1-phenylazo-2-naphthol

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:

data from handbook or collection of data

Justification for type of information:

Data is from study report

Data source

Reference

Reference Type:

publication

Title:

CARCINOGENESIS BIOASSAY of C.I. SOLVENT YELLOW 14 (CAS No. 842-07-9) IN F344/N RATS AND B6C3F1 MICE (FEED STUDY)

Author:

National Toxicology Program

Year:

1982

Bibliographic source:

NATIONAL TOXICOLOGY PROGRAM, Technical Report Series No. 226, NTP-80-80, NIH Publication No. 82-1782, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, Public Health Service, National Institutes of Health, September 1982, page no. 1-164

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

14 day repeated dose toxicity study of C. I. Solvent Yellow 14 orally in B6C3F1 mice.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-phenylazo-2-naphthol

EC Number:

212-668-2

EC Name:

1-phenylazo-2-naphthol

Cas Number:

842-07-9

Molecular formula:

C16H12N2O

IUPAC Name:

1-[(E)-2-phenyldiazen-1-yl]naphthalen-2-ol

Details on test material:

- Name of test material (as cited in study report):C. I. Solvent Yellow 14 - Molecular formula (if other than submission substance):C16-H12-N2-O- Molecular weight (if other than submission substance):248.284 g/mole - Substance type:Organic- Physical state:solid- purities (identity and concentrations): 94.1 % pure- Impurities (identity and concentrations):5.9 %

Specific details on test material used for the study:

- Name of test material: C. I. Solvent Yellow 14 (1-phenylazo-2-naphthol)
- Molecular formula: C16H12N2O
- Molecular weight: 248.284 g/mol
- Substance type: Organic
- Physical state: solid
- Impurities (identity and concentrations): 5.9 %
- Purity: 94.1% pure

Test animals

Species:

mouse

Strain:

B6C3F1

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: NCI Frederick Cancer Research Center (Frederick, MD)
- Age at study initiation: 6 week old
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Mice were housed by species, five per cage, in solid-bottom polycarbonate cage supplied with hardwood chip bedding. Cages and bedding were changed twice per week. Rack Filters with Dupon 2024 Spun-Bonded polyester filters were used.
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum in feed hoppers that were changed weekly.
- Water (e.g. ad libitum): Tap water supplied and analyzed by the Columbus, Ohio, water department, ad libitum via an automatic watering system.
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21° to 23°C
- Humidity (%): 40%-60% (relative humidity)
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): Standard white fluorescent lighting provided illumination 12 hours per day.

IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:

oral: feed

Details on route of administration:

No data

Vehicle:

other: Feed (Purina Laboratory Chow animal meal)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Diets were formulated by mixing weighed amounts of Purina Laboratory Chow animal meal and the test chemical for 15 minutes in a Patterson-Kelly twin-shell blender equipped with an intensifier bar to give a dose range of 0, 1200, 2500, 5000, 10000 and 20000 mg/kg/day.

DIET PREPARATION
- Rate of preparation of diet (frequency): In every 10 days
- Mixing appropriate amounts with (Type of food): Purina Laboratory Chow
- Storage temperature of food: Formulated diets were stored at 23°C for no longer than 10 days

VEHICLE
- Justification for use and choice of vehicle (if other than water): Purina Laboratory Chow
- Concentration in vehicle: 6,000, 12,500, 25,000, 50,000 and 100,000 ppm (0, 1200, 2500, 5000, 10000 and 20000 mg/kg/day)
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): Not required
- Purity: No data available

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Analytical verification of doses were performed by using Gilford 2400-S spectrophotometer

Duration of treatment / exposure:

14 days

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

0, 6,000, 12,500, 25,000, 50,000 and 100,000 ppm (0, 1200, 2500, 5000, 10000 and 20000 mg/kg/day)
nominal in diet

No. of animals per sex per dose:

Total: 60
0 mg/Kg/day : 5 male, 5 female
1200 mg/Kg/day : 5 male, 5 female
2500 mg/Kg/day : 5 male, 5 female
5000 mg/Kg/day : 5 male, 5 female
10000 mg/Kg/day : 5 male, 5 female
20000 mg/Kg/day : 5 male, 5 female

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: No data available
- Rationale for animal assignment (if not random): Animals assigned to cages according to a table of random numbers.
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included: Mortality was observed.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data available

BODY WEIGHT: No data available
- Time schedule for examinations: No data available

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

FOOD EFFICIENCY: No data available
- 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 available

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

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

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

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

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

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

OTHER: No data available

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
Gross pathological abnormalities were examined.

HISTOPATHOLOGY: No data available

Other examinations:

No data available

Statistics:

No data available

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

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:

not specified

Gross pathological findings:

effects observed, treatment-related

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

Clinical signs and mortality :
Mortality:
When treated with 12500, 25000, 50000 and 100000 ppm, all male and female mice were died.

Clinical signs:
No sign of toxicity were observed in treated mice.

Body weight and weight gain: No data available

Food consumption and compound intake: No data available

Food efficiency: No data available

Water consumption and compound intake: No data available

Opthalmoscopic examination: No data available

Haematology: No data available

Clinical chemistry: No data available

Urinanalysis: No data available

Neurobehaviour: No data available

Organ weights: No data available

Gross pathology: When treated with 2500, 5000, 10000 and 20000 mg/kg/day, severe effects were observed in male and female mice. Dark red intestines and mildly congested livers were observed in 1200 mg/Kg/day treated male and female mice. Dark red intestines and mildly congested livers were observed in 6000 ppm treated male and female mice.

Histopathology: No data available

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 200 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant alterations were noted at the mentioned dose level

Target system / organ toxicity

Critical effects observed:

no

Any other information on results incl. tables

Table: Survival of mice in 14 days study period

Dose (mg/Kg/day)	Survival
	Male	Female
1200	5/5	5/5
2500	0/5	0/5
5000	0/5	0/5
10000	0/5	0/5
20000	0/5	0/5

Applicant's summary and conclusion

Conclusions:

The No Observed Adverse Effect Level (NOAEL) was 1200 mg/kg/day when B6C3F1 male and female mice were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14).

Executive summary:

Repeated dose oral toxicity study was performed on mice to determine the toxic nature of C. I. Solvent Yellow 14. In a 14 day repeated dose toxicity study ,  B6C3F₁ male and female mice were treated with C. I. Solvent Yellow 14 in the concentration of 0,6,000, 12,500, 25,000, 50,000, or 100,000 ppm orally in diet. All male and female mice were died at 12500, 25000, 50000 and 100000 ppm (2500, 5000, 1000 and 20000 mg/kg/day) dose. The mice were observed for clinical signs and mortality, gross and histopathology. No clinical signs of toxicity were noted and severe gross pathological effects such as dark red intestines and mildly congested livers were observed at 2500 mg/Kg/day and at higher doses. Therefore, No Observed Adverse Effect Level (NOAEL) was 1200 mg/kg/day when B6C3F1 male and female mice were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14).