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Description of key information

Carcinogenic LOAEL was considered to be 37.5 mg/kg bw/day when F344/N male and female rats were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) orally in feed for 103 weeks.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: 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 peer-reviewed journal
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
Principles of method if other than guideline:
Combined Chronic toxicity and carcinogenicity study of C. I. Solvent Yellow 14 in rats
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): C. I. Solvent Yellow 14
- Molecular formula: C16H12N2O
- Molecular weight: 248.284 g/mole
- Substance type: Organic
- Physical state: solid
- Purity:94.1% pure
- Impurities (identity and concentrations): remaining 6% of the test material was comprised of various chemical intermediates used in the manufacturing process; no inorganic salts were present.
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: NCI Frederick Cancer Research Center (Frederick, MD)
- Age at study initiation: Four week old
- Weight at study initiation: No data available
- Fasting period before study:No data available
- Housing: Rats were housed, five per cage, in solid-bottom polycarbonate cages supplied with hardwood chip bedding (source-Lab products, Inc. Cages and bedding were changed twice per week.
- Diet (e.g. ad libitum): Purina Laboratory Chow. Control and test diets were available 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, was available ad libitum via an automatic watering system.
- Acclimation period:

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:

Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: No data available
Details on 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.

DIET PREPARATION
- Rate of preparation of diet (frequency): once in 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: 0, 250 and 500 ppm
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analytical verification of doses was performed by using Gilford 2400-S spectrophotometer and target levels of 250 and 500 ppm were within ±10% of the desired concentrations.
Duration of treatment / exposure:
103 weeks
Frequency of treatment:
Daily
Post exposure period:
1 weeks
Remarks:
0, 37.5 and 75 mg/kg bw/day
No. of animals per sex per dose:
Total: 300
0 mg/kg bw/day: 50 male, 50 female
37.5 mg/kg bw/day: 50 male, 50 female
75 mg/kg bw/day: 50 male, 50 female
Control animals:
yes, concurrent vehicle
Details on study design:
- Rationale for animal assignment (if not random): Random
Positive control:
No data available
Observations and examinations performed and frequency:
Observation and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations checked in table [No.?] were included. No data available

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: each month

DERMAL IRRITATION (if dermal study): Not applicable
- Time schedule for examinations: Not applicable

BODY WEIGHT: Yes
- Time schedule for examinations: every 4 to 5 weeks

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

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

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. No data

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

OTHER:
Sacrifice and pathology:
GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes

Moribund animals and animals that survived to the end of the bioassay were killed by suffocation in carbon dioxide and necropsied.

Gross and microscopic examinations were performed on major tissues, major organs, and all gross lesions from killed animals and from animals found dead, unless precluded in whole or in part by autolysis or cannibalization.

The tissues were preserved in 10% neutral buffered formalin, embedded in paraffin-, sectioned, and stained with hematoxylin and eosin. The following were examined microscopically: skin (abdominal), lungs and bronchi, trachea, bone, bone marrow (femur), thigh muscle, spleen, lymph nodes, thymus, heart, salivary glands, liver, pancreas, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, kidney, urinary bladder, pituitary, adrenal, thyroid, parathyroid, testis, prostate, mammary gland, uterus, ovary, brain, epididymus, and all tissue masses.
Statistics:
Probabilities of survival were estimated by the product-limit procedure of Kaplan and Meier (1958).

Statistical analyses for a possible dose-related effect on survival used the method of Cox (1972) for testing two groups for equality and Tarone's (1975) extensions of Cox's method for testing for a dose-related trend. One-tailed P values have been reported for all tests except the departure from linearity test, which is reported only when its two-tailed P value is less than 0.05.

The one-tailed Fisher exact test (Cox, 1970) was used to compare the tumor incidence of a control group with that of a group of dosed animals at each dose level.

The Cochran-Armitage test for linear trend in proportions, with continuity correction (Armitage, 1971), was also used. Under the assumption of a linear trend, this test determines if the slope of the dose-response curve is different from zero at the one-tailed 0.05 level of significance.

Life table methods were used to analyze the incidence of tumors.
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, non-treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
no effects observed
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:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Histopathological findings: neoplastic:
effects observed, treatment-related
Other effects:
not specified
Details on results:
Mortality: In male rats, 34/50 (68%) of 37.5 mg/kg bw/day and 34/50 (68%) of 75 mg/kg bw /day lived till 104 weeks. In female rats, 42/49 (86%) of 37.5 mg/kg bw/day and 38/50 (76%) of 75 mg/kg bw /day lived till at 104 weeks. No significant differences in survival were observed in treated rats as compared to control.

Clinical sign: No compound-related clinical signs were observed in treated rats as compared to control.

Body weight: After week 16 for males and after week 50 for females mean body weights were decreased in treated rats as compared to control.

Food consumption: No compound-related effects on feed consumption were observed as compared to control.

Histopathology: non-neoplastic: multifocal fibrosis of the cardiac valve, atrophy of the pancreatic animus and nephropathy in male and female rat, lymphoid hyperplasia of the lung in male rats and bile duct focal hyperplasia in female rats were observed when treated with 37.5 and 75 mg/kg bw/day as compared to control.
A variety of other nonneoplastic lesions were seen in dosed rats. These were the usual types seen in aging F344 rats (Goodman et al., 1979) and were not considered to be associated with chemical administration.

Histopathology: neoplastic: Increase in Neoplastic nodules of the liver, composed of eosinophilic or basophilic hepatocytes and were accompanied by an angiectactic or cystic change were observed in treated male and female rats as compared to control. Dose related Basophilic and clear cell changes were also generally observed in treated rats.
Dose descriptor:
LOAEL
Effect level:
37.5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
histopathology: neoplastic
Critical effects observed:
not specified

Mean Body Weight Change (Relative to Controls) of Rats Fed Diet Containing C. I. Solvent Yellow 14

Week no.

Cumulative Mean Body Weigh Change

(grams)

 

 

 

Weigh Change Relative to Control (a) %

 

Control

Low Dose

High Dose

Low Dose

High Dose

Male

 

 

 

 

 

0

131 (b)

131 (b)

131 (b)

 

 

5

97

100

99

+3

+2

26

240

226

231

-6

-4

46

275

260

261

-5

-5

67

297

282

278

-5

-6

88

282

265

261

-6

-7

103

283

251

259

-11

-8

Female

 

 

 

 

 

0

103 (b)

104 (b)

102 (b)

 

 

5

38

35

24

-8

-37

26

104

100

100

-4

-4

46

122

115

120

-6

-2

67

144

134

138

-7

-4

88

163

145

156

-11

-4

103

183

181

176

-1

-4

(a) Weight Change Relative to Controls = {[Weight Change (Dose 1 Group) - Weight Change (Control Group)] X100}/Weight Change (Control Group)

(b) Initial weight.

Analyses of the Incidence of Primary Tumors in Male Rats Fed Diets Containing C. I. Solvent Yellow 14 (a)

Topography: Morphology

Untreated Control

Low dose

High dose

Subcutaneous Tissue: Fibroma (b)

3/50 (6)

2/50 (4)

6/50 (12)

P Values (c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.667

0.058

5.570

2.000

0.454

11.761

Weeks to First Observed Tumor

95

78

97

Hematopoietic System:

 

 

 

Lymphocytic Leukemia (b)

19/50 (38)

1/50 (2)

3/50 (6)

P Values (c),(d)

P<0.001 (N)

P<0.001 (N)

P<0.001 (N)

Departure from Linear Trend (f)

P=0.002

 

 

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.053

0.001

0.308

0.158

0.032

0.492

Weeks to First Observed Tumor

89

92

72

Hematopoietic System:

 

 

 

All Leukemias (b)

23/50 (46)

1/50 (2)

3/50 (6)

P Values (c),(d)

P<0.001 (N)

P<0.001 (N)

P<0.001 (N)

Departure from Linear Trend (f)

P<0.001

 

 

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.043

0.001

0.248

0.130

0.027

0.393

Weeks to First Observed Tumor

89

92

72

Hematopoietic System:

 

 

 

All Lymphomas or Leukemias (b)

25/50 (50)

2/50 (4)

4/50 (8)

P Values (c),(d)

P<0.001 (N)

P<0.001 (N)

P<0.001 (N)

Departure from Linear Trend (f)

P<0.001

 

 

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.080

0.010

0.294

0.160

0.044

0.418

Weeks to First Observed Tumor

89

92

72

Liver:

 

 

 

Neoplastic Nodule (b)

5/50 (10)

10/50 (20)

30/50 (60)

P Values (c),(d)

P<0.001 (N)

N.S.

P<0.001 (N)

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

2.000

0.675

6.944

6.000

2.595

17.463

Weeks to First Observed Tumor

95

103

95

Liver:

 

 

 

Hepatocellular Carcinoma (b)

1/50 (2)

0/50(0)

2/50(4)

P Values (c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.000

0.000

18.658

2.000

0.108

115.621

Weeks to First Observed Tumor

104

--

103

Liver:

 

 

 

Neoplastic Nodule or Hepatocellular Carcinoma (b)

6/50(12)

10/50(20)

31/50(62)

P Values (c),(d)

P<0.001 (N)

N.S.

P<0.001 (N)

Departure from Linear Trend (f)

P<0.030

 

 

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

1.667

0.597

5.164

5.167

2.408

12.155

Weeks to First Observed Tumor

95

103

95

Pituitary:

 

 

 

Chromophobe

Adenoma (b)

5/44(11)

5/45(11)

4/43(9)

P Values (c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control)

Lower Limit

Upper Limit

 

0.978

0.242

3.960

0.819

0.173

3.545

Weeks to First Observed Tumor

92

104

76

Adrenal:

 

 

 

Pheochromocytoma (b)

6/50(12)

6/49(12)

6/50(12)

P Values (c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control)

Lower Limit

Upper Limit

 

1.020

0.293

3.556

1.000

0.287

3.489

Weeks to First Observed Tumor

101

79

104

Thyroid:

 

 

 

C-Cell Carcinoma (b)

3/50(6)

4/49(8)

2/50(4)

P Values(c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

1.361

0.243

8.854

0.667

0.058

5.570

Weeks to First Observed Tumor

97

104

104

Pancreatic Islets: Islet-Cell

 

 

 

Adenoma (b)

4/50(8)

3/48(6)

0/46(0)

P Values (c),(d)

N.S

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.781

0.120

4.374

0.000

0.000

1.170

Weeks to First Observed Tumor

81

104

Pancreatic Islets: Islet-Cell

 

 

 

Adenoma or Carcinoma (b)

4/50(8)

3/48(6)

1/46(2)

P Values (c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.781

0.120

4.374

0.272

0.006

2.613

Weeks to First Observed Tumor

81

104

104

Testis:

 

 

 

Interstitial-Cell Tumor (b)

48/50(96)

46/50(92)

47/50(94)

P Values (c),(d)

N.S.

N.S.

 N.S

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.958

0.890 0

1.071

0.910

0.979

1.076

Weeks to First Observed Tumor

78

68

72

Analyses of the Incidence of Primary Tumors in Female Rats Fed Diets Containing C. I. Solvent Yellow 14 (a)

Topography: Morphology

Untreated Control

Low dose

High dose

Subcutaneous Tissue: Fibroma (b)

0/50(0)

0/49(0)

3/49(6)

P Values (c),(d)

P=0.036

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

--

--

--

Infinite

0.614

Infinite

Weeks to First Observed Tumor

--

--

97

Hematopoietic System:

 

 

 

Lymphocytic Leukemia (b)

9/50 (18)

0/49 (0)

0/49 (0)

P Values (c),(d)

P<0.001 (N)

P<0.001 (N)

P<0.001 (N)

Departure from Linear Trend (f)

P=0.029

 

 

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.000

0.000

0.388

0.000

0.000

0.388

Weeks to First Observed Tumor

76

--

--

Hematopoietic System:

 

 

 

All Leukemias (b)

9/50 (18)

1/49 (2)

0/49 (0)

P Values (c),(d)

P<0.001 (N)

P<0.001 (N)

P<0.001 (N)

Departure from Linear Trend (f)

P<0.001

 

 

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.113

0.003

0.771

0.000

0.000

0.388

Weeks to First Observed Tumor

76

103

--

Hematopoietic System:

 

 

 

All Lymphomas or Leukemias (b)

11/50 (22)

2/49 (4)

0/49 (0)

P Values (c),(d)

P<0.001 (N)

P=0.008 (N)

P<0.001 (N)

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.186

0.021

0.793

0.000

0.000

0.307

Weeks to First Observed Tumor

76

103

--

Liver:

 

 

 

Neoplastic Nodule (b)

2/50 (4)

3/49 (6)

10/48 (21)

P Values (c),(d)

P=0.005 (N)

N.S.

P=0.011 (N)

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

1.531

0.183

17.671

5.208

1.189

46.803

Weeks to First Observed Tumor

104

104

91

Liver:

 

 

 

Hepatocellular Carcinoma (b)

0/50 (0)

0/49(0)

2/48(4)

P Values (c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

--

--

--

Infinite

0.308

Infinite

Weeks to First Observed Tumor

--

--

104

Liver:

 

 

 

Neoplastic Nodule or Hepatocellular Carcinoma (b)

2/50(4)

3/49(6)

11/48(23)

P Values (c),(d)

P=0.003

N.S.

P=0.006

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

1.531

0.183

17.671

5.729

1.342

50.869

Weeks to First Observed Tumor

104

104

91

Pituitary:

 

 

 

Chromophobe

Adenoma (b)

28/44(64)

19/45(42)

18/46(39)

P Values (c),(d)

P=0.014 (N)

P=0.035 (N)

P=0.017 (N)

Relative Risk (Untreated Control)

Lower Limit

Upper Limit

 

0.663

0.430

1.029

0.615

0.392

0.968

Weeks to First Observed Tumor

96

94

87

Adrenal:

 

 

 

Pheochromocytoma (b)

0/49(0)

1/48(2)

3/48(6)

P Values (c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control)

Lower Limit

Upper Limit

 

Infinite

0.555

Infinite

 

Infinite

0.614

Infinite

 

Weeks to First Observed Tumor

--

104

86

Thyroid:

 

 

 

C-Cell Carcinoma (b)

2/50(4)

3/49(6)

3/48(6)

P Values(c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

1.531

0.138

17.671

1.563

0.187

18.028

Weeks to First Observed Tumor

104

104

104

 

Mammary Gland:

 

 

 

Fibroadenoma (b)

7/50(14)

8/49(16)

7/49(14)

P Values (c),(d)

N.S

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

1.166

0.401

3.489

1.020

0.330

3.155

Weeks to First Observed Tumor

97

77

86

Mammary Gland:

 

 

 

Cystfibroadenoma (b)

4/50(8)

2/49(4)

3/49(6)

P Values (c),(d)

N.S.

N.S.

N.S.

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

0.510

0.048

3.383

0.765

0.118

4.288

Weeks to First Observed Tumor

104

101

102

Mammary Gland:

 

 

 

NOS or Adenocarcinoma, NOS (b)

2/50(4)

3/50(6)

0/50(0)

P Values (c),(d)

N.S.

N.S.

 N.S

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

1.500

0.180

17.329

0.000

0.000

3.381

Weeks to First Observed Tumor

104

103

--

Uterus:

 

 

 

Endometrial Stromal Polyp (b)

18/49(37)

20/47(43)

11/48(23)

P Values (c),(d)

N.S.

N.S.

 N.S

Relative Risk (Untreated Control) (e)

Lower Limit

Upper Limit

 

1.158

0.672

2.002

0.624

0.300

1.238

Weeks to First Observed Tumor

97

94

104

(a) Dosed groups received doses of 250 or 500 ppm in the diet.

(b) Number of tumor-bearing animals/number of animals examined at site (percent).

(c) Beneath the incidence of tumors in the control group is the probability level for the Cochran Armitage test when P is less than 0.05; otherwise, not significant (N.S.) is indicated. Beneath the incidence of tumors in a dosed group is the probability level for the Fisher exact test for the comparison of that dosed group with the untreated control group when P is less than 0.05; otherwise, not significant (N.S.) is indicated.

(d) A negative trend (N) indicates a lower incidence in a dosed group than in a control group.

(e) The 95 percent confidence interval of the relative risk between each dosed group and the control group.

(f) The probability level for departure from linear trend is given when P is less than 0.05 for any comparison.

SUMMARY OF THE INCIDENCE OF NEOPLASMS IN MALE RATS FED DIETS CONTAINING C.I. SOLVENT YELLOW 14

 

Control

Low dose

High dose

Animals initially in study

50

50

50

Animals necropsied

50

50

50

Animals examined histopathalogycally

50

50

50

 

 

 

 

Integumentary System

 

 

 

*Skin

SQUAMOUS CELL CARCINOMA

FIBROMA

CARCINOSARCOMA

(50)

(50)

1 (2%)

1 (2%)

1 (2%)

(50)

*SUBCUT TISSUE

SQUAMOUS CELL CARCINOMA

BASAL-CELL TUMOR

FIBROMA

FIBROSARCOMA

NEURILEMOMA, MALIGNANT

(50)

 

 

3 (6%)

2 (4%)

1 (2%)

(50)

 

 

2 (4%)

(50)

1 (2%)

1 (2%)

6 (12%)

RESPIRATORY SYSTEM

 

 

 

*NASAL CAVITY

SQUAMOUS CELL CARCINOMA, INVASIV

(50)

 

(50)

(50)

1 (2%)

*LUNG

CARCINOSARCOMA, METASTATIC

MESOTHELIOMA, METASTATIC

(50)

1 (2%)

(50)

1 (2%)

(50)

HEMATOPOIETIC SYSTEM

 

 

 

*MULTIPLE ORGANS

MALIGNANT LYMPHOMA, NOS

MALIG.LYMPHOMA, LYMPHOCYTIC TYPE

MALIG.LYMPHOMA, HISTIOCYTIC TYPE

LEUKEMIA, NOS

LYMPHOCYTIC LEUKEMIA

 

(50)

1 (2%)

 

1 (2%)

4 (8%)

19 (38%)

(50)

 

1 (2%)

 

 

1 (2%)

 

(50)

 

 

 

 

3 (6%)

*SPLEEN

FIBROSARCOMA

(50)

(50)

(50)

2 (4%)

*CERVICAL LYMPH NODE

ASTROCYTOMA, METASTATIC

(47)

(41)

(2%)

(41)

*MESENTERIC L. NODE

MALIG.LYMPHOMA, HISTIOCYTIC TYPE

(47)

(45)

(41)

1 (2%)

CIRCULATORY SYSTEM

 

 

 

*MULTIPLE ORGANS

ANGIOSARCOMA

(50)

(50)

1 (2%)

(50)

*SPLEEN

HEMANGIOSARCOMA

(50)

(50)

(50)

1 (2%)

DIGESTIVE SYSTEM

 

 

 

*LIVER

NEOPLASTIC NODULE

HEPATOCELLULAR CARCINOMA

(50)

5 (10%)

1 (2%)

(50)

10 (20%)

(50)

30 (60%)

2 (4%)

*PANCREAS

ACINAR-CELL ADENOMA

(50)

(48)

(46)

1 (2%)

*CARDIAC STOMACH

SQUAMOUS CELL PAPILLOMA

LEIOMYOSARCOMA

(50)

 

1 (2%)

(50)

(49)

2 (4%)

*JEJUNUM

LEIOMYOMA

(47)

(45)

(47)

1 (2%)

*ILEUM

ADENOCARCINOMA, NOS

PAPILLARY ADENOCARCINOMA

(47)

(45)

1 (2%)

(47)

1 (2%)

*COLON

ADENOMATOUS POLYP, NOS

(50)

(48)

(47)

1 (2%)

URINARY SYSTEM

 

 

 

*KIDNEY

TUBULAR-CELL ADENOMA

(50)

1 (2%)

(50)

1 (2%)

(50)

*KIDNEY/PELVIS

TRANSITIONAL-CELL PAPILLOMA

(50)

 

(50)

 1 (2%)

(50)

*URINARY BLADDER

TRANSITIONAL-CELL PAPILLOMA

(47)

(46)

(45)

1 (2%)

ENDOCRINE SYSTEM

 

 

 

*PITUITARY

CARCINOMA,NOS

ADENOMA, NOS

CHROMOPHOBE ADENOMA

(44)

 

1 (2%)

5 (11%)

(45)

1 (2%)

1 (2%)

5 (11%)

(43)

 

 

4 (9%)

*ADRENAL

CORTICAL ADENOMA

PHEOCHROMOCYTOMA

GANGLIONEUROBLASTOMA

(50)

 

6 (12%)

 

(49)

 

6 (12%)

(50)

1 (2%)

6 (12%)

1 (2%)

*ADRENAL MEDULLA

GANGLIONEUROBLASTOMA

(50)

(49)

2 (4%)

(50)

1 (2%)

*THYROID

C-CELL CARCINOMA

(50)

3 (6%)

(49)

4 (8%)

(50)

2 (4%)

*PANCREATIC ISLETS

ISLET-CELL ADENOMA

ISLET-CELL CARCINOMA

(50)

4 (8%)

(48)

3 (6%)

(46)

1 (2%)

REPRODUCTIVE SYSTEM

 

 

 

*MAMMARY GLAND

ADENOMA, NOS

FIBROADENOMA

(50)

2 (4%)

 

(50)

1 (2%)

1 (2%)

(50)

1 (2%)

 

*PREPUTIAL GLAND

CARCINOMA,NOS

ADENOMA, NOS

(50)

1 (2%)

1 (2%)

(50)

1 (2%)

 

(50)

1 (2%)

*PROSTATE

PAPILLARY ADENOMA

(48)

 

(42)

2 (5%)

(47)

*TESTIS

INTERSTITIAL-CELL TUMOR

(50)

48 (96%)

(50)

46 (92%)

(50)

47 (94%)

NERVOUS SYSTEM

 

 

 

*BRAIN/MENINGES

GRANULAR-CELL TUMOR, NOS

(50)

(50)

(50)

1 (2%)

*BRAIN

ASTROCYTOMA

(50)

(50)

1 (2%)

(50)

*CEREBELLUM

ASTROCYTOMA

(50)

(50)

1 (2%)

(50)

MEDULLA OBLONGATA

GRANULAR-CELL TUMOR, NOS

(50)

1 (2%)

(50)

(50)

SPECIAL SENSE ORGANS

NONE

 

 

 

MUSCULOSKELETAL SYSTEM

NONE

 

 

 

BODY CAVITIES

 

 

 

*TUNICA VAGINALIS

MESOTHELIOMA, NOS

(50)

(50)

1 (2%)

(50)

ALL OTHER SYSTEMS

 

 

 

*MULTIPLE ORGANS

MESOTHELIOMA, MALIGNANT

(50)

1 (2%)

(50)

(50)

ORBITAL REGION

SQUAMOUS CELL CARCINOMA, INVASIV

 

 

 

ANIMAL DISPOSITION SUMMARY

 

 

 

ANIMALS INITIALLY IN STUDY

NATURAL DEATHS 

MORIBUND SACRIFICE

SCHEDULED SACRIFICE

ACCIDENTALLY KILLED

TERMINAL SACRIFICE 

ANIMAL MISSING

50

14

8

 

 

28

50

12

4

 

 

34

 

50

11

5

 

 

34

TUMOR SUMMARY

 

 

 

TOTAL ANIMALS WITH PRIMARY TUMORS*

TOTAL PRIMARY TUMORS

50

112

48

97

49

120

TOTAL ANIMALS WITH BENIGN TUMORS

TOTAL BENIGN TUMORS

49

71

46

71

49

73

TOTAL ANIMALS WITH MALIGNANT TUMORS

TOTAL MALIGNANT TUMORS

28

35

13

15

14

16

TOTAL ANIMALS WITH SECONDARY TUMORS

TOTAL SECONDARY TUMORS

1

1

2

2

1

2

TOTAL ANIMALS WITH TUMORS UNCERTAINBENIGN

OR MALIGNANT

TOTAL UNCERTAIN TUMORS

 

6

6

 

11

11

 

30

31

Conclusions:
Carcinogenic LOAEL was considered to be 37.5 mg/kg bw/day when F344/N male and female rats were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) orally in feed.
Executive summary:

In a Combined Chronic toxicity and carcinogenicity study, Fischer F344/N male and female rats were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) in the concentration of 0, 37.5 and 75 mg/kg bw/day orally in feed. In male rats, 34/50 (68%) of 37.5 mg/kg bw/day and 34/50 (68%) of 75 mg/kg bw /day lived till 104 weeks. In female rats, 42/49 (86%) of 37.5 mg/kg bw/day and 38/50 (76%) of 75 mg/kg bw /day lived till at 104 weeks. No significant differences in survival were observed in treated rats as compared to control. No compound-related clinical signs and effects on feed consumption were observed as compared to control. After week 16 for males and after week 50 for females mean body weights were decreased in treated rats as compared to control. In addition, non-neoplastic: multifocal fibrosis of the cardiac valve, atrophy of the pancreatic animus and nephropathy in male and female rat, lymphoid hyperplasia of the lung in male rats and bile duct focal hyperplasia in female rats were observed when treated with 37.5 and 75 mg/kg bw/day as compared to control. A variety of other nonneoplastic lesions were seen in dosed rats. These were the usual types seen in aging F344 rats (Goodman et al., 1979) and were not considered to be associated with chemical administration. Increase in Neoplastic nodules of the liver, composed of eosinophilic or basophilic hepatocytes and were accompanied by an angiectactic or cystic change were observed in treated male and female rats as compared to control. Dose related Basophilic and clear cell changes were also generally observed in treated rats. Therefore, Carcinogenic LOAEL was considered to be 37.5 mg/kg bw/day when F344/N male and female rats were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) orally in feed for 103 weeks.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
37.5 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
Data is from Klimisch 2 and from peer-reviewed journal.

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the data available for target 1-phenylazo-2-naphthol (CAS no 842-07-9) is considered to be carcinogenic by oral route of exposure. 

Additional information

Carcinogenicity:

Based on the data available for target 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS no 842-07-9) is summarized below

In a study conducted by National Toxicology Program (1982), Combined Chronic toxicity and carcinogenicity was evaluated in Fischer F344/N male and female rats by using 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) in the concentration of 0, 37.5 and 75 mg/kg bw/day orally in feed. In male rats, 34/50 (68%) of 37.5 mg/kg bw/day and 34/50 (68%) of 75 mg/kg bw /day lived till 104 weeks. In female rats, 42/49 (86%) of 37.5 mg/kg bw/day and 38/50 (76%) of 75 mg/kg bw /day lived till at 104 weeks. No significant differences in survival were observed in treated rats as compared to control. No compound-related clinical signs and effects on feed consumption were observed as compared to control. After week 16 for males and after week 50 for females mean body weights were decreased in treated rats as compared to control. In addition, non-neoplastic: multifocal fibrosis of the cardiac valve, atrophy of the pancreatic animus and nephropathy in male and female rat, lymphoid hyperplasia of the lung in male rats and bile duct focal hyperplasia in female rats were observed when treated with 37.5 and 75 mg/kg bw/day as compared to control. A variety of other nonneoplastic lesions were seen in dosed rats. These were the usual types seen in aging F344 rats (Goodman et al., 1979) and were not considered to be associated with chemical administration. Increase in Neoplastic nodules of the liver, composed of eosinophilic or basophilic hepatocytes and were accompanied by an angiectactic or cystic change were observed in treated male and female rats as compared to control. Dose related Basophilic and clear cell changes were also generally observed in treated rats. Therefore, Carcinogenic LOAEL was considered to be 37.5 mg/kg bw/day when F344/N male and female rats were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) orally in feed for 103 weeks.

Thus, based on the data available for target 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS no 842-07-9) is considered to be carcinogenic by oral route of exposure. 

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