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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
68.7 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
DNEL related information

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
Dose descriptor:
NOAEC
Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.7 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
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Trichloro(3-chloropropyl)silaneis a moderately volatile liquid whichhydrolyses very rapidly in moist air and in contact with tissues to form hydrogen chloride (HCl) and 3-chloropropylsilanetriol. 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 fortrichloro(3-chloropropyl)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.

 

Trichloro(3-chloropropyl)silane (read-across from trimethoxy(3-chloropropyl)silane)

 

There are no repeated dose toxicity data on trichloro(3-chloropropyl)silane or its hydrolysis product, 3-chloropropylsilanetriol, so good quality data for the read-across substance trimethoxy(3-chloropropyl)silane have been used to assess the general systemic toxicity of trichloro(3-chloropropyl)silane via the inhalation route. Local effects from the other hydrolysis product (HCl) are no addressed by these data on trimethoxy(3-chloropropyl)silane.No read-across data are available for the dermal and oral routes.

Trimethoxy(3-chloropropyl)silane was tested in an inhalation OECD 422 study, whole-body in rats, up to and including the highest concentration of 100 ppm. In this study there were no signs of general toxicity. Therefore based on these results the NOAEC was established to be at least 100 ppm (867 mg/m3). In a 90-day inhalation study in rats, conducted in accordance with OECD 413, the NOEC for trimethoxy(3-chloropropyl)silane was determined to be 5 ppm (41 mg/m3) based on treatment-related histopathological effects observed in animals in 100 ppm treatment group. These were minimal/mild hyperplasia of the urinary bladder epithelium in both sexes (Dow Corning, 1993) and species specific changes in the kidneys.It is not known whether the urinary bladder was inflated by a fixative before microscopic examination; without inflation of the urinary bladder the relevance of the hyperplasia is questionable (Wanda M, 1991). There is no evidence for genotoxicity of CPTMO. Therefore, it is highly unlikely that the minimal /mild proliferative changes of the bladder are caused by a urinary bladder carcinogen. Based on the fact that the hyperplasia of the bladder was mild / minimal and associated with a minimal inflammation (cystitis) it can presumed that if the stimulus for the inflammation is removed the hyperplasia will resolve within a matter of weeks and the urinary bladder will return to a normal histological appearance (Wanda M, 1991). A minimal / mild reversible effect is not adverse. Therefore the NOAEC is considered to be 100 ppm (867 mg/m3).Test animals were exposed for 6 hours per day, 5 days per week.

There are no reproductive or developmental toxicity data on or its hydrolysis product, 3-chloropropylsilanetriol, so good quality data for the read-across substance trimethoxy(3-chloropropyl)silane have been used to assess the reproductive and developmental toxicity of trichloro(3-chloropropyl)silane.

No treatment-related effects were observed in any of the reproductive or developmental parameters evaluated in an oral OECD 422 study in rats. Based on the results of this screening study, the NOAEL for reproductive and developmental toxicity of trimethoxy(3-chloropropyl)silane in the rat via oral dosing was determined to be equal to or greater than 100 ppm (867 mg/m3). Test animals were exposed for 6 hours per day, 7 days per week. 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 (effects noted in read-across substancein vitrowere not confirmedinvivo so it is concluded that substance is not mutagenic)

Carcinogenicity (no data) In the absence of any findings relating to reproductive or developmental endpoints in appropriate screening tests, the critical health effect is considered to be repeated dose toxicity. Trichloro(3-chloropropyl)silane is not classified as mutagenic, carcinogenic or sensitising.

The DNELs used for risk characterisation are therefore:

DNEL (long-term, inhalation): 15.5 mg/m3

DNEL (long-term, dermal): 9.7 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

General Population - Hazard for the eyes

Additional information - General Population

There is no potential for exposure of consumers to trichloro(3-chloropropyl)silane, therefore DNELs for consumers are not calculated.