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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
data is from experimental reports

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
To determine the dermal reaction profile of the test chemical in Sprague Dawley rats.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material: Triclocarban
- Molecular formula: C13H9Cl3N2O
- Molecular weight: 315.5861 g/mol
- Smiles notation: c1cc(ccc1NC(=O)Nc2ccc(c(c2)Cl)Cl)Cl
- InChl: 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)
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: National Institute of Biosciences, Pune
- Sex: Females
- Age at study initiation: Young adult (8 to 10 weeks old) female rats
- Weight at study initiation: weight range of approximately 221.6 to 233.3 grams at initiation of dosing.
Body weights at the start :
Female
Mean : 227.60 g (= 100 %)
Minimum : 221.6 g (- 2.64 %)
Maximum : 233.3 g (+ 2.50 %)
Total No. of animals : 5
- Identification: Each rat was individually identified by the cage number.
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- 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:All animals were acclimatized to laboratory conditions for minimum of 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature was maintained at 19.0 to 22.5 degree centigrade
- Humidity (%): room humidity was maintained at 55.3% to 58.8%.
- Air changes (per hr): The animal room was independently provided with 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.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
Dose Range Finding Study: 200, 1000, 2000 mg/kg bodyweight
Main study: 2000 mg/kg bodyweight
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
5 female rats
Details on study design:
TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.
OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : Dermal reaction was observed daily for study period of 14 days.
SCORING SYSTEM: Draize Method.
Other Observations:
Viability:
Twice daily.
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 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.
Gross Pathology:
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).
Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed
Preparation of Animals:
The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
14 d
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
14 d
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Evaluation of Dermal Reaction
Sex : Female
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.
Other effects:
Clinical Signs of Toxicity and Mortality
Sex : Female
Dose Range Finding Study:
Group I : Animal treated at the dose level of 200 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. The animal survived through 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 signs of toxicity during the study period of 14 days. The animal survived through 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 signs of toxicity during the study period of 14 days. The animal survived through 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. All animals survived through the study period of 14 days.

Any other information on results incl. tables

Summary of Evaluation of Dermal Reaction

 

Laboratory Test Item Code :TAS/122/067

Test System : Sprague Dawley Rat

Sex : Female

Finding Study:

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

Animal Nos.

Period of signs

in days

 From - to

I

200

No dermal reaction observed

1

1

Day 0 - Day 14

 

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

Animal Nos.

Period of signs

in days

 From - to

I

1000

No dermal reaction observed

1

2

Day 0 - Day 14

 

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

Animal Nos.

Period of signs

in days

 From - to

I

2000

No dermal reaction observed

1

3

Day 0 - Day 14

 

Main Study:

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

Animal Nos.

Period of signs

in days

 From - to

II

2000

No dermal reaction observed

2

4, 5

Day 0 - Day 14

Summary of Clinical Signs of Toxicity and Mortality

 

Laboratory Test Item Code :TAS/122/067

Test System : Sprague Dawley Rat

Sex : Female

Finding Study:

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

200

No clinical signs observed

1

1

Day 0 - Day 14

0/1

 

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

1000

No clinical signs observed

1

2

Day 0 - Day 14

0/1

 

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

2000

No clinical signs observed

1

3

Day 0 - Day 14

0/1

 

Main Study:

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

II

2000

No clinical signs observed

2

4, 5

Day 0 - Day 14

0/2

Individual Animal - Evaluation of Dermal Reaction

 

Laboratory Test Item Code :TAS/122/067

Test System : Sprague Dawley Rat

Sex : Female  

Finding Study:

Group : I                                                                      Dose  : 200 mg/kg body weight

Animal

Dermal

D A Y S

No.

Reaction

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Group : I                                                                    Dose  : 1000 mg/kg body weight

Animal

Dermal

D A Y S

No.

Reaction

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Group : I                                                                    Dose  : 2000 mg/kg body weight

Animal

Dermal

D A Y S

No.

Reaction

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

3

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Main Study:

Group : II                                                                   Dose  : 2000 mg/kg body weight

Animal

Dermal

D A Y S

No.

Reaction

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

4

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

5

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

 

 

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
Conclusions:
The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were found at the end of 14 days observation period after patch removal.
Hence, it was concluded that the test chemical was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested and classified as “Category-
Not Classified” as per CLP Classification.
Executive summary:

A study was designed and conducted to determine the dermal reaction profile of the test chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. 5 females (nulliparous and non-pregnant) were used for the study.

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.

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were found at the end of 14 days observation period after patch removal.

Hence, it was concluded that the test chemical was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested and classified as “Category-

Not Classified” as per CLP Classification.