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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:
weight of evidence
Study period:
April to June 1980
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail, test method comparable to guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not specified
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Remarks:
TNO/W 74
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier.
- Age at study initiation: Not reported.
- Weight at study initiation: 150 - 200 g
- Fasting period before study: Not reported
- Housing: Makrolon type III or II cages.
- Diet: Altromin-R maintenance diet for rats and mice, ad libitum.
- Water: ad libitum
- Acclimation period: Not reported.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported.
- Humidity (%): Not reported.
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): Not reported.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
poloxamer
Remarks:
given by its alternative trade name "Lutrol" in study report.
Details on oral exposure:
Administered once via ,,Schlundsonde'' ("Gullet-tube"), i.e. oral gavage.
Doses:
100, 500, 750, 1000, 1500, 2000 and 2500 mg/kg bw (M); 100, 250, 500, 600, 750, 1000, 1250, 1750 and 2000 mg/kg bw (F).
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: At least once daily for 14 days.
- Necropsy of survivors performed: Yes.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 258 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
988 mg/kg bw
Based on:
test mat.
Mortality:
Mortalities occurred.
Clinical signs:
Poisoning symptoms occured about 5 minutes after treatment, including disturbances of general behaviour (apathy), laboured breathing, convulsions, tremors, and lying in prone/lateral positions. The symptoms persisted in surviving animals for up to 24 hours and disturbances in general condition for up to 6 days after treatment. (Translated from German).
Body weight:
No data
Gross pathology:
Post-mortem examinations of mortalities indicated pale, spotted livers, spleen and kidneys. Empysematous lung-changes were also noticeable. No pathalogical features were found in surviving animals upon euthanisation at the end of the study period. (Translated from German).

Any other information on results incl. tables

Table 1: Acute oral toxicity in "soberly-handled" rats (translated from German)

 Dose [mg/kg bw]  Toxicology Result [Dead / With Symptoms / Total Used]  Time of Death following Treatment  LD50 (14 -days) [mg/kg bw]
Male Rats
 100  0/0/10*  -

1258 (1044 - 1502)

b = 5.92**

 500  0/10/10  -
 750  1/10/10  1h 13'
 1000  3/10/10  2h 32'
 1500  7/10/10  1h 30' - 4h 20'
 2000  8/10/10  0h 15' - 24h 0'
 2500  10/10/10  0h 50' - 4h 20'
Female Rats
 100  0/10/10*  -

988 (841 - 1164)

b = 5.63**

 250  0/10/10  -
 500  0/10/10  -
 600  2/10/10  1h 40'
 750  3/10/10  2h 15' - 24h 0'
 1000  4/10/10  1h 5' - 2h 10'
 1250  7/10/10  0h 32' - 2h 47'
 1750  9/10/10  0h 20' - 4h 20'
 2000  10/10/10

 0h 30' - 24h 0'

* Maximum dose without negative effects

** Regression coefficient

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
EU criteria met
Conclusions:
Under the conditions of this study the LD50 was determined to be 1258 mg/kg bw in the male Wistar rat and 988 mg/kg bw in the female Wistar rat.
Executive summary:

The study was performed following a method equivalent or similar to OECD TG 401 to assess the acute oral toxicity potential of the test substance to male and female Wistar rats. The test item was administered as a single dose via oral gavage to groups of 10 male and 10 female rats per dose-level orally. Under the conditions of this study the LD50 was determined to be 1258 mg/kg bw for male Wistar rats and 988 mg/kg bw for female Wistar rats.