Dichloro(chloromethyl)methylsilane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: DOT guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: DOT

Deviations:

no

GLP compliance:

no

Test type:

other:

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dichloro(chloromethyl)methylsilane

EC Number:

216-319-5

EC Name:

Dichloro(chloromethyl)methylsilane

Cas Number:

1558-33-4

Molecular formula:

C2H5Cl3Si

IUPAC Name:

dichloro(chloromethyl)methylsilane

Details on test material:

Purity: 98 %

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male

Details on test animals or test system and environmental conditions:

Young adult male Crl:CD8(SD)BR rats were received from Charles River Breeding Laboratories, Kingston, New York. Each rat was assigned a unique 6-digit identification number which corre-sponded to a numbered card affixed to the cage. Rats were quarantined for one week prior to
testing, and were weighed and observed twice during quarantine. During the test, rats were housed in pairs in 8" x 8" x 14" suspended, steel-mesh cages in rooms maintained at 37 -65% relative humidity and 23 - 28°C on a timer-controlled 12 hour light/12 hour dark cycle. Prior to
exposure cage cards and rats' tails were colour coded with •water-insoluble markers to identify individual rats. The rats assigned the lower number in each cage was identified by a slash in the right ear. Except during exposure, Purina Certified Rodent Chow 5002"•and water were available ad libitum.

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

Groups of 10 rats, 8 weeks old and weighing between 221 and 291 grams were restrained in perforated, stainless steel cylinders with conical nose pieces. Each group was exposed nose only for a single 4-hour period to a vapor atmosphere of chloromethyl(dichloro)methlysilane
in air. Rats were weighed prior to exposure and were observed for clinical signs during exposure. Surviving rats were weighed and observed daily for 14 days post exposure, weekends excluded except when deemed necessary by the rats condition.
Atmospheres of choromethyl(dichloro)methylsilane vapor in air were generated by pumping the liquid test material (at room temperature) into a three-neck round bottom flask, heated to 110-118 °C. The vaporized test material was swept into the exposure chamber with dried and fil-tered air. Dilution air was added to the vapour stream prior to discharge into the exposure chamber.
Since the test material hydrolyzes in the presence of water vapor, analytical techniques were developed to determine both the absolute chamber concentration of chloromethyl (di-chloro)methylsilane based on its chlorine content, and the amount of unhydrolyzed test mate-rial. Methodology for the respective analyses included quantification of total chloride with a chloride-selective electrode and gas chromatography with flame ionization detection.
The absolute chamber concentration of chloromethyl (dichloro)methylsilane vapor, representing the total amount of hydrolyzed and unhydrolized test material was monitored at approximately 30 minute intervals. Samples were collected by bubbling known volumes of chamber atmos-pheres through tandem midget impingers. Each impinger contained destilled deionized water as the collection media to ensure complete sample hydrolysis. Aliquots from both impingers were diluted in 0,5 M sodium acetate buffer (pH 5.0) and analyzed with a Corning Model 135pH/ion
meter and Orian Model 96-17B combination chloride ion electrod. The absolute chamber con-centration of the test material was determined by comparing the sample response (mV) with the response or 10-1 M to 10-5 M chloride standards. The chloride standards were prepared by quantitatively diluting stock solutions of sodium chloride with distilled, deionized water.
The chamber concentration of unhydrolized chloromethyl (dichloro)methylsilane was measured at approximately 1 hour interval s during most exposures. .Known volumes of chamber atmos-phere were drawn through tandem midget impingers containing methylene chloride (0.008% water) at 0 °C. Samples were injected directly into a Hewlett Packard 5710A gas chromatograph (GC ) equipped with a flame ionization detector. Samples were chromatographed iso-thermally at 80 °C on a 6 foot x 2 mm ID 1.0 glass column packed with 10% SE-30 on 80/100 mesh Supelcoport. Chamber concentrations of unhydrolyzed test material were determined by comparing the GC response of the sample with standard curves, prepared by quantitatively
diluting the neat test material in diethylene chloride. The extent of chloromethyl(dichloro)methylsilane hydrolysis was estimated from the difference between the absolute and unhydrolyzed test material concentrations. Chamber temperature was measured with a mercury thermometer. Chamber oxygen content was measured with a Biomarine Model 225 oxygen analyzer. Relative humidity was measured with either a Bendix Model 566 psychrometer or an ETC Psychrodyne.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1,5; 4,8; 4,9; 7,0; 8,6; 13 mg/L
The absolute concentration represents the total atmospheric concentration of test material and includes both unreacted and hydrolyzed chloromethyl(dichloro)methylsilane.

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

6.8 mg/L air

Based on:

test mat.

95% CL:

6.1 - 7.9

Exp. duration:

4 h

Clinical signs:

other: During exposure to chloromethyl(dichloro)methylsilane vapors at levels of 4.8 mg/L or greater, rats exhibited gasping, labored breathing and staining of nose and head with test material. In general, the number of rats displaying these clinical signs incre

Body weight:

Moderate to severe weight loss was encountered in all rats during
the post-exposure period. A 7% mean body weight loss was observed for the 1.5 mg/L group one day post exposure; all animals subsequently recovered and normal weight gain was ob-served. In the 4.8. 4.9 and 7.0 mg/l exposure groups, all surviving rats experienced a mean body weight loss of approximately 19% one day after exposure. Most surviving animals in the 4.8 and 7.0 mg/L groups continued to lose weight (approximately 5% per day) throughout the observation period. Similarly, weight loss also occurred at the higher exposure levels but
was more severe. Although body weights decreased approximately 18% within 4 hours of expo-sure in rats from the 8.6 and 13 mg/L exposure groups, 19/20 animals experienced a consistent and severe (approximately 10% per day) weight loss until their eventual death.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Although the test compound is toxic by inhalation, much of the toxicology of chloro-methyl(dichloro)methylsilane is dominated by its dermal effects. Chloro-methyl(dichloro)methylsilane is a highly reactive compound which readily and rapidly hydrolyzes in moist air forming HCl. The corrosive nature of the test material was demonstrated by a severe dermal ulceration of the facial area. Under the conditions of this study, the inhalation LC50 for chloromethyl(dichloro)methylsilane was 6.8 mg/l.

Executive summary:

Groups of 10 male Crl:CD(SD)BR rats were exposed to atmospheres of chloromethyl(dichloro)methylsilane vapors for a single, 4-hour period. Under the conditions of this test, the inhalation LC50 for chloromethyl(dichloro)methylsilane was 6.8 mg/L. This material is considered toxic by inhalation.