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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 21 apr 1992 to 18 dec 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was GLP, OECD 401 compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Slight variation of humidity: 74% max instead of 70%. Animals of one group received food 4h05 after intubation instead of 3 to  4 hours. These deviations were not considered to have affected the outcome or the  objectives of the study
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

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, BP 0109 (69592 L'Arbresle Cedex - France)
- Age at study initiation: 5 to 7 weeks old
- Weight at study initiation: 175 - 180 g
- Fasting period before study: 15 to 20 hours
- Housing: by sex and in groups of up to 5 (or of 2 for the preliminary studies), in polycarbonate cages type FI (internal dimensions 305*180*184 mm) for the main study.
- Diet (e.g. ad libitum): standard Rat-Mouse Diet, ad libitum (U.A.R, formula A.04 C10 - U.A.R., Villemoisson - 91360 Epinay-sur-Orge, France).
- Water (e.g. ad libitum): softened and filtered mains drinking water, ad libitum. Bacteriological and chemical controls every six months.
- Acclimation period: at least 5 days before the start of the treatment.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30 to 70% relative humidity
- Air changes (per hr): minimum 8
- Photoperiod (hrs dark / hrs light): 12h / 12h


IN-LIFE DATES: within 3 days after receipt signed protocol and quotation.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5, 10 and 20% (w/v) for preliminary study,  and 20% for the main study (limit test)
- Justification for choice of vehicle: vehicle which renders the test article soluble
- Lot/batch no. (if required): 101267 of 19/05/1992; 102123 of 09/06/1992; 102679 of  30/06/1992
- Purity: 1% (w/v) aqueous dispersion of CMC

MAXIMUM DOSE VOLUME APPLIED: 10 mg/ml

DOSAGE PREPARATION (if unusual): on the day of administration. Formulations were used within 4 hours of preparation.

- Rationale for the selection of the starting dose: depending on the results of the preliminary study and calculated according to a logarithmic
progression.
Doses:
0; 2000; 2510; 3160 mg/kg
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: Observations: for mortality and clinical signs, 15 min after  administration of the substance, then at 1, 2 
and 4 hours, and daily for the 14 day study period. Weight: day before treatment, immediately before treatment, on Day 8 and Day 15 and at death 
from day 2 onwards
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: gross pathology
Statistics:
Bliss' method and Lichtfield & Wilcoxon.

Results and discussion

Preliminary study:
No deaths observed at doses of 2000, 2510 and 3160 mg/kg, when the substance was administered at these three dose levels in the main study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 160 mg/kg bw
Based on:
test mat.
Remarks on result:
other: in the limit test at 2000 mg/kg (before the main study), 1/5 male rat died, no mortality in females.
Mortality:
No deaths at the 3 dose levels 2000, 2510 and 3160 mg/kg.
Clinical signs:
In some cases, subdued behaviour and lethargy (or prostration) within 4 hours after treatment were observed. All animals were normal on Day 2.
Body weight:
Similar to that of the control animals throughout the observation period.
Gross pathology:
No macroscopic findings.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
not classified



Executive summary:

In a study (Hazleton, 1992), Sprague-Dawley rats (5M/5F/dose) received ethylvanillin at different doses of 2000, 2510 and 3160 mg/kg in vehicle carboxymethylcellulose (CMC).

Animals were observed for 14 days.

Clinical signs: subdued behaviour and lethargy were noted at 15 min, 1, 2, 4 hours after treatment. All animals were normal on day 2 for the 3 tested doses.

No mortality was observed.

The LD50 was higher than 3160 mg/kg.

In these conditions, ethylvanillin is not classified as harmful by ingestion.