Vanillin

Acute Toxicity: oral

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Vanillin

EC Number:

204-465-2

EC Name:

Vanillin

Cas Number:

121-33-5

Molecular formula:

C8H8O3

IUPAC Name:

1-butoxypropan-2-ol

Test animals

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

Administration / exposure

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

Results and discussion

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.

Effect levels

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

Any other information on results incl. tables

 

Table 1: Number of animals dead and with evident toxicity, and range within which mortality occured for limit test

 

Dose (mg/kg bw)	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 (mg/kg bw)	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

 

Applicant's summary and conclusion

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.