Tetrakis(2-butoxyethyl) orthosilicate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

44 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Dose descriptor starting point:

NOAEL

Value:

25 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

44.08 mg/m³

Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEL (oral): Correction respiratory volume rat (8 hour) 1/0.38 m³/kg bw/day, Correction for respiratory volume (worker): 6.7 m³/10 m³. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: oral 25*(1/0.38) *(6.7 m³/10 m³) = 44.08 mg/m³.

AF for dose response relationship:

1

Justification:

ECHA default

AF for differences in duration of exposure:

2

Justification:

The toxicity of the registered substance is due to the haemotoxicity of the metabolite (BAA) of the hydrolysis product (2-butoxyethanol). Oral subchronic data for 2-butoxyethanol gave a similar NOAEL as was concluded in the sub-acute study on the registered substance. There is also evidence that sublethal doses of 2-butoxyethanol are protective against the haemotoxic effects of subsequent exposures, and chronic data for 2-butoxyethanol show that effects are secondary to haemotoxicity. Therefore, it is reasonable to use the assessment factor for subchronic to chronic exposure duration as a conservative measure.

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA default for rat oral to human inhalation exposure

AF for other interspecies differences:

0.1

Justification:

There is a well-developed PBPK model for 2-butoxyethanol and data which show humans are at least an order of magnitude less susceptible than rats to the haemolytic effects of BAA. The OECD 422 test on the registered substance clearly showed that all observed toxicity related to haemolytic effects, which it is reasonable to assume were due to the hydrolysis product. Therefore, an assessment factor of less than one is justified. This assessment factor is in line with that agreed in the EU risk assessment of 2-butoxyethanol (2008).

AF for intraspecies differences:

5

Justification:

ECHA default as the variation in susceptibility is not known for the human population.

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:

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:

25 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):

1

Dose descriptor starting point:

NOAEL

Value:

25 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:

The toxicity of the registered substance is due to the haemotoxicity of the metabolite (BAA) of the hydrolysis product (2-butoxyethanol). Oral subchronic data for 2-butoxyethanol gave a similar NOAEL as was concluded in the sub-acute study on the registered substance. There is also evidence that sublethal doses of 2-butoxyethanol are protective against the haemotoxic effects of subsequent exposures, and chronic data for 2-butoxyethanol show that effects are secondary to haemotoxicity. Therefore, it is reasonable to use the assessment factor for subchronic to chronic exposure duration as a conservative measure.

AF for interspecies differences (allometric scaling):

1

Justification:

See explanation for interspecies differences

AF for other interspecies differences:

0.1

Justification:

There is a well-developed PBPK model for 2-butoxyethanol and data which show humans are at least an order of magnitude less susceptible than rats to the haemolytic effects of BAA. The OECD 422 test on the registered substance clearly showed that all observed toxicity related to haemolytic effects, which it is reasonable to assume were due to the hydrolysis product. Therefore, an assessment factor of less than one is justified. This assessment factor is in line with that agreed in the EU risk assessment of 2-butoxyethanol (2008).

AF for intraspecies differences:

5

Justification:

ECHA default

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:

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:

10.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

2

Dose descriptor starting point:

NOAEL

Value:

25 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

21.74 mg/m³

Explanation for the modification of the dose descriptor starting point:

The following correction was made to the NOAEL (oral): Correction respiratory volume rat (24 hour) 1/1.15 m³/kg bw. Therefore, the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 25*(1/1.15) = 21.74 mg/m³.

AF for dose response relationship:

1

Justification:

ECHA default

AF for differences in duration of exposure:

2

Justification:

The toxicity of the registered substance is due to the haemotoxicity of the metabolite (BAA) of the hydrolysis product (2-butoxyethanol). Oral subchronic data for 2-butoxyethanol gave a similar NOAEL as was concluded in the sub-acute study on the registered substance. There is also evidence that sublethal doses of 2-butoxyethanol are protective against the haemotoxic effects of subsequent exposures, and chronic data for 2-butoxyethanol show that effects are secondary to haemotoxicity. Therefore, it is reasonable to use the assessment factor for subchronic to chronic exposure duration as a conservative measure.

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA default for rat oral to human inhalation exposure

AF for other interspecies differences:

0.1

Justification:

There is a well-developed PBPK model for 2-butoxyethanol, and data which show humans are at least an order of magnitude less susceptible than rats to the haemolytic effects of BAA. The OECD 422 test on the registered substance clearly showed that all observed toxicity related to haemolytic effects, which it is reasonable to assume were due to the hydrolysis product. Therefore, an assessment factor of less than one is justified. This assessment factor is in line with that agreed in the EU risk assessment of 2-butoxyethanol (2008).

AF for intraspecies differences:

10

Justification:

ECHA default as the variation in susceptibility is not known for the human population.

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:

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:

12.5 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):

2

Dose descriptor starting point:

NOAEL

Value:

25 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:

The toxicity of the registered substance is due to the haemotoxicity of the metabolite (BAA) of the hydrolysis product (2-butoxyethanol). Oral subchronic data for 2-butoxyethanol gave a similar NOAEL as was concluded in the sub-acute study on the registered substance. There is also evidence that sublethal doses of 2-butoxyethanol are protective against the haemotoxic effects of subsequent exposures, and chronic data for 2-butoxyethanol show that effects are secondary to haemotoxicity. Therefore, it is reasonable to use the assessment factor for subchronic to chronic exposure duration as a conservative measure.

AF for interspecies differences (allometric scaling):

1

Justification:

See explanation in interspecies differences

AF for other interspecies differences:

0.1

Justification:

There is a well-developed PBPK model for 2-butoxyethanol, and data which show humans are at least an order of magnitude less susceptible than rats to the haemolytic effects of BAA. The OECD 422 test on the registered substance clearly showed that all observed toxicity related to haemolytic effects, which it is reasonable to assume were due to the hydrolysis product. Therefore, an assessment factor of less than one is justified. This assessment factor is in line with that agreed in the EU risk assessment of 2-butoxyethanol (2008).

AF for intraspecies differences:

10

Justification:

ECHA default as the variation in susceptibility is not known for the human population.

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:

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:

DNEL (Derived No Effect Level)

Value:

12.5 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):

2

Dose descriptor starting point:

NOAEL

Value:

25 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:

The toxicity of the registered substance is due to the haemotoxicity of the metabolite (BAA) of the hydrolysis product (2-butoxyethanol). Oral subchronic data for 2-butoxyethanol gave a similar NOAEL as was concluded in the sub-acute study on the registered substance. There is also evidence that sublethal doses of 2-butoxyethanol are protective against the haemotoxic effects of subsequent exposures, and chronic data for 2-butoxyethanol show that effects are secondary to haemotoxicity. Therefore, it is reasonable to use the assessment factor for subchronic to chronic exposure duration as a conservative measure.

AF for interspecies differences (allometric scaling):

1

Justification:

See explanation in interspecies differences

AF for other interspecies differences:

0.1

Justification:

There is a well-developed PBPK model for 2-butoxyethanol, and data which show humans are at least an order of magnitude less susceptible than rats to the haemolytic effects of BAA. The OECD 422 test on the registered substance clearly showed that all observed toxicity related to haemolytic effects, which it is reasonable to assume were due to the hydrolysis product. Therefore, an assessment factor of less than one is justified. This assessment factor is in line with that agreed in the EU risk assessment of 2-butoxyethanol (2008).

AF for intraspecies differences:

10

Justification:

ECHA default as the variation in susceptibility is not known for the human population.

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:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified