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Description of key information

Acute oral toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity 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 acute oral toxicity study was designed and conducted for test chemical in wistar albino female rats according to the OECD Guideline-423. The healthy wistar albino rats of body weight 200±20 gm were selected for study after acclimatization to standard laboratory condition and divided into test compound and vehicle control group each having three animals. Initially, the test compound was mixed with distilled water and administered orally at the dose level of 2000 mg/kg body weight (dose volume 10ml/kg) to three female rats. However; vehicle control group treated with distilled water at the dose level of 10 ml/kg b.wt. The treated animals were closely observed for clinical signs of intoxication during first 4 hours of test compound administration. Thereafter, all the animals were observed periodically at 1 hour interval for 24 hrs and twice daily for a period of 14 days. The necropsy was performed on all animals at the termination of the study. The test compound did not produce any mortality at the dose level of 2000 mg/kg body weight during the entire observation period. Animals did not produce any clinical signs of toxicity during the entire observation period. Animals showed normal gain in body weight on day 7th and 14th as compared to control group. No significant gross pathological changes related to compound toxicity were observed. Skin and hair coat was observed wet. It was concluded that the test compound is non-toxic at the tested dose level 2000 mg/kg body weight. According to criteria of CLP, it comes under the “Category Not classified".

2. Acute oral toxicity test was conducted in male Sprague-Dawley white mice using test chemical at the dose concentration of 1250 mg/kg, 2500 mg/kg, 3750 mg/kg 5000 mg/kg, 6250 mg/kg to 6 animals per dose by oral route. Control animals received distilled water only. The mice were observed for 3 days for the signs and symptoms of toxicity as well as the death rate of each group were recorded. Test material administration at single dose has not been found to be any toxic effects even at higher dose used (6250 mg/Kg BW) at the same time there is no mortality or morbidity was recorded in all grouped animals. Hence, LD50 was considered to be >6250 mg/kg bw when male Sprague- Dawley white mice was treated with test chemical for 3 days via oral route.

Thus, based on the above summarised studies, 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 it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 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) cannot be classified for acute oral toxicity. Hence, based on the data available for the structurally similar read across 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 is not likely to be toxic in the dose range of >2000 - >6250 mg/Kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
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:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
WoE report is based on 2 acute oral toxicity studies as- WoE-2 and WoE-3.
Acute Oral toxicity test was carried out to study the effects of the test chemicals on rodents.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Specific details on test material used for the study:
Name: 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
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+;;
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
Molecular Weight: 563.954 g/mole
Molecular Formula: C16H12N4O9S2.CH5N3.ClH
Species:
other: 1. rat 2. mouse
Strain:
other: 1. Wistar 2. Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
1. TEST ANIMALS
- Source: Institute for Industrial Research & Toxicology
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7 to 9 weeks
- Weight at study initiation: 200±20g
- Fasting period before study: Fasted overnight prior to treatment
- Housing:Groups of three animals of similar sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk.
- Diet (e.g. ad libitum): Pelleted feed
- Water (e.g. ad libitum):Aqua Guard filter water was kept in PVC bottles, ad libitum
- Acclimation period:One week in experimental room after veterinary examination.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature between 22-25°C
- Humidity (%): relative humidity 40-60%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
IN-LIFE DATES: From:18/03/2013 To:28/04/2013
2. TEST ANIMALS
- Source: college of science at the University of Babylon
- Age at study initiation:8-9 weeks old
- Weight at study initiation: 25-30 gm
- Housing: animals were housed in polyacrylic cages, not more than three animals per cage under standard laboratory condition
- Diet (e.g. ad libitum): standard diet
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2C°
- Humidity (%):50-55%
- Photoperiod (hrs dark / hrs light): 12 hrs. Light: dark cycle
Route of administration:
other: 1. oral cannula 2. oral: unspecified
Vehicle:
other: 1. water 2. unchanged (no vehicle)
Details on oral exposure:
1. VEHICLE
- Concentration in vehicle: 2000 mg/ml
- Amount of vehicle (if gavage):10 ml/kg
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:2000 mg/kg
2. No data available
Doses:
1. 2000 mg/kg
2. 1250 mg/kg ,2500 mg/kg ,3750 mg/kg ,5000 mg/kg , 6250 mg/kg
No. of animals per sex per dose:
1. Three (3 females)/step
2. 1250 mg/kg- 6 animals
2500 mg/kg-6 animals
3750 mg/kg-6 animals
5000 mg/kg-6 animals
6250 mg/kg-6 animals
Control animals:
other: 1. Group I: Dist. water, 10ml/kg body wt. 2. yes
Details on study design:
1. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment).Rats were observed for mortality at the time interval of 30 minutes, 1hr, 2hr, 4 hr, and 6hr time interval on the day of test compound administration and thereafter twice a day for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: The treated animals were closely observed for clinical signs of intoxication, first 4 hours and every 1 hrs interval for 24 hrs after dosing and thereafter twice a day for 14 days. All the rats were observed at least twice daily to observe any clinical signs or behavioral changes. The organ which showed gross pathological change during necropsy subjected for histopathological study.
2. - Duration of observation period following administration:3 days
- Frequency of observations and weighing:No data available
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The mice were observed for 3 days for the signs and symptoms of toxicity as well as the death rate of each group were recorded.
Statistics:
1. No data
2. No data available
Preliminary study:
1. No data
2. The LD50 of the substances was calculated using the arithmetic method of Karber
The LD50 was calculated using the following formula:
LD50 =LDy – Σ (Dd x md)/N
Where LDy =Highest dose (LD100)
N =Number of animals per group
Dd =Dose difference
Md =Mean dead
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Sex:
male
Dose descriptor:
LD50
Effect level:
> 6 250 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
1. No mortality was observed at 2000 mg/kg body weight
2. No mortality was recorded at highest dose 6250 mg/kg BW.
Clinical signs:
1. At the dose level of 2000 mg/kg body weight did not produce any clinical signs of toxicity during the entire observation period.
2. No toxic effects were recorded in all the doses administered.
Body weight:
1. At the dose level of 2000 mg/kg body weight showed normal gain in body weight on day 7th and 14th as compared to control group.
2. No data available
Gross pathology:
1. No significant gross pathological changes related to compound toxicity were observed.
2. No data available
Other findings:
1. Skin and hair coat was observed wet.
2. No data available
Interpretation of results:
other: Not classified
Conclusions:
The test chemcial 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) is not likely to be toxic atleast in the dose range of >2000 - >6250 mg/Kg bw.
Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity 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 acute oral toxicity study was designed and conducted for test chemical in wistar albino female rats according to the OECD Guideline-423. The healthy wistar albino rats of body weight 200±20 gm were selected for study after acclimatization to standard laboratory condition and divided into test compound and vehicle control group each having three animals. Initially, the test compound was mixed with distilled water and administered orally at the dose level of 2000 mg/kg body weight (dose volume 10ml/kg) to three female rats. However; vehicle control group treated with distilled water at the dose level of 10 ml/kg b.wt. The treated animals were closely observed for clinical signs of intoxication during first 4 hours of test compound administration. Thereafter, all the animals were observed periodically at 1 hour interval for 24 hrs and twice daily for a period of 14 days. The necropsy was performed on all animals at the termination of the study. The test compound did not produce any mortality at the dose level of 2000 mg/kg body weight during the entire observation period. Animals did not produce any clinical signs of toxicity during the entire observation period. Animals showed normal gain in body weight on day 7th and 14th as compared to control group. No significant gross pathological changes related to compound toxicity were observed. Skin and hair coat was observed wet. It was concluded that the test compound is non-toxic at the tested dose level 2000 mg/kg body weight. According to criteria of CLP, it comes under the “Category Not classified".

 2. Acute oral toxicity test was conducted in male Sprague-Dawley white mice using test chemical at the dose concentration of 1250 mg/kg, 2500 mg/kg, 3750 mg/kg 5000 mg/kg, 6250 mg/kg to 6 animals per dose by oral route. Control animals received distilled water only. The mice were observed for 3 days for the signs and symptoms of toxicity as well as the death rate of each group were recorded. Test material administration at single dose has not been found to be any toxic effects even at higher dose used (6250 mg/Kg BW) at the same time there is no mortality or morbidity was recorded in all grouped animals. Hence, LD50 was considered to be >6250 mg/kg bw when male Sprague- Dawley white mice was treated with test chemical for 3 days via oral route.

Thus, based on the above summarised studies, 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 it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 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) cannot be classified for acute oral toxicity. Hence, based on the data available for the structurally similar read across 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 is not likely to be toxic in the dose range of >2000 - >6250 mg/Kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
6 250 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from publication.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity 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 acute oral toxicity study was designed and conducted for test chemical in wistar albino female rats according to the OECD Guideline-423. The healthy wistar albino rats of body weight 200±20 gm were selected for study after acclimatization to standard laboratory condition and divided into test compound and vehicle control group each having three animals. Initially, the test compound was mixed with distilled water and administered orally at the dose level of 2000 mg/kg body weight (dose volume 10ml/kg) to three female rats. However; vehicle control group treated with distilled water at the dose level of 10 ml/kg b.wt. The treated animals were closely observed for clinical signs of intoxication during first 4 hours of test compound administration. Thereafter, all the animals were observed periodically at 1 hour interval for 24 hrs and twice daily for a period of 14 days. The necropsy was performed on all animals at the termination of the study. The test compound did not produce any mortality at the dose level of 2000 mg/kg body weight during the entire observation period. Animals did not produce any clinical signs of toxicity during the entire observation period. Animals showed normal gain in body weight on day 7th and 14th as compared to control group. No significant gross pathological changes related to compound toxicity were observed. Skin and hair coat was observed wet. It was concluded that the test compound is non-toxic at the tested dose level 2000 mg/kg body weight. According to criteria of CLP, it comes under the “Category Not classified".

2. Acute oral toxicity test was conducted in male Sprague-Dawley white mice using test chemical at the dose concentration of 1250 mg/kg, 2500 mg/kg, 3750 mg/kg 5000 mg/kg, 6250 mg/kg to 6 animals per dose by oral route. Control animals received distilled water only. The mice were observed for 3 days for the signs and symptoms of toxicity as well as the death rate of each group were recorded. Test material administration at single dose has not been found to be any toxic effects even at higher dose used (6250 mg/Kg BW) at the same time there is no mortality or morbidity was recorded in all grouped animals. Hence, LD50 was considered to be >6250 mg/kg bw when male Sprague- Dawley white mice was treated with test chemical for 3 days via oral route.

Thus, based on the above summarised studies, 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 it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 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) cannot be classified for acute oral toxicity. Hence, based on the data available for the structurally similar read across 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 is not likely to be toxic in the dose range of >2000 - >6250 mg/Kg bw.

Justification for classification or non-classification

Based on the above experimental studies on 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 it’s structurally similar related read across substances, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, 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 cannot be classified for acute oral toxicity.