Triethoxypropylsilane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

135 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: substance-specific

Overall assessment factor (AF):

5.5

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

741 mg/m³

Explanation for the modification of the dose descriptor starting point:

The long-term DNEL for systemic effects via the inhalation route is determined on the basis of the OECD 414 oral NOAEL for fetal toxicity of 300 mg/kg bw/day.

The following corrections were made:

 

Correction for metabolic rate: 1 / 0.38 m³/kg bw/day

Correction for respiratory volume (worker, light physical activity): 6.7 m³/day/10 m³/day

A correction based on different exposure times between experimental animal and worker are considered (7 days exposure for rat and 5 days exposure for workers)

Therefore the corrected NOAEC for long-term systemic effects via the inhalation route is:

300 mg/kg bw/day × (1/0.38 m³/kg bw/day) × (6.7 m³/day /10 m³/day) x (7 days exposure rat/5 days exposure worker) = 741 mg/m³

In contrast to the recommendations of the ECHA Guidance, a factor of 1 (equal absorption of 100% assumed for the oral and the inhalative route for animals and humans) was included for the extrapolation from oral to inhalation absorption, as there is no valid data suggesting that inhalation leads to higher absorption than oral ingestion (recommendation of the VCI Working group "Toxicology", 2008). Molecules with a molecular weight <500 and a log Kow between 0 and 4 can be assumed to be well absorbed equivalently by the oral and inhalation route. Oral absorption may be reduced for acids and bases depending on their pKa value and their electric charge in the GI tract. More lipophilic substances may be better absorbed in the GI tract due to solubilisation with bile acids, and thus oral absorption may be higher than inhalation absorption (VCI Working group "Toxicology", 2008). Unless valid data suggest that inhalation leads to higher absorption than oral ingestion, equal absorption will be assumed when extrapolating from oral to inhalation route.

(ABSoral-rat = oral absorption in rats, ABSinh-human = inhalation absorption rate in humans)

Intraspecies differences

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 silanes to silanols and their excretion proceeds without enzymatic involvement. Individual genetic dispositions and other 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 dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEC.

AF for differences in duration of exposure:

1

Justification:

The relevant period is covered in the OECD 414 study.

AF for interspecies differences (allometric scaling):

1

Justification:

AF is not used for inhalation route.

AF for other interspecies differences:

2.5

Justification:

ECHA default

AF for intraspecies differences:

2.2

Justification:

Substance-specific (for further details please see above)

AF for the quality of the whole database:

1

Justification:

The DNEL is based on high quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

19 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: substance-specific

Overall assessment factor (AF):

22

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

420 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The long-term DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the OECD 414 oral study on triethoxy(propyl)silane, which showed a NOAEL for fetal toxicity of 300 mg/kg bw/day. The following correction was made to the NOAEL:

No correction for relative absorption oral vs. dermal: 1 (worst case).

The corrected NOAEL is therefore: 300 mg/kg bw/day * 1 * (7 days exposure rat/5 days exposure worker) = 420 mg/kg bw/day.

Intraspecies differences

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 silanes to silanols and their excretion proceeds without enzymatic involvement. Individual genetic dispositions and other 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 dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL.

AF for differences in duration of exposure:

1

Justification:

The relevant period is covered in the OECD 414 study.

AF for interspecies differences (allometric scaling):

4

Justification:

The experimental animal was the rat.

AF for other interspecies differences:

2.5

Justification:

ECHA default

AF for intraspecies differences:

2.2

Justification:

Substance-specific (for further details please see above)

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a high-quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

33 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: substance-specific

Overall assessment factor (AF):

8

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

261 mg/m³

Explanation for the modification of the dose descriptor starting point:

The long-term DNEL for systemic effects via the inhalation route is determined on the basis of the OECD 414 oral NOAEL for fetal toxicity of 300 mg/kg bw/day.

The following corrections were made:

= NOAELoral * (1/1.15 m³/kg bw/day (24h)) * (ABSoral-rat / ABSinh-human)

= 300 mg/kg bw/day * (1/1.15 m³/kg bw/day) * (1/1) = 261 mg/m³

Intraspecies differences

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 silanes to silanols and their excretion proceeds without enzymatic involvement. Individual genetic dispositions and other 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 dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEC.

AF for differences in duration of exposure:

1

Justification:

The relevant period is covered in the OECD 414 study.

AF for interspecies differences (allometric scaling):

1

Justification:

AF is not used for inhalation route.

AF for other interspecies differences:

2.5

Justification:

ECHA default

AF for intraspecies differences:

3.2

Justification:

substance-specific (for further details please see above)

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a high quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

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:

DNEL (Derived No Effect Level)

Value:

9.4 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: substance-specific

Overall assessment factor (AF):

32

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The long-term DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the OECD 414 oral study on triethoxy(propyl)silane, which showed a NOAEL for fetal toxicity of 300 mg/kg bw/day.

No correction for relative absorption oral vs. dermal: 1 (worst case).

Intraspecies differences

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 silanes to silanols and their excretion proceeds without enzymatic involvement. Individual genetic dispositions and other 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 dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL.

AF for differences in duration of exposure:

1

Justification:

The relevant period is covered in the OECD 414 study.

AF for interspecies differences (allometric scaling):

4

Justification:

The experimental animal was the rat.

AF for other interspecies differences:

2.5

Justification:

ECHA default

AF for intraspecies differences:

3.2

Justification:

substance-specific (for further details please see above)

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a high quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

9.4 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: substance-specific

Overall assessment factor (AF):

32

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No correction was applied to the dose descriptor starting point.

The long-term systemic DNEL by the oral route is based on the NOAEL for fetal toxicity of 300 mg/kg bw/day from the OECD 414 oral study on triethoxy(propyl)silane.

Intraspecies differences

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 silanes to silanols and their excretion proceeds without enzymatic involvement. Individual genetic dispositions and other 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 dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL.

AF for differences in duration of exposure:

1

Justification:

The relevant period is covered in the OECD 414 study.

AF for interspecies differences (allometric scaling):

4

Justification:

The experimental animal was the rat.

AF for other interspecies differences:

2.5

Justification:

ECHA default

AF for intraspecies differences:

3.2

Justification:

substance-specific (for further details please see above)

AF for the quality of the whole database:

1

Justification:

The DNEL is based on a high quality study.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties.

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