Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November / December 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Sample code n°: 507-43

Test animals

Species:
rat
Strain:
other: CFY
Sex:
male/female
Details on test animals and environmental conditions:
weight range 94 to 124 g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
0.1 g/kg
0.4 g/kg
1.0 g/kg
4.0 g/kg
16.0 g/kg
No. of animals per sex per dose:
2 for "preliminary range"

5 for "larger group evaluation"
Control animals:
yes

Results and discussion

Preliminary study:
The results of preliminary range finding test indicated that the median lethal oral dose (LD50), was greater than 16 g/Kg bodyweight


MORTALITY DATA FOR GROUPS OF RAT DOSED ORALLY WITH 507.43
Dosage (g/kg) Mortaliy ratio (N° of deaths/ N° dosed) Time of death after closing (hours)
Male Female Combined
0.1 0/2 0/2 0/4 -
0.4 0/2 0/2 0/4 -
1.0 0/2 0/2 0/4 -
4.0 0/2 0/2 0/4 -
16.0 0/2 0/2 0/4 -
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 16 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities
Clinical signs:
Signs of reaction to treatment observed shortly after dosing, included lethargy and piloerection in all treated animals and control animals. There signs were accompanied by decreased respiratory rate in eight rats at the preliminary screen levels of 0.1, 0.4 and 1.0 g/kg and in all rats at 16 g/kg. increased respiratory rate was observed in two rats at each screening level of 0.4 and 1.0 g/kg. Abnormal body carriage (hunched posture) was also observed in all rats at screening levels of 0.1, 0,4 and 1,0 g/kg and seven rats at 16 g/Kg.

Recovery of the treated rats, as judged by external appearance and behavior, was apparently complete within eight days of treatment. This observation was substantiated by normal bodyweight gains and normal autopsy findings.
Body weight:
Sex Dosage (g/kg) Bodyweight (g) at Mortaliy ratio (N° of deaths/ No dosed) Time of death after dosing (hours)

Dosing 1 week 2 week
Male 0 102 183 243 0/5 -
16 109 180 237 0/5 -

Female 0 98 194 194 0/5 -
16 101 190 190 0/5 -

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute median lethal oral dose (LD_50) to rats of 507.43 was found to be greater than 16 g/Kg bodyweight
Executive summary:

EXPERIMENTAL PROCEDURE

Rats of the CFY strain, in the were starved overnight before treatment with 507.43.

The material was prepared as a 40% suspension in carn oil and administered by oral  intubation at the maximum practical dosage volume in the full scale test of 40 ml/Kg bodyweight. Rats treated with the vehicle alone (40ml/Kg) served as controls.

During the observation period of 14 days, a record was kept of all signs of toxicity. All rats were sacrificed terminally and examined macroscopically in an attempt to identify any target organs.

RESULT

The results of preliminary range finding test indicated that the median lethal oral dose (LD_50), was greater than 16 g/Kg bodyweight.

Dosing was then extended to a large group of rats (five males and five females) in order to confirm this finding.

There were no mortalities.

igns of reaction to treatment observed shortly after dosing, included lethargy and piloerection in all treated animals and control animals. There signs were accompanied by decreased respiratory rate in eight rats at the preliminary screen levels of 0.1, 0.4 and 1.0 g/kg and in all rats at 16 g/kg. increased respiratory rate was observed in two rats at each screening level of 0.4 and 1.0 g/kg. Abnormal body carriage (hunched posture) was also observed in all rats at screening levels of 0.1, 0,4 and 1,0 g/kg and seven rats at 16 g/Kg.

Recovery of the treated rats, as judged by external appearance and behavior, was apparently complete within eight days of treatment. This observation was substantiated by normal bodyweight gains and normal autopsy findings.

CONCLUSION

The acute median lethal oral dose (LD50) to rats of 507.43 was found to be.

Greater than 16 g/Kg bodyweight