Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 275-170-4 | CAS number: 71077-14-0
- 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
Endpoint summary
Administrative data
Description of key information
Skin irritation
Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin irritation potential of the test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0). The studies are as mentioned below:
1. The skin irritation study of read across chemical was performed as per OECD Guidelines 404 in three female New Zealand White rabbits and complying with the GLP procedures. The animals were prepared 24 hours prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 500gm (0.5g) of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. 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 and the responses were scored according to Draize method. The Primary Irritation Index (PII) fortest chemicalafter 14 days of observation was 0.0.Alsothe chemicaldid not produce pain and any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions,the test substancecan be concluded to be not irritating to New Zealand White rabbit skin.
2. The above result was further supported by another experimental study conducted for the read cross chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. 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. 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. The overall irritation score of the substance was obtained to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal. Hence, it was concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.
Based on the above summarized studies for target chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.
Eye irritation
Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0). The studies are as mentioned below:
The experimental study was conducted for the structurally similar read across substance in three female New Zealand White rabbits as per OECD Guidelines 405 and complying to the GLP procedures. About 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed. The overall irritation index of test chemical was 0.0 after 72 hours. Also did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, the chemical can be concluded to be not irritating to New Zealand White rabbit eyes.
The above results were further supported by an eye irritation study conducted by peer reviewed journal on 6 female and 6 male New Zealand White rabbits for read across chemical. About 30 μl of test chemical in aq. solution was administered into the right eye of rabbits and left eyes served as untreated controls. Ocular irritation was determined according to a modification of the Draize test. All animals were checked for viability twice daily. Ocular irritation was scored 24 h after each treatment and prior to the next instillation. On days 1, 3, 7, 14, and 21 the eyes were also evaluated 1 h after treatment. 24 h after each treatment additionally eye stain and particle depositions were scored. Ophthalmic observations were conducted on days 3, 7 and 14 always prior to instillation. No lethality or significant clinical signs, and no substance-related weight change were observed. Except slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed. Hence, the test substance was not expected to cause irritant effects following repeated treatment of eyes in a concentration of 3 % in aqueous solution.
Based on the above summarized studies for target chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- 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 of read across substances
- Justification for type of information:
- Data for the target chemical is summarized based on the structurally similar read across chemicals
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- WoE report is based on 2 skin irritation studies as- WoE-2 and WoE-3.
Skin irritation study of test chemical was conducted on rats and rabbits to assess its skin irritating effects. - GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material : 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N'-bis(mixed Ph, tolyl and xylyl) derivs.
- Molecular formula: C17H18ClN7O9S2
- Molecular weight: 563.954g/mol
- Substance type: Organic
- Physical state: solid
-Smiles: N1(c2ccc(cc2)S(=O)(=O)O)N=C(C(O)=O)[C@@H](\N=N\c2ccc(cc2)S(=O)(=O)O)C1=O.C(=N)(N)N.Cl
-InChI: 1S/C16H12N4O9S2.CH5N3.ClH/c21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29;2-1(3)4;/h1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);(H5,2,3,4);1H/b18-17+;; - Species:
- other: 1.Rabbit 2. Rat
- Strain:
- other: 1.New Zealand White 2.Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- 1. 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
2. TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Age at study initiation: Young adult male and female rats aged between 6 – 9 weeks were used.
- Weight at study initiation: The weight range of approximately 217.1 to 255.7 grams at initiation of dosing were used.
Body weights at the start :
Male
Mean : 246.04 g (= 100 %)
Minimum : 238.3 g (- 3.15 %)
Maximum : 255.7 g (+ 3.93 %)
Total No. of animals : 5
Female
Mean : 223.74 g (= 100 %)
Minimum : 217.1 g (- 2.97 %)
Maximum : 231.3 g (+ 3.38 %)
Total No. of animals : 5
- 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): Room temperature was maintained at 20.0 to 22.3 degree centigrade.
- Humidity (%): Room humidity was maintained at 55.7% to 59.6%.
- 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: No data - Type of coverage:
- occlusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not specified
- Amount / concentration applied:
- 1. 500 mg (0.5g)
2. 2000 mg/kg bw - Duration of treatment / exposure:
- 1. 4 hours
2. 24 hours - Observation period:
- 1.60 min., 24, 48 and 72 hours after application.
2. 14 days - Number of animals:
- 1. 3 female rabbits
2. 10 (5/sex). - Details on study design:
- 1. 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.
2. TEST SITE
- Area of exposure: Dorsal surface and sides from scapular to pelvic area.
- % coverage: Approximately 10% of the total 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.
- Time after start of exposure: 24 hours
OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : 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.
SCORING SYSTEM: Draize Method. - Irritation parameter:
- primary dermal irritation index (PDII)
- Basis:
- mean
- Time point:
- 14 d
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- overall irritation 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:
- 1. 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.
2.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.
Results based on erythema and edema score:
Irritation parameter : erythema score
Basis : animal:1-5
Time point : other: 0 - 14 d
Score : 0
Max. score : 0
Reversibility: no data
Remarks on result : no indication of irritation
Irritation parameter : edema score
Basis : animal:1-5
Time point : other: 0 - 14 d
Score : 0
Max. score : 0
Reversibility: no data
Remarks on result : no indication of irritation
Irritation parameter : erythema score
Basis : animal: 6-10
Time point : other: 0 - 14 d
Score : 0
Max. score : 0
Reversibility: no data
Remarks on result : no indication of irritation
Irritation parameter : edema score
Basis : animal:6-10
Time point : other: 0 - 14 d
Score : 0
Max. score : 0
Reversibility: no data
Remarks on result : no indication of irritation - Other effects:
- 1. 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.
2.Clinical signs
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 10.18% and 19.28% respectively.
Sex : Female
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.60% and 11.43% respectively.
Mortality
Sex : Male
Group I - All animals survived through the study period of 14 days.
Sex : Female
Group I - All animals survived through the study period of 14 days.
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 test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) was considered to be not irritating to the skin.
- Executive summary:
Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin irritation potential of the test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0). The studies are as mentioned below:
1. The skin irritation study of read across chemical was performed as per OECD Guidelines 404 in three female New Zealand White rabbits and complying with the GLP procedures. The animals were prepared 24 hours prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 500gm (0.5g) of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. 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 and the responses were scored according to Draize method. The Primary Irritation Index (PII) fortest chemicalafter 14 days of observation was 0.0.Alsothe chemicaldid not produce pain and any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions,the test substancecan be concluded to be not irritating to New Zealand White rabbit skin.
2. The above result was further supported by another experimental study conducted for the read cross chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. 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. 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. The overall irritation score of the substance was obtained to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal. Hence, it was concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.
Based on the above summarized studies for target chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.
Reference
1.
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
2.
Table No. I
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 |
0 - 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 |
0 - 14 |
0/5 |
Table No.II
Individual Animal - Evaluation of Dermal Reaction
Laboratory Test Item Code :TAS/122/008
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 |
|
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- 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 of read across substances
- Justification for type of information:
- Data for the target chemical is summarized based on the structurally similar read across chemicals
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- WoE report is based on 2 eye irritation studies as- WoE-2 and WoE-3.
An eye irritation study of test chemical was conducted on rats and rabbits to assess its eye irritating effects. - GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material : 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N'-bis(mixed Ph, tolyl and xylyl) derivs.
- Molecular formula: C17H18ClN7O9S2
- Molecular weight: 563.954g/mol
- Substance type: Organic
- Physical state: solid
-Smiles: N1(c2ccc(cc2)S(=O)(=O)O)N=C(C(O)=O)[C@@H](\N=N\c2ccc(cc2)S(=O)(=O)O)C1=O.C(=N)(N)N.Cl
-InChI: 1S/C16H12N4O9S2.CH5N3.ClH/c21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29;2-1(3)4;/h1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);(H5,2,3,4);1H/b18-17+;; - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- 1. 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
2. Details on test animal
TEST ANIMALS
- Source: Summit View Farm, Hazelton, PA, USA
- Age at study initiation:
- Weight at study initiation: 3.0-3.5 kg,
- Housing: Rabbits were individually housed in stainless steel, wire mesh-floor cages in a room
- Diet (e.g. ad libitum): feed (Certified Lab Rabbit Chow HF; Purina No. 5325) was limited to 125g/day
- Water (e.g. ad libitum): ad libitum
- Acclimation period: All animals were acclimatized for at least 2 wk prior to the start of the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-21°C
- Humidity (%):38%
- Photoperiod (hrs dark / hrs light): 12-hr light/dark cycle - Vehicle:
- other: 1.unchnged 2. aqueous solution with 0.5 % (w/v) hydroxypropyl methylcellulose and 0.25 % (w/v) laureth-10 acetate)
- Controls:
- yes
- Amount / concentration applied:
- 1. 100mg (0.1g)
2. 30 μl of test solution (3 % (w/v) - Duration of treatment / exposure:
- 1. 24 hours
2. 1 application daily for 21 days - Observation period (in vivo):
- 1. The eyes were examined at 1, 24, 48 and 72 hours after test substance application
2. Ophthalmic observations were conducted on days 3, 7 and 14 always prior to instillation. - Number of animals or in vitro replicates:
- 1. 3 female rabbits
2. 6 female and 6 male New Zealand White rabbits - Details on study design:
- 1. REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed
SCORING SYSTEM:Scale of weighted scores for grading the severity of ocular lesions developed by Draize et al
TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: hand-slit lamp
Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. After recording the observations at 24 hours, the eyes were further examined with the aid of fluorescein.
2. Details on study design
TEST SITE
- Area of exposure:Right eye of rabbit
- % coverage:
- Type of wrap if used:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:
SCORING SYSTEM:Draize procedure - Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- 72 h
- Score:
- 0
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- 24 h
- Reversibility:
- not specified
- Remarks on result:
- other: slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation, No significant signs of eye staining or particle depositions were observed.
- Irritant / corrosive response data:
- 1.The test compound when applied to the eye of New Zealand white rabbit at the dose level of 0.1gm did not produce any lesions such as pannus, staining throughout the observation period of 72 hours.
2. slight conjunctival redness or discharge, that were seen sporadically in the eyes of the
animals, all animals were free of significant signs of ocular irritation, No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed. - Other effects:
- 1.The test compound applied in conjunctival sac of rabbits did not show any observable clinical signs of eye irritation throughout the observation period of 21 days.
2.No lethality or significant clinical signs, and no substance-related weight change were observed - Interpretation of results:
- other: not irritating
- Conclusions:
- The test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N'-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) was considered to be not irritating to the rabbits' eyes.
- Executive summary:
Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0). The studies are as mentioned below:
The experimental study was for the structurally similar read across substance in in three female New Zealand White rabbits as per OECD Guidelines 405 and complying to the GLP procedures. About 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed. The overall irritation index of test chemical was 0.0 after 72 hours. Also did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, the chemical can be concluded to be not irritating to New Zealand White rabbit eyes.
The above results were further supported by an eye irritation study conducted by peer reviewed journal on 6 female and 6 male New Zealand White rabbits for read across chemical. About 30 μl of test chemical in aq. solution was administered into the right eye of rabbits and left eyes served as untreated controls. Ocular irritation was determined according to a modification of the Draize test. All animals were checked for viability twice daily. Ocular irritation was scored 24 h after each treatment and prior to the next instillation. On days 1, 3, 7, 14, and 21 the eyes were also evaluated 1 h after treatment. 24 h after each treatment additionally eye stain and particle depositions were scored. Ophthalmic observations were conducted on days 3, 7 and 14 always prior to instillation. No lethality or significant clinical signs, and no substance-related weight change were observed. Except slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed. Hence, the test substance was not expected to cause irritant effects following repeated treatment of eyes in a concentration of 3 % in aqueous solution.
Based on the above summarized studies for target chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.
Reference
1.
TABLE- 1 GRADING OF OCULAR LESIONS
S.NO/ SEX |
|
OBSERVATION |
Score |
Total |
Total Score |
|||
1/F
|
1 hr |
24hrs |
48 hrs |
72 hrs |
||||
Cornea |
A. Opacity-Degree of Density |
0 |
0 |
0 |
0 |
0 |
0×0×5=0 |
|
B. Area of Cornea Involved |
0 |
0 |
0 |
0 |
0 |
|||
Iris |
A. Values |
0 |
0 |
0 |
0 |
0 |
0 |
|
Conjunctivae |
A. Redness |
1 |
0 |
0 |
0 |
1 |
0+0+0×5=5 |
|
B. Chemosis |
0 |
0 |
0 |
0 |
0 |
|||
C. Discharge |
0 |
0 |
0 |
0 |
0 |
|||
2/F |
Cornea |
A. Opacity-Degree of Density |
0 |
0 |
0 |
0 |
0 |
0×0×5=0 |
B. Area of Cornea Involved |
0 |
0 |
0 |
0 |
0 |
|||
Iris |
A. Values |
0 |
0 |
0 |
0 |
0 |
0 |
|
Conjunctivae |
A. Redness |
1 |
0 |
0 |
0 |
1 |
0+0+0×5=5 |
|
B. Chemosis |
0 |
0 |
0 |
0 |
0 |
|||
C. Discharge |
0 |
0 |
0 |
0 |
0 |
|||
3/F |
Cornea |
A. Opacity-Degree of Density |
0 |
0 |
0 |
0 |
0 |
0×0×5=0 |
B. Area of Cornea Involved |
0 |
0 |
0 |
0 |
0 |
|||
Iris |
A. Values |
0 |
0 |
0 |
0 |
0 |
0 |
|
Conjunctivae |
A. Redness |
1 |
0 |
0 |
0 |
1 |
0+0+0×5=5 |
|
B. Chemosis |
0 |
0 |
0 |
0 |
0 |
|||
C. Discharge |
0 |
0 |
0 |
0 |
0 |
|||
Grand total |
0.00 |
|||||||
Mean |
0.00 |
|||||||
Eye Irritation Scoring index |
0.00 |
2. Not specified
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation
Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin irritation potential of the test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0). The studies are as mentioned below:
1. The skin irritation study of read across chemical was performed as per OECD Guidelines 404 in three female New Zealand White rabbits and complying with the GLP procedures. The animals were prepared 24 hours prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 500gm (0.5g) of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. 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 and the responses were scored according to Draize method. The Primary Irritation Index (PII) fortest chemicalafter 14 days of observation was 0.0.Alsothe chemicaldid not produce pain and any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions,the test substancecan be concluded to be not irritating to New Zealand White rabbit skin.
2. The above result was further supported by another experimental study conducted for the read cross chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. 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. 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. The overall irritation score of the substance was obtained to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal. Hence, it was concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.
Based on the above summarized studies for target chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.
Eye irritation
Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0). The studies are as mentioned below:
The experimental study was conducted for the structurally similar read across substance in three female New Zealand White rabbits as per OECD Guidelines 405 and complying to the GLP procedures. About 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed. The overall irritation index of test chemical was 0.0 after 72 hours. Also did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, the chemical can be concluded to be not irritating to New Zealand White rabbit eyes.
The above results were further supported by an eye irritation study conducted by peer reviewed journal on 6 female and 6 male New Zealand White rabbits for read across chemical. About 30 μl of test chemical in aq. solution was administered into the right eye of rabbits and left eyes served as untreated controls. Ocular irritation was determined according to a modification of the Draize test. All animals were checked for viability twice daily. Ocular irritation was scored 24 h after each treatment and prior to the next instillation. On days 1, 3, 7, 14, and 21 the eyes were also evaluated 1 h after treatment. 24 h after each treatment additionally eye stain and particle depositions were scored. Ophthalmic observations were conducted on days 3, 7 and 14 always prior to instillation. No lethality or significant clinical signs, and no substance-related weight change were observed. Except slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed. Hence, the test substance was not expected to cause irritant effects following repeated treatment of eyes in a concentration of 3 % in aqueous solution.
Based on the above summarized studies for target chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.
Justification for classification or non-classification
The skin and eye irritation potential of test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) and its structurally and functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical is unlikely to cause skin and eye irritation. Hence 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) can be classified under the category “Not Classified” for skin and eye as per CLP.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.