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EC number: 204-465-2
CAS number: 121-33-5
The oral route is not
relevant for workers. But the data should be used for extrapolation
route to 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.
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
then were observed for 14 days.
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
Dermal LD50 Combined >
2000mg/kg bw. No clinical sign, except yellowish coloration of the skin
and no mortality occurred at this dose.
classification criteria of EC regulation 1272/2008, Vanillin should not
be classified for acute dermal toxicity based on the LD50 in male and
No DNEL can be
calculated because no effects were seen after dermal acute exposure to
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
rabbits (6 animals) were dermally exposed to0.5
(purity unknown) for 24 hours. In this study, vanillin was not a dermal
It is not relevant
to derive a DNEL for the skin irritation.
Five studiesin vitroandin
vivowere available on Vanillin. Twoin
vivoselected studies and thein vitroHCE test gave the same
result:irritating to the eyes. Summaries of these studies are the
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.
criteria of EC regulation 1272/2008 Vanillin should be classified as
irritant for the eyes.
No DNEL can be
derived, but aqualitative
approach to risk assessment and management is required because Vanillin
should be classified as irritant for eyes (chapter R8, appendix R8 -9).
Physico chemistry data
available and validated according to Klimish scale for Vanillin
- The substance is a
solid powder with a density of1.06g/cm3
- 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 aqualitative
approach to risk assessment and management is required for worker
protection to dust.
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).
results lead to same conclusion, no effect on sensitization with
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
criteria of EC regulation 1272/2008 Vanillin should not be classified
In the absence of
effects, no DNELcould be derived.
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 is10000ppm
(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
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.
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 could be
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 could be derived.
explanation for no DNEL derivation, please see the discussion above
developed for workers.
is classified irritant for eyes (Eye irrit Cat. 2, H319: causes serious
eye irritation under CLP criteria) and upper tract irritation after dust
exposure is expected.
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.
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