Triethoxy(2,4,4-trimethylpentyl)silane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

45 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

33.5

Dose descriptor starting point:

NOAEC

Value:

3 000 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

1 507.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

The following corrections were made: Correction for experimental exposure duration (6 h/d to 8 h/d): 6/8 (ECHA default) Correction for respiratory volume (worker): 6.7 m3/d/10 m3/d (ECHA default) Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 3000*(6 h/ 8 h)*(6.7 m3/day/10 m3/day) = 1507.5 mg/m3.

AF for dose response relationship:

1

Justification:

ECHA Default

AF for differences in duration of exposure:

6

Justification:

ECHA Default

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 Triethoxy(2,4,4-trimethylpentyl)silane on the following grounds: 1) The silanol hydrolysis product of the substance (and many other related substances) shows no biodegradation in a ready biodegradation test other than can be accounted for by degradation of non-silanol hydrolysis products (see Section 4); this suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems. 2) Toxicokinetic arguments show that the silanol hydrolysis product has low log Kow and hence low uptake, rapid excretion via urine, which would be true in all mammals, with minimal interspecies differences.

AF for other interspecies differences:

2.5

Justification:

ECHA Default

AF for intraspecies differences:

2.2

Justification:

ECHA Default, modified. 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 the quality of the whole database:

1

Justification:

ECHA Default

AF for remaining uncertainties:

1

Justification:

ECHA Default

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

45 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

33.5

DNEL extrapolated from long term DNEL

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:

13.4 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):

11.2

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No correction was applied to the dose descriptor starting point.

AF for dose response relationship:

1

Justification:

ECHA Default

AF for differences in duration of exposure:

2

Justification:

ECHA Default

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 Triethoxy(2,4,4-trimethylpentyl)silane on the following grounds: 1) The silanol hydrolysis product of the substance (and many other related substances) shows no biodegradation in a ready biodegradation test other than can be accounted for by degradation of non-silanol hydrolysis products (see Section 4); this suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems. 2) Toxicokinetic arguments show that the silanol hydrolysis product has low log Kow and hence low uptake, rapid excretion via urine, which would be true in all mammals, with minimal interspecies differences.

AF for other interspecies differences:

2.5

Justification:

ECHA Default

AF for intraspecies differences:

2.2

Justification:

ECHA Default, modified. 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 the quality of the whole database:

1

Justification:

Default

AF for remaining uncertainties:

1

Justification:

Default

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13.4 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):

11.2

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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:

11.3 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

47.4

Dose descriptor starting point:

NOAEC

Value:

3 000 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

536 mg/m³

Explanation for the modification of the dose descriptor starting point:

The following corrections were made: Correction for experimental exposure duration (6 h/d to 24 h/d): 6/24 (ECHA default) Correction for number of exposures per week: 5 exposures to 7 exposures, (ECHA default). Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 3000*(6 h/ 24 h)*(5/7) = 536 mg/m3.

AF for dose response relationship:

1

Justification:

ECHA Default

AF for differences in duration of exposure:

6

Justification:

ECHA Default

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 Triethoxy(2,4,4-trimethylpentyl)silane on the following grounds: 1) The silanol hydrolysis product of the substance (and many other related substances) shows no biodegradation in a ready biodegradation test other than can be accounted for by degradation of non-silanol hydrolysis products (see Section 4); this suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems. 2) Toxicokinetic arguments show that the silanol hydrolysis product has low log Kow and hence low uptake, rapid excretion via urine, which would be true in all mammals, with minimal interspecies differences.

AF for other interspecies differences:

2.5

Justification:

ECHA Default

AF for intraspecies differences:

3.2

Justification:

ECHA Default, modified. 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 the quality of the whole database:

1

Justification:

ECHA Default

AF for remaining uncertainties:

1

Justification:

ECHA Default

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

67 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

7.9

Dose descriptor starting point:

NOAEC

Value:

3 000 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

536 mg/m³

Explanation for the modification of the dose descriptor starting point:

The following corrections were made: Correction for experimental exposure duration (6 h/d to 24 h/d): 6/24 (ECHA default) Correction for number of exposures per week: 5 exposures to 7 exposures (ECHA default). Therefore the corrected NOAEC for repeated-dose local effects via the inhalation route is: 3000*(6 h/ 24 h)*(5/7) = 536 mg/m3.

AF for dose response relationship:

1

Justification:

ECHA Default

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 Triethoxy(2,4,4-trimethylpentyl)silane on the following grounds: 1) The silanol hydrolysis product of the substance (and many other related substances) shows no biodegradation in a ready biodegradation test other than can be accounted for by degradation of non-silanol hydrolysis products (see Section 4); this suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems. 2) Toxicokinetic arguments show that the silanol hydrolysis product has low log Kow and hence low uptake, rapid excretion via urine, which would be true in all mammals, with minimal interspecies differences.

AF for other interspecies differences:

2.5

Justification:

ECHA Default

AF for intraspecies differences:

3.2

Justification:

ECHA Default, modified. 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 the quality of the whole database:

1

Justification:

ECHA Default

AF for remaining uncertainties:

1

Justification:

ECHA Default

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:

9.5 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):

15.8

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No correction was applied to the dose descriptor starting point.

AF for dose response relationship:

1

Justification:

ECHA Default

AF for differences in duration of exposure:

2

Justification:

ECHA Default

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 Triethoxy(2,4,4-trimethylpentyl)silane on the following grounds: 1) The silanol hydrolysis product of the substance (and many other related substances) shows no biodegradation in a ready biodegradation test other than can be accounted for by degradation of non-silanol hydrolysis products (see Section 4); this suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems. 2) Toxicokinetic arguments show that the silanol hydrolysis product has low log Kow and hence low uptake, rapid excretion via urine, which would be true in all mammals, with minimal interspecies differences.

AF for other interspecies differences:

2.5

Justification:

ECHA Default

AF for intraspecies differences:

3.2

Justification:

ECHA Default, modified. 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 the quality of the whole database:

1

Justification:

ECHA Default

AF for remaining uncertainties:

1

Justification:

ECHA Default

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

19 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):

7.9

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No correction was applied to the dose descriptor starting point.

AF for dose response relationship:

1

Justification:

ECHA Default

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 Triethoxy(2,4,4-trimethylpentyl)silane on the following grounds: 1) The silanol hydrolysis product of the substance (and many other related substances) shows no biodegradation in a ready biodegradation test other than can be accounted for by degradation of non-silanol hydrolysis products (see Section 4); this suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems. 2) Toxicokinetic arguments show that the silanol hydrolysis product has low log Kow and hence low uptake, rapid excretion via urine, which would be true in all mammals, with minimal interspecies differences.

AF for other interspecies differences:

2.5

Justification:

ECHA Default

AF for intraspecies differences:

3.2

Justification:

ECHA Default, modified

AF for the quality of the whole database:

1

Justification:

ECHA Default

AF for remaining uncertainties:

1

Justification:

ECHA Default

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:

DNEL (Derived No Effect Level)

Value:

9.5 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):

15.8

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No correction was applied to the dose descriptor starting point.

AF for dose response relationship:

1

Justification:

ECHA Default

AF for differences in duration of exposure:

2

Justification:

ECHA Default

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 Triethoxy(2,4,4-trimethylpentyl)silane on the following grounds: 1) The silanol hydrolysis product of the substance (and many other related substances) shows no biodegradation in a ready biodegradation test other than can be accounted for by degradation of non-silanol hydrolysis products (see Section 4); this suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems. 2) Toxicokinetic arguments show that the silanol hydrolysis product has low log Kow and hence low uptake, rapid excretion via urine, which would be true in all mammals, with minimal interspecies differences.

AF for other interspecies differences:

2.5

Justification:

ECHA Default

AF for intraspecies differences:

3.2

Justification:

ECHA Default, modified. 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 the quality of the whole database:

1

Justification:

ECHA Default

AF for remaining uncertainties:

1

Justification:

ECHA Default

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

19 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):

7.9

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No correction was applied to the dose descriptor starting point.

AF for dose response relationship:

1

Justification:

ECHA Default

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 Triethoxy(2,4,4-trimethylpentyl)silane on the following grounds: 1) The silanol hydrolysis product of the substance (and many other related substances) shows no biodegradation in a ready biodegradation test other than can be accounted for by degradation of non-silanol hydrolysis products (see Section 4); this suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems. 2) Toxicokinetic arguments show that the silanol hydrolysis product has low log Kow and hence low uptake, rapid excretion via urine, which would be true in all mammals, with minimal interspecies differences.

AF for other interspecies differences:

2.5

Justification:

ECHA Default

AF for intraspecies differences:

3.2

Justification:

ECHA Default

AF for the quality of the whole database:

1

Justification:

ECHA Default

AF for remaining uncertainties:

1

Justification:

ECHA Default

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified