Silicic acid (H4SiO4), tetraethyl ester, reaction products with bis(acetyloxy)dibutylstannane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no guidline information, no glp information, study and protocol documented

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1994

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1995

Materials and methods

Principles of method if other than guideline:

Four week-old male ICR mice (SPF grade, Nippon SLC) were purchased and acclimated for 1 week. Five mice each were housed in plastic cages in filtrated air-ventilated housing for small animal breeding. Animals were maintained at 24 +/- 1°C, 60 +/- % relative humidity, and a 12-h light, 12-h dark cycle, and fed pelleted rodent chow (CRF-1, Oriental Kobo) and water ad libitum. Pure TEOS (99.999%, Kojyundo Kagaku Kenkyusho) was bubbled with dry air. The TEOS vapor was diluted with filtered room air, and introduced into a 550 l stainless steel chamber with a dynamic flow rate of 30 l/min. Groups of ten mice in stainless steel wire cages were exposed to 1000 ppm TEOS for I, 2, 4 or 8 h in the acute inhalation study, or 50, 100 and 200 ppm TEOS 6 h/day, 5 days/week, for 2 or 4 weeks in the subchronic inhalation study. During exposure, animals were fed pelleted rodent chow and water ad libitum. Control mice were exposed to filtered room air using the same type of exposure chamber. The air sample was collected from the center of the chamber, and the TEOS concentration was monitored at approximately 10-rain intervals in the acute inhalation study and 20-min intervals in the subchronic inhalation study using a gas chromatograph (163, Hitachi). At the end of daily exposure, the chamber was quickly ventilated by filtrated room air at flow rate of 150 l/rain.
The behavior and external appearance of mice were checked every day, and body weight was measured before starting TEOS exposure, during the inhalation period and in the morning during the observation period. After finishing TEOS exposure, all mice in the acute inhalation study and half those in the subchronic inhalation study were observed lbr 2 weeks. The other mice in the subchronic inhalation study were killed I day after exposure. Prior to cervical dislocation, mice were anesthetized with diethylether, and blood was collected from the axillary vessels. Red blood cells (RBC), hemoglobin (Hb), hematocrit IHt) and white blood cells {WBC) were measured using an automated blood cell counter (CC- 170. Toa lyo Denshi). The differential WBC count was determined by counting 200 Wright-Giemsa stained white blood cells under a microscope. Blood urea nitrogen (BUN), serum creatinine, asparlate aminotransferase (EC 2.6. I. I, AST). and alanine aminotransferase (EC _.6.1._+ AUF) were measured using a dry chemistry analyzer (Dry Labo 80 M, Konica). The lung, liver, kidney, spleen and pancreas were removed, and fixed with 10% buffered neutral formalin. The skull was decalcified in 10% formic acid after fixation. The organ weight was measured in the subchronic inhalation study. The organs were embedded in paraffin. sectioned, and stained with hematoxylm-eosin. One dead mouse in the group exposed for 2 h was not examined istopathologicalty because of autolysis.

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetraethyl orthosilicate

EC Number:

201-083-8

EC Name:

Tetraethyl orthosilicate

Cas Number:

78-10-4

IUPAC Name:

tetraethyl orthosilicate

Details on test material:

TEOS (99.999%, Kojyundo Kagaku Kenkyusho)

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: n.a.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

acute: 1, 2, 4, 8 h
repeated: 6d / 5 d, 2 or 4 wks

Frequency of treatment:

see duration of treatment / exposure

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
acute: 1000 ppm
Basis:
analytical conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
repeated: 50, 100, 200 ppm
Basis:
analytical conc.

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

1

Dose descriptor:

other: LC50(4h)

Effect level:

> 1 000 ppm

Based on:

test mat.

Sex:

male

2

Dose descriptor:

LOAEC

Effect level:

< 50 ppm

Based on:

test mat.

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The LOAEC is lower than 50 ppm ( 0.433 mg / L)