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Toxicological information

Acute Toxicity: oral

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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:
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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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:
3 925 - 3 978 mg/kg bw
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:
Lethargy, prostration or subdued behaviour were observed in all groups, and sialorrhea was observed in some animals
Body weight:
No effect were observed in males. In females of the high dose group, a significant decrease in body weight was observed (P <= 0.05)
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 o 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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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 dose level tested 2000 mg/kg.