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EC number: 277-492-0 | CAS number: 73507-17-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- Experimental data from various test chemicals
- Justification for type of information:
- Data for the target chemical is summarized based on data from various test chemicals
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Data is from experimental study report
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Principles of method if other than guideline:
- Acute dermal irritation study was performed to determine the irritant nature of the test chemical
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- Species : Rabbit (Oryctolagus cuniculus)
Strain : New Zealand White
Age : 3.5 to 4.7 Months (Approximately)
Sex : Male
Number of Animals : Three
Supplier/Source : Procured from GENTOX BIOSERVICES PVT. LTD.
Health Status : Healthy young adult rabbits were used for the study
Body weight of animals : Minimum: 2.090 kg & Maximum: 2.354 kg (Prior to Treatment)
Acclimatisation :Rabbits were acclimatised to the test conditions for a period of 6 days (Animal No. 1) and 9 days (Animal No. 2 and 3) prior to the application of the test item.
Identification : During acclimatization marking was done with non toxic marker pen in the inside of left ear of rabbits and after acclimatization, animals were marked with permanent number in the inner side of right ear of rabbits. Permanent marker and cage card was used for identification. The individual cage cards were labelled with study no., study type, test system, sex, dose, animal number, experimental start and completion date.
Husbandry Conditions
Diet : All animals were provided conventional laboratory rabbit diet
Water : Aqua guard filtered tap water was provided ad libitum.
Husbandry : The animals were housed individually in stainless steel cages.
Room Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
Cages and water bottle : All the cages and water bottles were changed minimum twice a week.
Experimental Room Condition
Temperature : Minimum: 18.70 °C Maximum: 21.60 °C
Relative humidity : Minimum: 49.10% Maximum: 69.40%
Light-dark-rhythm : 12 hour light and 12 hour dark
Air Changes : More than 12 changes per hour - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- Preparation of Application Site
Approximately 24 h prior to treatment, the fur coat of each rabbit was removed from dorsal lumbar region approximately 6 X 6 cm at contralateral sites on each rabbit using clipper, one as control and other site as treatment. Rabbits with healthy intact skin were selected for the study.
Test Item Application Procedure
The 0.5 ml of test item (as such) was applied uniformly over clipped area (approximately 6 X 6 cm) of the trunk of each rabbit skin (treated site) and 0.5 ml distilled water was applied at control site. Test item was held in contact with the skin with a porous gauze dressing and non-irritating tape (Micropore 3”) throughout a 4-hour exposure period, to prevent access by the rabbits to the patch and resultant ingestion of the test item. At the end of the exposure period, residual test item was removed by using cotton soaked in distilled water.
A single rabbit (Animal No. 1) was used for initial testing. The patch was removed after 4 h and the responses graded, no erythema and oedema was observed at 1 hour, 24 hour, 48 hour and 72 hour in animal no. 1. Hence the confirmatory test was conducted on additional two rabbits (No. 2 and 3) after 24 hour to confirm the non irritant nature of the test item. - Duration of treatment / exposure:
- 4 hours
- Observation period:
- 72 hours
- Number of animals:
- 3
- Details on study design:
- A dose of 0.5 gm of test item moistened with 0.5 ml of distilled water was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits.
- Irritation parameter:
- erythema score
- Basis:
- mean
- Time point:
- other: 24 hrs
- Score:
- 0.67
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritation parameter:
- edema score
- Basis:
- mean
- Time point:
- other: 24 hrs
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritation parameter:
- erythema score
- Basis:
- mean
- Time point:
- other: 48 hrs
- Score:
- 0.33
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritation parameter:
- edema score
- Basis:
- mean
- Time point:
- other: 48 hrs
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritation parameter:
- erythema score
- Basis:
- mean
- Time point:
- other: 72 hrs
- Score:
- 0
- Max. score:
- 0.67
- Reversibility:
- fully reversible
- Irritation parameter:
- edema score
- Basis:
- mean
- Time point:
- other: 72 hrs
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritant / corrosive response data:
- No erythema and edema (skin irritation) were found at the end of 72 hour observation period after patch removal.
- Other effects:
- no effects observed
- Interpretation of results:
- not irritating
- Conclusions:
- No erythema and no oedema (skin irritation) were found at the end of 72 hour observation period after patch removal. Hence, it was concluded that the test chemical was "Non-Irritating" to the skin of Male New Zealand White rabbits under the experimental conditions tested and hence the test chemical is "Not Classified as Skin Irritant" as per CLP regulation.
- Executive summary:
A dermal irritation study was conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of Test chemical. Three male New Zealand White rabbits were used for the study. The hair of al the rabbits were clipped at contraleteral sites, approximately 24 hrs prior to treatment. A dose of 0.5g of pulverised form of test chemical moistened with 0.5mL distilled water was applied to the skin over an area of 6X6 cm clipped of hair on one side of rabbits. The other untreated site served as control area and 0.5mL distilled water was applied at this site. At the end of 4hrs, the gauze patch was removed and test item application site was wiped with water without altering the epidermis. Initially the test chemical was applied to the clipped skin of one rabbit. The test site was covered with gauze patch. After 4 hrs of exposure, very slight erythema and no oedema was observed at 1 hr of observation. At 24 and 48 hrs, very slight erythema and no oedema was observed. At 72 hrs, no erythema and no oedema was observed. Hence the confirmatory test was conducted on two more animals. The patch was removed at 4hrs and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hrs after patch removal, evaluated and graded as per draize method. In the animal no. 2 and 3 at 1 and 24 hrs observation post patch removal, revelaed very slight erythema and no oedema. At 48 hrs, animal no. 2 was observed with no erythema and no oedema whereas animal no. 3 was observed with slight erythema and no oedema. At 72 hrs, no erythema and no oedema was observed in animals no. 2 and 3. The other untreated site revealed no erythema and no oedema and was found to be normal throughout the experimental period. The individual mean score at treated site at 24, 48 and 72 hrs for animals 1, 2, 3 were 0.67, 0.33, 0.67 and 0.00, 0.00, 0.00 for erythema and oedema formation, respectively. At 72 hrs, no erythema and no oedema was observed after patch removal. Hence, it was concluded that the test chemical was "Non-Irritating" to the skin of Male New Zealand White rabbits under the experimental conditions tested and hence the test chemical is "Not Classified as Skin Irritant" as per CLP regulation.
Table 1
Skin Reaction
In Treated area Dose : 0.5 g (Pulverized form) Sex:Male
Animal No. |
Test |
Treated area |
Erythema score |
Oedema score |
||||||
1h |
24h |
48h |
72h |
1h |
24h |
48h |
72h |
|||
1 |
Initial |
Right |
1 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
2 |
Confirmatory |
Left |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
3 |
Right |
1 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
In Control areaDose:0.5 ml of distilled water Sex:Male
Animal No. |
Test |
Treated area |
Erythema score |
Oedema score |
||||||
1h |
24h |
48h |
72h |
1h |
24h |
48h |
72h |
|||
1 |
Initial |
Left |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
Confirmatory |
Right |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3 |
Left |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Key: h = Hour.
Erythema Oedema
0 =No erythema 0 =No oedema
1 = Very slight erythema(barely perceptible)
Table 1 Continued…
Mean Individual Animal Score at 24, 48 and 72 hours (Treated Site)
Animal Number Observations |
1 |
2 |
3 |
Erythema |
0.67 |
0.33 |
0.67 |
Oedema |
0.00 |
0.00 |
0.00 |
Table 2
Individual Animal BodyWeight
Sex:Male
Animal No. |
Body Weight (kilogram) |
|
Prior to Dosing |
At termination |
|
1 |
2.090 |
2.178 |
2 |
2.144 |
2.172 |
3 |
2.354 |
2.386 |
Table 3
Individual AnimalClinicalSigns
Sex:Male
Animal No. |
Days (Post dosing Observation) |
|||
0 |
1 |
2 |
3 |
|
1 |
1 |
1 |
1 |
1 |
2 |
1 |
1 |
1 |
1 |
3 |
1 |
1 |
1 |
1 |
Key: 1 = Normal.
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Data is from experimental report
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Principles of method if other than guideline:
- The test compound was tested for its dermal irritation potential in New Zealand White Rabbits according to OECD guideline 404 Guidelines
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- Details on test animals
Age: 10 to 12 weeks
Sex:Female
Body weight range: 2.0kg±200g
Identification : By cage tag and corresponding colour body marking
Housing:Animals were housed individually in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle.
Diet:Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi
Water:Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad libitum
Acclimatization: The healthy rabbits selected for study was acclimatized to standard laboratory condition for one week in experimental room under Veterinary examination.
Randomization: After acclimatization and Veterinary examination three females were randomly selected.
Details on environmental conditions:
- Temperature (°C): temperature between 22-25 deg C
- Humidity (%): relative humidity 40-60%
- Air changes (per hr): Air conditioned rooms with 10-15 air changes per hour,
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
HUSBANDRY
Environmental conditions :Air conditioned rooms with 10-15 air changes per hour, temperature between 19-25 0C, relative humidity 30-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
Accommodation Animals were housed individually in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle.
Diet : Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India
Water : Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles,mad-libitum - Type of coverage:
- occlusive
- Preparation of test site:
- clipped
- Remarks:
- intact skin
- Vehicle:
- water
- Controls:
- not specified
- Amount / concentration applied:
- 0.5 gm was moistened with distilled water
- Duration of treatment / exposure:
- 4 hours
- Observation period:
- 60 min., 24, 48 and 72 hours after application.
- Number of animals:
- 3 female rabbits
- Details on study design:
- TEST SITE
- Area of exposure: dorsal area of trunk
- % coverage: small area (approximately 6 cm2)
- Type of wrap if used: impervious dressing which was secured in position with adhesive tape
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure:after patch removal the test site was washed with lukewarm water
OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application.
SCORING SYSTEM:
- Method of calculation:The intact skin site of application of each animal was observed for signs of erythema and oedema and the responses were scored following Draize’s method - Irritation parameter:
- primary dermal irritation index (PDII)
- Basis:
- mean
- Time point:
- 14 d
- Score:
- 0
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- The test compound applied at the dose level of 500mg on shaven back skin of rabbit did not produced any irritation to skin during period of observation.
- Other effects:
- The test compound applied on the shaven back skin of rabbit did not produce pain and any clinical signs of toxicity throughout the examination period of 14 days.
- Interpretation of results:
- other: not irritating
- Conclusions:
- The Primary Irritation Index (PII) for Test chemical after 14 days of observation was 0.0. Also Test chemical did not produce pain and any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, the Test chemical can be concluded to be not irritating to New Zealand White rabbit skin.
- Executive summary:
A dermal irritation study was conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of Test chemical. Three female New Zealand White rabbits.
In the initial test one healthy rabbit of body weight 2.04 kg selected for study after acclimatization. The test compound in the amount of 0.5 gm was applied uniformly at the different sites on the shaven back skin of animal. The hairs of back sides were removed (approximately 6 cm2) one day earlier before the treatment. 0.5 gm was moistened with distilled water and then applied to a small area (approximately 6 cm2) of skin and covered with a gauze patch, which was held in place with non-irritating tape. The first patch was applied on the shaven back skin of rabbit and removed after three minutes. No serious reaction was observed at the site of application. The second patch was applied on the different shaven back side and removed after one hour. There were no signs of skin reaction observed at this site of application. Finally, a third patch was applied at a different site and was removed after four hour. No dermal irritation was observed at the site of application of the test compound after 4 hours of patch removal. Finally, the animal was observed for 14 days, for any irritation and corrosion.
Because of there was no corrosive effect was observed in the initial test, a confirmatory test was done in order to confirm the irritant or negative response of the test substance by using two additional animals. In the confirmatory test the test compound in the amount of 0.5 gm was applied on the shaven back skin (approximately 6 cm2) of two animals (body weight of each animal was 2.17 and 2.13kg), each with one patch, for an exposure period of four hours. After four hours the patch was removed and the skin reactions were graded according to Draize’s method.
The Primary Irritation Index (PII) for Test chemical after 14 days of observation was 0.0. Also the test chemical did not produce pain and any clinical signs of toxicity throughout the examination period of 14 days.
Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit skin and hence it is classified in Category "Not classified" as per the criteria mention in CLP regulation.
TABLE - 1
INDIVIDUAL ANIMAL DERMAL IRRITATION SCORES
Rabbit No. |
Sex |
INTACT SKIN |
|||||||||||
3 Min. |
4 Hours |
24 Hours |
48 Hours |
72 Hours |
14 days |
||||||||
Erythema |
Oedema |
Erythema |
Oedema |
Erythema |
Oedema |
Erythema |
Oedema |
Erythema |
Oedema |
Erythema |
Oedema |
||
01 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
02 |
F |
- |
- |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
03 |
F |
- |
- |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Total |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Grand Total |
0.00 |
Dermal Irritation Index: 0.0/4 = 0.0
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Data is from experimental study report
- 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 test chemical in Sprague Dawley rat
- GLP compliance:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females (if applicable) nulliparous and non-pregnant: No data available
- Age at study initiation: Young adult male and female rats aged between 6 – 9 weeks were used.
- Weight at study initiation: The weight ranges of approximately 239.1 to 272.5 grams at initiation of dosing were used.
Body weights at the start :
Male
Mean : 269.94 g (= 100 %)
Minimum : 266.4 g (- 1.31 %)
Maximum : 272.5 g (+ 0.95 %)
Total No. of animals : 5
Female
Mean : 244.56 g (= 100 %)
Minimum : 239.1 g (- 2.23 %)
Maximum : 250.4 g (+ 2.39 %)
Total No. of animals : 5
- Fasting period before study: No data
- 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: 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 22.3 degree centigrade.
- Humidity (%): 55.7% to 59.6%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
IN-LIFE DATES: 30-09-2016 to 15-10-2016 - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not specified
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): No data available
VEHICLE
- Amount(s) applied (volume or weight with unit): No data available
- Concentration (if solution): No data available
- Lot/batch no. (if required): No data available
- Purity: No data
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): No data available
- Concentration (if solution): No data available
POSITIVE CONTROL
- Amount(s) applied (volume or weight): No data available
- Concentration (if solution): No data available - Duration of treatment / exposure:
- 24 hours
- Observation period:
- 14 days
- Number of animals:
- 10 (5/sex).
- 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
Type and Frequency of Tests, Analyses and Measurements
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 were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.
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.
- Irritation parameter:
- erythema score
- Basis:
- mean
- Time point:
- 14 d
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- mean
- Time point:
- 14 d
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- Overall result:
Sex : Male
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.
Sex : Female
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. - Other effects:
- Other effects:
Clinical Signs of Toxicity and Mortality
Sex : Male
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. All animals survived through the study period of 14 days.
Sex : Female
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. All animals survived through the study period of 14 days.
Body Weight
Sex : Male
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 9.69% and 16.50% respectively.
Sex : Female
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.02% and 9.12% respectively.
Gross Pathological Findings
Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group. - 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 observed at the end of 14 days after patch removal. Hence, it was concluded that the test substance was not-Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance can be considered as not irritating.
- Executive summary:
A study was designed and conducted to determine the dermal reaction profile of test chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. Ten rats (5 male and 5 female) were used for conducting dermal irritation/ corrosion 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.
The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Also, the erythema and edema score of rats was calculated as 0. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.
Hence, it was concluded that the test substance was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested.
Individual Animal - Evaluation of Dermal Reaction
Laboratory Test Item Code :TAS/122/013
Test System : Sprague Dawley Rat
Sex : Male
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 |
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 |
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 |
Sex : Female
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 |
6 |
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 |
7 |
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 |
8 |
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 |
9 |
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 |
10 |
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 |
Table No. I
Summary of Clinical Signs of Toxicity and Mortality
Test System : Sprague Dawley Rat
Sex : Male
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 |
5 |
1 - 5 |
Day 0 - Day 14 |
0/5 |
Sex : Female
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 |
5 |
6 - 10 |
Day 0 - Day 14 |
0/5 |
Table No. II
Summary of Evaluation of Dermal Reaction
Test System : Sprague Dawley Rat
Sex : Male
Group No. |
Dose mg/kg |
Dermal Reaction |
Total Number of Animals |
Animal Nos. |
Period of signs in days From - to |
Mortality |
I |
2000 |
No dermal reaction observed |
5 |
1 - 5 |
Day 0 - Day 14 |
0/5 |
Sex : Female
Group No. |
Dose mg/kg |
Dermal Reaction |
Total Number of Animals |
Animal Nos. |
Period of signs in days From - to |
Mortality |
I |
2000 |
No dermal reaction observed |
5 |
6 - 10 |
Day 0 - Day 14 |
0/5 |
Table No.III
Mean Body Weight and Percent Body Weight Gain (g)
Test System : Sprague Dawley Rat
Sex : Male
Group No. |
Dose (mg/kg body weight) |
|
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 |
2000 |
Mean |
269.94 |
296.10 |
9.69 |
314.52 |
6.22 |
16.50 |
± SD |
2.32 |
6.07 |
1.61 |
7.10 |
1.18 |
1.65 |
Sex : Female
Group No. |
Dose (mg/kg body weight) |
|
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 |
2000 |
Mean |
244.56 |
256.84 |
5.02 |
266.86 |
3.89 |
9.12 |
± SD |
4.41 |
5.32 |
1.27 |
6.98 |
0.78 |
2.08 |
Table No.IV
Summary of Gross Pathological Findings
Test System : Sprague Dawley Rat
Sex : Male
Group No. |
Dose mg/kg |
Animal Numbers |
Animal Fate |
Gross Pathological Findings |
I |
2000 |
1 - 5 |
TS |
No abnormality detected |
Sex : Female
Group No. |
Dose mg/kg |
Animal Numbers |
Animal Fate |
Gross Pathological Findings |
I |
2000 |
6 - 10 |
TS |
No abnormality detected |
TS = Terminal Sacrifice
Data source
Reference
- Reference Type:
- publication
- Title:
- WoE of dermal irritation study for CAS no 73507-17-2
- Author:
- Sustainability Support Services (Europe) AB
- Year:
- 2 019
- Bibliographic source:
- WoE report, Sustainability Support Services (Europe) AB, 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Principles of method if other than guideline:
- WoE for the target chemical is summarized based on experimental data from various test chemicals
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Hydrogen tetrasodium bis[2-[[6-[[4-chloro-6-[3-sulphoanilino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulpho-2-naphthyl]azo]benzoato(4-)]chromate(5-)
- EC Number:
- 277-492-0
- EC Name:
- Hydrogen tetrasodium bis[2-[[6-[[4-chloro-6-[3-sulphoanilino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulpho-2-naphthyl]azo]benzoato(4-)]chromate(5-)
- Cas Number:
- 73507-17-2
- Molecular formula:
- C52H28Cl2CrN14O18S44Na
- IUPAC Name:
- Hydrogen tetrasodium bis[2-[[6-[[4-chloro-6-[3-sulphoanilino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulpho-2-naphthyl]azo]benzoato(4-)]chromate(5-)
- Details on test material:
- - Name of the test chemical: Hydrogen tetrasodium bis[2-[[6-[[4-chloro-6-[3-sulphoanilino]-1,3,5-triazin-2-yl]amino]-1-hydroxy-3-sulpho-2-naphthyl]azo]benzoato(4-)]chromate(5-)
- Molecular formula: C52H28Cl2CrN14O18S4.H.4Na
- Molecular weight: 2693.61 g/mol
- Substance type: Organic
Constituent 1
Test animals
- Species:
- other: 2/3. rabbit 4. rat
- Strain:
- other: 2./3. New Zealand White 4. Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- 2. Species : Rabbit (Oryctolagus cuniculus)
Strain : New Zealand White
Age : 3.5 to 4.7 Months (Approximately)
Sex : Male
Number of Animals : Three
Supplier/Source : Procured from GENTOX BIOSERVICES PVT. LTD.
Health Status : Healthy young adult rabbits were used for the study
Body weight of animals : Minimum: 2.090 kg & Maximum: 2.354 kg (Prior to Treatment)
Acclimatisation :Rabbits were acclimatised to the test conditions for a period of 6 days (Animal No. 1) and 9 days (Animal No. 2 and 3) prior to the application of the test item.
Identification : During acclimatization marking was done with non toxic marker pen in the inside of left ear of rabbits and after acclimatization, animals were marked with permanent number in the inner side of right ear of rabbits. Permanent marker and cage card was used for identification. The individual cage cards were labelled with study no., study type, test system, sex, dose, animal number, experimental start and completion date.
Husbandry Conditions
Diet : All animals were provided conventional laboratory rabbit diet
Water : Aqua guard filtered tap water was provided ad libitum.
Husbandry : The animals were housed individually in stainless steel cages.
Room Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
Cages and water bottle : All the cages and water bottles were changed minimum twice a week.
Experimental Room Condition
Temperature : Minimum: 18.70 °C Maximum: 21.60 °C
Relative humidity : Minimum: 49.10% Maximum: 69.40%
Light-dark-rhythm : 12 hour light and 12 hour dark
Air Changes : More than 12 changes per hour
3. Details on test animals
Age: 10 to 12 weeks
Sex:Female
Body weight range: 2.0kg±200g
Identification : By cage tag and corresponding colour body marking
Housing:Animals were housed individually in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle.
Diet:Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi Water:Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bott les, ad libitum
Acclimatization: The healthy rabbits selected for study was acclimatized to standard laboratory condi tion for one week in experimental room under Veterinary examination.
Randomization: After acclimatization and Veterinary examination three females were randomly s elected.
Details on environmental conditions:
- Temperature (°C): temperature between 22-25 deg C
- Humidity (%): relative humidity 40-60%
- Air changes (per hr): Air conditioned rooms with 10-15 air changes per hour,
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
HUSBANDRY
Environmental conditions :Air conditioned rooms with 10-15 air changes per hour, temperature be tween 19-25 0C, relative humidity 30-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
Accommodation Animals were housed individually in stainless steel cages provided with stainless s teel mesh bottom and facilities for food and water bottle.
Diet : Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India Water : Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles,mad-libitum
4. TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females (if applicable) nulliparous and non-pregnant: No data available
- Age at study initiation: Young adult male and female rats aged between 6 – 9 weeks were used.
- Weight at study initiation: The weight ranges of approximately 239.1 to 272.5 grams at initiation of dosing were used.
Body weights at the start :
Male
Mean : 269.94 g (= 100 %)
Minimum : 266.4 g (- 1.31 %)
Maximum : 272.5 g (+ 0.95 %)
Total No. of animals : 5
Female
Mean : 244.56 g (= 100 %)
Minimum : 239.1 g (- 2.23 %)
Maximum : 250.4 g (+ 2.39 %)
Total No. of animals : 5
- Fasting period before study: No data
- 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: 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 22.3 degree centigrade.
- Humidity (%): 55.7% to 59.6%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
IN-LIFE DATES: 30-09-2016 to 15-10-2016
Test system
- Type of coverage:
- other: 2. semiocclusive 3. occlusive 4. semiocclusive
- Preparation of test site:
- clipped
- Remarks:
- clipped intact skin
- Vehicle:
- other: 2. unchanged (no vehicle) 3. water 4. unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- 2. Preparation of Application Site
Approximately 24 h prior to treatment, the fur coat of each rabbit was removed from dorsal lumbar region approximately 6 X 6 cm at contralateral sites on each rabbit using clipper, one as control and other site as treatment. Rabbits with healthy intact skin were selected for the study.
Test Item Application Procedure
The 0.5 ml of test item (as such) was applied uniformly over clipped area (approximately 6 X 6 cm) of the trunk of each rabbit skin (treated site) and 0.5 ml distilled water was applied at control site. Test item was held in contact with the skin with a porous gauze dressing and non-irritating tape (Micropore 3”) throughout a 4-hour exposure period, to prevent access by the rabbits to the patch and resultant ingestion of the test item. At the end of the exposure period, residual test item was removed by using cotton soaked in distilled water.
A single rabbit (Animal No. 1) was used for initial testing. The patch was removed after 4 h and the responses graded, no erythema and oedema was observed at 1 hour, 24 hour, 48 hour and 72 hour in animal no. 1. Hence the confirmatory test was conducted on additional two rabbits (No. 2 and 3) after 24 hour to confirm the non irritant nature of the test item.
3. 0.5 gm was moistened with distilled water
4. TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): No data available
VEHICLE
- Amount(s) applied (volume or weight with unit): No data available
- Concentration (if solution): No data available
- Lot/batch no. (if required): No data available
- Purity: No data
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): No data available
- Concentration (if solution): No data available
POSITIVE CONTROL
- Amount(s) applied (volume or weight): No data available
- Concentration (if solution): No data available - Duration of treatment / exposure:
- 2./3. 4 hours
4. 24 hrs - Observation period:
- 2. 72 hours
3. 60 min., 24, 48 and 72 hours after application
4. 14 days - Number of animals:
- 2. 3
3. 3 female rabbits
4. 10 (5/sex) - Details on study design:
- 2. A dose of 0.5 gm of test item moistened with 0.5 ml of distilled water was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits.
3. TEST SITE - Area of exposure: dorsal area of trunk - % coverage: small area (approximately 6 cm2) - Type of wrap if used: impervious dressing which was secured in position with adhesive tape
REMOVAL OF TEST SUBSTANCE - Washing (if done): yes - Time after start of exposure:after patch removal the test site was washed with lukewarm water
OBSERVATION TIME POINTS (indicate if minutes, hours or days) : The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application.
SCORING SYSTEM: - Method of calculation:The intact skin site of application of each animal was observed for signs of erythema and oedema and the responses were scored following Draize’s method
4. 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 Type and Frequency of Tests, Analyses and Measurements
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 observ ations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily t hereafter 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 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
Resultsopen allclose all
- Irritation parameter:
- erythema score
- Remarks:
- 2
- Basis:
- mean
- Time point:
- other: 24 hrs
- Score:
- 0.67
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritation parameter:
- edema score
- Remarks:
- 2
- Basis:
- mean
- Time point:
- other: 24 hrs
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritation parameter:
- erythema score
- Remarks:
- 2
- Basis:
- mean
- Time point:
- other: 48 hrs
- Score:
- 0.33
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritation parameter:
- edema score
- Remarks:
- 2
- Basis:
- mean
- Time point:
- other: 48 hrs
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritation parameter:
- erythema score
- Basis:
- mean
- Time point:
- other: 72 hrs
- Score:
- 0
- Max. score:
- 0.67
- Reversibility:
- fully reversible
- Irritation parameter:
- edema score
- Basis:
- mean
- Time point:
- other: 72 hrs
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible
- Irritation parameter:
- primary dermal irritation index (PDII)
- Remarks:
- 3
- Basis:
- mean
- Time point:
- 14 d
- Score:
- 0
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- erythema score
- Remarks:
- 4
- Basis:
- mean
- Time point:
- 14 d
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Remarks:
- 4
- Basis:
- mean
- Time point:
- 14 d
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- 2. No erythema and edema (skin irritation) were found at the end of 72 hour observation period after patch removal.
3. The test compound applied at the dose level of 500mg on shaven back skin of rabbit did not produced any irritation to skin during period of observation.
4. Overall result:
Sex : Male 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.
Sex : Female 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. - Other effects:
- 2. no effects observed
3. The test compound applied on the shaven back skin of rabbit did not produce pain and any clinical si gns of toxicity throughout the examination period of 14 days.
4. Other effects:
Clinical Signs of Toxicity and Mortality
Sex : Male
Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity dur ing the study period of 14 days. All animals survived through the study period of 14 days.
Sex : Female
Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity d uring the study period of 14 days. All animals survived through the study period of 14 days.
Body Weight
Sex : Male
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 9.69% and 16.50% respectively.
Sex : Female
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.02% and 9.12% respectively.
Gross Pathological Findings Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
Applicant's summary and conclusion
- Interpretation of results:
- not irritating
- Conclusions:
- No erythema and no oedema (skin irritation) were found at the end of observation period after patch removal. Hence, it was concluded that the test chemical was "Non-Irritating" to the skin of animals under the experimental conditions tested and hence the test chemical is "Not Classified as Skin Irritant" as per CLP regulation.
- Executive summary:
Data available for the various test chemicals was reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:
A dermal irritation study was conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of Test chemical. Three male New Zealand White rabbits were used for the study. The hair of al the rabbits were clipped at contraleteral sites, approximately 24 hrs prior to treatment. A dose of 0.5g of pulverised form of test chemical moistened with 0.5mL distilled water was applied to the skin over an area of 6X6 cm clipped of hair on one side of rabbits. The other untreated site served as control area and 0.5mL distilled water was applied at this site. At the end of 4hrs, the gauze patch was removed and test item application site was wiped with water without altering the epidermis. Initially the test chemical was applied to the clipped skin of one rabbit. The test site was covered with gauze patch. After 4 hrs of exposure, very slight erythema and no oedema was observed at 1 hr of observation. At 24 and 48 hrs, very slight erythema and no oedema was observed. At 72 hrs, no erythema and no oedema was observed. Hence the confirmatory test was conducted on two more animals. The patch was removed at 4hrs and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hrs after patch removal, evaluated and graded as per draize method. In the animal no. 2 and 3 at 1 and 24 hrs observation post patch removal, revelaed very slight erythema and no oedema. At 48 hrs, animal no. 2 was observed with no erythema and no oedema whereas animal no. 3 was observed with slight erythema and no oedema. At 72 hrs, no erythema and no oedema was observed in animals no. 2 and 3. The other untreated site revealed no erythema and no oedema and was found to be normal throughout the experimental period. The individual mean score at treated site at 24, 48 and 72 hrs for animals 1, 2, 3 were 0.67, 0.33, 0.67 and 0.00, 0.00, 0.00 for erythema and oedema formation, respectively. At 72 hrs, no erythema and no oedema was observed after patch removal. Hence, it was concluded that the test chemical was "Non-Irritating" to the skin of Male New Zealand White rabbits under the experimental conditions tested and hence the test chemical is "Not Classified as Skin Irritant" as per CLP regulation.
A dermal irritation study was conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of Test chemical. Three female New Zealand White rabbits. In the initial test one healthy rabbit of body weight 2.04 kg selected for study after acclimatization. The test compound in the amount of 0.5 gm was applied uniformly at the different sites on the shaven back skin of animal. The hairs of back sides were removed (approximately 6 cm2) one day earlier before the treatment. 0.5 gm was moistened with distilled water and then applied to a small area (approximately 6 cm2) of skin and covered with a gauze patch, which was held in place with non-irritating tape. The first patch was applied on the shaven back skin of rabbit and removed after three minutes. No serious reaction was observed at the site of application. The second patch was applied on the different shaven back side and removed after one hour. There were no signs of skin reaction observed at this site of application. Finally, a third patch was applied at a different site and was removed after four hour. No dermal irritation was observed at the site of application of the test compound after 4 hours of patch removal. Finally, the animal was observed for 14 days, for any irritation and corrosion. Because of there was no corrosive effect was observed in the initial test, a confirmatory test was done in order to confirm the irritant or negative response of the test substance by using two additional animals. In the confirmatory test the test compound in the amount of 0.5 gm was applied on the shaven back skin (approximately 6 cm2) of two animals (body weight of each animal was 2.17 and 2.13kg), each with one patch, for an exposure period of four hours. After four hours the patch was removed and the skin reactions were graded according to Draize’s method. The Primary Irritation Index (PII) for Test chemical after 14 days of observation was 0.0. Also the test chemical did not produce pain and any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, the test chemical can be concluded to be not irritating to New Zealand White rabbit skin and hence it is classified in Category "Not classified" as per the criteria mention in CLP regulation.
A study was designed and conducted to determine the dermal reaction profile of test chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. Ten rats (5 male and 5 female) were used for conducting dermal irritation/ corrosion 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. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Also, the erythema and edema score of rats was calculated as 0. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. Hence, it was concluded that the test substance was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested.
No erythema and no oedema (skin irritation) were found at the end of observation period after patch removal. Hence, it was concluded that the test chemical was "Non-Irritating" to the skin of New Zealand White rabbits under the experimental conditions tested and hence the test chemical is "Not Classified as Skin Irritant" as per CLP regulation.
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