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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
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 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
This study was designed to determine the dermal LD50 of the test item (up to 2000 mg/kg bw) or to establish a non-lethal dose level of 2000 mg/kg bw.
GLP compliance:
yes
Test type:
other: Acute Dermal Toxicity
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
- Physical state:Solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
- Source: National institute of biosciences Pune
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks
- Weight at study initiation: Mean:227.60g (=100%)
Minimum:221.6 g (-2.64%)
Maximum: 233.3 g (+2.50%)
- Housing:The rats were housed in polycarbonate cages with paddy husk and bedding
- 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):Water was provied ad libitum
- Acclimation period: acclimatized 5 days prior to study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22.5 degree celcius
- Humidity (%): 55.3-58.8%
- Air changes (per hr): 10-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light and dark period

IN-LIFE DATES: From: 06-03-2018 To: 04-04-2018

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: the trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.
- Time after start of exposure:24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):200, 1000 and 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: yes
Duration of exposure:
24 hrs
Doses:
Dase range finding study: Group I: 200, 1000 and 2000 mg/kg bw
Main study: Group II: 2000 mg/kg bw
No. of animals per sex per dose:
Dase range finding study: Group I: 200, 1000 and 2000 mg/kg bw : 1/dose
Main study: Group II: 2000 mg/kg bw: 2/dose
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, until sacrifice. Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 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.
Evaluation of Dermal Reaction: Dermal reaction was observed daily for study period of 14 days.
Body weights: Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.
- Necropsy of survivors performed: yes, necropsy was performed on animals surviving 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: Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
Statistics:
not specified

Results and discussion

Preliminary study:
Dose range finding study: A single dose of 200 mg/kg bw of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, addtional 1 female animal was administered at the dosr 1000 mg/kg bw. Administration of 1000 mg/kg bw did not reveal any clinical signs of toxicity or death during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg bw. Administration of 2000 mg/kg bw did not reveal any clinical signs of toxicity or death during first 48 hours.
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:
Dose Range Finding Study: All animals survived through the study period of 14 days at 200 mg/kg, 1000 mg/kg and 2000 mg/kg body weight .
Main Study: Group II : All animals survived through the study period of 14 days.
Clinical signs:
Dose Range Finding Study: Animals treated at the dose level of 200 mg/kg, 1000 mg/kg and 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Main Study: Group II : Animals treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Body weight:
Dose Range Finding Study:
Group 1 (200 mg/kg) - Percent body weight gain after 7 days and I4 days was found to be 4.61% and 8.15% respectively.
Group I (1000 mg/kg) - percent body weight gain utter 7 days and 14 days was found to be 5.4296 and 9.70% respectively.
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.939% and 8.99% respectively.
Main Study:
Group II (2000 mg/kg) - Percent body weight gain alter 7 days and 14 days was found to be 3.58% and 9.0394% respectively.
Gross pathology:
Gross pathological examination did not reveal any abnormalities in animals from 200 mg/kg, 1000 mg/kg and 2000 mg/kg dose groups from dose range finding study and main study sacrificed terminally.
Other findings:
Evaluation of Dermal Reaction -
Dose Range Finding Study: Group I : Animal treated at the dose level of 200 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Group I : Animal treated at the dose level of 1000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Group I : Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Main Study: Group II : Animals treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Any other information on results incl. tables

TABLE 1:SUMMARY OF BODY WEIGHT (GM)

Group

Animal ID

Day 0

Day 7

%

Gain/loss

Day 14

%

Gain/loss

Group-I

2000 mg/kg bw

201320-1

202.5

211.1

4.24

218.7

8.00

 

201320-2

200.9

210.7

4.87

215.1

7.07

 

201320-3

203.2

212.9

4.78

217.8

7.19

 

201320-4

203.2

210.2

3.09

216.9

6.38

 

201320-5

201.2

209.7

4.23

216.1

7.41

 

201320-6

200.4

211.9

5.82

218.5

9.10

 

201320-7

205.7

213.9

4.00

219.9

6.90

 

201320-8

204.9

212.4

3.70

220.1

7.50

 

201320-9

208.4

214.9

3.20

221.8

6.50

 

201320-10

206.9

213.9

3.40

219.9

6.30

Group-II

2000 mg/kg bw

201320-11

208.2

214.5

3.10

222.1

6.70

 

201320-12

206.8

213.9

3.50

220.8

6.78

 

201320-13

209.6

215.9

3.00

219.1

4.60

 

201320-14

203.4

213.6

5.10

218.4

7.40

 

201320-15

205.9

214.7

4.40

220.0

6.90

 

201320-16

208.7

217.9

4.40

221.8

6.30

 

201320-17

205.9

214.1

3.99

219.8

6.75

 

201320-18

207.8

215.5

4.00

219.8

6.20

 

201320-19

202.6

212.9

5.10

217.3

7.30

 

201320-20

201.6

212.6

5.50

218.6

8.50

TABLE 3: CLINICAL SIGNS AND MORTALITY

Group-I Limit test                            Dose :2000 mg/kg b.wt.

Parameters

Incidence of clinical signs observed after dosing on

Mortality

 

Day 0

 

DAY

 

Min

Hour

 

 

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total

%

%

Mortality (total)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/10

 

00

Clinical signs-local

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

 

 

Redness

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Pain

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Swelling

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Systemic signs

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

- = OBSERVED AFTER 24 HOURS

0 = NO CLINICAL SIGNS

+ =MILD

++ = MODERATE

+++ =HIGH

++++=SEVERE

 

 

TABLE 3 CONTINUED

GROUP :II CONFIRMATORY TEST        Dose:2000 mg/kg b.wt

Parameters

Incidence of clinical signs observed after dosing on

Mortality

Day 0

 

DAY

Min

Hour

 

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total

%

Mortality (total)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/10

0

Clinical signs-local

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Redness

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Pain

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Swelling

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Systemic signs

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

- = OBSERVED AFTER 24 HOURS

0 = NO CLINICAL SIGNS

+ =MILD

++ = MODERATE

+++ =HIGH

++++=SEVERE

  

 

Table 4 :SUMMARY OF NECROPSY FINDINGS

S. NO.

FATE

WISTAR ALBINO RATS

DOSE (mg/kg b.wt)

2000

(limit test)

2000

(confirmatory test)

1.

Terminal sacrifice

10/10

10/10

2.

Found dead

0/10

0/10

3.

Abnormalities detected

0/10

0/10

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.
Executive summary:

The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) in Sprague Dawley rats.

In the dose range finding study a single dose of 200 mg/kg body weight of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, additional 1 female animal was administered with the dose of 1000 mg/kg body weight. Administration of 1000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours; hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight. Administration of 2000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours.

As the dose range finding study revealed no mortality or clinical signs at the maximum dose of 2000 mg/kg, the main study was initiated with two additional animals. The animals were administered with a dose of 2000 mg/kg body weight in sequential manner at 48 hours intervals.

Animals from dose range finding study treated at the dose levels of 200 mg/kg, 1000 mg/kg and 2000 mg/kg and animals from main study treated at the dose level of 2000 mg/kg exhibited normal body weight gain and revealed no clinical signs of toxicity or mortality during the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.