m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid

Endpoint summary

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid. The study assumed the use of male and female Sprague Dawley rats in a 28 days toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichloro benzenesulphonic acid is predicted to be 881.966674805 mg/Kg bw/day.

Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

Quality of whole database:

Data is from K2 prediction database

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Prediction model based estimation for the target chemical and data from read across chemicals has been reviewed to determine the toxic nature of 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid. The study assumed the use of male and female Sprague Dawley rats in a 28 days toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichloro benzenesulphonic acid is predicted to be 881.966674805 mg/Kg bw/day.

The predicted data is further supported by the data from read across chemicals as mentioned below:

In a study mentioned in J-check (2016), 28 days repeated oral toxicity study was performed for the functionally similar read across chemical 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (RA CAS no 87 -02 -5) using rats. The animals were dosed at dose levels of 0, 250, 500 or 1000 mg/Kg bw. In addition, recovery group was also included in the study at dose levels of 0 or 1000 mg/Kg bw for 14 days.There was no change due to administration in any of the general condition, body weight, food intake, urinalysis, hematology examination, blood biochemical examination, organ weight, necropsy, and histopathological examination. At 4 weeks of dosing, loss of the maxillary incisor tip was observed in one male in the 1000 mg / kg group, but it was considered to be an accidental change. In addition to this there was no change in general condition. No mortality was noted in the treated animals. No significant difference between the control group and each administration group throughout the administration period and recovery period was noted. A transient increase in food intake was observed in males of the 1000 mg / kg group at the 4th week of administration, but it was thought that there was minor fluctuation and was of no toxicological significance. There was no change at the end of the administration period, and as a minor change only at the end of the recovery period, GOT increased in male at 1000 mg / kg group and calcium was decreased in female of the same group. A slight rise in urine specific gravity in males at 500 mg / kg group at 4 weeks of dosing was noted. A decrease in the relative weight of the heart in females in all treatment groups was noted. In addition, in the 250 and 1000 mg / kg group, the absolute weight of the heart was decreased, and the same tendency was observed in the females of the 500 mg / kg group. However, these were considered to be minor fluctuations, and because there was no constant trend in the dose and the degree of change, it was considered to be an accidental fluctuation unrelated to administration. At the end of the recovery period, there was an increase in the absolute weight of the lungs and a decrease in the relative weight of the heart in males in the 1000 mg / kg group. A single grayish white spot and mild pyeloid dilatation in the right kidney was noted in one male in the 1000 mg / kg test group. The same extent of renal pelvic dilation in the right kidney was also seen in 2 males in the 250 mg / kg group, and in one of them, mild atrophy of the left testis was also observed. In these histopathological examinations, renal pelvic dilation was observed in the kidneys, and 1 of them in the 1000 mg / kg group had basophilization of localized proximal renal tubular epithelium, dilation of distal tubule, and Lymphocyte infiltration into the interstitium as well as calcification of the papilla were observed. Atrophy was also confirmed in the testis by histopathological examination. These changes were frequently observed changes in normal rats, and since their frequency of appearance was not related to the dose, it was considered that these changes were spontaneous changes. No other macroscopic and histopathological changes were observed at the end of the administration period. No changes were noted in the recovery group. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for the test compound 7-Amino-4-hydroxy-2-naphthalenesulfonic acid is found to be 1000 mg/Kg bw.

In another study (SCCP, 2006) for 50 -60% structurally and functionally similar read across chemical, 2-phenyl-1H-benzimidazole-5-sulphonic acid (RA CAS no 27503 -81 -7) was administered orally to male and female Wistar rats 7 days/week for 13 weeks. The study was conducted according to OECD guideline 408. The dosage was 0, 100, 330 and 1000 mg/kg bw, and the vehicle (5% aqueous tylose) administration group was provided as a control. Animals were examined with respect to in-life-observations (viz. mortalities and clinical signs of toxicity, body weight and food-/water consumption were recorded.), clinical pathology (viz. haematology, clinical chemistry and urinalysis) and anatomic pathology (viz. organ weights, necropsy, histopathology.). Three mortalities (1♂, week 5, control group; 1♀, week 13, 330 mg/kg-group; 1♀, week 6, 1000 mg/kg-group) occurred intercurrently but were not substance related. No clinical signs of toxicity were seen in any group. Food- and water consumption were the same in test- and control groups. Haematology results (total and differential blood count) of test animals did not differ from controls throughout the experiment. The same holds for clinico-chemical parameters, except for protein content in serum in females of the 1000 mg/kg-group, which was increased as compared to controls. However, the level found was within the biological variability range on record for female rats of this age and was therefore not considered substance related. Necropsy-findings in the animals which had died intercurrently, revealed no pathological changes attributable to the test substance. Neither did the animals which were sacrificed pursuant to protocol at the end of the study exhibit any such changes. Differences in organ weights, if observable at all (e.g. spleen in♀'s), were small and not dose dependent. Histopathology did not reveal any organ change or –damage in any one of the dose groups. Based on the above study, the toxicologically no adverse effect amount by repetitive oral administration of 2-phenyl-1H-benzimidazole-5-sulphonic acid ( Novantisol saure) (CAS No. 27503 -81 -7) for 13 weeks was observed and hence under this test condition NOAEL was considered to be1000 mg/kg bw/day.

Based on the data available for the target chemical and its read across and by applying the weight of evidence approach, 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid is not likely to classify as a toxicant upon repeated exposure by oral route.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across and by applying the weight of evidence approach, 4-[(5-amino-3- methyl-1-phenyl- 1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid is not likely to classify as a toxicant upon repeated exposure by oral route.