Silane

Endpoint summary

Description of key information

There is one study (Omae et al., 1992, Reliability score 2) for repeated dose inhalation of silane (CAS 7803-62-5; EC No. 232-263-4) conducted using a protocol similar to OECD Test Guideline 412 (no information on GLP status) in male ICR mice. Following exposure for 6 hours/day, 5 days/week for four weeks to 1000 ppm silane, no adverse effects were recorded. Therefore, the NOAEC was considered to be ≥1000 ppm (≥1310 mg/m3).  There are no oral or dermal repeated dose toxicity studies.

There is one study (Omae et al., 1992, Reliability score 2) for repeated dose inhalation of silane conducted using a protocol similar to OECD Test Guideline 412 (no information on GLP status) in male ICR mice. Following exposure for 6 hours/day, 5 day/week for four weeks to 1000 ppm silane, no adverse effects were recorded. Therefore, the NOAEC was considered to be ≥1000 ppm (≥1310 mg/m³). There are no oral or dermal repeated dose toxicity studies.

There is one study (Omae et al., 1992, Reliability score 2) for repeated dose inhalation of silane conducted using a protocol similar to OECD Test Guideline 412 (no information on GLP status) in male ICR mice. Following exposure for 6 hours/day, 5 day/week for four weeks to 1000 ppm silane, no adverse effects were recorded. Therefore, the NOAEC was considered to be ≥1000 ppm (≥1310 mg/m³). There are no oral or dermal repeated dose toxicity studies.

There is one study (Omae et al., 1992, Reliability score 2) for repeated dose inhalation of silane conducted using a protocol similar to OECD Test Guideline 412 (no information on GLP status) in male ICR mice. Following exposure for 6 hours/day, 5 day/week for four weeks to 1000 ppm silane, no adverse effects were recorded. Therefore, the NOAEC was considered to be ≥1000 ppm (≥1310 mg/m³). There are no oral or dermal repeated dose toxicity studies.

There is one study (Omae et al., 1992, Reliability score 2) for repeated dose inhalation of silane conducted using a protocol similar to OECD Test Guideline 412 (no information on GLP status) in male ICR mice. Following exposure for 6 hours/day, 5 day/week for four weeks to 1000 ppm silane, no adverse effects were recorded. Therefore, the NOAEC was considered to be ≥1000 ppm (≥1310 mg/m³). There are no oral or dermal repeated dose toxicity studies.

There is one study (Omae et al., 1992, Reliability score 2) for repeated dose inhalation of silane conducted using a protocol similar to OECD Test Guideline 412 (no information on GLP status) in male ICR mice. Following exposure for 6 hours/day, 5 day/week for four weeks to 1000 ppm silane, no adverse effects were recorded. Therefore, the NOAEC was considered to be ≥1000 ppm (≥1310 mg/m³). There are no oral or dermal repeated dose toxicity studies.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

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

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

Only males and one concentration used. No urinalysis. Food and water consumption not measured.

GLP compliance:

not specified

Limit test:

no

Species:

mouse

Strain:

ICR

Details on species / strain selection:

None specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan
- Age at study initiation: Five weeks
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: Five animals per transparent plastic cages with stainless steel wire-lined ceilings.
- 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

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Animals were exposed in a tightly sealed 550 l stainless steel inhalation chamber with glass windows.
- Method of holding animals in test chamber: None
- Source and rate of air: filtered room air (no further details)
- Method of conditioning air: HEPA filter (no further details)
- Temperature, humidity, pressure in air chamber: No data
- Air flow rate: No data
- Air change rate: No data
- Treatment of exhaust air:


TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography (no further details)
- Samples taken from breathing zone: no data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Silane concentrations were monitored at ten minute intervals using a gas chromatograph.

Duration of treatment / exposure:

14 or 28 days

Frequency of treatment:

Six hours/day, five days/week

Remarks:

Doses / Concentrations:
1000 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

Ten males

Control animals:

yes

Details on study design:

- Dose selection rationale: 1) the concentration was 200 or 2000 times higher than the recommended TWA exposure limits by many countries, 2) sufficient to adversely affect the health of the mice, 3) the effect of oxygen deficiency on the mice would not need to be taken into account.
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No satellite groups
- Post-exposure recovery period in satellite groups: No post-exposure recovery group
- Section schedule rationale (if not random): No data

Positive control:

None

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: Body weights were monitored for several days before exposure. The schedule during exposure was not reported.


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: Assumed to be prior to sacrifice, but not stated in report.
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: All
- Parameters checked in table 1 were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Assumed to be prior to sacrifice, but not stated in report.
- Animals fasted: No data
- How many animals: All
- Parameters checked in table 1 were examined.


URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

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

Statistics:

No information.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Immediately after being exposed to silane on each day of exposure, most mice began to perform face washing movements and lick the lower abdomen for short periods.

Mortality:

mortality observed, treatment-related

Description (incidence):

There were no deaths.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Average daily weight gains (ADWG) from Monday morning to Friday morning (four days exposure) were always smaller in exposed than nonexposed mice, but were not statistically significant. ADWG from Friday morning to Monday morning (one day of exposure and two days nonexposure), was greater in exposed than nonexposed mice (statistically significant in 3/4 week) (see Table 3).

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

Description (incidence and severity):

White blood cell counts, lymphocytes, and nonsegmented neutrophils were increased significantly in animals exposed for four weeks (see Table 4).

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

There were no effects on organ weights.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Mucous exudates and inflammatory and/or necrotic cells were observed in the nasal cavity more frequently in mice exposed for four weeks than in nonexposed mice, but the changes were mild.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Key result

Dose descriptor:

NOAEC

Effect level:

> 1 000 ppm

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No significant adverse effects.

Critical effects observed:

not specified

Table 3 Average daily weight gain (Friday to Monday morning)

	Week 1 -2 (n=20)	Week 2 -3 (n=10)	Week 3 -4 (n=10)
Exposed	0.35 ± 0.26	0.44 ± 0.25	0.59 ± 0.17*
Nonexposed	0.46 ± 0.14	0.47 ± 0.14	0.27 ± 0.17

*p<0.01

Table 4 Summary of haemaology results.

Parameter	Nonexposed	Exposed
Alkaline phosphatase	56 ± 12	52.± 12
Aspartate aminotransferase	69 ± 22	61 ± 14
Alanine aminotransferase	19 ± 6	23 ± 10
Cholinesterase	364 ± 96	376 ± 87
Blood urea nitrogen	40 ± 5	35 ± 9
Sodium	167 ± 3	168 ± 5
Potassium	6.3 ± 1.4	7.1 ± 1.6
Red blood cell	926 ± 46	951 ± 54
White blood cell	25 ± 9	40 ± 14*
Stab	0.5 ± 0.2	1.1 ± 0.6*
Steg	5.2 ± 2.2	5.5 ± 1.9
Lymphocytes	19.2 ± 8.2	32.9 ± 13.6*
Monocytes	0.1 ± 0.1	0.2 ± 0.3

*p<0.05

Taken from publication - no further details, such as units.

Conclusions:

In a well conducted 14/28 day inhalation study (reliability score 2; no information on GLP status) conducted using a protocol similar to OECD 412, the NOAEL was greater than 1000 ppm (6 h/d, 5d/wk; the only concentration tested).

Executive summary:

In a well conducted 14/28 day inhalation study (reliability score 2; no information on GLP status) conducted using a protocol similar to OECD Test Guideline 412, male ICR mice (n=10/group) were exposed to 1000 ppm silane for 6 hours/day, 5 days/week for 4 weeks. These treatments did not induce mortality. Mild irritation manifested in the form of a small amount of exudate in 8/10 animals and inflammation and/or necrosis of the cells of the nasal mucosa were observed in 6/10 animals. No histopathological changes were observed in the trachea, lung or cornea. Regarding haematology/biochemical parameters, there was a statistically significant increase in white blood cell (lymphocytes and neutrophils only) counts. The NOAEC was therefore greater than 1000 ppm.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

1 310 mg/m³

Study duration:

subacute

Species:

mouse

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

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

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

Only males and one concentration used. No urinalysis. Food and water consumption not measured.

GLP compliance:

not specified

Limit test:

no

Species:

mouse

Strain:

ICR

Details on species / strain selection:

None specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan
- Age at study initiation: Five weeks
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: Five animals per transparent plastic cages with stainless steel wire-lined ceilings.
- 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

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Animals were exposed in a tightly sealed 550 l stainless steel inhalation chamber with glass windows.
- Method of holding animals in test chamber: None
- Source and rate of air: filtered room air (no further details)
- Method of conditioning air: HEPA filter (no further details)
- Temperature, humidity, pressure in air chamber: No data
- Air flow rate: No data
- Air change rate: No data
- Treatment of exhaust air:


TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography (no further details)
- Samples taken from breathing zone: no data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Silane concentrations were monitored at ten minute intervals using a gas chromatograph.

Duration of treatment / exposure:

14 or 28 days

Frequency of treatment:

Six hours/day, five days/week

Remarks:

Doses / Concentrations:
1000 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

Ten males

Control animals:

yes

Details on study design:

- Dose selection rationale: 1) the concentration was 200 or 2000 times higher than the recommended TWA exposure limits by many countries, 2) sufficient to adversely affect the health of the mice, 3) the effect of oxygen deficiency on the mice would not need to be taken into account.
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No satellite groups
- Post-exposure recovery period in satellite groups: No post-exposure recovery group
- Section schedule rationale (if not random): No data

Positive control:

None

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: Body weights were monitored for several days before exposure. The schedule during exposure was not reported.


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: Assumed to be prior to sacrifice, but not stated in report.
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: All
- Parameters checked in table 1 were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Assumed to be prior to sacrifice, but not stated in report.
- Animals fasted: No data
- How many animals: All
- Parameters checked in table 1 were examined.


URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

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

Statistics:

No information.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Immediately after being exposed to silane on each day of exposure, most mice began to perform face washing movements and lick the lower abdomen for short periods.

Mortality:

mortality observed, treatment-related

Description (incidence):

There were no deaths.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Average daily weight gains (ADWG) from Monday morning to Friday morning (four days exposure) were always smaller in exposed than nonexposed mice, but were not statistically significant. ADWG from Friday morning to Monday morning (one day of exposure and two days nonexposure), was greater in exposed than nonexposed mice (statistically significant in 3/4 week) (see Table 3).

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

Description (incidence and severity):

White blood cell counts, lymphocytes, and nonsegmented neutrophils were increased significantly in animals exposed for four weeks (see Table 4).

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

There were no effects on organ weights.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Mucous exudates and inflammatory and/or necrotic cells were observed in the nasal cavity more frequently in mice exposed for four weeks than in nonexposed mice, but the changes were mild.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Key result

Dose descriptor:

NOAEC

Effect level:

> 1 000 ppm

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No significant adverse effects.

Critical effects observed:

not specified

Table 3 Average daily weight gain (Friday to Monday morning)

	Week 1 -2 (n=20)	Week 2 -3 (n=10)	Week 3 -4 (n=10)
Exposed	0.35 ± 0.26	0.44 ± 0.25	0.59 ± 0.17*
Nonexposed	0.46 ± 0.14	0.47 ± 0.14	0.27 ± 0.17

*p<0.01

Table 4 Summary of haemaology results.

Parameter	Nonexposed	Exposed
Alkaline phosphatase	56 ± 12	52.± 12
Aspartate aminotransferase	69 ± 22	61 ± 14
Alanine aminotransferase	19 ± 6	23 ± 10
Cholinesterase	364 ± 96	376 ± 87
Blood urea nitrogen	40 ± 5	35 ± 9
Sodium	167 ± 3	168 ± 5
Potassium	6.3 ± 1.4	7.1 ± 1.6
Red blood cell	926 ± 46	951 ± 54
White blood cell	25 ± 9	40 ± 14*
Stab	0.5 ± 0.2	1.1 ± 0.6*
Steg	5.2 ± 2.2	5.5 ± 1.9
Lymphocytes	19.2 ± 8.2	32.9 ± 13.6*
Monocytes	0.1 ± 0.1	0.2 ± 0.3

*p<0.05

Taken from publication - no further details, such as units.

Conclusions:

In a well conducted 14/28 day inhalation study (reliability score 2; no information on GLP status) conducted using a protocol similar to OECD 412, the NOAEL was greater than 1000 ppm (6 h/d, 5d/wk; the only concentration tested).

Executive summary:

In a well conducted 14/28 day inhalation study (reliability score 2; no information on GLP status) conducted using a protocol similar to OECD Test Guideline 412, male ICR mice (n=10/group) were exposed to 1000 ppm silane for 6 hours/day, 5 days/week for 4 weeks. These treatments did not induce mortality. Mild irritation manifested in the form of a small amount of exudate in 8/10 animals and inflammation and/or necrosis of the cells of the nasal mucosa were observed in 6/10 animals. No histopathological changes were observed in the trachea, lung or cornea. Regarding haematology/biochemical parameters, there was a statistically significant increase in white blood cell (lymphocytes and neutrophils only) counts. The NOAEC was therefore greater than 1000 ppm.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

1 310 mg/m³

Study duration:

subacute

Species:

mouse

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is one repeated dose toxicity study (Omae et al., 1992, reliability score 2) available for the inhalation of silane. In this study, which was similar to OECD Test Guideline 412, groups of 10 male ICR mice were exposed to 1000 ppm silane for 6 hours/day, 5 days/week for four weeks. These treatments did not induce mortality. Mild irritation manifested in the form of a small amount of exudate in 8/10 animals and inflammation and/or necrosis of cells of the nasal mucosa were observed in 6/10 animals. No histopathological changes were observed in the trachea, lung or cornea. There was also a statistically significant increase in white blood cell (lymphocytes and neutrophils only) counts. None of these changes were considered to be adverse and therefore the No-Observed-Adverse-Effect-Concentration (NOAEC) was ≥1000 ppm (1310 mg/m³). There are no oral or dermal repeated dose toxicity studies.

Justification for classification or non-classification

Based on the available repeated dose toxicity data silane does not require classification for Specific Target Organ Toxicity following repeat exposure (STOT RE) according to Regulation (EC) 1272/2008.