Diphenylsilanediol

Repeated dose toxicity: oral

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

Test material information

Constituent 1

Reference substance name:

000947-42-2

Cas Number:

000947-42-2

IUPAC Name:

000947-42-2

Constituent 2

Reference substance name:

Diphenylsilanediol

EC Number:

213-427-4

EC Name:

Diphenylsilanediol

Cas Number:

947-42-2

Molecular formula:

C12H12O2Si

IUPAC Name:

diphenylsilanediol

Test material form:

not specified

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system 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.