Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
see below

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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

Administration / exposure

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
Doses / concentrations
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

Examinations

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

Results and discussion

Results of examinations

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.

Effect levels

Key result
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food efficiency
haematology
clinical biochemistry
urinalysis
behaviour (functional findings)
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic

Target system / organ toxicity

Critical effects observed:
no

Applicant's summary and conclusion

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.