Dichloro(methyl)silane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09/09/1998 to 22/08/2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 1b The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dichloro(methyl)silane

EC Number:

200-877-1

EC Name:

Dichloro(methyl)silane

Cas Number:

75-54-7

Molecular formula:

CH4Cl2Si

IUPAC Name:

dichloro(methyl)silane

Details on test material:

- Name of test material (as cited in study report): Methylhydrogendichlorosilane
- Substance type: chlorosilane
- Physical state: Colourless liquid
- Analytical purity: > 99%
- Purity test date: No data
- Lot/batch No.: Several
- Expiration date of the lot/batch: No data
- Stability under test conditions: Not stable
- Storage condition of test material: dry inert atmosphere

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: Approximately seven-week old
- Weight at study initiation: 141-217 grams (males) and 120-154 grams (females) 
- Fasting period before study: No
- Housing: Individually in suspended wire-mesh cages
- Diet (e.g. ad libitum): ad libitum (except during exposure)
- Water (e.g. ad libitum): ad libitum (except during exposure)
- Acclimation period: Seven days quarantine, but no acclimitisation period


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±4
- Humidity (%): 30-70
- Air changes (per hr): 44-48
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 19.10.1998 To: 13.06.2000

Administration / exposure

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: Barrel shaped PVC chamber with plexiglass lid
- Exposure chamber volume: 175 litre
- Method of holding animals in test chamber: The animals were loaded into the exposure caging using a staggered by sex arrangement. This exposure caging was circular and divided into approximately 10 equally sized pie-shaped sections. Cage diameter was 21 inches and 6 inches heigh.
- Source and rate of air: Room air, 46 chamber volumes per hour
- Method of conditioning air: Filtered with a series of Balston filters
- Treatment of exhaust air: Not treated
- Temperature, humidity, pressure in air chamber: slight negative pressure


TEST ATMOSPHERE
- Brief description of analytical method used: GC/MSD
- Samples taken from breathing zone: no data

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC/MSD

Duration of exposure:

1 h

Remarks on duration:

(after equilibration, T90 = 6 minutes)

Concentrations:

1431, 1678 and 1889 ppm (nominal)

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations immediately after exposure and then daily, body weights recorded on days 1 (prior to exposure), 3, 8 and 15
- Necropsy of survivors performed: yes

Statistics:

LD50 values were calculated by Probit Analysis.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 785 ppm

95% CL:

> 1 671 - < 1 963

Exp. duration:

1 h

Remarks on result:

other: Based on nominal concentrations

Mortality:

See table below

Clinical signs:

other: The principal clinical signs were indicative of respiratory and ocular effects.  Labored breathing, gasping and rales were seen in all rats, first noted on the day of exposure and often persisting until well into the observation period (or until death). 

Body weight:

Significant body weight losses were observed on day 8, but there was marked recovery in those animals that survived.

Gross pathology:

Among rats that survived, the predominant necropsy findings were associated with extensive ocular damage (opacity, hemorrhage, ruptured, shrunken, ulcerated, exudate in chambers), seen in 17/20 survivors (all groups).  In addition, 11/20 survivors (all groups) had varying degrees of alopecia of the eyelids/peri-ocular areas.  Discolored and consolidated lungs were each seen in one 1678 ppm male.  Missing tissue from the nose pad/nares was noted for two survivors.  There were no other remarkable necropsy findings in rats that survived to the scheduled necropsy. All rats that died exhibited abnormalities of the nose (obstructed, encrusted, missing tissue, dried/firm), eyes (opacity, ulceration, external encrustation) and gastrointestinal tract (gaseous distension, hemorrhage, ulcers, abnormal contents, reduced ingesta).  In addition, all dead rats had reduced or absent body fat and various external staining/soiling.  Spleens of decreased size were present in 9/10 rats that died.  Seven dead rats were observed to be dehydrated and five had lung abnormalities (mottled, congested, failed to collapse, atelectisis).  Epididymides/testes and uteri of reduced size were seen in all 1889 ppm rats that died.  In addition, thymi of reduced size and generalized cyanosis were seen in four and three rats that died, respectively.

Other findings:

Potential target organs:  Although not specifically identified as such in the report, the clinical and necropsy findings indicate the eyes and respiratory tract to be target organs.

Responses were consistent between males and females.

Any other information on results incl. tables

Number of deaths at each dose level:

Sex	Dose level (ppm)	No. Deaths	Days to Death
Males	1431	0	N/A
	1678	1	8
	1889	4	7, 8, 8 9
Females	1431	0	N/A
	1678	2	5, 10
	1889	3	8, 8, 11

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a good quality, GLP, acute inhalation study (reliability score 1) that was comparable to OECD 403, the one-hour combined male/female LC50, based on nominal dichloro(methyl)silane concentrations, was determined to be 1785 ppm in rats.

Executive summary:

In a good quality, GLP, acute inhalation study (reliability score 1) that was comparable to OECD 403, Fischer 344 rats (5/sex/group) were exposed, whole-body to dichloro(methyl)silane vapour at nominal concentrations of 1431, 1678 and 1889 ppm, for one hour. The animals were then observed for 14 days for signs of toxicity and their body weights recorded on days 1, 3, 8 and 15. At the end of the observation period all animals were necropsied. The combined male/female LC₅₀, based on nominal dichloro(methyl)silane concentrations, was determined to be 1785 ppm with 95% confidence limits of 1671 - 1963 ppm. Significant body weight losses were observed on day 8, but there was marked recovery in those animals that survived Clinical signs of toxicity were typical of chlorosilane exposures in that all exposure groups had corneal opacities, rales, laboured breathing and gasping immediately after the exposure period. Most of these signs showed a marked resolution in the animals that survived to the end of the observation period. Macroscopic observations in animals that died were haemorrhage/congestion/consolidation of the lungs, ocular lesions and empty, gaseous distention of the gastrointestinal tract. In animals that survived, the most prominent necropsy findings were ocular lesions.