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
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:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
IUPAC name: 3, 4,4`-Trichlorocarbanilide
Smiles:c1cc(ccc1NC(=O)Nc2ccc(c(c2)Cl)Cl)Cl
InChI: 1S/C13H9Cl3N2O/c14-8-1-3-9(4-2-8)17-13(19)18-10-5-6-11(15)12(16)7-10/h1-7H,(H2,17,18,19)
- Name of test material :Triclocarban
- Molecular formula:C13H9Cl3N2O
- Molecular weight:315.5861 g/mol
- Substance type:Organic
- Batch Number: GF01
- Laboratory Test Item Code: TAS/122/067
- Manufacturing Date: 22-6-2017
- Expiry Date : 22-5-2018
- Consistency: Solid, crystalline
- Safety Precautions: Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).
- Storage Condition: Test Item and prepared formulation(s) were stored at ambient temperature.
- Preparation of Test Item : Test item was suspended in corn oil. The formulation was prepared fresh on the day of dosing. The test item was administered in the dose volume of 10 ml/kg body weight. Actual preparation procedures are documented in the raw data.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: National institute of biosciences Pune
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: Mean:202.98g (=100%)
Minimum:196.1 g (-3.39%)
Maximum: 207.1 g (+2.03%)
- Fasting period before study: Approx. 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 libimm from individual feeders.
- Water (e.g. ad libitum):Rodent feed supplied by the Nutrivet Life Sciences. Pune, was provided ad libimm from individual feeders
- Acclimation period: acclimatized 5 days prior to study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-23.0 degree celcius
- Humidity (%): 56-58.9%
- Air changes (per hr): 10-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light and dark period

IN-LIFE DATES: From: 05-03-2018 To: 04-04-2018

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300, and 2000 mg/kg bw
- Amount of vehicle (if gavage): 10 ml/kg body weight
Doses:
Group I: Step I and Step II: 300 mg/kg bw
Group II: Step I and Step II: 2000 mg/kg bw
No. of animals per sex per dose:
Three females were used at each step.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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.
- Necropsy of survivors performed: yes, necropsy was performed on all animals at the end of the study period on day 15. 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.
- Other examinations performed: Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
Statistics:
Not specified

Results and discussion

Preliminary study:
Not specified
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No Mortality observed
Mortality:
All animals survived through the study period of 14 days.
Clinical signs:
Group I Step I : Animals treated at the dose level of 300 mg/kg body weight resulted in polyurea with onset at 1 to 4 hours after the dosing. All animals were free of signs of toxicity on day 1 after the dosing.
Group I Step II : Animals treated at the dose level of 300 mg/kg body weight resulted in polyurea with onset at 4 to 6 hours after the dosing. All animals were free of signs of toxicity on day 1 after the dosing.
Group II Step I : Animals treated at the dose level of 2000 mg/kg body weight resulted in polyurea with onset at 1 to 2 hours after the dosing. All animals were free of signs of toxicity on day 1 to day 2 after the dosing.
Group II Step II : Animals treated at the dose level of 2000 mg/kg body weight resulted in polyurea with onset at 1 to 2 hours after the dosing. All animals were free of signs of toxicity on day 2 after the dosing.
Body weight:
Group I Step l (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.6496 and 15.90% respectively.
Group l Step ll (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.71% and 14.46% respectively.
Group ll Step 1 (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.4691% and 12.33% respectively.
Group II Step II (2000 mg/kg) – Percent body weight gain after 7 days and 14 days was found to be 6.4892% and 12.77% respectively.
Gross pathology:
Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.
Other findings:
Not specified

Any other information on results incl. tables

Table 1: Summary of clinical signs of toxicity ad mortality

Group No.

Step No.

Dose

Mg/kg

Observed signs

Total no. of animals

Animal no.

Period of signs in days

From-To

Mortality

I

1

300

Polyurea

3

1

1 hrs-6hrs

0/3

 

 

 

 

 

2

4 hrs-6hrs

 

 

 

 

 

 

3

2 hrs-6hrs

 

I

2

300

Polyurea

3

4,6

4 hrs-6hrs

0/3

 

 

 

 

 

5

6 hrs

 

II

1

2000

Polyurea

3

7

1 hrs-6hrs

0/3

 

 

 

 

 

8

2 hrs-day 1

 

 

 

 

 

 

9

1 hrs- day 1

 

II

2

2000

Polyurea

3

10,12

2 hrs-day 1

0/3

 

 

 

 

 

11

1 hrs- day 1

 

 

Table 2: Mean body weight and percent body weight gain (g)

Group

Step no.

 

Before fasting body weight

Day 0

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

1

Mean

201.13

218.50

8.64

233.07

6.67

15.90

 

 

± SD

4.78

3.97

0.68

3.81

1.31

2.08

I

2

Mean

202.30

215.87

6.71

231.57

7.26

14.46

 

 

± SD

3.56

2.86

0.47

6.16

1.45

1.07

II

1

Mean

204.97

216.17

5.46

230.23

6.52

12.33

 

 

± SD

2.53

3.95

0.65

2.45

0.90

0.47

II

2

Mean

203.50

216.70

6.48

229.50

5.91

12.77

 

 

± SD

4.19

5.52

0.66

5.32

0.26

0.56

 

 

Table 3: Summary of gross pathological findings

Group

Step no.

Dose

Mg/kg

Animal numbers

Animal fate

Gross Pathological Findings

I

1

300

1-3

TS

No abnormality detected

I

2

300

4-6

TS

No abnormality detected

II

1

2000

7-9

TS

No abnormality detected

II

2

2000

10-12

TS

No abnormality detected

TS= Terminal Sacrifice

Table 4: Individual animal-Body weight and Percent body weight gain (g)

Group I                       Step 1                                          Dose: 300 mg/kg bw

Animal no.

Before fasting body weight

Day 0

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

1

205.6

221.8

7.88

233.4

5.23

13.52

2

196.1

214.1

9.18

229.1

7.01

16.83

3

201.7

219.6

8.87

236.7

7.79

17.35

 

Group I                       Step 2                                          Dose: 300 mg/kg bw

Animal no.

Before fasting body weight

Day 0

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

4

202.6

216.1

6.66

231.2

6.99

14.12

5

198.6

212.9

7.20

225.6

5.97

13.60

6

205.7

218.6

6.27

237.9

8.83

15.65

 

Group II                       Step 1                                          Dose: 2000 mg/kg bw

Animal no.

Before fasting body weight

Day 0

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

7

205.9

217.2

5.49

230.2

5.99

11.80

8

202.1

211.8

4.80

227.8

7.55

12.72

9

206.9

219.5

6.09

232.7

6.01

12.47

 

Group II                       Step 2                                          Dose: 2000 mg/kg bw

Animal no.

Before fasting body weight

Day 0

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

10

198.9

210.4

5.78

223.4

6.18

12.32

11

204.5

219.0

7.09

231.9

5.89

13.40

12

207.1

220.7

6.57

233.2

5.66

12.60

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
It was concluded that the acute oral toxicity dose (LD50) value was considered to be >2000 mg/kg bw, when Sprague Dawley rats were treated with the given test chemical via oral route.
Executive summary:

The reported study was designed and conducted to determine the acute oral toxicity profile 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 polyurea with onset at 6 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 female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg resulted in polyurea with onset at 4 to 6 hours after the dosing and no mortality at 24 hours after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in polyurea with onset at 1 to 2 hours after the dosing and no mortality at 24 hours after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg resulted in polyurea with onset at 1 to 2 hours after the dosing and no mortality at 24 hours after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.

It was concluded that the acute oral toxicity dose (LD50) value was considered to be >2000 mg/kg bw, when Sprague Dawley rats were treated with the given test chemical via oral route.