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

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from NTP.

Data source

Reference

Reference Type:

review article or handbook

Title:

Toxicology and Carcinogenesis Studies of C.I. Pigment Red 23 (CAS No. 6471-49-4) in F344 Rats and B6C3F1 Mice (Feed Studies)

Author:

NTP

Year:

1992

Bibliographic source:

NATIONAL TOXICOLOGY PROGRAM. Technical Report Series. No.411, November 1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

17 days repeated dose toxicity study of C.I. Pigment Red 23 in F344 male and female rats were observed to evaluate its toxic potential.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

229-313-2

EC Name:

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

Cas Number:

6471-49-4

Molecular formula:

C24H17N5O7

IUPAC Name:

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

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material : 3-hydroxy-4-[(E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N-(3-nitrophenyl)naphthalene-2-carboxamide
- Common name : 3-hydroxy-4-[(2-methoxy-5-nitrophenyl)azo]-N-(3-nitrophenyl)naphthalene-2-carboxamide, C.I. Pigment Red 23
- Molecular formula : C24H17N5O7
- Molecular weight : 487.4263 g/mol
- Smiles notation : c12c(c(c(cc1cccc2)C(=O)Nc1cc(ccc1)[N+](=O)[O-])O)/N=N/c1c(ccc(c1)[N+](=O)[O-])OC
- InChl : 1S/C24H17N5O7/c1-36-21-10-9-17(29(34)35)13-20(21)26-27-22-18-8-3-2-5-14(18)11-19(23(22)30)24(31)25-15-6-4-7-16(12-15)28(32)33/h2-13,30H,1H3,(H,25,31)/b27-26+
- Substance type : Organic
- Physical state : Solid

Specific details on test material used for the study:

Name of test material : 3-hydroxy-4-[(E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N-(3-nitrophenyl)naphthalene-2-carboxamide
- Common name : 3-hydroxy-4-[(2-methoxy-5-nitrophenyl)azo]-N-(3-nitrophenyl)naphthalene-2-carboxamide, C.I. Pigment Red 23
- Molecular formula : C24H17N5O7
- Molecular weight : 487.4263 g/mol
- Smiles notation : c12c(c(c(cc1cccc2)C(=O)Nc1cc(ccc1)[N+](=O)[O-])O)/N=N/c1c(ccc(c1)[N+](=O)[O-])OC
- InChl : 1S/C24H17N5O7/c1-36-21-10-9-17(29(34)35)13-20(21)26-27-22-18-8-3-2-5-14(18)11-19(23(22)30)24(31)25-15-6-4-7-16(12-15)28(32)33/h2-13,30H,1H3,(H,25,31)/b27-26+
- Substance type : Organic
- Physical state : Solid
-Purity: >96 %

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Frederick Cancer Research Center (Frederick, MD)
- Age at study initiation: 56 days old
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: rats were housed five per cage throughout the study
cage: Polycarbonate, solid bottom (Lab Products Inc., Garfield, NJ)

- Diet (e.g. ad libitum): NIH-07 rat, meal (Zeigler Bros., Inc., Gardners, PA), available ad libitum
- Water (e.g. ad libitum): Tap water (Birmingham Water Works)
in glass water bottles with stainless steel sippers (Edstrom Automatic Watering Systems, Waterford, WI), available ad
libitum
- Acclimation period: 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2-23.3 °C
- Humidity (%): 47%-61%
- Air changes (per hr): Minimum 15 change per hours
- Photoperiod (hrs dark / hrs light): 12 hours/day

Administration / exposure

Route of administration:

oral: feed

Details on route of administration:

PREPARATION OF DOSING SOLUTIONS: Not applicable

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): premix of NIH-07 rat as meal, with the appropriate amount of C.I. Pigment Red 23.
- Storage temperature of food: 2 weeks for 45 °C

Vehicle:

other: NIH-07 rat, meal

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Not applicable

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): premix of NIH-07 rat as meal, with the appropriate amount of C.I. Pigment Red 23.
- Storage temperature of food: 2 weeks for 45 °C

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data available
- Concentration in vehicle: 0, 6,000, 12,500, 25,000, 50,000 or 100,000 ppm

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Periodic analyses of the dosed-feed formulations were conducted at the study laboratory and at the analytical chemistry laboratory throughout. the studies

Duration of treatment / exposure:

from day 15 to 17th

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

0, 6,000, 12,500, 25,000, 50,000 or 100,000 ppm (0, 1200, 2500, 5000, 10000, 50000 mg/kg/day)

No. of animals per sex per dose:

5animals/dose

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Examinations

Observations and examinations performed and frequency:

Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice/day
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once/week and at sacrifice

BODY WEIGHT: Yes
- Time schedule for examinations: once/week and at sacrifice

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): daily/cage (calculated per
animal)
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined.

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: No data sensory activity / grip strength / motor activity / other: No data

Sacrifice and pathology:

Sacrifice and pathology
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

Mean ±Standard deviation was observed.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

No significant effect were observed at all dose level 0, 1200, 2500, 5000, 10000, 50000 mg/kg/day of treated group compare to control.

Mortality:

no mortality observed

Description (incidence):

No significant mortality were observed at all dose level 0, 1200, 2500, 5000, 10000, 50000 mg/kg/day of treated group compare to control.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Differences in mean body weight change and weight gain of exposed group than control were not significant.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

No significant effect were observed at all dose level 0, 1200, 2500, 5000, 10000, 50000 mg/kg/day of treated group compare to control.

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Decreased erythrocyte count observed in all male dose groups and the two highest female dose groups, indicating a mild anemia

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

No significant effect were observed at all dose level 0, 1200, 2500, 5000, 10000, 50000 mg/kg/day of treated group compare to control.

Gross pathological findings:

no effects observed

Description (incidence and severity):

No significant effect were observed at all dose level 0, 1200, 2500, 5000, 10000, 50000 mg/kg/day of treated group compare to control.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Description (incidence and severity):

No significant effect were observed at all dose level 0, 1200, 2500, 5000, 10000, 50000 mg/kg/day of treated group compare to control.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

5 000 other: mg/kg/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant effect were observed at this dose

Remarks on result:

other: No toxic effct were observed.

Target system / organ toxicity

Critical effects observed:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

The NOAEL value for substance C.I. Pigment Red 23 is considered to be 5000 mg/kg/day in F344 male and female rats for 17 days study.

Executive summary:

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.