Tetramethyl orthosilicate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

93 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

other: Substance-specific

Overall assessment factor (AF):

1

Dose descriptor:

NOAEC

AF for dose response relationship:

1

Justification:

A NOAEC was established

AF for differences in duration of exposure:

1

Justification:

Substance specific: local effects already very severe, unlikely to be worse with longer exposure duration

AF for interspecies differences (allometric scaling):

1

Justification:

Default (inhalation route)

AF for other interspecies differences:

1

Justification:

Substance specific: local effects unlikely to be more severe in humans than in rats

AF for intraspecies differences:

1

Justification:

Substance specific: local effects already very severe, including death, so unlikely to cause specific effects in sensitive populations

AF for the quality of the whole database:

1

Justification:

Guideline, GLP study

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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:

0.3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

33

Modified dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the oral NOAEL for TEOS as follows: NOAEL = 10 mg/kg bw/day No corrections were made to the NOAEL (oral).

AF for dose response relationship:

1

Justification:

A clear NOAEL was established

AF for differences in duration of exposure:

6

Justification:

Default (subacute to chronic)

AF for interspecies differences (allometric scaling):

1

Justification:

The allometric scaling factor accounts for metabolic differences between the test species and humans. This factor is not considered to be relevant for tetramethyl orthosilicate on the following grounds: The hydrolysis product, silicic acid, is inorganic (the soluble form of silica) and is not susceptible to enzymatic metabolism in vivo. The observed biodegradation of the related substance tetraethylorthosilicate (see Section 5) is accounted for by the non-silanol hydrolysis product, ethanol. Toxicological effects of tetramethyl and tetraethylorthosilicate are not attributable to methanol or ethanol (see Section 7.5).

AF for other interspecies differences:

2.5

Justification:

Default

AF for intraspecies differences:

2.2

Justification:

The intraspecies assessment factor takes account for the variability in sensitivity between individuals. The human population is far more diverse than experimental animals that are bred to be as similar as possible, and unhealthy animals are not allowed to start the study. This AF also covers differences between ethnic groups and age groups. The default intraspecies factors are typically broken down into equal factors accounting for toxicodynamic and toxicokinetic differences, respectively. Accordingly, an interspecies factor of 10 is composed of two identical factors of √10 = 3.2. Likewise, the default for workers (AF = 5) can be split into AFs of √5 = 2.2. The conversion of tetramethyl and tetraethylorthosilicate to their excretion proceeds without enzymatic involvement. Individual genetic dispositions are therefore without effect on these processes. As a result, the toxicokinetic components (3.2 and 2.2 for general population and workers, respectively) can be eliminated from the intraspecies AF for substances that hydrolyse fast into the ultimate excretion product.

AF for the quality of the whole database:

1

Justification:

Guideline, GLP study

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

33

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Short-term high exposures are considered unlikely given the high levels of control in place at sites producing and using the substance. DNELs for long-term exposure are therefore adequate to protect against short-term exposures and no separate short-term DNELs are calculated.

The critical effect for the inhalation exposure route is severe respiratory tract damage. The DNEL used for risk characterisation for the inhalation route is therefore based on the local NOAEC from the existing 28-day inhalation study with the registered substance. There were no adverse systemic effects observed in that study up to the highest dose level tested.

For the dermal exposure route, it is not appropriate to use route-to-route extrapolation from local inhalation effects. The DNEL is therefore based, as a worst case, on read-across of the subacute oral toxicity NOAEL for the related substance tetraethyl orthosilicate. Read-across is discussed in Section 7.5. In practice, the potential for systemic uptake of tetramethyl orthosilicate by the dermal route is limited.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

There are no consumer uses of tetramethyl orthosilicate therefore DNELs for the inhalation and oral routes are not required. Humans exposed via the environment are not assessed for this substance (see Section 9 of the CSR) therefore no oral DNEL is required.