Trichloroisobutylsilane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

14 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

Additional information - workers

Trichloroisobutylsilaneis a volatile liquid whichhydrolyses very rapidly in moist air and in contact with tissues to form hydrogen chloride (HCl) andisobutylsilanetriol (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 fortrichloroisobutylsilane.

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.

 

Trichloroisobutylsilane (read-across from triethoxyisobutylsilane)

 

There are no repeated dose toxicity data ontrichloroisobutylsilaneor its hydrolysis product,isobutylsilanetriol, so good quality data for the read-across substancetriethoxyisobutylsilane (CAS 17980-47-1; whichalso hydrolyses toisobutylsilanetriol, as well as ethanol) have been used to assess the general systemic toxicity oftrichloroisobutylsilane. No read-across data are available for the dermal and oral routes.Local effects from the other hydrolysis product, hydrogen chloride (HCl) are not addressed by these data on triethoxyisobutylsilane.

The key repeated dose toxicity study was a 90-day nose-only inhalation study conducted in male and female rats, according to OECD 413 (SafePharm Laboratories Ltd (1992a)). The study identified a NOAEC value of at least 2.54 mg/l (measured concentration), which was the highest dose tested (determined in a range-finding study). There were no significant treatment-related effects.

There are no reproductive or developmental toxicity data fortrichloroisobutylsilaneor its hydrolysis product, isobutylsilanetriol, so good quality data for the read-across substance triethoxyisobutylsilane have been used to assess the reproductive and developmental toxicity oftrichloroisobutylsilane.

A one-generation oral study (OECD 415) is available in which triethoxyisobutylsilane was given by gavage at up to 1000 mg/kg bw/day in arachis oil to male and female rats for ten weeks prior to mating and throughout gestation and lactation (SafePharm Laboratories Ltd, (1992)). The study found no evidence of adverse reproductive effects in the parents or offspring.

The key developmental toxicity study was an oral study in rats conducted according to OECD 414, with gavage administration of up to 1000 mg/kg bw/day of triethoxyisobutylsilane in arachis oil on gestation days 6-15 and examination at gestation day 20 (SafePharm Laboratories Ltd (1992b)). The study reported slight maternal toxicity but no evidence of developmental effects at 1000 mg/kg bw/day. No maternal toxicity was observed at the lower dose of 250 mg/kg bw/day. These data are not suitable for use for systemic toxicity DNEL since pregnant animals may be more susceptible than non-pregnant. Furthermore, the effects on pregnant females were not serious.

At the dose levels relevant for testing and human exposure, ethanol generated in the stomach from hydrolysis of triethoxy(2,4,4-trimethylpentyl)silane is not expected to contribute any systemic toxicity effects.

In the absence of any significant findings relating to systemic, reproductive or developmental endpoints in appropriate tests, the critical health effect is considered to be corrosion. Trichloroisobutylsilaneis not classified as mutagenic, carcinogenic or sensitising.

The DNEL used for risk characterisation is therefore:

DNEL (long-term, inhalation): 14 mg/m³

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 trichloroisobutylsilane by any route, therefore DNELs for consumers are not calculated.