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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25-03-1986 to 08-04-1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Acute oral toxicity study of the given test chemical in rats.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material: Tetraethylammonium bromide (4E-ammBr)
- IUPAC name: N,N,N-triethylethanaminium bromide (TEAB)
- Molecular formula: C8H20NBr
- Molecular weight: 210.6 g/mole
- Substance type: Organic
- Purity : 100.1-100.2 % based on Br-
- Appearance: Crystalline powder
- Storage: At ambient temperature in the dark
- Batch No. : HH 85-83A

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, Rrussels, Belgium
- Age at study initiation: 8 weeks, 6 days
- Weight at study initiation: Male: 360-402 g, Female: 205-251 g
- Fasting period before study: Animals were fasted overnight before dosing till 3-4 hours after administration of test substance.
- Housing: Animals were housed in Macrolon cage
- Diet (e.g. ad libitum): Standard laboratory animal diet (RMH-B, pellet diameter 10 mm)
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 °C
- Humidity (%):30-75 %
- Photoperiod (hrs dark / hrs light): Artificial light sequence was 12 hrs dark, 12 hrs light

IN-LIFE DATES: From: 25-03-1986 to 08-04-1986

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Milli-RO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1800, 2400 and 3200 mg/kg body weight
- Amount of vehicle (if gavage): 10 ml/kg body weight
- Justification for choice of vehicle: Milli-RO water
DOSAGE PREPARATION (if unusual): test substance was formulated in Milli-RO water at 1800, 2400 and 3200 mg/kg body weight.
Doses:
1800, 2400 and 3200 mg/kg body weight
No. of animals per sex per dose:
Total: 30
1800 mg/kg bw: 5 male, 5 female
2400 mg/kg bw: 5 male, 5 female
3200 mg/kg bw: 5 male, 5 female
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical sign observed daily and body weight on day 0,7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: survival,clinical signs, body weight, gross pathology and histopathology were examined.
Statistics:
LD50 was calculated with U-distribution and maximum likelihood (Finney).

Results and discussion

Preliminary study:
Dose range finding investigation: In order to establish an appropriate dose range, eleven groups of Sprague-Dawley rats, each comprising 1 male and 1 female, were dosed with a single oral dose of the test substance at 75, 100, 130, 180, 240, 320, 420, 750, 1300, 2400 and 4200 mg/kg bw, respectively. Both animals of the 4200 mg/kg bw and the male of the 2400 mg/kg bw group were found dead within a few minutes after dosing. Surviving animals revealed no signs of evident systemic toxicity during the 7 days observation period. Macroscopic examination at autopsy of all animals revealed no gross abnormalities.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 800 mg/kg bw
Based on:
test mat.
95% CL:
2 500 - 3 400
Remarks on result:
other: 50 % mortality observed
Sex:
male
Dose descriptor:
LD50
Effect level:
2 500 mg/kg bw
Based on:
test mat.
95% CL:
2 300 - 3 100
Remarks on result:
other: 50 % mortality observed
Sex:
female
Dose descriptor:
LD50
Effect level:
2 800 mg/kg bw
Based on:
test mat.
95% CL:
2 200 - 16 500
Remarks on result:
other: 50 % mortality observed
Mortality:
When treated with 3200 mg/kg bw, 5 male and 3 female died.
When treated with 2400 mg/kg bw, 1 male and 2 female died.
When treated with 1800 mg/kg bw, No mortality were observed in treated male and female rats.
Clinical signs:
Lethargy, tremors, convulsions, coma, laboured breathing and diarrhoea sign of toxicity were observed.Other findings were observed unbalanced gait and bloody nose or eye encrustation.
In surviving animals, these signs were reversible since generally as of day 3 no more abnormalities were observed during the 14 day observation period
Body weight:
No effect on body weight gain was observed in treated male and female rats.
Gross pathology:
Hyperemia, petechiae or erosion of stomach frequently followed by bloody gastrointestinal content were observed in dead animals. Other gross internal findings were renal hyperemia, motteled kidney, aqueous gastrointestinal content (possibly test substance) and autolysis.At the end of study in surviving animals no test substance related gross abnormalities were observed
Other findings:
not specified

Any other information on results incl. tables

Table 1: Day of death and Number of Mortalities after oral administration of TEAB in the rats

Day of Death

Mortalities (Male/ Female)

 

Dosage mg/kg

 

1800

2400

3200

0

0/0

1/1

5/3

1

0/0

0/1

0/0

Sum

 

 

 

Male / Female

0/0

1/2

5/3

Sexes combined

0

3

8

Note: the dose groups comprised 5 male and 5 female rats. Indicated are the number of animals (Male / Female) found dead during the 14 day observation period.

Table 2: Daily incidence of Cage side observation for male and female rats after a single oral dose of TEAB: 1800 mg/kg bw

 

Day of observation

observation

Sex

0a)

0b)

0c)

0d)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

No abnormalities

M

2/5

3/5

3/5

4/5

2/5

4/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

 

5/5

5/5

5/5

 

F

2/5

2/5

1/5

 

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

Lethargy

M

3/5

2/5

2/5

1/5

1/5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

3/5

3/5

4/5

5/5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Tremors

M

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

 

 

 

2/5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Bloody nose/eye encrustation

M

 

 

 

 

2/5

1/5

 

 

 

 

 

 

 

 

2/5

 

 

 

 

F

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Diarrhoea

M

 

 

 

 

1/5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3: Daily incidence of Cage side observation for male and female rats after a single oral dose of TEAB: 2400 mg/kg bw

 

Day of observation

observation

Sex

0a)

0b)

0c)

0d)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

No abnormalities

M

 

 

 

 

2/4

4/4

4/4

4/4

4/4

4/4

4/4

4/4

4/4

4/4

4/4

4/4

4/4

4/4

 

F

 

 

1/5

 

2/3

3/3

3/3

3/3

3/3

3/3

3/3

3/3

3/3

3/3

3/3

3/3

3/3

3/3

Lethargy

M

4/4

4/4

4/4

4/4

1/4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

5/5

5/5

4/5

5/5

1/3

 

 

 

 

 

 

 

 

 

 

 

 

 

Tremors

M

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

 

 

 

3/5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Laboured breathing

M

 

1/4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Unbalanced gait

M

 

 

 

1/5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Bloody nose/eye encrustation

M

 

 

 

 

1/4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 4: Daily incidence of Cage side observation for male and female rats after a single oral dose of TEAB: 3200 mg/kg bw

 

Day of observation

observation

Sex

0a)

0b)

0c)

0d)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

No abnormalities

M

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

1/4

 

 

 

1/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

Lethargy

M

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

1/4

2/2

2/2

2/2

1/2

 

 

 

 

 

 

 

 

 

 

 

 

 

Tremors

M

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

 

 

 

2/2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Convulsions

M

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

 

1/4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Comatous

M

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

F

 

1/4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

a)     Approx. 1/4 - 1 1/4   hours postdosing

b)     Approx. 1 3/4- 2 3/4 hours postdosing

c) Approx. 3 1/4 – 4 1/4 hours postdosing

d) Approx. 4 1/2 – 5 1/2 hours hours postdosing

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
The acute oral LD50 value was considered to be 2800 mg/kg bw, with 95% confidence limit of 2500-3400 mg/kg bw for both male and female rats, 2500 mg/kg bw, with 95% confidence limit of 2300-3100 mg/kg bw for male rats and 2800 mg/kg bw, with 95% confidence limit of 1650- 2200 mg/kg bw for female rats, when groups of 5 male and 5 female Sprague-Dawley rats were treated with the given test chemical orally by gavage in Milli-RO water.
Executive summary:

In a acute oral toxicity study, groups of 5 male and 5 female Sprague-Dawley rats were treated with the given test chemical at the dose concentrations of 1800, 2400 and 3200 mg/kg body weight as per OECD 401.

The given test substance was formulated in Milli-RO water and administered as 10 ml/kg body weight via oral gavage route.

In order to establish an appropriate dose range, eleven groups of Sprague-Dawley rats, each comprising 1 male and 1 female, were dosed with a single oral dose of the test substance at 75, 100, 130, 180, 240, 320, 420, 750, 1300, 2400 and 4200 mg/kg bw, respectively. Both animals of the 4200 mg/kg bw and the male of the 2400 mg/kg bw group were found dead within a few minutes after dosing. Surviving animals revealed no signs of evident systemic toxicity during the 7 days observation period. Macroscopic examination at autopsy of all animals revealed no gross abnormalities.

Based on the toxicity observed in the dose range finding investigation three groups of animals, each comprising 5 males and 5 females, were dosed with a single oral dose of the test substance at 1800, 2400 and 3200 mg/kg body weight, respectively.

Animals were observed for mortality and clinical signs daily and body weight on day 0,7 and 14 day. Necropsy of survivors performed. Gross pathology and histopathology were examined. LD50 was calculated with U-distribution and maximum likelihood (Finney).

Mortality was observed as, when treated with 3200 mg/kg bw, 5 male and 3 female died; when treated with 2400 mg/kg bw, 1 male and 2 female died; when treated with 1800 mg/kg bw, no mortality were observed in male and female rats.

Lethargy, tremors, convulsions, coma, laboured breathing and diarrhoea sign of toxicity were observed. Other findings were observed unbalanced gait and bloody nose or eye encrustation.

In surviving animals, these signs were reversible since generally as of day 3 no more abnormalities were observed during the 14 day observation period. No effect on body weight gain was observed in treated male and female rats. Hyperemia, petechiae or erosion of stomach frequently followed by bloody gastrointestinal content were observed in dead animals. Other gross internal findings were renal hyperemia, motteled kidney, aqueous gastrointestinal content (possibly test substance) and autolysis.At the end of study in surviving animals no test substance related gross abnormalities were observed

Under the condition of the study, the acute oral LD50 value was considered to be 2800 mg/kg bw, with 95% confidence limit of 2500-3400 mg/kg bw for both male and female rats, 2500 mg/kg bw, with 95% confidence limit of 2300-3100 mg/kg bw for male rats and 2800 mg/kg bw, with 95% confidence limit of 1650- 2200 mg/kg bw for female rats, when groups of 5 male and 5 female Sprague-Dawley rats were treated with the given test chemical orally by gavage in Milli-RO water.