Dichloro(methyl)(vinyl)silane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

6

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

6

Modified dose descriptor starting point:

NOAEC

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

15.5 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

Overall assessment factor (AF):

1

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

15.5 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

Overall assessment factor (AF):

1

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.69 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

6

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.69 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

6

Modified dose descriptor starting point:

NOAEL

Additional information - workers

Dichloro(methyl)(vinyl)silaneis a volatile liquid whichhydrolyses very rapidly in moist air and in contact with tissues to form hydrogen chloride (HCl) and methyl(vinyl)silanediol. Local effects (corrosion) are therefore influenced by the formation of HCl, while systemic effects may occur following exposure to the silanol hydrolysis product.

 

Hydrogen chloride (HCl)

An EU long-term inhalation Occupational Exposure Limit (OEL) has been set for HCl as 8 mg/m³(8 h TWA) in Commission Directive2000/39/EC.

The SIDS Initial Assessment Report (SIAR) for HCl describes a systemic NOAEL of 20 ppm from a 90-day repeated dose inhalation study (OECD, 2002). However, since the NOAEL for local effects in the same study was 10 ppm it is considered by the author of this CSR that the observed effects at 20 ppm were secondary to corrosion and were not indicative of true systemic toxicity.

The OECD SIAR (2002) reports the following:

For repeated dose toxicity, 13 inhalation and 7 oral dose studies has been reported. Among those, only the inhalation studies reported by CIIT (1984) were reliable. They were performed in compliance with FDA-GLP, and they are considered to be the critical studies for assessment. Four groups of 10 males and 10 females (mice: B6C3F1; rats: SD and F344) individually housed were exposed to hydrogen chloride gas at concentrations of 0, 10, 20 and 50 ppm for 90 days (6 hours/day, 5 days/week). For male and female mice at 50 ppm, a decrease in body weight gain, food consumption and liver weight (male) was noted. For male SD rats at 50 ppm, a decrease in food consumption was observed. For F344 rats, a decrease in body weight gain was observed in males at 50 ppm and a decrease in food consumption was observed in both sexes at 20 and 50 ppm. No biologically significant difference was observed in urinalysis, haematology and serum chemistry. Inflammatory histopathological changes in lips or nasal cavity were observed in B6C3F1 mice and F344 rats above 10 ppm or in SD rats above 20 ppm. In addition, the histopathological examination of reproductive organs (testis, epididymis, prostate, seminal vesicle; ovary, uterus, oviduct, mammary glands) could not find any exposure related effects. The NOAEL for repeated dose inhalation toxicity, except for the local effects of irritation, is considered to be 20 ppm for rats and mice.

 

It is therefore considered appropriate to use the existing EU OEL for HCl as the starting point to quantify local DNELs fordichloro(methyl)(vinyl)silane.

Typical worker exposure involveslow levels of exposure on a repeated basis (below the OEL for HCl). Any exposure will result in hydrolysis to silanol, hydrogen ions and chloride ions; the ions will enter the body's natural buffering and homeostatic processes independently of the silanol.The silanol hydrolysis product must therefore be considered for systemic DNELs because it is expected that this substance will be systemically available. This might be particularly important in situations when inhalation occurs and HCl is neutralised before it reaches the lower respiratory tract, so the silanol hydrolysis product is available for absorption, but there is no irritation from which secondary effects could arise. Also, a systemic DNEL based on the silanol must be considered to allow for situations when the exposure to the silanol is below the local DNEL, but could still cause systemic effects.

Dichloro(methyl)(vinyl)silane (read-across from trimethoxy(vinyl)silane)

 

There are no repeated dose toxicity data on dichloro(methyl)(vinyl)silane or its hydrolysis product, methyl(vinyl)silanediol, so good quality data for the read-across substance trimethoxy(vinyl)silane has been used to assess the general systemic toxicity of dichloro(methyl)(vinyl). Local effects from the other hydrolysis product, hydrogen chloride (HCl) are not addressed by these data on trimethoxy(vinyl)silane.No read-across data are available for the dermal route.

In an oral OECD 422 study (Hashima Labs, no date) in rats, trimethoxy(vinylsilane was administered by gavage at doses up to 1000 mg/kg bw/day, for approximately 28 days. The LOAEL was 62.5 mg/kg bw/day (based on decreased relative thymus weight in females and histopathological changes in the urinary bladder of males), and therefore the NOAEL was <62.5 mg/kg bw/day for both sexes.

In a 14-week whole-body inhalation study (BRRC, 1990) in which rats were exposed to concentrations oftrimethoxy(vinyl)silaneup to 400 ppm, a concentration of 100 ppm was a LOAEC (effects included decreased urine osmolality and sodium, potassium and chloride concentrations in males and slight decrease in body weight and body weight gain in females), and 10 ppm (58 mg/m³) was the NOAEC. Test animals were exposed for 6 hours per day, 5 days per week.

Since a NOAEL was not established in the oral study, the inhalation study is considered to be the most appropriate starting point for determining both the dermal and inhalation DNEL values for systemic effects.

There are no reproductive or developmental toxicity data for dichloro(methyl)(vinyl)silane or its hydrolysis product, methyl(vinyl)silanediol, so good quality data for the read-across substance trimethoxy(vinyl)silane have been used to assess the reproductive and developmental toxicity of dichloro(methyl)(vinyl)silane.

In an oral OECD 422 study (Hashima Labs, no date) in rats, trimethoxy(vinyl)silane was administered by gavage at doses up to 1000 mg/kg bw/day, and no effects on reproductive parameters were observed. The NOAEC was therefore greater than or equal to 1000 mg/kg bw/day.

Exposure of pregnant rats during organogenesis to trimethoxy(vinyl)silane by inhalation resulted in slight maternal toxicity at 100 and 300 ppm as evidenced by concentration-dependent reductions in gestational body weight gain (gestation days 6-9). There was evidence of slightly delayed development in fetuses from the 300 ppm group as indicated by delayed ossification in several skeletal districts. No exposure-related embryotoxicity or teratogenicity was observed in this study (BRRC, 1993). The observed variations are not considered toxicological, particularly in the presence of maternal toxicity, and therefore the NOAEC is greater than or equal to 300 ppm (approx. 1730 mg/m³). Test animals were exposed for 6 hours per day, on gestation days 6-15.

In the absence of any significant findings relating to reproductive or developmental endpoints in appropriate screening tests, the critical health effect is considered to be repeated dose toxicity. Dichloro(methyl)(vinyl)silaneis not classified as mutagenic, carcinogenic or sensitising.

The DNELs used for risk characterisation are therefore:

DNEL (long-term, inhalation): 4.9 mg/m³

DNEL (long-term, dermal): 0.69 mg/kg/day

Qualitative risk characterisation for corrosive effects following dermal exposure will also be required.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

There is no potential for exposure of consumers to dichloro(methyl)(vinyl)silane via any route; therefore, DNELs for the general population are not calculated.