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Description of key information

The acute oral toxicity of the test substance was assessed.  The acute oral median lethal dose (LD50) is 2.8 g/kg with 95 % confidence limits of 2.24 – 3.50 g/kg for males. The LD50 is 2.75 g/kg with 95 % confidence limits of 2.27 – 3.33 g/kg for females. The LD50 is 2.70 g/kg with 95 % confidence limits of 2.31 – 3.16 g/kg for males and females.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was conducted between 04 March 1980 and 18 March 1980.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards with acceptable restrictions.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
GLP compliance:
no
Remarks:
Pre-dates GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Range finding
Two fasted rats of each sex were used per dose. Animals were acclimatized to the study room for six days. Each animal received a single oral dose of the prepared test article and was observed for the next 72 hours to determine the mortality only.
The dosages were 0.05, 0.16, 0.5, 1.6 and 5.0 g/kg body weight. There were 3 out of 4 deaths over the 72 hours observation period in the 5.0 g/kg test group.

Test system
Five groups of ten (5 male and 5 female) young adult albino rats (Sprague-Dawley CD strain) were used. The animals were obtained from Charles River (Wilmington, Mass.). The animals were housed singly in wire cages 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). The rats were fed Purina Rodent Laboratory Chow 5001 and allowed water ad. libitum.
Animals were acclimatized to the study room for seven days and were assigned to the study using a system of random numbers. The animals were individually numbered and were marked by ear tag. The entire study was identified by a color coded label bearing a notation of the dose on each cage. Within the dose group, the caging was arranged vertically.
The animals were examined by a veterinarian and all animal assigned to the study had to be in good health and condition prior to the start of the study.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test substance (10 g) was diluted in Mazola corn oil) (q.s. ad 20 mL) constantly mixed during dosing, and 1.0 mL / 100 g was the volume administered.
Doses:
Based on the mortality in the range-finding study, five male and five female rats were treated by gavage with single oral doses of 2.0, 2.4, 2.8, 3.3 and 3.6 grams of the test article administered per kilogram of body weight.
No. of animals per sex per dose:
Five / sex / dose
Control animals:
not specified
Details on study design:
Food was withdrawn at approximately 3:00 pm on the day prior to treatment and the rats were fasted overnight. Water was available at all times.
Before being dosed, the animals were weighed. Gavage was accomplished using a No. 14G feeding needle/ After dosing food was withheld for one hour and was then returned to the animals.
The day of dosing was designated Day 0.

Observations
Animals were observed for mortality and pharmacotoxic signs at 1, 3, 6 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 prior to dosing and at the end of the observation period.

Necropsy
All surviving animals underwent a gross necropsy at the end of the experiment. The animals were killed using ether. All others were necropsied immediately following the discovery of their death.
Sex:
male
Dose descriptor:
LD50
Effect level:
2 800 mg/kg bw
Based on:
test mat.
95% CL:
2 240 - 3 500
Sex:
female
Dose descriptor:
LD50
Effect level:
2 750 mg/kg bw
Based on:
test mat.
95% CL:
2 270 - 3 320
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 700 mg/kg bw
Based on:
test mat.
95% CL:
2 310 - 3 160
Mortality:
Males: No deaths occurred at 2.0 g/kg. Deaths occurred in 1 / 5 rats at 2.4 g/kg, 2/5 deaths occurred at 2.8 g/kg and 4/5 deaths occurred at 3.3 and 3.9 g/kg.
The acute oral median lethal dose (LD50) is 2.8 g/kg with 95 % confidence limits of 2.24 – 3.50 g/kg.
Females: No deaths were observed at 2.0 g/kg. Deaths occurred in 1/5 rats at 2.4 g/kg and 4/5 deaths occurred at 2.8, 3.3 and 3.9 g/kg.
The acute oral median lethal dose (LD50) is 2.75 g/kg with 95 % confidence limits of 2.27 – 3.33 g/kg.
Clinical signs:
Pharmacotoxic signs observed in the test animals included hyperesthesia, ataxia, lethargy, tremors, diarrhea, clonic convulsions, chromodacryorrhea and chromorhinorrhea. At most doses the pharmacotoxic sings subsided within 24 h after dosing.
Body weight:
The surviving animals all gained weight in a normal pattern.
Gross pathology:
2.0 g/kg: There were no gross signs of systemic toxicity in any animals necropsied.
2.4 g/kg: There were no gross signs of systemic toxicity in any animals, except F-1878 where yellow fluid was observed in the stomach and small intestine.
2.8 g/kg: Three were no gross signs of systemic toxicity in any animals except F-1885 where yellow fluid was observed in the small intestine.
3.3 g/kg: Yellow fluid was observed in the stomach and / or small intestine of F-1959, F1961, F-1863 and F-1867. A clear fluid was observed in the stomach of M-1693.
3.9 g/kg: Yellow fluid was observed in the stomach and / or small intestine of M-1714, M-1713, M-1717, F-1966, F-1967 and F-1955.
No other sings of toxicity were observed at this dose.

Mortality distribution for the acute oral median lethal toxicity in rats

Dose level

(g/kg)

No & sex

Hours

days

Total by sex

Percent

Total

Percent

1

3

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2.0

5M

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

0

0/10

0

5F

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

0

2.4

5M

0

0

0

0

0

1

0

0

0

0

0

0

0

0

0

0

0

1/5

20

2/10

20

5F

0

0

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

1/5

20

2.8

5M

0

0

0

1

0

1

0

0

0

0

0

0

0

0

0

0

0

2/5

40

6/10

60

5F

0

0

0

3

0

1

0

0

0

0

0

0

0

0

0

0

0

4/5

80

3.3

5M

0

0

1

3

0

0

0

0

0

0

0

0

0

0

0

0

0

4/5

80

8/10

80

5F

0

0

0

4

0

0

0

0

0

0

0

0

0

0

0

0

0

4/5

80

3.9

5M

0

0

0

3

1

0

0

0

0

0

0

0

0

0

0

0

0

4/5

80

8/10

80

5F

0

0

0

4

0

0

0

0

0

0

0

0

0

0

0

0

0

4/5

80

M = Male

F = Female

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity of the test substance was assessed. The acute oral median lethal dose (LD50) is 2.8 g/kg with 95 % confidence limits of 2.24 – 3.50 g/kg for males. The LD50 is 2.75 g/kg with 95 % confidence limits of 2.27 – 3.33 g/kg for females. The LD50 is 2.70 g/kg with 95 % confidence limits of 2.31 – 3.16 g/kg for males and females.
Executive summary:

The acute oral LD50 of the test substance was assessed. Following a range-finding study, five groups of five male and five female rats were dosed by gavage at 2.0, 2.4, 2.8, 3.3 or 3.9 g/kg.

Deaths occurred in both male and female rats at all but the lowest dose. All surviving rats gained weight. Clinical observations and necropsy results were not remarkable.

The calculated LD50 in male rats is 2.85 g/kg (2.57 – 3.16) and in female rats is 2.60 g/kg (2.43 – 2.78). The combined oral LD50 is 2.70 g/kg (2.31 – 3.16).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 700 mg/kg bw

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

In the key study, the acute oral LD50 of the test substance was assessed. Following a range-finding study, five groups of five male and five female rats were dosed by gavage at 2.0, 2.4, 2.8, 3.3 or 3.9 g/kg. Deaths occurred in both male and female rats at all but the lowest dose. All surviving rats gained weight. Clinical observations and necropsy results were not remarkable.

The calculated LD50 in male rats is 2.85 g/kg (2.57 – 3.16) and in female rats is 2.60 g/kg (2.43 – 2.78). The combined oral LD50 is 2.70 g/kg (2.31 – 3.16).

In a supporting study, the acute oral toxicity of the test substance was assessed in male and female SPF albino mice. The LD50 was 4000 - 8000 mg/kg-1.


Justification for selection of acute toxicity – oral endpoint
The study was conducted on the target substance in vivo in an appropriate test species.

Justification for classification or non-classification

Acute toxicity is defined as the adverse effects occurring following a single administration of a substance, or multiple doses given within 24 hours by the oral or dermal routes, or an inhalation exposure of 4 hours.

Substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the Globally Harmonized Classification System and Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures. Acute toxicity values are expressed as approximate LD50 or LC50 (inhalation) values.

A test substance is classified according to one of these four toxicity categories when the acute LD50 value is ≤ 2000 mg/kg for exposure via the oral route.

The LD50 of the test substance was 2700 mg/kg and is therefore not classified for acute oral toxicity.