Tetrapropyl orthosilicate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was well documented and meets generally accepted scientific principles, but there was no information on whether the study was conducted in compliance with GLP.

Data source

Reference

Reference Type:

review article or handbook

Title:

No-effect level of subacute tetraethoxysilane inhalation on the mouse kidney.

Author:

Omae K, Nakashima H, Takebayashi T, Uemura T, Ishizuka C, Yamazaki K, Sakurai H

Year:

1995

Bibliographic source:

Journal of occupational health, 37(1): pp. 1-4; Jan 1995.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

yes

Remarks:

limited examinations, males only, limited information on exposure conditions.

GLP compliance:

not specified

Limit test:

no

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:

- Name of test material (as cited in study report): tetraethoxy silane
- Analytical purity: 99.99%
No further details available.

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan, Inc.
- Age at study initiation: Four weeks
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: Five per transparent plastic cages with stainless steel wire mesh ceiling.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: One week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 60
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: No data

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- tetraethyl orthosilicate was supplied from an organic solvent vapour generator.
No further details available.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Monitored at 10 minute intervals by means of a gas chromatograph.

Duration of treatment / exposure:

6 hours/day for 2 or 4 weeks

Frequency of treatment:

5 days/week

Doses / concentrations

Remarks:

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

No. of animals per sex per dose:

10 males

Control animals:

other: filtered room air

Details on study design:

- Dose selection rationale: No data
- Rationale for animal assignment (if not random): Random
- Rationale for selecting satellite groups: No satellite groups
- Post-exposure recovery period in satellite groups: No post-exposure recovery period

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Behaviour and external appearance checked daily.


DETAILED CLINICAL OBSERVATIONS: No


BODY WEIGHT: Yes
- Time schedule for examinations: Weighed on Monday, Wednesday and Friday prior to exposure.


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No


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


WATER CONSUMPTION: No


OPHTHALMOSCOPIC EXAMINATION: No


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


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table No.1 were examined.


URINALYSIS: Yes
- Time schedule for collection of urine: Every Friday
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No data
- Parameters checked in table No.1 were examined.


NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see table 2)
HISTOPATHOLOGY: Yes (see table 2)

Statistics:

Student's t test or Welch's methods were adopted for the statistical test of difference between means of the effects indices.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY: No mice died during either inhalation study.  Immediately after being exposed to TEOS on each day of exposure, most mice began to perform face-washing movements and lick the lower abdomen for short periods more frequently than non-exposed mice.


BODY WEIGHT AND WEIGHT GAIN: No differences were observed between the exposed and non-exposed groups in body weight gain.


HAEMATOLOGY: RBC, Hb and Ht values were lower in exposed mice than in non-exposed mice (see Table 3).


CLINICAL CHEMISTRY: No adverse findings.


URINALYSIS: No adverse findings.


ORGAN WEIGHTS: No significant changes.


GROSS PATHOLOGY: No findings reported.


HISTOPATHOLOGY: No lesions were observed in the liver, lungs, respiratory  tract, spleen, pancreas, thymus, thyroid or cornea. In the kidney, 2/10  
mice exposed to 100 ppm for 2 weeks and 2/10 mice exposed to 100 ppm for 4 weeks developed histopathological lesions (tubulo-interstitial  
nephritis). Inflammation of the nasal mucosa was observed in almost all of the mice exposed to 100 ppm or 50 ppm for 2 or 4 weeks. The findings were slightly more severe in the mice exposed to 100 ppm. No kidney lesions or renal function changes were observed in mice exposed to 50 ppm.  

Effect levels

Dose descriptor:

LOAEL

Effect level:

50 ppm

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 3 Summary of haematological findings following two and four weeks exposure.

Exposure Concentration (ppm)	Two week exposure			Four week exposure
	100	50	0	100	50	0
RBC (x10000/µ l)	823± 60*	866± 51	895± 60	840± 39	815± 36*	859± 35
Hg (g/dl)	-	-	-	14.1± 0.5*	13.7± 0.5**	14.7± 0.6
Ht (%)	42.9± 3.2**	45.1± 2.7	47.5± 3.2	43.1± 1.4	42.3± 1.6**	44.6± 1.8
WBC (x100 µ l)	-	-	-	36± 13	21± 6	28± 14
Neutrophil (%)	30± 10**	27± 5*	13± 7	34± 9	24± 11	25± 18
Lymphocyte (%)	68± 10**	72± 5**	85± 7	64± 9	75± 12	74± 19

Table 4 Number of mice with significant histopathological findings on the kidney and nasal cavity.

Exposure concentration (ppm)	100		50		0
Exposure duration (weeks)	2	4	2	4	2	4
Kidney TIN	2	2	0	0	0	0
Nasal cavity
SIN	10	10	7	10	0	0
All positive findings	10	10	9	10	0	0

TIN: tubulo-interstitial nephritis.

SIN: submucosal infiltration of neutrophilic leukocytes.

Applicant's summary and conclusion

Conclusions:

In a repeated inhalation study which was similar to OECD 412 (reliabilty score 2; no information on GLP status) the LOAEC for tetraethoxysilane was 50 ppm in mice, based on haematological changes. Effects on the kidney were observed at 100ppm when exposure was over two or four weeks. There were also signs of irritation in the nasal mucosa.

Executive summary:

In a repeated inhalation study which was similar to OECD 412 (reliabilty score 2; no information on GLP status) the LOAEC for tetraethoxysilane was 50 ppm in mice, based on haematological changes. Effects on the kidney were observed at 100 ppm when exposure was over two or four weeks. There were also signs of irritation in the nasal mucosa.