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Administrative data

Description of key information

The acute oral LD50 was determined to be 1470.0 mg/kg bw in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1969-05-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
In principle, the methods described in OECD Guideline 401 (Acute Oral Toxicity) were used.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- Purity: assumed to contain 100% active ingredient
- Appearance: clear, colorless liquid, pungent odor
- Date received:1969-03-25
Species:
rat
Strain:
other: Carworth (Sprague-Dawley-derived) strain
Sex:
male
Route of administration:
other: gastric intubation
Vehicle:
water
Details on oral exposure:
After a three to four-hour fasting period, the test material was administered by gastric intubation as a 50% weight-per-volume suspension in distilled water to groups of five male rats each at dosage levels of 100, 215, 464, 1000 and 2150 mg/kg of body weight.
Doses:
100, 215, 464, 1000, 2150, and 4640 mg/kg bw
No. of animals per sex per dose:
5 males per dose
Control animals:
no
Details on study design:
- Fasting period: three to four hours before exposure
- Diet (postdose): Purina Laboratory Chow and water available ad libitum
- Frequency of weighing: initially and terminally
- Frequency of observations on mortality and toxic effects: 1, 4 and 24 hours after dosing; once daily thereafter
- Necropsy of survivors performed: yes (on all animals which died during the study or were sacrificed at termination)
- Other examinations performed: clinical signs
- Duration of observation period following administration: 7 days
- Sacrifice: barbiturate (Diabutal) overdose after observation period
Statistics:
Analysis of mortality data was performed according to Thompson, W. R., Bact. Rev. 11, 115-145, 1947, using the tables of Horn, H. J., Biometrics 11, 311, 1956. No confidence limits were determined due to "all-or-none" response.
Preliminary study:
Not performed.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 470 mg/kg bw
Based on:
test mat. (dissolved fraction)
Mortality:
Five of five male rats died on day four at the 2150 mg/kg bw level.
Clinical signs:
DOSE-DEPENDEND PRINCIPAL TOXIC EFFECTS
- 100 mg/kg bw: no effects
- 215 mg/kg bw: slight depression (1-24 hours)
- 464 mg/kg bw: slight depression (1-24 hours)
- 1000 mg/kg bw: labored respiration, ptosis, lacrimation, ataxia, bloody crust on eyes, and gasping
- 2150 mg/kg bw: labored respiration, ptosis, lacrimation, ataxia, bloody crust on eyes, and gasping

RECOVERY
- by Day 6 (dose: 1000 mg/kg bw)
Body weight:
139 - 191 g (at initiation)
Gross pathology:
AT DEATH
- 2150 mg/kg bw: dark red zone at corticomedullary junction of kidney, stomach distended with dark red fluid, soft consistency of stomach walls, lining of pyloric portion dark red, cardiac portion thickened and pink in color.

AT SACRIFICE
- no gross pathology observed

Table 1: Mortality after 1 h, 4 h, 24 h and 2 -7 d due to an initial application of an aqueous solution of the test substance at dose levels of 100, 215, 464, 1000 and 2150 mg/kg bw. Number of animals dead per number of animals tested, cumulative.

Time of Death

Dose [mg/kg bw]

Immediate

Hours

Days

1

4

24

2 -7

100

0/5

0/5

0/5

0/5

0/5

215

0/5

0/5

0/5

0/5

0/5

464

0/5

0/5

0/5

0/5

0/5

1000

0/5

0/5

0/5

0/5

0/5

2150

0/5

0/5

5/5

Interpretation of results:
Category 4 based on GHS criteria
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1972-10-06
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
In principle, the methods described in OECD TG 401 were used.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- Concentration: 8% and 16% aqueous solution
- Physical state: liquid
Species:
rat
Strain:
other: Gassner strain
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
aqueous solution
Doses:
Single dose of 800, 1000, 1250,1600, 2000, 2500, 3200 or 4000 mg/kg bw
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Test duration: 14 d
- Frequency of observations: 1 h, 24 h, 48 h, 7 d, 14 d
- Duration of observation period following administration: 14 days
- Necropsy performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Statistics:
Graphical evaluation of the dose response curve on probability paper.
Preliminary study:
Not performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1.7 mL/kg bw
Based on:
not specified
Remarks on result:
other: no confidence limits determined
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 397.4 mg/kg bw
Based on:
not specified
Remarks on result:
other: value derived from density at 25 °C noted in Beilstein (2006) (see section 4.4)
Mortality:
One hour after application no mortality occured at all dose levels. At dose levels of 800, 1000 and 1250 cmm/kg bw no mortality was observed during the study period neither at male nor at female rats. Five of five male rats died after 24 h at the 4000, 3200 and 2500 cmm/kg bw level. Four of five female rats died after 24 h at the 4000 cmm/kg bw level and five of five female rats dies after 24 hours at the 3200 and 2500 cmm/kg bw level. For details on mortality please see table in "Any other infromation on results incl. tables".
Clinical signs:
- at all doses and immediately after application: crouching, abdominal position, apathy and irregular respiration
- day 4-7: crouching and gasping respiration
- after 7 days: all surviving animals unconscious
Body weight:
- Mean body weight males: 243 g (before start of the study)
- Mean body weight females: 194 g (before start of the study)
Gross pathology:
- cardiac dilation
- hyperemia
- stomach dilated with thin pulpy contents
- gastritis
- haematized and diarrheal intestinal contents
- liver clay-colored

Table: Mortality after 1 h, 24 h, 48 h, 7 d and 14 d due to an initial application of an aqueous solution of the test substance at dose levels of 4000, 3200, 2500, 2000, 1600, 1250, 1000 and 800 cmm / kg bw. Number of animals dead per number of animals tested, cumulative.

Dose [cmm / kg bw]

Concentration [%]

Number of animals

Mortality after

1 hour

24 hours

48 hours

7 days

14 days

4000

16

5 M

0/5

5/5

5/5

5/5

5/5

5 F

0/5

4/5

4/5

5/5

5/5

3200

16

5 M

0/5

5/5

5/5

5/5

5/5

5 F

0/5

5/5

5/5

5/5

5/5

2500

16

5 M

0/5

5/5

5/5

5/5

5/5

5 F

0/5

5/5

5/5

5/5

5/5

2000

16

5 M

0/5

2/5

2/5

4/5

4/5

5 F

0/5

1/5

2/5

4/5

4/5

1600

16

5 M

0/5

0/5

3/5

3/5

3/5

5 F

0/5

0/5

0/5

1/5

1/5

1250

16

5 M

0/5

0/5

0/5

0/5

0/5

5 F

0/5

0/5

0/5

0/5

0/5

1000

16

5 M

0/5

0/5

0/5

0/5

0/5

5 F

0/5

0/5

0/5

0/5

0/5

800

16

5 M

0/5

0/5

0/5

0/5

0/5

5 F

0/5

0/5

0/5

0/5

0/5

Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 470 mg/kg bw
Quality of whole database:
The studies were conducted comparable to guideline with sufficient documentation.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An in vivo study with 6 groups of five male rats (Carworth strain) was carried out according to a method comparabel to OECD Guideline 401 (Dow AgroSciences, DR-0385 - 4500 - 099, 1969). After a fasting period of three to four hours, a 50% aqueous suspension of the test substance was administered by a gastric intubation at dosage levels of 100, 215, 464, 1000 and 2150 mg/kg bw. Both mortality and toxic effects were recorded immediately after dosing and after one, four, 24 hours and once daily thereafter for the period of 7 days. Additionally, gross necropsy was performed on all animals which died during the study and on those euthanized at termination of the experiment. Several unspecific clinical symptoms were observed in increasing intensity with increasing dose. The derived LD50 was 1470 mg/kg bw.

Additionally, an in vivo study (BASF SE, XXI-245, 1972) with low reliability was conducted according to an internal method in order to investigate the acute oral toxicity of the test substance at rats (Gassner strain). After oral application of the test substance, several unspecific clinical symptoms were noted. For the 16% aqueous solution of the test item a LD50 of ca. 1.7 mL/kg bw was derived (after an observation period of 14 days). This value corresponds to a LD50 of 1397.4 mg/kg bw.

The most reliable study is used as key study.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the tenth time in Reguglation (EU) 2017/776. As a result the substance is considered to be classified Category 4 (H302: Harmful if swallowed) for acute oral toxicity.