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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:
The study was undertaken between 17. October and 6. November 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
particle size not specified

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
All rats were acclimated to the experimental environment for a minimum of 7 days prior to the start of the main study. The rats were randomly allocated to cages within the treatment groups. They were house in groups by sex in metal cages with wire mesh floors. A standard laboratory rodent diet and water were provided ad libitum.
Temperature: 20 - 23 °C
Relative humidtiy: 62%
Air exchange: 15/h
Aritificial light: 12h in each 24 hour period

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
The test substance was administered to each rat using a syringe and plastic catheter
Doses:
1.6 g/kg
2.5 g/kg
3.2 g/kg
4.0 g/kg
No. of animals per sex per dose:
5
Control animals:
no

Results and discussion

Preliminary study:
The results of the preliminary studies indicated that the LD 50 of VA-044 was in the region of 2500 mg/kg BW
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
2 800 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
3 200 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 000 mg/kg bw
Based on:
test mat.
Mortality:
Death occurred amongst rats treated at 2.5 g/kg BW and above generally within one and three hours of dosing. One animal treated at 4.0 g/kg was found dead an Day 2.
Clinical signs:
Pilo - erection was observed shortly after dosing in all rats. Abnormal body carriage (hunched posture) also observed in all rats treated at 1.6, 2.5 and 3.2 g/kg and in thre rats treated at 4.0 g/kg bw. These signs were accompaniedby:
abnormal gait (waddling), lethargy, decreased resiratory rate and Palloepf the extremities amomgst rats treated at 2.5 g/kg and above
increased salivation in all rats treated at 3.2 and 4,0 g/kg
prostration in one female rat treated at 2.5 and one male and three female rats treated at 4.0 g/kg
clonic convulsion in one male rat dosed at 4.0 g/kg.
Recovery of survivors, as judged by external appearance and behaviour, was apparently complete by day 3 or 4.
Body weight:
No bodyweight loss or minimal bodyweight losses were recorded for the animals that dies.
Gross pathology:
Renal pallor was observed at autopsy of the rat found dead on Day 2.
Autopsy findings of all other rats that died were normal

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute median lethal oral dose (LD50) and their 95 % confidence limits to rats of VA-044 were estimated to be:

Males and females combined: 3000 mg/kg bw
Males only : 3200 mg/kg bw
Females only : 2800 mg/kg bw