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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.7 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Chloro(methyl)silaneis an extremely flammable gas which hydrolysesvery rapidly in moist air and in contact with tissues to form hydrogen chloride (HCl) and methylsilanol (half-life <1 min at pH 4, 7 and 9 and 1.5°C). 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 forchloro(methyl)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.

 

Chloro(methyl)silane (read-across from trimethylsilanol)

 

There are no adequate repeated dose toxicity data on chloro(methyl)silane or its hydrolysis product, methylsilanol, so good quality data for the read-across substance trimethylsilanol (CAS number 1066-40-6) have been used to assess the general systemic toxicity of chloro(methyl)silane.[1]Local effects from the other hydrolysis product, hydrogen chloride (HCl) are not addressed by these data on trimethylsilanol.No read-across data are available for the dermal route, and significant dermal contact is not anticipated for this gaseous substance.

In a 28-day oral study in rat (Ramm & Bomhard, 1986) on trimethylsilanol adverse effects (reduced body weight gain, reduced alkaline phosphatase, reduced glucose (males), increased liver weights (females), and increased adrenal weights (males), and minor deposits in the bile ducts) were observed at the highest dose of 750 mg/kg bw/day. The NOAEL was 250 mg/kg bw/day, as effects observed at this or the lower dose of 80 mg/kg bw/day, were not dose-dependent and often values were within the normal range for historical controls.

In the key 28-day repeated inhalation study in rat (Fleeman, 2008; an OEDCD 422 study) using trimethylsilanol, treatment-related effects were limited to changes in hematology (lower eosinophil and lymphocyte counts for males) and serum chemistry (higher alanine aminotransferase for males and toxicity phase females) at 600 ppm trimethylsilanol. These changes occurred in the absence of correlating histologic changes and were not considered adverse. Therefore, under the conditions of this screening study, an exposure level of at least 600 ppm (2214 mg/m3) was considered to be the NOAEL for trimethylsilanol. Test animals were exposed for 6 hours per day, 7 days per week.

There are no reproductive or developmental toxicity data for chloro(methyl)silane or its hydrolysis product, methylsilanol, so good quality data for the related substancetrimethylsilanolhave been used to assess the reproductive and developmental toxicity of chloro(methyl)silane.

In the key repeated inhalation study (Fleeman, 2008; an OECD 422 study) on trimethylsilanol, there were no adverse effects on reproductive or developmental parameters. Therefore, under the conditions of this screening study, an exposure level of at least 600 ppm (2214 mg/m3) was considered to be the NOAEL for trimethylsilanol.

No quantitative DN(M)ELs could be derived for:

Acute toxicity – local effects

Long-term toxicity – local effects, dermal (available OEL is for inhalation exposure)

Reproductive/developmental toxicity (no effects)

Mutagenicity (not mutagenic)

Carcinogenicity (no data)

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 corrosion. For the inhalation route, the DNEL long-term, local is lower than that for DNEL long-term systemic. Chloro(methyl)silane is not classified as mutagenic, carcinogenic or sensitising.

Significant dermal exposure is not expected because the substance is a gas.

The DNEL used for risk characterisation is therefore:

DNEL (long-term, inhalation): 17.7 mg/m3

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

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[1]An alternative read-across substance, methylsilanetriol, was considered because it is the substance expected to form after hydrolysis of both the Si-Cl and Si-H bonds in methylchlorosilane. However, in the absence of conclusive evidence that the Si-H bond would hydrolyse under relevant conditions, the best read-across for the initial hydrolysis product methylsilanol was sought. The number of -OH groups at Si, rather than the number of -Me groups, is considered to be the key determinant of the toxicology of the substance. Therefore, trimethylsilanol was selected. The substance is an intermediate used under highly controlled conditions and exposures are low. The key DNEL is based on the effects of HCl. Therefore, the choice of read-across substance will not affect the outcome of the risk characterisation.

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

General Population - Hazard for the eyes

Additional information - General Population

There is no potential for exposure of consumers to chloro(methyl)silane by any route, therefore DNELs for consumers are not calculated.

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