4'-aminoazobenzene-4-sulphonic acid

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

The no observed adverse effect level (NOAEL) value of the test chemical is considered to be 142.85 mg/Kg/day as no adverse effects were observed at this dose level.

Repeated dose toxicity: Inhalation

4'-aminoazobenzene-4-sulphonic acid (CAS no 104-23-4) has very low vapor pressure (1.41011576258983e-11 mmHg at 25˚C), so the potential for the generation of inhalable vapours is very low. The particle size distribution was determined to be in the range of 75 micrometer to 500 micrometer. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver

Repeated dose toxicity: Dermal

The acute toxicity value for 4'-aminoazobenzene-4-sulphonic acid (as provided in section 7.2.3) is 5823.333 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 4'-aminoazobenzene-4-sulphonic acid shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 4'-aminoazobenzene-4-sulphonic acid 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

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data from various test chemicals

Justification for type of information:

Data for the target chemical is based on data from various test chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

WoE derived based on the experimental data of various test chemicals

GLP compliance:

no

Species:

other: 1. mouse, 2. Rats, 3. Rats

Strain:

other: 1. B6C3F1, 2. Crj: CD (SD), 3. Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. TEST ANIMALS
- Source: Mixed shipments from A. R. Schmidt, Madison, Wisconsin, and from Charles River Laboratories
- Age at study initiation: Male animals were 34 days of age and females 38 days of age when placed on study
- Housing: Solid bottom stainless steel cages with clay bedding. Mice were housed seven per cage.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 40-60%
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): In addition to natural light, illumination was provided by fluorescent light for 9 hours per day

2. TEST ANIMALS
- Source: Japan SD system was carried from Charles River (Ltd.) [Crj: CD (SD)]
- Age at study initiation: 5 week old
- Weight at study initiation: male -168-183 g, female 138 162 g
- Fasting period before study: No data available.
- Housing: Housed individually in wire mesh cages
- Diet (e.g. ad libitum): Solid feed [Nosan Co., lab MR stock] ad libitum
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: Male rat 8 days ,female rat 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ℃,
- Humidity (%):55± 10%
- Air changes (per hr): 10 or more times
- Photoperiod (hrs dark / hrs light): lighting 12 hours (at 6-18)

3. TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc.
(Atsugi, Japan)
- Age at study initiation: 6 weeks
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): pelleted chow food (CRF-1, Oriental Yeast, Co., Ltd) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%):No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Route of administration:

other: 1. Feed, 2. Gavage, 3. Gavage

Vehicle:

other: 1. Wayne Lab Blox, 2. Sesame oil, 3. 1% CMC

Details on oral exposure:

1. DIET PREPARATION
- Rate of preparation of diet (frequency): Test diets were formulated every 2 weeks using finely ground Wayne Lab Blox to which was added the required amount of the test chemical for each dietary concentration
- Mixing appropriate amounts with (Type of food): A given amount of the test chemical was first hand-mixed with a small amount of feed. This mixture was then added to a larger quantity of feed to give the desired concentration of the chemical, and mixed mechanically in a twin-shell blender for not less than 10 minutes to assure homogeneity of the mixture
- Storage temperature of food: Formulated diets were stored in plastic bags at room temperature until used

2. PREPARATION OF DOSING SOLUTIONS: Administration solution, which was prepared by suspending the pharmacopoeial sesame oil (Miyazawa Pharmaceutical), was sealed stored under the cold shielding until use. Test substance drug substance and administration solution of the test substance was confirmed to be stable.

VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 0,100 ,300 and 1000 mg/kg/bw/day
- Amount of vehicle (if gavage): 0.5 ml per body weight 100 g.
- Lot/batch no. (if required): No data available.
- Purity:

3. PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with No data at dose levels of 0 or 100 mg/Kg/day

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Concentration in vehicle: 0 or 100 mg/Kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1. 108 weeks
2. 28 days
3. 28 days

Frequency of treatment:

1. Animals were fed diets containing dapsone 5 days per week, and control diets 2 days per week
2. Once a day
3. Once a day

Remarks:

Doses / Concentrations:
0, 500 or 1000 ppm (equivalent to 0, 71.42 or 142.85 mg/kg bw) / 1
Basis:
nominal in diet

Remarks:

0, 100 ,300 or 1000 mg/kg/bw/day / 2

Remarks:

0 or 100 mg/Kg/day / 3

No. of animals per sex per dose:

1. Matched control: 14 males and 14 females
500 ppm: 35 males and 35 females
1000 ppm: 35 males and 35 females

2. Total no of animals 72
0 mg/kg/bw/day- 6 male and 6 female
100 mg/kg/bw/day - 6 male and 6 female
300 mg/kg/bw/day - 6 male and 6 female
1000 mg/kg/bw/day - 6 male and 6 female
In 14 days recovery period
0 mg/kg/bw/day- 6 male and 6 female
1000 mg/kg/bw/day- 6 male and 6 female

3. Total: 8
0 mg/Kg/day: 4 male rats
100 mg/Kg/day: 4 male rats

Control animals:

yes, concurrent vehicle

Details on study design:

1. No data
2. - Dose selection rationale: A 14 days repeated oral toxicity
Study was observed in 1 group 4 males and 4 females, and the 0,100,250,500,1000 and 2000 mg / kg / day dose was
administered for 14 day daily by oral gavage.
General state, body weight, food consumption, urinalysis, hematology testing, in the blood biochemical examination and organ weight, suggest change the toxicity of the test substance was observed. In the autopsy, the cecum of expansion was observed in male and female in all cases of 2000 mg / kg group. Therefore the final dose selected for this study was 100, 300 and 1000 mg/kg/bw/day.

3. - Dose selection rationale: The administration dose for each chemical was set around their minimum carcinogenic doses for carcinogens or maximum tolerable doses based on the information in NTP and CCRIS database as well as other literatures for non-carcinogens.
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data

Positive control:

No data

Observations and examinations performed and frequency:

1. CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All animals were observed twice daily for signs of toxicity and palpated for masses at each weighing

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: yes
- Time schedule for examinations: Weighed individually each week for 8 weeks and every 2 weeks for the remainder of the study.

2. CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked in table [No.?] were included.- General behaviour

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Body weight was measured on day1 of administration (immediately before administration on the first day of administration), 3 days and thereafter twice a week, every 3 or 4 days, and on the day of slaughter.
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: Yes

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 available.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): - No data available.

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

HAEMATOLOGY: Yes
Blood collection was performed in the administration period and at the time of necropsy, the day after the end of the recovery period. Animals were excreted from 5 pm the day before blood collection and only water was fed. The collected blood was divided into three, a part of which was subjected to coagulation (prevention treatment with EDTA), and the number of red blood cells (electric resistance detection method), the number of red blood cells Hematocrit value (pulse detection method), average red blood cell volume, average red blood cell
hemoglobin amount, mean red blood cell hemoglobin concentration (calculated values), white blood cell count and platelet count (both above, electric resistance detection Method), smear samples were prepared, and reticulocyte count (Brilliant cresyl blue staining) and leukocyte% (MayGiemsa staining) were measured. In addition, a part was treated with a 3.8% sodium citrate solution to obtain plasma, and the plasma prothrombin time (Quick single step method) and activated partial thromboplastin time (elastinic acid activity Method) was measured.

CLINICAL CHEMISTRY: Yes
Serum was separated from a part of the collected blood and analyzed for total protein (Biuret method), albumin (BCG), A / G (BCG) by a biochemical automated analyzer [JEOL Ltd., JCAVX1000 type cleaner] the ratio (calculated value), blood glucose, triglycerides, total cholesterol (or more, enzymatic method), total bilirubin (Jendrassik method), urea nitrogen (UreaseUV method), creatinine (Jaff method), GOT, GPT, γGTP ( or more Sodium, potassium and chlorine were added to an alkaline phosphatase (GSCC method), calcium (OCPC method) and
inorganic phosphorus (enzymatic method) by an electrolyte automatic analyzer [Toa Denpa Kogyo Co., Ltd., NAKL1]
.
URINALYSIS: Yes
Male urine sample was received on 22 days of administration and 13 days after the administration, female’s urine sample was received on 26 or 27 days after administration and 12 days after administration finished. In order to collect the sample , rats were housed in a metabolism cage for about 3 hours .Urine sample was observed for appearance, specific gravity , pH, occult blood, proteins, sugar, ketone bodies, bilirubin, urobilinogen [all of these, Martistics, Miles • Sankyo Co., Ltd.] and sediment (stained with URICEL solution, Cambridge Chemical Products Co.) .

NEUROBEHAVIOURAL EXAMINATION: No data available.

OTHER:

3. CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

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

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

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- 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: No data
- 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. No data

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: No data

Sacrifice and pathology:

1. GROSS PATHOLOGY: Yes
Gross examination of major tissues, major organs, and all gross lesions from killed animals and from animals found dead
HISTOPATHOLOGY: Yes
The following tissues were examined microscopically: skin, muscle, lungs and bronchi, trachea, bone and bone marrow, spleen, lymph nodes, thymus, heart, salivary gland, liver, gallbladder and bile duct (mice), pancreas, esophagus, stomach, small intestine, large intestine, kidney, urinary bladder, pituitary, adrenals thyroid, parathyroid, mammary gland, prostate or uterus, testis or ovary, brain and sensory organs. Peripheral blood smears were prepared from each animal.

2. GROSS PATHOLOGY: Yes
Organ weight was observed for following organs- brain, heart, thymus, liver, kidney, spleen, adrenal glands, testis, epididymis and ovaries.
HISTOPATHOLOGY: Yes
Histopathological examination was performed by fixing the organs in 10% neutral phosphate buffered formalin solution.
In control group and 1000 mg / kg/day group, the brain, pituitary, eyeball, thyroid (including parathyroid gland), thymic gland, The pancreas, the testicle, the epididymis, the seminal vesicle, the prostate, the ovary, the uterus (cyst), the trachea, the lung, the liver, the kidney, the spleen, the adrenal gland, the stomach, the small intestine (duodenum jejunum ileal) , Vagina, bladder, lymph node (cervical lymph node / mesenteric lymph node), spinal cord (neck enlarged part • hip swollen part), sciatic nerve, bone marrow were examined. In addition, since thymus weight was changed in females of 100 mg / kg group, 100 and 300 mg / kg group was also examined for female thymus. In the examination, paraffin sections were prepared by a conventional method and subjected to microscopic examination with haematoxylineosin staining.

3. GROSS PATHOLOGY: Yes, Rats were humanly sacrificed with CO2-O2 (4:1) gas inhalation at 3, 14 or 28 days after administration. The livers were immediately excised and weighed

HISTOPATHOLOGY: Yes, A portion of the left lateral lobe was also taken for histopathology. Tissues were fixed in 10% neutral-buffered formalin, and subsequently sectioned and stained with hematoxylin and eosin.

Other examinations:

No data

Statistics:

1. Probabilities of survival were estimated by the product-limit procedure of Kaplan and Meier.
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 methods for testing for a dose-related trend.

2. Statistics was observed by Dunnett's multiple comparison tests in administration group while in recovery group it is measured by T-test and U-test.

3. No data

Clinical signs:

no effects observed

Description (incidence and severity):

2. No significant change were observed in the clinical sign at dose level of 100, 300 and 1000 mg/kg/bw/day in treated group compare to control both in administration and recovery group.

Mortality:

no mortality observed

Description (incidence):

1. The test chemical did not adversely affect the survival of mice. Several control males died early in the study, while survival of the other groups of mice was not affected until week 75.

2. Mortality was not observed at all dose level in treated group both in administration and recovery group.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

1. Lower body weights in males

2. No significant change were observed in the body weight at dose level of 100, 300 and 1000 mg/kg/bw/day in treated group compare to control both in administration and recovery group.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

2. No significant change were observed in the food consumption at dose level of 100, 300 and 1000 mg/kg/bw/day in treated group compare to control both in administration and recovery group.

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

2. Significant decrease in white blood cell count was observed in males in the 1000 mg / kg treated group compare to control. Decrease in white blood cell count was mainly due to the decrease in lymphocytes in view of the percentage of white blood cells. There was no significant change in white blood cell count in the recovery group of 1000 mg / kg /day treated group.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

2. Significant decrease in total cholesterol was observed in male at dose level of 1000 mg / kg/day group.

Significant increase in GPT was observed in females while significant decreases in blood glucose were observed in females in the 100 and 1000 mg / kg groups.

Reduction in blood glucose was observed in the 1000 mg / kg/ day treated group compare to control group. In the 1000 mg / kg recovery group, such changes were not observed, and were recovered.

Urinalysis findings:

effects observed, treatment-related

Description (incidence and severity):

2. Significant increase in specific gravity and decrease in pH were observed in males at the dose level of 1000 mg/kg/day in treated group compare to control both in administration and recovery group.

Behaviour (functional findings):

not examined

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

2. Significant decrease in the absolute and relative weights of the thymus was found in females in the 100 mg / kg/day treated group compare to control.
A significant increase in the relative weight of the spleen was observed in the females of each group (100, 300 and 1000 mg/kg/bw/day) treated with the test substance .But when dose and organ weight were correlated, No specific change was observed in result.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

1. In the males, alveolar/bronchiolar adenoma was observed in 5/33 low-dose animals. Similar tumors were not observed in female mice.

2. Mild dilatation due to cecal contents retention was observed at dose level of 1000 mg / kg/day of treated group compare to control. There was no change in the cecum in the recovery group of 1000 mg / kg.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

2. Mild changes in the lung, liver, pancreas, kidney and prostate were observed in the control group and 1000 mg / kg/day group, but findings were dose independent.

3. No histological abnormalities

Histopathological findings: neoplastic:

not examined

Other effects:

not specified

Details on results:

Gross pathology: In the males, alveolar/bronchiolar adenoma was observed in 5/33 low-dose animals. Although significant when compared with pooled controls, the tumors cannot clearly be associated with treatment, because of the low incidence in the low-dose group, and because only one tumor was found in the high-dose group. Similar tumors were not observed in female mice

Dose descriptor:

NOAEL

Remarks:

1

Effect level:

142.85 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed

Dose descriptor:

NOAEL

Remarks:

2

Effect level:

300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effects were noted at the mentioned dose level

Dose descriptor:

NOAEL

Remarks:

3

Effect level:

100 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significat effects were noted at the mentioned dose level

Critical effects observed:

not specified

Conclusions:

The no observed adverse effect level (NOAEL) value of the test chemical is considered to be 142.85 mg/Kg/day as no adverse effects were observed at this dose level.

Executive summary:

Data available for the test chemicals were reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:

The test chemical is the parent chemical of the sulfone drugs, and the major therapeutic agent in this group for the treatment of leprosy. This test chemical was selected for screening by the carcinogenesis program in an attempt to evaluate the carcinogenicity of certain drugs that are used extensively and for prolonged periods in humans. The test chemical was administered in diet to B6C3F1 mice at dose levels of 500 or 1000 ppm for 78 weeks and a further observation period of 28-30 weeks was provided. The test chemical did not adversely affect the survival of mice. Several control males died early in the study, while survival of the other groups of mice was not affected until week 75. In the males, alveolar/bronchiolar adenoma was observed in 5/33 low-dose animals. Although significant when compared with pooled controls, the tumors cannot clearly be associated with treatment, because of the low incidence in the low-dose group, and because only one tumor was found in the high-dose group. Similar tumors were not observed in female mice. Based on the observations made, the no observed adverse effect level (NOAEL) value of the test chemical is considered to be 1000 ppm (142.85 mg/Kg/day) for B6C3F1 mice, as no adverse effects were observed at this dose level.

 

28 days repeated dose toxicity study for the test chemical was determined in male and female Crj: CD (SD) rats when they were exposed in a concentration of 0, 100, 300 and 1000mg/ kg /day for 28 days by oral gavage. There was recovery period of 14 days in control and 1000 mg/kg/day group. No significant change were observed in mortality, clinical sign, body weight food consumption at dose level of 100 ,300 and 1000 mg/kg/bw/day in treated group compare to control. Significant change were observed in the haematology , clinical chemistry and urine analysis , organ weight and gross pathology and histopathology at dose level of 1000 mg/kg/day of treated group. These changes were not recovered during recovery period. No significant changes were observed at the dose level of 300 mg/kg/day. Therefore the No Observed Adverse Effect Level (NOAEL) was considered to be 300 mg/kg/day for the test chemiical in male and female Crj: CD (SD) rats during 28 days repeated dose toxicity study.

Combined repeated dose & carcinogenicity study was performed to determine the toxic nature of the test chemical. The study was performed using 6 week old male F344 rats in a 28 days study. The test chemical was mixed with 1% CMC and used at dose level of 0 or 100 mg/Kg/day. Rats were humanly sacrificed with CO2-O2 (4:1) gas inhalation at 3, 14 or 28 days after administration. The livers were immediately excised and weighed. Tissues were fixed in 10% neutral-buffered formalin, and subsequently sectioned and stained with hematoxylin and eosin. No histological abnormalities were noted due to test chemical treatment. The No Observed Adverse Effect Level (NOAEL) for the test chemical is considered to be 100 mg/kg/day.

Based on the observations made, the no observed adverse effect level (NOAEL) value of the test chemical is considered to be 142.85 mg/Kg/day as no adverse effects were observed at this dose level.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

142.85 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is from company data

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation, other

Data waiving:

other justification

Justification for data waiving:

other:

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

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Data available for the test chemicals were reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:

The test chemical is the parent chemical of the sulfone drugs, and the major therapeutic agent in this group for the treatment of leprosy. This test chemical was selected for screening by the carcinogenesis program in an attempt to evaluate the carcinogenicity of certain drugs that are used extensively and for prolonged periods in humans. The test chemical was administered in diet to B6C3F1 mice at dose levels of 500 or 1000 ppm for 78 weeks and a further observation period of 28-30 weeks was provided. The test chemical did not adversely affect the survival of mice. Several control males died early in the study, while survival of the other groups of mice was not affected until week 75. In the males, alveolar/bronchiolar adenoma was observed in 5/33 low-dose animals. Although significant when compared with pooled controls, the tumors cannot clearly be associated with treatment, because of the low incidence in the low-dose group, and because only one tumor was found in the high-dose group. Similar tumors were not observed in female mice. Based on the observations made, the no observed adverse effect level (NOAEL) value of the test chemical is considered to be 1000 ppm (142.85 mg/Kg/day) for B6C3F1 mice, as no adverse effects were observed at this dose level.

 

28 days repeated dose toxicity study for the test chemical was determined in male and female Crj: CD (SD) rats when they were exposed in a concentration of 0, 100, 300 and 1000mg/ kg /day for 28 days by oral gavage. There was recovery period of 14 days in control and 1000 mg/kg/day group. No significant change were observed in mortality, clinical sign, body weight food consumption at dose level of 100 ,300 and 1000 mg/kg/bw/day in treated group compare to control. Significant change were observed in the haematology , clinical chemistry and urine analysis , organ weight and gross pathology and histopathology at dose level of 1000 mg/kg/day of treated group. These changes were not recovered during recovery period. No significant changes were observed at the dose level of 300 mg/kg/day. Therefore the No Observed Adverse Effect Level (NOAEL) was considered to be 300 mg/kg/day for the test chemiical in male and female Crj: CD (SD) rats during 28 days repeated dose toxicity study.

Combined repeated dose & carcinogenicity study was performed to determine the toxic nature of the test chemical. The study was performed using 6 week old male F344 rats in a 28 days study. The test chemical was mixed with 1% CMC and used at dose level of 0 or 100 mg/Kg/day. Rats were humanly sacrificed with CO2-O2 (4:1) gas inhalation at 3, 14 or 28 days after administration. The livers were immediately excised and weighed. Tissues were fixed in 10% neutral-buffered formalin, and subsequently sectioned and stained with hematoxylin and eosin. No histological abnormalities were noted due to test chemical treatment. The No Observed Adverse Effect Level (NOAEL) for the test chemical is considered to be 100 mg/kg/day.

Based on the observations made, the no observed adverse effect level (NOAEL) value of the test chemical is considered to be 142.85 mg/Kg/day as no adverse effects were observed at this dose level.

Repeated dose toxicity: Inhalation

4'-aminoazobenzene-4-sulphonic acid (CAS no 104-23-4) has very low vapor pressure (1.41011576258983e-11 mmHg at 25˚C), so the potential for the generation of inhalable vapours is very low. The particle size distribution was determined to be in the range of 75 micrometer to 500 micrometer. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver

Repeated dose toxicity: Dermal

The acute toxicity value for 4'-aminoazobenzene-4-sulphonic acid (as provided in section 7.2.3) is 5823.333 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 4'-aminoazobenzene-4-sulphonic acid shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 4'-aminoazobenzene-4-sulphonic acid shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Based on the data available for the various test chemicals and applying the weight of evidence approach, the test chemical is not likely to be toxic upon repeated exposure by oral, dermal and inhalation toute of exposure.

Justification for classification or non-classification

Based on the data available for the various test chemicals and applying the weight of evidence approach, the test chemical is not likely to be toxic upon repeated exposure by oral, dermal and inhalation toute of exposure.