Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
not specified

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries, Indiana, the USA
- Age at study initiation: 35 days old
- Housing: Prior to study initiation the animals were housed in rooms, then in standard stainless steel cages.
- Diet: Purina Rat Chow, ad libitum
- Water: fresh water, ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 50 - 60 %

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: The test material was ground finely in a mortar and suspended in sesame oil.

VEHICLE
- sesame oil

The proper dose was contained in 1 ml sesame oil/ kg rat body weight/ day.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
21 days
Frequency of treatment:
Daily administration for 5 consecutive days for 3 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
10, 200, 400 mg/kg bw
Basis:
other: actual dose administered
No. of animals per sex per dose:
3 groups of 10 male and 10 female rats
Control animals:
yes
Details on study design:
- Dose selection rationale: no data

Positive control:
Not used

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice a day during the study period

BODY WEIGHT: Yes
- Time schedule for examinations: before study initiation and then every fourth day

FOOD CONSUMPRION: Yes

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination of the study
- Anaesthetic used for blood collection: Yes
- Animals fasted: No data
- How many animals:
- Parameters checked in table [No. 1] were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination of the study
- Animals fasted: No data
- How many animals: all test animals
- Parameters checked in table [No.2] were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: at termination of the study
- Metabolism cages used for collection of urine: No data
- Animals fasted: Yes, overnight
- Parameters checked in table [No.3] were examined.

Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
Dunnett's test: used for comparison of group means to control means

Results and discussion

Results of examinations

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 examined
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Increased liver weight
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
HAEMATOLOGY
Lower mean weight blood cell counts in males and females when compared to the control group at 400 mg/kg bw

CLINICAL CHEMISTRY
Increased levels of serum calcium in male and female test groups treated with 400 mg/kg bw

ORGAN WEIGHTS
Statistically significant increase in liver weights in male and female rats treated with 200 and 400 mg/kg bw of test substance. However, the liver weight change was not associated with any unusual histological findings.

Effect levels

Dose descriptor:
NOAEL
Effect level:
> 400 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects observed

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Haematologic parameters examined

Haematology

Haemoglobin levels

 

X

Haematocrit value

 

X

Platelet count

 

X

Erythrocyte count

 

X

Total and differential leucocytes count

Lymphocytes

X

Neutrophils

X

Monocytes

X

Eosinophils

X

Basophils

X

Reticulocyte counts

 

X

Table 2: Clinical blood chemistry parameters examined

Clinical blood chemistry

Serum glutamic oxalacetic transaminase

X

Serum glutamic pyruvate transaminase

X

Lactic dehydrogenase

X

Serum alkaline phosphatase

X

Serum calcium

X

Total protein

X

Total cholesterol

X

Blood urea nitrogen

X

Glucose

X

Direct and total Bilirubin

X

Creatinine

X

Triglycerides

X

Table 3: Parameters examined at urinalysis

Urinalysis

Specific gravity

X

Glucose

X

Bile pigments

X

Ketone bodies

X

Protein

X

pH

X

Calcium

X

Phosphorus

X

Table 4: Organ tissues examined at histopathology

Histopathology

Liver (medial and left lateral lobes)

X

Kidney (both)

X

Pancreas (multiple sections)

X

Brain (3 levels)

X

Heart

X

Lung

X

Gonad (both)

X

Thyroid/parathyroid

X

Spleen

X

Adrenal gland (both)

X

Pituitary

X

Bone (femur)

X

x: examined

Applicant's summary and conclusion

Conclusions:
In the 21-day oral repeated dose study, conducted according to a protocol similar to OECD test guideline 407, not compliant with GLP, the NOAEL value reported for diphenylsilanediol was >400 mg/kg bw.