4-[[5-(anilino)carbonyl-2-methoxyphenyl]azo]-3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

  The endpoint for the repeated dose toxicity by oral route was considered to be in a dose range of 1 % (1300 mg/kg/day) -6000 mg/kg/day concentration of  test substace to mice for 12 weeks by oral route .

Repeated dose toxicity: inhalation

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 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}-N-(3-nitrophenyl)-2-naphthamide (6448-96-0 ) which is reported as 0.0001860153mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl] diazenyl}- N-(3-nitrophenyl)-2-naphthamide is highly unlikely. Therefore this study is considered for waiver.

Repeated dose toxicity: dermal

The acute toxicity value for 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}-N-(3-nitrophenyl)-2-naphthamide (6448-96-0 ) (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}-N-(3-nitrophenyl)-2-naphthamide shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 4-(2-methylprop-2-en-1-yl) benzenesulfonate shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

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

1 300 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

WoE prepared from various publication

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

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

Various data available for the test chemical was reviewed to determine the toxic nature of 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}- N-(3-nitrophenyl)-2-naphthamide (6448-96-0 )upon repeated exposure by oral route. The studies are as summarized below:

Repeated dose toxicity: Oral

Repeated dose toxicity test were performed for test chemical on mice with different concentrations from 0.1, 0.25,0.5 or 1.0% (130,325,650,1300 mg/kg bw/d) for 80 wk. 30 males and 30 females was used for the treatment and group of 60 mice of each sex as control. The general condition and behaviour of the animals were observed frequently and any mouse that showed signs of ill-health was isolated, to be returned to its cage on recovery or to be killed if its condition deteriorated. The mice were weighed at the start of the experiment, at wk 3 and then at intervals of 2 wk until wk 73 of the experiment. Blood sample were taken at week 28 and 55.At 80 wk, blood samples were collected from the aorta of all surviving mice during the autopsy. For haematology blood samples were collected and for urine sample from 6-hr period from three groups of five mice of each sex from the controls and the groups on the two highest dietary levels of test substance. Histopathology was also conducted. There were no dose-related effects on body-weight gain, haematology or organ weights. The incidence of histopathological findings, including tumours, was not altered by the feeding of test substance. Therefore, the endpoint for the repeated dose toxicity was found to be NOAEL at 1 % (1300 mg/kg/day) concentration of test substance to mice.

In the subchronic study that was conducted to determine the adverse effects, groups of 10 males and 10 females B6C3F1 mouse was fed diets containing 0, 6,000, 12,500, 25,000, 50,000, or 100,000 mg/kg test substance or 12 weeks and then given control diets for 1 week. The animals were observed twice per day and weighed weekly. Necropsies were performed on all animals. Gross and histopathological examinations were performed on all animals. Mean body weight gain was decreased compared to controls among male mice receiving the 100,000 mg/kg diet intake level. Decreases in body weight gain were also reported for female mice at all intake levels, and was dose related from 12,500 mg/kg diet to 100,000 mg/kg diet. Gross and histopathological examinations revealed no treatment related lesions in male or female mice at any intake level. Thus, on the basis of study results the NOAEL (No observed adverse effect level) was observed to be less than 6000 ppm and 50000 ppm.

Repeated dose toxicity: inhalation

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 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}-N-(3-nitrophenyl)-2-naphthamide (6448-96-0 ) which is reported as 0.0001860153mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}-N-(3-nitrophenyl)-2-naphthamide is highly unlikely. Therefore this study is considered for waiver.

 

 

Repeated dose toxicity: dermal

The acute toxicity value for 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}-N-(3-nitrophenyl)-2-naphthamide (6448-96-0 ) (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}-N-(3-nitrophenyl)-2-naphthamide shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 4-(2-methylprop-2-en-1-yl) benzenesulfonate shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

 

Based on the data available from the test chemical, 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}-N-(3-nitrophenyl)-2-naphthamide (6448-96-0 )not likely to exhibit repeated dose dermal toxicity. Hence the test chemical is not likely to classify as a repeated dose dermal toxicity as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available from the test chemical, 3-hydroxy-4-{[2-methoxy-5-(phenylcarbamoyl)phenyl]diazenyl}-N-(3-nitrophenyl)-2-naphthamide (6448-96-0 )not likely to exhibit repeated dose dermal toxicity. Hence the test chemical is not likely to classify as a repeated dose dermal toxicity as per the criteria mentioned in CLP regulation.

.