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Description of key information

In a 90-day oral repeated dose toxicity study conducted according to OECD 408 and in compliance with GLP (BSL Bioservice, 2015), there were no observed treatment-related adverse findings. Therefore, a NOAEL of 150 mg/kg bw/day (the highest dose tested) triethoxy(2,4,4 -trimethylpentyl)silane was identified.

There are no repeated dose inhalation toxicity data on triethoxy(2,4,4-trimethylpentyl)silane, so good quality data for the read-across substance trimethoxy(2,4,4-trimethylpentyl)silane (CAS 34396-03-7), have been used to assess the repeated dose inhalation toxicity of triethoxy(2,4,4-trimethylpentyl)silane. The only available 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 (Hoechst, 1986b). Overall the NOAEC for this study was considered to be 3 mg/l.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
150 mg/kg bw/day
Study duration:
subchronic
Species:
rat
System:
gastrointestinal tract
Organ:
liver

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
3 000 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
3 000 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key 90-day oral repeated dose toxicity study reports a NOAEL of 150 mg/kg bw/day (the highest dose tested) (BSL BioService, 2015) in a study that was conducted according to OECD 408 and in compliance with GLP. Four groups of 10 male and 10 female rats were dosed via gavage with 0, 15, 50 and 150 mg/kg bw/day for 90 consecutive days. There were no treatment related findings in any of the animals.

The key subchronic study is supported by two reliable repeated dose toxicity studies with triethoxy(2,4,4-trimethylpentyl)silane. The first (CERI, 2001) was a 28-day oral (gavage) study conducted in male and female rats, with a 14-day recovery period. The study was conducted according to OECD 407 and in compliance with GLP. The study identified an NOEL value of 40 mg/kg bw/day, with bladder and liver effects, possibly reversible, at the LOAEL of 200 mg/kg bw/day. Dosing was performed 7 days per week. The second study (BSL Bioservice, 2001d), was conducted according to OECD 407, and in compliance with GLP. The NOAEL for Wistar rats was determined to be 150 mg/kg bw/day for the oral route. There were treatment and dose-related changes in the keratinised gastric mucosa in male rats, the change being present in all dose groups (male high, medium and low, and female high, medium and low dose groups 5/5, 4/5, 2/5 and 1/5, 3/5, 1/5, respectively). In female rats the changes were detected at a lesser frequency and only a 'minimal' severity. The associated changes were acanthosis and hyperkeratosis.

In these two subacute (28-days repeated) oral toxicity studies different strains of rats and different vehicles for substance application were used. Based on these differences, the partially different behaviour of the substance in these two tests can be explained (strain specific effects, normal biological variation, different resorption due to different vehicles). Nevertheless, in general no severe systemic toxicological effects were observed in either test.

Changes in the liver (both tests) can be described as an adaptative response to the substance because of metabolism of the parent substance and/or the hydrolysis products, especially ethanol. Irritation effects of the substance were observed on the keratinized gastric mucosa (BSL Bioservice, 2001d) and on the transitional epithelium of the bladder (CERI, 2001). There is an indication of reversibility of the effects.

Different NOAELs were defined in these two tests, which can be explained by the different dose levels selected for each. Effects in the 200 mg/kg dose group (CERI, 2001) were without morphological findings (relative liver weight) or were very slight to slight in few animals, only (hyperplasia of transitional epithelium of the bladder).

Note: Based on the findings of the key study (subchronic 90-day oral repeated dose toxicity study) bladder epithelial hyperplasia findings in the supporting oral subacute toxicity studies of similar degree of severity and missing recovery data have been re-evaluated as being non-adverse.

A supporting oral OECD 422 study on the analogue substance, triethoxy(octyl)silane is included to support the read-across justification for the reproductive toxicity endpoint.

There are no repeated dose inhalation toxicity data on triethoxy(2,4,4-trimethylpentyl)silane, so good quality data for the read-across substance trimethoxy(2,4,4-trimethylpentyl)silane (CAS 34396-03-7), have been used to assess the repeated dose inhalation toxicity of triethoxy(2,4,4-trimethylpentyl)silane. The submission substance and trimethoxy(2,4,4-trimethylpentyl)silane are close structural analogues and both hydrolyse (with predicted half-lives at pH 7 of 43 h and 5 h, respectively) to give 2,4,4-trimethylpentylsilanetriol. The other hydrolysis products are ethanol and methanol, respectively.

In a 28-day inhalation study with trimethoxy(2,4,4-trimethylpentyl)silane which was conducted according to OECD 412 and in compliance with GLP (Hoechst, 1986b), 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 day 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 alveolar irritation (isolated and small clusters of foam cells) in several high dose animals. Overall the NOAEC 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.

An OECD 422 screening test is planned for trimethoxy(2,4,4 -trimethylpentyl)silane (CAS 34396 -03-7), which will support the read-across of the inhalation test. See read-across justification in the test proposal (based on read-across) for toxicity to reproduction endpoint and Section 5.9.3 of the Chemical Safety Report.

Justification for classification or non-classification

The available data do not indicate that triethoxy(2,4,4-trimethylpentyl)silane should be classified for specific target organ toxicity according to Regulation (EC) No. 1272/2008.