Sodium 2-amino-4,6-dinitrophenoxide

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: Acute Dermal toxicity (OECD 402 Guidelines)

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:

Sodium 2-amino-4,6-dinitrophenoxide

EC Number:

212-603-8

EC Name:

Sodium 2-amino-4,6-dinitrophenoxide

Cas Number:

831-52-7

Molecular formula:

C6H5N3O5.Na

IUPAC Name:

sodium 2-amino-4,6-dinitrophenoxide

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: Female. Females were nulliparous and non-pregnant
- Age at study initiation: Young adult (8 to 10 weeks old) female rats
- Weight at study initiation: weight range of approximately 221.5 to 227.4 grams at initiation of dosing.
Body weights at the start :
Female
Mean : 225.23 g (= 100 %)
Minimum : 221.5 g (- 1.66 %)
Maximum : 227.4 g (+ 0.96 %)
Total No. of animals : 3
- 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, ad libitum
- 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): Room temperature was maintained at 19.0 to 21.8 degree centigrade
- Humidity (%): room humidity was maintained at 50.4% to 60.3%.
- 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

IN-LIFE DATES: From: 29/05/2018 To: 15/06/2018

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: 2000 mg/kg
Main Study: 2000 mg/kg

Duration of treatment / exposure:

24 hours exposure

Observation period:

Dermal reaction was observed daily for study period of 14 days.

Number of animals:

3 - [1- dose-range finding study;2 - main study]

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 we
re 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

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 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 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.

Body Weight
Sex : Female
Dose Range Finding Study:
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.35% and 15.85% respectively.
Main Study:
Group II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.88% and 12.57% respectively.

Gross Pathological Findings
Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group from dose range finding study and main study sacrificed terminally.

Any other information on results incl. tables

Summary of Evaluation of Dermal Reaction

 

Laboratory Test Item Code :TAS/122/084

Test System : Sprague Dawley Rat

Sex : Female

Finding Study:

Group No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal No.	Period of signs in days  From – to
I	2000	No dermal reaction observed	1	1	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	2, 3	Day 0 - Day 14

Individual Animal - Evaluation of Dermal Reaction

 

Laboratory Test Item Code :TAS/122/084

Test System : Sprague Dawley Rat

Sex : Female  

Finding Study:

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
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

 

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
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
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

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 not 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 female young adult, non-pregnant rats were used for the study. 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.

Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. 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. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

\ A single dose of 2000 mg/kg body weight of the test item was applied to 1 female animal respectively in the dose range finding study. Since no signs of irritation were observed at the maximum dose of 2000 mg/kg in the test animals, 2 additional animals were tested in the main study with 2000 mg/kg. The animals were applied with a dose of 2000 mg/kg body weight in sequential manner at 48 hours intervals. Dermal reaction was observed daily for study period of 14 days.

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 female Sprague Dawley rats under the experimental conditions tested and classified as “Category- Not Classified” as per CLP Classification.