3-hydroxy-4-[(2-methoxy-5-nitrophenyl)azo]-N-(3-nitrophenyl)naphthalene-2-carboxamide

Endpoint summary

Description of key information

17 days repeated dose toxicity study was conducted in F344 male and female rats by administratingC.I. Pigment Red 23 orally at doses0, 600, 1200, 2500, 5000, 10000 mg/kg/day. There were no clinical and mortality were observed. No biologically significant differences recorded in organ weights among exposed and control rats. Decreased erythrocyte count observed in the two highest female and male dose groups, indicating a mild anemia. Therefore, NOAEL value for substanceC.I. Pigment Red 23 is considered to be 5000 mg/kg/day in F344 female rats.

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

5 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Qualified publication of Experimental study

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: via oral route

Various experimental studies were reviewed to determine the toxic nature of target substance C.I. Pigment Red 23; IUPAC: 3-hydroxy-4-[(E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N-(3-nitrophenyl)naphthalene-2-carboxamide; (6471-49-4)upon repeated exposure by oral route. The studies are as mentioned below:

17 days repeated dose toxicity study was conducted in F344 male and female rats by administratingC.I. Pigment Red 23 orally at doses0, 600, 1200, 2500, 5000, 10000 mg/kg/day. There were no clinical and mortality were observed. No biologically significant differences recorded in organ weights among exposed and control rats. Decreased erythrocyte count observed in the two highest female and male dose groups, indicating a mild anemia. Therefore, NOAEL value for substanceC.I. Pigment Red 23 is considered to be 5000 mg/kg in F344 female rats.

Supported by other 17 days repeated dose study .It was conducted by administrating C.I.Pigment Red 23 orally at dose0, 6,000, 12,500, 25,000, 50,000, or 100,000 ppm (0, 1200, 2500, 5000, 10000 or 20000 mg/kg/day) to 5 male & 5 female B6C3F1 Mice. Weight gain observed in male mice was less than that of the controls and was significantly less in the 10,000 and 20,000 mg/kh/day groups.In females, final mean body weights were different at 5000 mg/kg/day group then Weight gain for exposed females receiving 1200, 2500, and 5,000 mg/kg/day C.1. Pigment Red 23 was significantly less than that of controls. Feed consumption by exposed males was slightly lower than that of the controls.Relative liver weight was significantly increased in the 10000 mg/kg/day females and in each sex receiving 20000 mg/kg/day.Relative liver weights was significantly increased in the 10000 mg/kg and in each sex receiving 20,000 mg/kg/day dose. Therefore NOAEL was considered to be 5000 mg/kg/day in male and female mice for C.I.Pigment Red for 17 days study by oral gavage.

Supported by other Two year repeated dose study. It was conducted by administrating C.I.Pigment Red 23 orally at0, 10,000, 25,000, or 50,000 ppm (1428.58, 3571.42 or 7142.86 mg/kg/day) to 60 male and 60 femaleB6C3F1 Mice.Changes observed in the incidences of mice with nonneoplastic lesions of the forestomach and other findings in lymphoid tissue of the small and large intestine.In male Forestomach: epithelial hyperplasia (0/49, 1/48, 1/50, 7/48); epithelial hyperkeratosis (0/49, 1/48, 3/50, 5/48) In female Forestomach: epithelial hyperplasia (6/49, 14/49, 43/50,47/49); epithelial hyperkeratosis (21/49, 1/49, 3/50, 18/49)Body weights from all dose groups of each sex were within 10% of the untreated controls throughout both the 15-month interim evaluation and the 2-year Study. Based on theIncidence of epithelial hyperplasia and hyperkeratosis the LOAEL value ofC.I.Pigment Red 23 was consedered to be7142.86 mg/kg/day in male mice and 1428.58 mg/kg/day in female mice respectively. ThereforeLOAEL were considered to be7142.86 and 1428.58 mg/kg/day in male and female mice respectively forC.I. Pigment Red 23 by oral feed for 2 years study.

Supported by another Two year repeated dose toxicity studies were conducted by administering of male and female rats doses of 0, 500, 1250, and 2500 mg/kg C.I. Pigment Red 23 in feed for 103 weeks.From week 20 to the end of the study, the mean body weights of mid- and high-dose females were consistently lower than that of the controls.There were one renal tubule adenoma was observed in a high-dose femaleandfour renal tubule cell adenomas or carcinomas were observed in kidney of males in the two highest dose groups.In female rats, Hematocrit values, hemoglobin concentration, and erythrocyte counts interim evaluation were significantly less than those of the controls and serum total bilirubin was significantly increased in 50000 ppm female rats at the 15-month. InPituitary Gland, adenoma or carcinoma (Combined) of the pars distalis occurred with a significant negative trend in female rats. The incidence in the high-dose group was significantly lower than in the control. In lymphoid Tissue, red pigment, presumably compound- related, was observed in the lymphoid tissue of the small intestine in females and in the mesenteric lymph nodes in males. There was a dose-related increase in the amount of pigment present. The pigment consisted of distinct red granules or small elongated crystals within the cytoplasm of the macrophages.Mononuclear cell leukemia occurred with a decreased incidence in male and female rats. The NOAEL value for repeated dose toxicity of C.I. Pigment Red 23 in male and female F344 rats is considered to be 1250mg/kg/day.

Supported by another 13 weeks repeated dose toxicity study. It was conducted in B6C3F1 male and female mice by administrating C.I. Pigment Red 23 orally at doses0, 600, 1200, 2500, 5000, 10000 mg/kg/day. No mortality observed. No histopathological and gross pathological treatment related effect observed. In male mice at dose 2500 mg/kg, absolute and relative liver weights were significantly increased compared to those of the controls. Relative liver weight in the 600 mg/kg group was also increased compared to that of the controls. Both absolute and relative thymus weights were significantly lower than those of the controls for all female at dose 2500 mg/kg. In female mice, in the 1200 mg/kg group had significantly lower hematocrit and hemoglobin concentrations than did untreated females. Therefore NOAEL was considered to ne1200 mg/kg/day inB6C3F1male and female mice for 13 week study by opral feed for C.I. Pigment Red 23.

Supported by another 13 weeks repeated dose toxicity study. It was conducted in F344 male and female rats by administratingC.I. Pigment Red 23 orally at doses0, 600, 1200, 2500, 5000, 10000 mg/kg/day. There were no clinical and mortality were observed. No biologically significant differences recorded in organ weights among exposed and control rats. In male, Hematocrit, hemoglobin concentration, and erythrocyte counts at the 10000 mg/kg dose level were significantly less than those of the controls, indicating minimal anemia. In female rats, the lymphocyte count at 600, 1200, and 10000 mg/kg and the leukocyte count at 600 mg/kg were significantly higher than those of the controls. Therefore, the NOAEL value for substance C.I. Pigment Red 23 is considered to be 600 mg/kg/day in F344 female rats.

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance C.I. Pigment Red 23; IUPAC: 3-hydroxy-4-[(E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N-(3-nitrophenyl) naphthalene-2-carboxamide; (6471-49-4) , which is reported as 5E-017 Pa at 25 C. Also considering the particle size distribution of the substance the majority of the particles was found to be in the size of 150 micron to 25 micron which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 3-hydroxy-4-[(E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N- (3-nitrophenyl) naphthalene -2-carboxamide is highly unlikely. Therefore this study is considered for waiver.

Based on the data available for the target chemical C.I. Pigment Red 23; IUPAC: 3-hydroxy-4-[(E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N-( 3-nitrophenyl) naphthalene-2-carboxamide; (6471-49-4) does not exhibit toxic nature upon repeated exposure by oral, inhalation route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical C.I. Pigment Red 23; IUPAC: 3-hydroxy-4-[(E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N-( 3-nitrophenyl) naphthalene-2-carboxamide; (6471-49-4) does not exhibit toxic nature upon repeated exposure by oral, inhalation route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.