2-(3-(4-amino-9,10-dihydro-3-sulpho-9,10-dioxoanthracen-4-yl)aminobenzenesulphonyl)vinyl) disodium sulphate

Endpoint summary

Description of key information

No adverse effects were seen in rats dosed up to the limit dose of 1000 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG
- Strain: Hoe:WISKf (SPF71)
- Age at study initiation: approx. 6 weeks
- Housing: 5 rats/cage
- Diet (ad libitum): Altromin 1324
- Water (ad libitum): tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 50±20
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Preparation: daily
- Concentration in vehicle: 1.25, 5, 20% (w/v)
- Amount of vehicle (if gavage): 5 ml/kg

Details on analytical verification of doses or concentrations:

Test substance preparation was done daily and correct preparation verified by weighing documentation

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

Remarks:

Doses / Concentrations:
62.5, 250, 1000 mg/kg/day
Basis:
nominal in water

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control:

not requested

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: twice weekly

FOOD CONSUMPTION: Yes
- Time schedule: twice per week
- Calculation: food consumption/100g bw/week

WATER CONSUMPTION : Yes
- Time schedule: once weekly

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to necropsy
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: all

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: prior to necropsy
- Animals fasted: No
- How many animals: all

URINALYSIS: Yes
- Time schedule for collection of urine: overnight Day 27/28
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
ORGAN WEIGHTS: Yes
HISTOPATHOLOGY: Yes

Statistics:

Body weight and body weight gain, clinical pathology, absolute and relative organ weights, urinalysis

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food efficiency:

no effects observed

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

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

The feces of all test substance-treated animals was bue discolored from Day 4 onwards.

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Critical effects observed:

no

Conclusions:

The oral administration of the test substance at dose levels of 62.5, 250, and 1000 mg/kg body weight/day did not result in any test substance-related toxicity. Consequently, the "no toxic effect level" was considered to be 1000 mg/kg bw/day or above.

Executive summary:

The test substance was administered orally by gavage to SPF-Wistar rats over a period of 29 days (a total of 28 applications, 7 days a week) at dose levels of 0.62.5.250 or 1000 mg kg body weight. Behavior and general state of health were examined in all study groups. Body weights and food consumption were recorded twice a week, water consumption once weekly.

Hematology, clinical chemistry and urinalysis were performed at study end. During necropsy the animals were examined for macroscopically visible abnormalities, the main organs were weighed and the organ to body weight ratios calculated. Relevant organs of the animals were processed for histopathological examination and checked for microscopically visible changes.

Body weights, hematological and clinical chemistry data, albumin and globulin values, urine data (pH-value and specific weight) as well as the absolute and relative organ weights were analyzed with the aid of a statistical program to show differences compared to control groups.

 

Behavior, general state of health, body weight development as well as food and water consumption remained unaffected by the administration of the test compound.

There was no evidence for compound-related toxicity in hematology and clinical chemistry. Urine was red to red-brown discolored in all animals of the 250 and 1000 mg/kg test groups.

Evaluation of absolute and relative organ weights showed no compound-related effects.

Macroscopic and microscopic examination revealed no test compound-related adverse effects.

Summarizing, the 29-day oral administration of Reaktiv- Blau F-64 357 FW at dose levels of 62.5, 250, and 1000 mg/kg body weight/day did not result in any test substance-related toxicity. Consequently, the "no toxic effect level" was considered to be 1000 mg/kg bw/day or above.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Guideline study

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

10 male and 10 female mixed-breed healthy albino rats with a body weight range of 100 - 130 g at study start were used in a 21-day study with 14 oral administrations. The animals were housed separated by sex in groups of 5 animals per cage. The test substance was administered in aqueous solution 14-times within 21 days by gavage at a dose level of 500 mg/kg bw.

All animals were weighed weekly and in 5 animals/sex, the urine and blood was analysed at start and end of the study. There was a 5-day recovery period at the end of the study prior to necropsy.

Body weight gains were slightly retarded in the 500 mg/kg bw group when compared to control animals. There were no changes in behaviour in substance-treated animals. There were no haematological changes. Urinalysis showed a slightly increased protein excretion. The dye was excreted via feces and urine. At necropsy, no macroscopic changes were observed. Histopathologically, substance-related changes in the kidneys were observed, however these changes were assessed not to be adverse effects.

The No Observed Adverse Effect Level determined to be above 500 mg/kg bw/day.

 

The structural analogue was administered orally by gavage to SPF-Wistar rats over a period of 29 days (a total of 28 applications, 7 days a week) at dose levels of 0.62.5.250 or 1000 mg kg body weight. Behavior and general state of health were examined in all study groups. Body weights and food consumption were recorded twice a week, water consumption once weekly.

Hematology, clinical chemistry and urinalysis were performed at study end. During necropsy the animals were examined for macroscopically visible abnormalities, the main organs were weighed and the organ to body weight ratios calculated. Relevant organs of the animals were processed for histopathological examination and checked for microscopically visible changes.

Body weights, hematological and clinical chemistry data, albumin and globulin values, urine data (pH-value and specific weight) as well as the absolute and relative organ weights were analyzed with the aid of a statistical program to show differences compared to control groups.

 

Behavior, general state of health, body weight development as well as food and water consumption remained unaffected by the administration of the test compound. There was no evidence for compound-related toxicity in hematology and clinical chemistry. Urine was red to red-brown discolored in all animals of the 250 and 1000 mg/kg test groups.

Evaluation of absolute and relative organ weights showed no compound-related effects.

Macroscopic and microscopic examination revealed no test compound-related adverse effects.

Summarizing, the 29-day oral administration of the test substance at dose levels of 62.5, 250, and 1000 mg/kg body weight/day did not result in any test substance-related toxicity. Consequently, the NOAEL was considered to be 1000 mg/kg bw/day or above.

Justification for classification or non-classification

No classification necessary