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EC number: 219-746-5 | CAS number: 2519-30-4
Toxicity to reproduction
Administrative data
- Endpoint:
- fertility, other
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
Data source
Reference
- Reference Type:
- publication
- Title:
- Acute (Mouse and Rat) and Short-term (Rat) Toxicity Studies on Black PN
- Author:
- I.F. Gaunt, Madge Farmer, P. Grasso, S.D. Gangolli
- Year:
- 1 967
- Bibliographic source:
- Food and Cosmetics Toxicology Volume 5, 1967, Pages 171-177
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: as below
- Principles of method if other than guideline:
- Evaluation on the testicular toxicity of Black PN in rats .
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Black PN
- IUPAC Name:
- Black PN
- Reference substance name:
- Tetrasodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate
- EC Number:
- 219-746-5
- EC Name:
- Tetrasodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate
- Cas Number:
- 2519-30-4
- Molecular formula:
- C28H21N5O14S4.4Na
- IUPAC Name:
- tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl)diazenyl]-1-naphthyl}diazenyl)naphthalene-1,7-disulfonate
- Details on test material:
- Name of test material (as cited in study report): Black PN- Molecular formula (if other than submission substance):C28-H21-N5-O14-S4.4Na- Molecular weight (if other than submission substance):867.6873 g/mol- Substance type:Organic- Physical state:- Analytical purity:83.6%- Impurities (identity and concentrations): Dye content (70 % min .); chloride and sulphate as sodium salts plus moisture (30% max); subsidiary dyes (15 % max); intermediates (1% max); water-insoluble material (0.2% max); arsenic (5 ppm max); lead (20 ppm max); antimony, copper, chromium, zinc, barium sulphate (100 ppm max taken separately or 200 ppm max taken together).
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: No data available.- Age at study initiation: (P) x wks; (F1) x wks- No data available.- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g- No data available.- Fasting period before study: No data available.- Housing: Rats were housed four /cage.- Diet (e.g. ad libitum): Spillers Small Laboratory Animal Diet ad libitum.- Water (e.g. ad libitum): Water ad libitum- Acclimation period: No data available.ENVIRONMENTAL CONDITIONS- Temperature (°C): No data available.- Humidity (%):No data available.- Air changes (per hr): No data available.- Photoperiod (hrs dark / hrs light): No data available.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: Spillers Small Laboratory Animal Diet
- Details on exposure:
- DIET PREPARATION- Rate of preparation of diet (frequency):- Mixing appropriate amounts with (Type of food): Spillers Small Laboratory Animal Diet- Storage temperature of food:VEHICLE- Justification for use and choice of vehicle (if other than water):- Concentration in vehicle: 0, 0.3, 1.0 and 3.0 %- Amount of vehicle (if gavage):- Lot/batch no. (if required):- Purity:
- Details on mating procedure:
- No data available.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Daily
- Details on study schedule:
- No data available
Doses / concentrations
- Remarks:
- Doses / Concentrations:0, 0.3, 1.0 and 3.0 % (0, 150, 500, 1000 mg/kg/day)Basis:nominal in diet
- No. of animals per sex per dose:
- Total no. of animals-1280 mg/kg/day- 16 male and 16 female150 mg/kg/day-16 male and 16 female500 mg/kg/day-16 male and 16 female1000 mg/kg/day-16 male and 16 female
- Control animals:
- yes, concurrent vehicle
- Positive control:
- No data available.
Examinations
- Parental animals: Observations and examinations:
- Parental animal: observation and examination-Body weight and food intake were observed weekly. Hematology-Terminal haematological investigations involved the determination of haemoglobin and methaemoglobin levels, haematocrits, erythrocyte, reticulocyte, and total and differential leukocyte counts. Erythrocytes were examined for the presence of Heinz bodies.Clinical chemistry- Liver and kidney function tests were carried out terminally. Levels of serum glutamic-oxaloacetic and glutamic-pyruvic transaminase and of blood urea nitrogen were determined.Urine analysis- The urine was examined at wk 6 and 12 for colour, pH, microscopic constituents and content of protein, reducing substances, bile salts and blood, and activity of glutamicoxaloacetic Transaminase. A concentration test conducted terminally, involved measurements of volume and specific gravity of the urine excreted during a 6-hr period of water deprivation and during a 4-hr period beginning 16 hr after a water load of 25 ml/kg.
- Oestrous cyclicity (parental animals):
- No data available.
- Sperm parameters (parental animals):
- No data available.
- Litter observations:
- No data available.
- Postmortem examinations (parental animals):
- At autopsy, the gross appearance of the organs and the weights of the liver, kidneys, brain, spleen, heart, adrenals and gonads were noted.Histopathology- Paraffin wax sections of these organs together with a wide range of other organs were stained with haematoxylin and eosin
- Postmortem examinations (offspring):
- No data available
- Statistics:
- Statistics was observed by Litchfield, J. T, Jr. & Wilcoxon, F. (1949) method.
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Other effects:
- effects observed, treatment-related
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
Details on results (P0)
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- reproductive performance
- Remarks on result:
- other: No significant increase in the relative weights of the testes.
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- reproductive performance
- Remarks on result:
- other: No significant change in the gonades
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
Effect levels (F1)
- Remarks on result:
- not measured/tested
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Body weight and food consumption:
Mean values of body weight in rats fed Black PN at 0-3% (1000mg/kg/day ) of the diet for 90 days
Dietary level | Body weight (g) at wk | |||
0‡ | 4 | 8 | 12 | |
| Males | |||
0.0 | 102 | 276 | 352 | 387 |
0.3 | 108 | 289 | 364 | 405 |
1.0 | 107 | 275 | 345 | 374 |
3.0 | 105 | 267 | 327 | 357٭* |
| Female | |||
0.0 | 101 | 194 | 226 | 235 |
0.3 | 99 | 190 | 220 | 233 |
1.0 | 99 | 188 | 215 | 235 |
3.0 | 100 | 193 | 222 | 225 |
"†'Calculated from data on body weight and food consumption.
"‡'Day 1 of feeding.
Values of body weight are the means for groups of 16 animals.
Value marked with asterisk differs significantly from that of the control:**P <0 01.
Food consumption-
Food consumption in rats fed Black PN at 0-3% of the diet for 90 days
Dietary level | Food consumption (g/rat/day) at wk | |||
0‡ | 4 | 8 | 12 | |
| Males | |||
0.0 | 14.4 | 18.0 | 19.7 | 19.2 |
0.3 | 14.3 | 16.2 | 19.0 | 19.5 |
1.0 | 15.1 | 17.7 | 19.0 | 17.1 |
3.0 | 14.4 | 19.7 | 16.1 | 15.9 |
| Female | |||
0.0 | 12.7 | 13.7 | 11.4 | 10.1 |
0.3 | ||||
289 | 364 | 405 | ||
1.0 | 107 | 275 | 345 | 374 |
3.0 | 105 | 267 | 327 | 357٭* |
| Female | |||
0.0 | 101 | 194 | 226 | 235 |
0.3 | 99 | 190 | 220 | 233 |
1.0 | 99 | 188 | 215 | 235 |
3.0 | 100 | 193 | 222 | 225 |
"†'Calculated from data on body weight and food consumption.
"‡'Day 1 of feeding.
Values of body weight are the means for groups of 16 animals.
Value marked with asterisk differs significantly from that of the control:**P <0 01.
Food consumption-
Food consumption in rats fed Black PN at 0-3% of the diet for 90 days
Dietary level | Food consumption (g/rat/day) at wk | |||
0‡ | 4 | 8 | 12 | |
| Males | |||
0.0 | 14.4 | 18.0 | 19.7 | 19.2 |
0.3 | 14.3 | 16.2 | 19.0 | 19.5 |
1.0 | 15.1 | 17.7 | 19.0 | 17.1 |
3.0 | 14.4 | 19.7 | 16.1 | 15.9 |
| Female | |||
0.0 | 12.7 | 13.7 | 11.4 | 10.1 |
0.3 | 12.8 | 9.9 | 12.8 | 10.8 |
1.0 | 13.7 | 11.3 | 12.7 | 10.5 |
3.0 | 13.5 | 12.6 | 12.7 | 10.2 |
Intake of colouring in rats fed Black PN at 0-3% of the diet for 90 days.
Dietary level | Intake of colouring (g/kg/day) t at wk | |||
0‡ | 4 | 8 | 12 | |
| Males | |||
0.0 | - | - | - | - |
0.3 | 0.40 | 0.17 | 0.16 | 0.14 |
1.0 | 1.41 | 0.64 | 0.55 | 0.46 |
3.0 | 4.11 | 2.20 | 1.47 | 1.34 |
| Female | |||
0.0 | - | - | - | - |
0.3 | 0.39 | 0.16 | 0.17 | 0.14 |
1.0 | 1.38 | 0.60 | 0.60 | 0.43 |
3.0 | 4.05 | 1.95 | 1.71 | 1.36 |
"†'Calculated from data on body weight and food consumption.
"‡'Day 1 of feeding.
Values of body weight are the means for groups of 16 animals. Values of food consumption are the means for four cages of four animals. Although growth and food consumption were recorded ‘weekly, values at monthly intervals are included in the Table.
Value marked with asterisk differs significantly from that of the control:**P <0.01.Relative organ weight | |||||||||
Sex/Dietary level(%) | Brain | Heart | Liver | Spleen | Kidney Left Right | Adrenal | Gonades | ||
Male | |||||||||
0.0 | 0.55 | 0.30 | 3.14 | 0.15 | 0.27 | 0.28 | 0.017 | 0.45 | |
0.3 | 0.51 | 0.30 | 2.97 | 0.17 | 0.27 | 0.28 | 0.017 | 0.43 | |
1 | 0.55 | 0.30 | 3.10 | 0.16 | 0.29 | 0.29 | 0.018 | 0.49 | |
3 | 0.57 | 0.30 | 3.12 | 0.16 | 0.30** | 0.31*** | 0.019 | 0.50* | |
Female | |||||||||
0.0 | 0.80 | 0.34 | 3.29 | 0.19 | 0.30 | 0.32 | 0.036 | 0.048 | |
0.3 | 0.82 | 0.36 | 3.04* | 0.20 | 0.30 | 0.32 | 0.037 | 0.052 | |
1 | 0.81 | 0.35 | 3.11 | 0.21 | 0.32 | 0.33 | 0.037 | 0.052 | |
3 | 0.81 | 0.33 | 2.95* | 0.18 | 0.31 | 0.32 | 0.035 | 0.046 | |
Values are the means of groups of 16 ammals and those marked with asterisks differ significantly from those of controls: *P <0"05; **P <0.01 ; ***P <0 001. Decreased liver weight in these instances arose from the fact that autopsles were performed late in the day, so that the animals were not fasted overmght, in accordance with the standard procedure but were only fasted during the day. | |||||||||
Applicant's summary and conclusion
- Conclusions:
- NOEL for Black PN was found to be 500 mg/kg/day in male rats and 1000 mg/kg/day in female rats respectivley ,for 90 days reprotox study.
- Executive summary:
Reprotox study for Black PN was conducted on male and female rats for 90 days by administrating in diet. When they were exposed at concentration of 0, 150, 500, 1000 mg/kg/day by oral diet for 90 days.
Clinical sign, body weight,food consumption,colour intake, Hematology, clinical chemistry , urine analysis , organ weight and histopathology was observed . No significant change were observed at any dose level in both treated male and female rats compare to control.
Significant growth retardation was observed in males at the 1000mg/kg/day level and it associated with a reduced food intake.There were significant increase in the relative weights of the testes and kidneys at the dose level of 1000 mg/kg/day in treated male was observed compare to control. The elevated relative kidney weights were not accompanied by changes in the kidney function tests or in organ pathology. Decrease liver weight were also observed in 150 and 1000 mg/kg/day in treated female compare to control. Significant change was observed in the foci of inflammatory cell infiltration of the myocardium in treated males at 1000 mg/kg/day .The foci of inflammatory cell infiltration of the myocardium which occurred occasionally in males of the 1000 mg/kg/day group were of spontaneous origin.
On the basis of results NOEL was predicted to be 500 mg/kg/day in male rats and 1000 mg/kg/day in female rats respectivley ,for 90 days reprotox study.
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