Tetrasodium 4-amino-5-hydroxy-3,6-bis[[4-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]azo]naphthalene-2,7-disulphonate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

other: Data sharing dispute

Adequacy of study:

key study

Study period:

1. Feb to 1 Mar 1990

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%
- Amount of vehicle (if gavage): 5 ml/kg

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

Dosing regime: 7 days/week

Dose / conc.:

250 OB/kg bw/day (nominal)

Remarks:

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

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Remarks:

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

Dose / conc.:

62.5 mg/kg bw/day (nominal)

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: at least once daily
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 26/27
- 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:

yes

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

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

Endocrine findings:

not specified

Description (incidence and severity):

not specified

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Details on results:

Gross pathology: Reddish discoloration in kidneys and testes at 1000 mg/kg/day
Histopathology: In 2 females resorption vacuoles with dye in tubular
epithelial cells of convoluted segment of the proximal tubulus of the renal cortex at 1000 mg/kg/day

Dose descriptor:

NOEL

Effect level:

250 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: other: histopathology - resorption of dye - no toxicological adverse effect

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: 1000 mg/kg: Discoloration of excreta and organs. Renal re-absorption of dye - not considered to be toxicological relevant adverse effects.

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: other: overall effects clinical signs; mortality; body weight; food consumption; food efficiency; water consumption and compound intake; haematology; clinical chemistry; urinalysis; gross pathology; organ weights; his topathology

Critical effects observed:

not specified

Conclusions:

The oral administration of Read across substance at a dose of 1000 mg/kg body weight/day for
4 weeks resulted in microsopically visible re-absorption of the dye in the kidneys of two female
animals. There was no evidence in clinical chemistry and histopathology of an adverse effect on the
renal function. The administration of the test compound in a dose of 1000 mg/kg body weight/day
did not induce any evident relevant compound-related changes in male animals. The NOAEL was t
herefore considered to be 1000 mg/kg bw/day.

Executive summary:

In a GLP compliant study performed according to OCED guildeline 407, the read across 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 (pHvalue
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. Feces of animals of the 1000 mg/kg
test group were red discolored, beginning with day 6.
There was no evidence for compound-related toxicity in hematology and clinical chemistry. Urine was
red-brown discolored in all animals of the 1000 mg/kg test group.
Evaluation of absolute and relative organ weights showed no compound-related effects.
Necropsy revealed red discoloration of the kidneys in all animals of the 1000 mg/kg test group.
Additionally, the testes of the male animals were red discolored. Vacuolization of the epithelial cells of the
renal cortex was microscopically observed in two female animals of this test group which are considered
to be a result of an increased re-absorption and subsequent deposition of the test compound.
Summarizing, the 29-day oral administration of read across substance at a dose of 1000 mg/kg body
weight/day resulted in two female animals in microsopic renal findings as described above. There was
no evidence in clinical chemistry and histopathology of an adverse effect on the renal function. The
administration of the test compound in a dose of 1000 mg/kg body weight/day did not induce any
evident relevant compound-related changes in male animals. The NOAEL was therefore considered to
be 1000 mg/kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Experimental exposure time per week (hours/week):

4

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed