Trichloro(2,4,4-trimethylpentyl)silane

Endpoint summary

Description of key information

No repeat-dose toxicity data are available for trichloro(2,4,4-trimethylpentylsilane), therefore good quality studies for the related substances triethoxy(2,4,4-trimethylpentylsilane) and (2,4,4-trimethylpentyl)silane have been read-across. 
A reliable 28-day oral (gavage) study conducted in male and female rats, with a 14-day recovery period, conducted according to OECD 407 and in compliance with GLP, is the key study for the read-across substance triethoxy(2,4,4-trimethylpentylsilane). This study identified an NOAEL value of 40 mg/kg bw/day, with bladder and liver effects, possibly but not clearly reversible, at the LOAEL of 200 mg/kg bw/day.
The key inhalation study was a 28-day inhalation study with trimethoxy(2,4,4-trimethylpentyl)silane which was conducted according to OECD 412 and in compliance with GLP. Four groups of 10 males and 10 females rats were exposed to trimethoxy(2,4,4-trimethylpentyl)silane (CAS 34396-03-7) at concentrations of 0, 0.3, 1.5 and 3 mg/l for 28 days (6 hours/day, 5 days/week). After the exposure period five male and five female rats of each group were kept during a 14 d recovery before necropsy. Only some clinical signs have been observed shortly after exposure in the high and mid dose group. There were no treatment related effects on hematology, clinical chemistry, urinalysis, organ weights and gross pathology. There were signs of minimal intense alveolar irritation (isolated and small clusters of foam cells) in several high dose animals. Overall the NOAEL for this study was considered to be 3 mg/l. Based on gravimetrical and chemical verification of the exposure concentrations it can be concluded that animals were exposed to a mixture of aerosol/vapour and therefore systemic availability of the substance is expected, too.  

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEL

200 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

3 000 mg/m³

Study duration:

subacute

Species:

rat

Additional information

The key studies for repeated dose toxicity via the oral and inhalation routes are read-across from the related substances triethoxy(2,4,4-trimethylpentyl)silane and trimethoxy(2,4,4-trimethylpentyl)silane. The registered substance, trichloro(2,4,4-trimethylpentyl)silane, and the surrogate substances all hydrolyse in contact with water to produce the common hydrolysis product (2,4,4-trimethylpentyl)silanetriol, with the other hydrolysis products being hydrogen chloride, ethanol and methanol, respectively. Although at pH 7, the triethoxy analogue hydrolyses more slowly than the trichloro (half-life 22 hours compared to <1 minute), under acidic conditions such as in the stomach following oral ingestion, the triethoxy substance is expected to hydrolyse rapidly, based on experience with other ethoxysilanes.

Since all substances generate a common hydrolysis product it is considered appropriate to read-across the result of the reliable OECD 407 test for triethoxy(2,4,4-trimethylpentyl)silane the oral route and the reliable OECD 412 study for trimethoxy(2,4,4-trimethylpentyl)silane the inhalation route. At the dose levels relevant for testing and human exposure, ethanol and methanol generated from hydrolysis of triethoxy(2,4,4-trimethylpentyl)silane would not contribute any systemic toxicity effects.

Hydrogen chloride, generated by hydrolysis of trichloro(2,4,4-trimethypentyl)silane can be expected to cause local irritant or corrosive effects at sufficiently high concentrations. These effects are not addressed by the read-across data.

The key oral study for triethoxy(2,4,4-trimethylpentyl)silane was chosen from two reliable 28-day oral studies. The supporting study (Albrecht, 2001), a guideline study of reliability 1, identified a NOAEL of 150 mg/kg bw/day (LOAEL 500 mg/kg bw/day) based on local effects to the gastric mucosa. The NOAEL for systemic effects appropriate for deriving DNELs was 1000 mg/kg bw/day. The key study (CERI, 2001) was selected from the two 28-days studies as the study identifying relevant effects at the lowest dose. Effects at 200 mg/kg/d in the key study were liver and bladder effects which may have been reversible but this is not certain.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; urogenital: urinary bladder

Justification for classification or non-classification

The LOAEL for the related substance triethoxy(2,4,4 -trimethylpentyl)silane is 200 mg/kg/d via the oral route in a 28 -day study and as such falls within the guidance dose range for classification for specific target organ toxicity category 2. However, the observed effects in this study, and supporting studies, are not considered to be serious adverse effects for the health of the test animal and therefore the substance is not classified for repeated dose toxicity.