Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20/03/1980 - 30/08/1980
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Test material form:
liquid

Test animals

Species:
rat
Strain:
other: TacN(SD)fBR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms (Germantown, N.Y.)
- Weight at study initiation: 180-280 grams
- Fasting period before study: animals were fasted overnight
- Housing: the animals were housed singly in wire cages
- Diet: Purina Rodent Laboratory Chow 5001 ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
Animals were kept under standard laboratory conditions meeting the standards described in the "Guide for the care and use of laboratory animals" (DHEW Publication No. (NIH) 78-23 Revised 1978).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
ethanol
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 0.5 ml/100 g body weight
Doses:
Preliminary assay: 4.0, 4.5 and 5.0 g/kg bw.
Definitive study: 3.5, 4.0, 4.5, 5.0 and 5.6 g/kg bw.
No. of animals per sex per dose:
Preliminary study: 1 male and 1 female per dose
Definitive study: 8 males and 8 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality and pharmacotoxic signs at 1, 3, 5 and 24 hours following dosing and twice daily (once daily on weekends) for the remainder of the 14 day observation period. Surviving animals were weighed at the end of the observation period.
- Necropsy of survivors performed: yes
Statistics:
LD50 determined by Probit analysis

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 750 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 020 - <= 3 740
Remarks on result:
other: This value is the key value
Sex:
male
Dose descriptor:
LD50
Effect level:
3 350 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 600 - <= 4 320
Mortality:
Most deaths occurred within 24 hours after dosing.
Clinical signs:
At 3.5 g/kg ataxia or adoption of the prone position were observed in all of males. All the females adopted the prone position.; the signs were observed in the first twenty-four hours and survivors had recovered by 48 hours after having been dosed. Similar signs including lethargy chromodacryorrhea, and oral discharge were observed in both males and females dosed at 4.0, 4.5, 5.0 and 5.6 g/kg. One animal at 4.0 and one animal at 4.5 g/kg became moribund within 24 hours and one animal at 5.0 became moribund at 24 hours and remained so through Day 2.
Body weight:
All survivors gained weight in a normal manner (>10 g).
Gross pathology:
There were no signs indicative of toxicity in any of the animals necropsied at term. In animals that died the only signs were of yellow fluid in the stomach and intestines and reddish fluid in the intestines.

Any other information on results incl. tables

Summary of mortality

Dose level

Mortality

Male

Female

Total

3.5 g/kg bw

6/8

7/8

13/16

4.0 g/kg bw

5/8

8/8

13/16

4.5 g/kg bw

4/8

5/8

9/16

5.0 g/kg bw

6/8

8/8

14/16

5.6 g/kg bw

7/8

6/8

13/16

Applicant's summary and conclusion

Interpretation of results:
other: not acute harmful
Remarks:
according to EU CLP (EC 1272/2008 and its amendments)
Conclusions:
The LC50 is 2750 mg/kg bw based on a similar to OECD TG 401 study. The LC50 is based on the lower LC50 for females.
GHS: For GHS this substance need to be classified as Acute Tox 5 (H303)
Executive summary:

The acute oral toxicity of the test substance towards rats was investigated according to methodology comparable to OECD Guideline 401 and under GLP conditions. Based on the results of a preliminary assay, the test substance was dosed at 3.5, 4.0, 4.5, 5.0 and 5.6 g/kg bw in the main test. Mortality was observed in all doses. The LD50 values were determined to be 3.35 (2.60 - 4.32) and 2.75 (2.02 - 3.74) g/kg for male and female rats respectively, under the conditions of this test. The value of 2750 will be used as the key value.