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Description of key information

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:
disregarded due to major methodological deficiencies
Study period:
1970
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: no GLP; no data on test sample; early study not according to current guideline, but including basic scientific standards of performance and reporting;
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
yes
Remarks:
limited range of laboratory investigations; No FOB
GLP compliance:
no
Remarks:
predates GLP regulation
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: no data
- Weight at study initiation:m: 141g (110-167); f: 119 (98 - 134)
- Fasting period before study: no
- Housing: groups of 5
- Diet (e.g. ad libitum): ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 35 -65
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: 1969-09-17 To: 1969-10-17
Route of administration:
oral: feed
Vehicle:
not specified
Details on oral exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): no data
- Mixing appropriate amounts with (Type of food): Altromin

Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
30 days
Frequency of treatment:
continuous
Remarks:
Doses / Concentrations:
0 %
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
1 %
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
5%
Basis:
nominal in diet
No. of animals per sex per dose:
10
Control animals:
yes, plain diet
Details on study design:
- Dose selection rationale: As the testmaterial was not toxic in an acute test the highest standard dose of 5% in diet was chosen
- Rationale for animal assignment (if not random): at random

- Post-exposure recovery period: all animals : 4-7 d
- Section schedule rationale (if not random): no data
Positive control:
no
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

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: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
- Fodd consumption measured on a weekly basis

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

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: before and at the end of treatment period
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all
- Parameters were examined: Numbers of red cells, white cells, differntial white cell count; hemoglobin content

CLINICAL CHEMISTRY: No data

URINALYSIS: Yes
- Time schedule for collection of urine: before and at the end of treatment period
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked : Protein, no further data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (heart, spleen, adrenals, kidneys, lungs, liver)
Statistics:
no data
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):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
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
Dose descriptor:
NOAEL
Effect level:
>= 50 000 mg/kg diet
Based on:
test mat.
Remarks:
nominal in diet
Sex:
male/female
Basis for effect level:
other: overall effects
Critical effects observed:
not specified
Conclusions:
The treatment of rats for 30 days via diet with the testmaterial did not induce any adverse effects.
Executive summary:

Wistar-K rats were treated for 30 days via diet at concentrations of 1 and 5 % (w/w) with the testmaterial. Clinical signs, body weights, blood as well as urine were examined on a regular basis. Four to 7 days after the end of treatment all anmals were killed and examined macroscopically. Hearts, livers, lungs, kidneys, spleen and adrenal glands were investigated microscopically.

No test substance related adverse effects were detected.

The NOAEL was 50000 ppm in diet (nominal) which corresponds to about 900 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
900 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
2 (early study with limited observational battery)

Additional information

Justification for classification or non-classification