Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
DNEL for WORKERS
1. Acute / short-term exposure - systemic effects
1.1 For oral route:
The oral route is not relevant for workers. But the data should be used for extrapolation route to route.
1.2 For 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/m3 after 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.
This study was not taken into account for the derivation of the DNEL value.
No DNEL could be derived and it is not relevant to use acute oral toxicity study because of the discrepancy in duration of exposure.
1.3 For dermal route:
In an acute dermal toxicity study (Hazleton, 1991), groups of 5 -7 weeks old Sprague-Dawley rats (male / female) were dermally 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.
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.
No DNEL is calculated because no effects were seen after dermal acute exposure to Vanillin.
2. local effects
2.1 Irritation and corrosion
2.1.1 Skin irritation
Three studies were available but two only were of validity 1 or 2. One of them performed on rat was selected as key study (Hazleton 1991, validity 1), and another one performed on rabbit (Birck 1976, validity 2) as supporting study.
The two selected studies gave the same results:not irritating to the skin. Summaries of these studies are the following:
In an acute dermal toxicity study (Hazleton, 1991), young adult Sprague-Dawley rats (5/sex) were dermally exposed to 2000 mg/kg bw of Vanilline Cristallisée (purity unknown) in water for 24 hours to 10% body surface area. Test sites were covered with a semi-occlusive dressing for 24 hours. Animals then were observed for 14 days. Irritation was scored by the method of EU guideline. In this study, cristallised Vanillin is not a dermal irritant based on the absence of skin reaction. Only a yellowish colour was observed from day 2 to 14.
In a primary dermal irritation study (Birck, 1976),New Zealandwhite rabbits (6 animals) were dermally exposed to0.5 gof vanillin (purity unknown) for 24 hours. In this study, vanillin was not a dermal irritant.
It is not relevant to derive a DNEL for the skin irritation.
2.1.2 Eye irritation
Five studies in vitro and in vivo were available on Vanillin. Twoin vivoselected studies and thein vitro HCE test gave the same result: irritating to the eyes. Summaries of these studies are the following:
In a primary eye irritation study (CIT, 2007) 100 mg of Vanillin (pure product) was instilled into the conjunctival sac of right eye of a young adult New Zealand White rabbit (3 males). Animals then were observed for 8 days (period of reversibility). Irritation was scored according to the OECD and EU guidelines.
Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 1.7 and 2.0 for chemosis, 2.0, 2.0 and 2.0 for redness of the conjunctiva, 0.7, 0.7 and 0.3 for iris lesions and 2.0, 2.0 and 2.0 for corneal opacity. In this study, Vanillin is irritating to the eye.
In a primary eye irritation study [Birck, 1976], 0.1 mL of vanillin (purity unknown) undiluted was instilled into the conjunctivae sac of New Zealand White rabbits (6 animals) for 24 hours. Animals then were observed for 7 days. Irritation was scored by the method of Kay and Calandra, and in this study, vanillin is an eye irritant.
According to the classification criteria of EC regulation 1272/2008 Vanillin should be classified as irritant for the eyes.
No DNEL can be derived, but a qualitative approach to risk assessment and management is required. According to the ECHA guidance on information requirements and chemical safety assessment, Part E, V3, May 2016, the classification Eye. Irrit. Cat. 2, H319 corresponds to low hazard.
2.1.3 Respiratory tract irritation
Physico chemistry data available and validated according to Klimish scale for Vanillin indicated that:
- The substance is a solid powder with a density of1.06g/cm3 (CLAYTON, 1993)
- The particle size distribution indicated that vanillin powders were characterized through laser diffraction analysis and by sieving for flakes. D10 were 100.7 µm and 121.2 µm respectively for the two powders tested. As concerning the flakes: no flakes above 5000 µm and no particles below 100 µm were collected. The finest particles collected were in the range 100 to 200 µm (0.2 %), 91% of weight was above 1000 µm. (CRTL 2010).
No DNEL can be derived for respiratory tract irritation of Vanillin powder dust but a qualitative approach to risk assessment and management is required for worker protection to dust.
2.2 Sensitizer
Several animal studies were available for skin sensitization with Vanillin. Four were of Validity 2; One of them, a maximization test, was selected as key study and had reliability 2 (Hazleton, 1992), two others were a LLNA and a MEST tests and were selected as supporting studies with reliability 2 (Basketter, 2001; Gad, 1986), the fourth was a buehler test (Wang, 1987).
All the results lead to same conclusion, no effect on sensitization with Vanillin.
Three Human data with validity 2 confirmed the results obtained in animal studies. These studies were Patch tests on Humans (Hausen, 2001; Francalanci, 2000; Wang, 1987).
All the results available indicated that Vanillin is not a skin sensitizer. According to the classification criteria of EC regulation 1272/2008 Vanillin should not be classified for sensitisation. In the absence of effects, no DNELcould be derived.
3. Long term exposure
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.
In most of these studies, no effects were observed (body weight, clinical signs, organ weight, histopathology. . .).
In the key study, a subchronic toxicity (26 weeks) 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 10000ppm (equivalent to ca. 650 mg/kg bw/d).
One study by dermal route and two studies by inhalation route were available. They were validity 3, poorly described and were not taken into account for assessment.
All the results available indicated that Vanillin had no effect in oral subchronic toxicity studies, and the NOEL= 650 mg/kg bw which was the highest dose tested (Monsanto, 1955). This NOEL could not be used as starting point for DNEL derivation due to the absence of effects. No DNEL could be derived.
4. Carcinogenicity
Seven studies are available, 4 had validity 3 and 3 validity 4. All available studies were not conducted according to recognized guidelines. In most of time the period of treatment was shorter than 2 years (from 8 days to 40 weeks), or only the tumor protective effects had been evaluated. These studies were not well described but in a "Weight of Evidence" approach, all results presented no carcinogenic effects with Vanillin.
In the absence of carcinogenic effect, no DNEL or DMEL are be derived.
5. Reprotoxicity
Only few data are available.
No specific data are available on toxicity to reproduction, but the data available on repeated dose toxicity studies indicated no effects on reproductive organs.
Three teratogenicity studies were available on different species (mouse, chicken, rat). Two of them were considered as validity 3 according to Klimish scale. Two studies were considered as validity 3, because of the poor detail information on material and methods and results, furthermore they did not follow the recognised OECD guidelines. However, the results were similar and indicated no teratogen effects. The study on rat (Vollmuth, 1990) is also poorly described but had been evaluated by EFSA (European Food Safety Authority) and hence was considered as validity 2.
10 female rats per group were exposed one week before mating until 4 days post partum to 0, 125, 250, 500 mg/kg bw/day of Vanillin. Maternal toxicity had been reported with only few details: death, clinical signs and change in body weight and feed consumption. The NOAEL maternal was consider to be 250 mg/kg bw. No effect on pups were reported and the NOEL for teratogenicity was the highest dose tested 500 mg/kg bw.
The “weight of evidence” approach permit to consider that Vanillin had no teratogen properties.
In the absence of effect no DNEL is derived.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
Vanillin is classified irritant for eyes (Eye irrit Cat. 2, H319: causes serious eye irritation under CLP criteria) and upper tract irritation after dust exposure can be expected. General population would not be exposed directly to the substance as such; the substance is always diluted and present in different types of products such as cosmetic and food. By this way, the eye and respiratory tract irritant hazard would be reduced, and no specific recommendation to protect general population would be proposed. Therefore for the chemical risk assessment, no quantitative nor qualitative approach would be done.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)