Dichloro(methyl)(vinyl)silane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999/01/11-2000/01/18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

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)(vinyl)silane

EC Number:

204-710-3

EC Name:

Dichloro(methyl)(vinyl)silane

Cas Number:

124-70-9

Molecular formula:

C3H6Cl2Si

IUPAC Name:

dichloro(methyl)vinylsilane

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, Raleigh, North Carolina, RO2 Facility.

- Age at study initiation: Approximately eight weeks.

- Weight at study initiation: 176 ± 38 grams (males) and 130 ± 17 grams (females) when exposed.

- Housing: Animals were individually housed in suspended wire-mesh cages (ca. 7"x10"x7"), during both the quarantine and the in-life phase of the study. The animals were transferred to clean cages at least once every two weeks.

- Diet: Certified Rodent Diet #5002, ad libitum, except during the exposure period.

- Water: Reverse osmosis purified municipal water was provided ad libitum, except during the exposure period via an automatic watering system.

- Acclimation period: No acclimation period, but a 'quarantine period' of 7 days.


ENVIRONMENTAL CONDITIONS

- Temperature (°F): 64-79

- Humidity (%): 30-70

- Air changes (per hr): 10-15

- Photoperiod (hrs dark / hrs light): 12/12 (approximately 6am-6pm)

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

- Exposure apparatus: The sampling system utilized a vacuum pump to pull samples of test article vapour/nitrogen gas stream or chamber atmosphere through a stream selector valve and the injector sample loop. The samples were drawn through heated (100-120°F) stainless steel tubing from the corresponding sampling sites.

- Exposure chamber volume: 175 litres

- Method of holding animals in test chamber: Stainless-steel wire mesh cage, designed specifically for the exposure chamber.

- Source and rate of air: Conditioned air passed through a series of HEPA and activated carbon filters at a flow rate of ca. 130 litres per minute.

- Temperature, humidity, pressure in air chamber: The rate of test atmosphere introduction into the chamber was approximately 130 lpm as calculated from the differential pressure across an orifice plate located in the lower portion of the chamber inlet. This flow rate provides for approximately 46 chamber volumes per hour, an exchange rate sufficient to maintain an adequate oxygen level. The chamber was operated at a slight negative pressure relative to the room. Chamber atmosphere flow rate, temperature and relative humidity were monitored continuously and recorded at intervals of approximately 10 minutes.


TEST ATMOSPHERE

- Brief description of analytical method used: The chamber atmosphere was sampled and analyzed twice during each exposure to identify methyvinyldichlorosilane and test article-derived materials. The chlorosilane vapour/nitrogen gas stream was sampled and analyzed multiple times during the exposure period to evaluate generation system efficiency. Analysis of the chamber atmosphere and methyvinyldichlorosilane vapour/nitrogen gas carrier stream from the vapour generation system was performed with a Gas Chromatograph (GC) utilizing both a Thermoconductivity Detector (TCD) and a Mass Selective Detector (MSD).

- Samples taken from breathing zone: yes


VEHICLE

- Composition of vehicle (if applicable): Nitrogen, served as the carrier gas for vapor generation to the exposure chamber.

- Justification of choice of vehicle: Nitrogen was selected for use as an inert carrier gas because of the potential hazards associated with the generation of vapour concentrations above the lower flammability limit for methylvinyldichlorosilane.



CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC/TCD

Duration of exposure:

1 h

Concentrations:

1597, 2005, 2119 and 2242 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: Body weights were recorded on the day of randomization and on study days 1 (prior to exposure), 3, 5, 8 and 15. Body weights were also collected on extra days (3,9 and 10) for some of the groups.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Clinical observations were recorded daily. No tissues were collected at necropsy.

Statistics:

The median lethal nominal chamber concentration (LC50), 95% fiducial limit and approximate slope of the dose response curve was be calculated using SAS/STAT Probit Procedure. If the mortality data did not meet the criteria for Probit analysis (parametric test), then the LC50 and 95% confidence limits were determined using Spearman-Karber analysis (nonparametric test). Means and standard deviations were determined for other data as appropriate.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 021 - <= 2 257 ppm

95% CL:

1 806

Exp. duration:

1 h

Mortality:

No animals died during the exposure period. All unscheduled deaths occurred within 10 days after exposure. See table 1.

Clinical signs:

other: The predominant clinical signs were indicative of effects on the respiratory tract, eyes and of generalized stress.   Labored breathing was observed in all groups and in a dose response; its onset was almost exclusively on the day of exposure (day 1).  Ra

Body weight:

Body weight was affected by exposure to the test atmosphere, body weight loss being apparent in all exposure groups. Recovery of body mass was common to those animals capable of surviving to study day 15.

Gross pathology:

Necropsy findings, included doses affected, severity and number of animals affected:  A total of 21 rats survived to the scheduled necropsy.  Of these, nearly all (17/21) were noted to have bilateral or unilateral corneal opacities and other ocular abnormalities.  Various external stains and areas of hair loss were seen in 16 rats that survived and nine  survivors had missing, misshapen or shrunken extremities.  Nineteen rats died on the study.  Necropsy findings seen in 60% or more of the rats that died included various external stains and areas of hair loss (N = 19),  eyelids crusted shut 
(N = 18), decreased or absent body fat (N =  18), obstructed nostrils (N = 17), gaseous distension of the  gastrointestinal tract (N = 17), dehydration (N = 15), a dried and firm  nose (N = 14), pulmonary congestion, consolidation, hemorrhage and/or ectasia (N = 14) and abnormal stomach contents (N = 13).  In addition, six rats that died (at least one in each group) had unilateral or  bilateral corneal opacities.

Other findings:

- Potential target organs: None specifically identified in the report, however, clinical signs and necropsy findings were consistent with the respiratory tract and eyes being target organs.

- Other observations: Responses were generally consistent between the sexes.

Any other information on results incl. tables

Table 1: Concentrations, exposure conditions and mortality per animals treated

Analytical Conc. Conc. (ppm)	Mortality (# dead/total)
	Males	Females	Combined
1597	1/5	0/5	1/10
2005	3/5	2/5	5/10
2119	3/5	3/5	6/10
2242	4/5	3/5	8/10

 

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A vapour pressure value based on the one-hour combined male/female LC50, based on nominal concentrations, was determined to be 2021 ppm with 95% confidence limits of 1806-2257 ppm in rats. The study was in compliance with GLP.