Triclocarban

Skin irritation / corrosion

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

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

Test material information

Constituent 1

Reference substance name:

Triclocarban

EC Number:

202-924-1

EC Name:

Triclocarban

Cas Number:

101-20-2

Molecular formula:

C13H9Cl3N2O

IUPAC Name:

1-(4-chlorophenyl)-3-(3,4-dichlorophenyl)urea

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 or test system 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

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

14 d

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

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.