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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
The purpose of this study was to assess the Toxicological profile of test item to a single administration via oral route to Sprague Dawley rats. This study was designed to determine the acute toxicity at fixed dose levels by oral route of the test item.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N,N-trimethylanilinium chloride
EC Number:
205-319-0
EC Name:
N,N,N-trimethylanilinium chloride
Cas Number:
138-24-9
Molecular formula:
C9H14N.Cl
IUPAC Name:
N,N,N-trimethylanilinium chloride
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): N,N,N-trimethylanilinium chloride
- Molecular formula : C9H14N.Cl
- Molecular weight : 171.67 g/mol
- Smiles notation: [Cl-].C[N+](C)(C)c1ccccc1
- InChl : InChI=1/C9H14N.ClH/c1-10(2,3)9-7-5-4-6-8-9;/h4-8H,1-3H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Female rats of the age of approximately 8 to 12 weeks old were used at the commencement of its dosing.
- Weight at study initiation: Body weight range was 193.7 to 201.8 grams.
Body weights at the start : Female Mean: 198.47 g (= 100 %); Minimum : 193.7 g (- 2.40 %); Maximum : 201.8 g (+ 1.68 %)
- Identification: Each female rat was individually identified by the picric acid marking.
- Fasting period before study: Approximately 16 hours or more.
- Housing: The rats were housed in polycarbonate cages.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 to 22.0 degree centigrade.
- Humidity (%): 54.4% to 58.9%.
- Air changes (per hr): at least ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room

IN-LIFE DATES: 10-10-2017 to 28-10-2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 mg/kg , 50 mg/kg and 300 mg/kg
MAXIMUM DOSE VOLUME APPLIED: 10 ml per kg of body weight
Doses:
Group I Step I : 300 mg/kg
Group II Step I : 50 mg/kg
Group II Step II : 50 mg/kg
No. of animals per sex per dose:
Total No. of animals : 9
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: yes, necropsy was performed on all animals, found dead and sacrificed at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).
- Other examinations performed:
Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality and morbidity, until sacrifice. Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at immediately (0 to 5 minutes), 5, 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time. The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.
Body weights:
Individual animal body weights were recorded, before fasting, prior to administration of the test item (fasting body weights), weekly thereafter and at termination on day 14. Weight changes were calculated and recorded.
Histopathology:
Gross pathological examination revealed unabsorbed residual test item in stomach in found dead animals from 300 mg/kg dose group. No gross pathological changes attributable to the treatment were observed in stomach and hence no histopathology was considered.
Statistics:
not specified

Results and discussion

Preliminary study:
not specified
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 50 - <= 300 mg/kg bw
Based on:
test mat.
Mortality:
Group I Step I : 300 mg/kg - Three animals died at 1 hour after the dosing.
Group II Step I : 50 mg/kg - All animals survived through the study period of 14 days.
Group II Step II : 50 mg/kg - All animals survived through the study period of 14 days.
Clinical signs:
other: Group I Step I : 300 mg/kg - Animals treated at the dose level of 300 mg/kg resulted in reduced locomotor activity, loss of righting reflex and convulsions with onset at 30 minutes after the dosing. Group II Step I : 50 mg/kg - Animals treated at the d
Gross pathology:
Gross pathological examination did not reveal any abnormalities in all animals sacrificed terminally from 50 mg/kg dose group.
Gross pathological examination revealed unabsorbed residual test item in the stomach in found dead animal from 300 mg/kg dose group.
Other findings:
not specified

Any other information on results incl. tables

Table No. I 

Summary of Clinical Signs of Toxicity and Mortality

 

Laboratory Test Item Code :TAS/122/058

Test System : Sprague Dawley Rat

Sex : Female

Group I :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

I

300

Reduced locomotor activity

3

1,2,3

30 min.

3/3

Loss of righting reflex   

3

1,2,3

30 min.

Convulsions

3

1,2,3

30 min.

 

Group II :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

I

50

Reduced locomotor activity

3

4,5,6

2 hrs.

0/3

Ataxic gait    

3

4,5,6

2 hrs. - 4 hrs.

 

Group II :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

II

50

Reduced locomotor activity

3

7,8,9

2 hrs.

0/3

Ataxic gait    

3

7,9

8

2 hrs. - 4 hrs.

1 hr. - 4 hrs.

  

Table No.II

Mean Body Weight and Percent Body Weight Gain (g)

 

Laboratory Test Item Code :TAS/122/058

Test System : Sprague Dawley Rat

Sex : Female

Group I :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

300

Mean

197.60

-

-

-

-

-

± SD

3.46

-

-

-

-

-

Group II :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

50

Mean

197.57

211.13

6.87

228.10

8.04

15.45

± SD

1.82

2.39

0.22

2.36

0.45

0.45

 Group II :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

II

50

Mean

200.23

214.80

7.27

232.67

8.31

16.19

± SD

1.78

1.87

0.10

3.76

0.93

0.92

Table No.III

Summary of Gross Pathological Findings

 

Laboratory Test Item Code :TAS/122/058

Test System : Sprague Dawley Rat

Sex : Female

                    Group I :

Step

No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

300

1 - 3

FD

Stomach : Unabsorbed residual test item

 

                     Group II : 

Step

No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

50

4 - 6

TS

No abnormality detected

 

                    Group II : 

Step

No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

II

50

7 - 9

TS

No abnormality detected

 

                    FD = Found dead

         TS = Terminal sacrifice

 

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Under the condition of the study, the acute oral LD50 value of the given test chemical was considered in between 50 – 300 mg/kg body weight. Thus, it was concluded that the acute toxicity study of test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category 3” according to criteria of CLP.
Executive summary:

The reported study was designed and conducted to determine the acute oral toxicity profile of the given test chemical as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in Sprague Dawley rats.

Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg resulted in reduced locomotor activity, loss of righting reflex and convulsions with onset at 30 minutes after the dosing. Three animals died at 1 hour after the dosing. As mortality was observed at 300 mg/kg dose group, additional three female animals were treated with the lower dose of 50 mg/kg of the test item (Step - I).

Administration of the test item at 50 mg/kg resulted in reduced locomotor activity and ataxic gait with onset at 2 hours after the dosing and no mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three additional female animals were added to the study and treated with the dose of 50 mg/kg of the test item (Step - II). Administration of the test item at 50 mg/kg resulted in reduced locomotor activity and ataxic gait with onset at 1 to 2 hours after the dosing and no mortality at 24 hours after the dosing.

All animals from 50 mg/kg dose group survived through the study period of 14 days. Gross pathological examination did not reveal any abnormalities in all animals sacrificed terminally from 50 mg/kg dose group. Gross pathological examination revealed unabsorbed residual test item in the stomach in found dead animal from 300 mg/kg dose group.

Under the condition of the study, the acute oral LD50 value of the given test chemical was considered in between 50 – 300 mg/kg body weight. Thus, it was concluded that the acute toxicity study of test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category 3” according to criteria of CLP.