 2000 mg/kg in the preliminary study.
Reference
Table 1: Number of animals dead and with evident toxicity, and range within which mortality occured for limit test
Dose | Mortality (# dead/total) | Time range of deaths (hours) | Number with evident toxicity(#/total) | ||||
Male | Female | Combined | Male | Female | Combined | ||
2000 | 1/5 | 1/5 | 2/10 | D1 | 5/10 | 5/10 | 10/10 |
Table 2: Number of animals dead and with evident toxicity, and time range within which mortality occurred for principal study
Dose | Mortality (# dead/total) | Time range of deaths (hours) | Number with evident toxicity(#/total) | ||||
Male | Female | Combined | Male | Female | Combined | ||
Control | 0/5 | 0/5 | 0/10 |
| 0/5 | 0/5 | 0/10 |
2000 | 1/5 | 0/5 | 1/10 | D1 | 5/5 | 5/5 | 10/10 |
2510 | 2/5 | 2/5 | 4/10 | D1-D2 | 5/5 | 5/5 | 10/10 |
3160 | 1/5 | 2/5 | 3/10 | D1 | 5/5 | 5/5 | 10/10 |
3980 | 3/5 | 2/5 | 5/10 | D1 | 5/5 | 5/5 | 10/10 |
Endpoint conclusion
- Dose descriptor:
- LD50
- Value:
- 3 978 mg/kg bw
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14-JUN-1991 to 13-NOV-1991
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted according a recognised guideline and under GLP conditions. Howerer, some deviations occurred and the purity of the test substance is unknown.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- yes
- Remarks:
- variation of humidity beyond the norms
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Iffa-Crédo (L'Arbresle, France)
- Age at study initiation: 5 - 8 weeks old
- Weight at study initiation: 204 - 271 g
- Fasting period before study: data not available
- Housing: housed individually in polycarbonate cages (305 x 180 x 184 mm)
- Diet: complete pelleted rat-mouse maintenance diet, ad libitum
- Water: softened and filered mains drinking water, ad libitum
- Acclimation period: 7 days before the start of treatment
ENVIRONMENTAL CONDITIONS:
- Temperature: 20 - 24 °C
- Humidity: 43 - 85 %
- Air changes: at least 8 per hr
- Photoperiod: 12 hrs dark / 12 hrs light (artificial)
In-life dates: from 26-AUG-1991 to 09-SEP-1991 - Type of coverage:
- semiocclusive
- Vehicle:
- water
- Details on dermal exposure:
- * Test site:
- Area of exposure: data not available
- % coverage: apprimately 10 %
- Type of wrap if used: perforated adhesive band 10 cm wide, applied onto an elastic crepe bandage covering the entire shaved area
* Removal of test substance:
- Washing: yes, with lukewarm water
- Time after start of exposure: 24 hours
* Test material:
- Amount(s) applied: 2000 mg/kg bw
- Concentration: 69.56 % (w/v)
- For solids, paste formed: yes
- pH: 4.7
* Vehicle:
- Amount applied: data not available
- Purity: purified water - Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- mortality and clinical signs: 15 minutes after administration, then at 1, 2 and 4 hours, and then daily for 14 days
- cutaneous lesions: daily from days 2 to 15
- weighing: immediately before application and at days 8 and 15
- Necropsy of survivors performed: yes - Statistics:
- Not applicable
- Preliminary study:
- 2 groups each composed of 2 males and 2 females were treated under the same conditions as those employed in the main study, at the dose levels of 1000 and 2000 mg/kg. No deaths were seen at the dose level of 2000 mg/kg.
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Mortality:
- no mortality occurred
- Clinical signs:
- other: none
- Gross pathology:
- no effects
- Other findings:
- no cutaneous lesions were observed. Only a yellowish coloration was noted.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The substance is not classified since no mortality occured at the dose level of 2000 mg/kg/day.
- Executive summary:
In an acute dermal toxicity study (Hazleton, 1991), groups of 5 -7 weeks old Sprague-Dawley rats (male / female) were dermally exposed to Vanilline for 24 hours to approximately 10% area of the body at doses of 2000 mg/kg bw. Animals then were observed for 14 days.
In the preliminary study, 2 males and 2 females per group were treated under the same conditions as those employed in the main study, at the dose levels of 1000 and 2000 mg/kg. No deaths were seen at all dose level tested of 2000 mg/kg.
Dermal LD50 Combined > 2000mg/kg bw. No clinical sign, except yellowish coloration of the skin and no mortality occurred at this dose.
According to classification criteria of EC regulation 1272/2008 Vanillin should not be classified for acute dermal toxicity based on the LD50 in male and female rats.
Reference
Table 1: Number of animals dead during limit test
Dose |
Mortality (# dead/total) |
Time range of deaths (hours) |
||
Male |
Female |
Combined |
||
1000 |
0/2 |
0/2 |
0/4 |
/ |
2000 |
0/2 |
0/2 |
0/4 |
/ |
Table 2: Number of animals dead and with evident toxicity for principal study = limit test
Dose |
Mortality (# dead/total) |
Time range of deaths (hours) |
Number with evident toxicity(#/total) |
||||
Male |
Female |
Combined |
Male |
Female |
Combined |
||
2000 |
0/5 |
0/5 |
0/10 |
/ |
0/5 |
0/5 |
0/10 |
Endpoint conclusion
- Dose descriptor:
- LD50
- Value:
- > 2 000 mg/kg bw
Additional information
Acute oral toxicity
Seven studies were available which 3 of them were of validity 2.
All data gave LD50 results above 2000 mg/kg, except results in Jenner (1964) publication (1580 mg/kg in rat and 1400 mg/kg in guinea pig) which was not taken into consideration, because it was validity 3 according to Klimish scale.
The three studies with validity 2 (Hazleton 1992, Monsanto 1955 and 1976,) were selected as key studies. The results were similar, the study of Hazleton(1992), was the most detailed.
In this study groups of fasted, 5-7 weeks old Sprague-Dawley rats (5/sex) were given a single oral dose of crystallised Vanilline (purity unknown) in CMC at doses of 0, 2000, 2510, 3160 and 3980 mg/kg bw and observed for 15 days. Lethargy, prostration or subdued behaviour were observed in all groups, and sialorrhea was observed in some animals. Death occurred in animals tested of main experiment: for limit test 2/10 at 2000 mg/kg bw for principal study: 0/10 at 0 mg/kg bw 1/10 at 2000 mg/kg bw 2/10 at 2510 mg/kg bw 3/10 at 3160 mg/kg bw 5/10 at 3980 mg/kg bw. In the preliminary study, 3 groups of 2 males and 2 females per group were treated under the same conditions as those employed in the main study, at the dose levels of 500, 1000 and 2000 mg/kg. Animals were observed for 15 days. Neither clinical signs nor death were seen at all dose level tested.
Oral LD50 Combined Males/Females = 3978 mg/kg bw (95% C.I. 2484 - 6368 mg/kg bw) according to Bliss' method
The key studies provided a LD50 range from 3300 to 3978 mg/kg.
According to classification criteria of EC regulation 1272/2008 Vanillin should not be classified for acute oral toxicity. However based on the LD50 the substance is classified Acute Tox Cat. 5 for oral route according to UN GHS criteria.
Inhalation route:
Only one study on rat (Makaruk, 1980) was available. In this study, only one dose was tested which is the saturated vapour concentration. It gave a result of LC50 above 41.7 mg/m3after 4 hours exposure for rats and 2 hours for mouse with no other details. It was in validity 3 according to Klimish scale, and no purpose flag was selected.
Dermal route:
In an acute dermal toxicity study (Hazleton, 1991) of validity 2, groups of 5 -7 weeks old Sprague-Dawley rats (male / female) were dermaly exposed to Vanillin for 24 hours to approximately 10% area of the body at doses of 2000 mg/kg bw. Animals then were observed for 14 days.
In the preliminary study, 2 males and 2 females per group were treated under the same conditions as those employed in the main study, at the dose levels of 1000 and 2000 mg/kg. No deaths were seen at all dose level tested of 2000 mg/kg.
Dermal LD50 Combined > 2000mg/kg bw. No clinical sign, except yellowish coloration of the skin and no mortality occurred at this dose.
According to the classification criteria of EC regulation 1272/2008 Vanillin should not be classified for acute dermal toxicity based on the LD50 in male and female rats. No classification is required according to UN GHS criteria since no mortality occured at the dose level of 2000 mg/kg.
Justification for classification or non-classification
Regarding data available, vanillin was not classified for acute toxicity by oral and dermal routes according to CLP criteria.
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