3-ethyloxetane-3-methanol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

35 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):

25

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

882 mg/m³

Explanation for the modification of the dose descriptor starting point:

The starting point is the NOAEL of 1000 mg/kg bw/d from the rat oral 90 -day toxicity study. This starting point is corrected for the relative extent of oral absorption (default assumption, 50%) and inhalation absorption (100%) and for activity and breathing rate (x1/0.38 x 6.7/10) to give a corrected inhalation starting point (NOAEC) of 882 mg/m3.

AF for dose response relationship:

1

Justification:

Default factor

AF for differences in duration of exposure:

2

Justification:

A default value of 2 is proposed for extrapolation from a sub-chronic study to chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

Not required: already accounted for in correction of the starting point

AF for other interspecies differences:

2.5

Justification:

Default factor

AF for intraspecies differences:

5

Justification:

Default factor for workers

AF for the quality of the whole database:

1

Justification:

Default factor

AF for remaining uncertainties:

1

Justification:

Default factor: no significant 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:

10 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):

100

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The starting point is the NOAEL of 1000 mg/kg bw/d from the rat oral 90 -day study. In the absence of dermal absorption data, dermal absorption is assumed to be equivalent to oral absorption. The corrected dermal starting point is therefore 1000 mg/kg bw/d.

AF for dose response relationship:

1

Justification:

Default factor

AF for differences in duration of exposure:

2

Justification:

Default factor for extrapolating from a sub-chronic study to chronic exposure.

AF for interspecies differences (allometric scaling):

4

Justification:

Default factor (starting point is a rat study)

AF for other interspecies differences:

2.5

Justification:

Default factor

AF for intraspecies differences:

5

Justification:

Default factor for workers

AF for the quality of the whole database:

1

Justification:

Default factor

AF for remaining uncertainties:

1

Justification:

Default factor: no significant 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

Worker DNEL derivation

Inhalation DNELs

The starting point is the NOAEL of 1000 mg/kg bw/d from the rat oral 90 -day toxicity study. This starting point is corrected for the relative extent of oral absorption (default assumption, 50%) and inhalation absorption (100%) and for activity and breathing rate (x1/0.38 x 6.7/10) to give a corrected inhalation starting point (NOAEC) of 882 mg/m3. Individual assessment factors of 1 (for dose-response relationship), 2 (exposure duration), 1 (allometric scaling), 2.5 (other interspecies differences), 5 (intraspecies differences), 1 (database quality) and 1 (remaining uncertainties) are combined to give an overall assessment factor of 25. Applying the overall assessment factor to the corrected starting point results in a long-term systemic DNEL of 35 mg/m3.

The substance is of low systemic toxicity. No acute toxicity hazard resulting in classification has been identified, therefore a DNEL for acute systemic effects is not proposed.

No data are available for respiratory irritation; no hazard is identified therefore local inhalation DNELs are not proposed.

Dermal DNELs

The starting point is the NOAEL of 1000 mg/kg bw/d from the rat oral 90 -day toxicity study. In the absence of dermal absorption data, dermal absorption is assumed to be equivalent to oral absorption. The corrected dermal starting point is therefore 1000 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 2 (for exposure duration), 4 (allometric scaling), 2.5 (other interspecies differences), 5 (intraspecies differences), 1 (database quality) and 1 (remaining uncertainties) are combined to give an overall assessment factor of 100. Applying the overall assessment factor to the corrected starting point results in a DNEL of 10 mg/kg bw/d.

The substance is of low systemic toxicity. No acute toxicity hazard resulting in classification has been identified, therefore a DNEL for acute systemic effects is not proposed.

The substance is not a skin irritant or skin sensitiser; therefore local dermal DNELs are not derived.

An eye irritation study indicates that the substance is an eye irritant (CLP Cat 2). Low hazard is assigned according to ECHA CSA Guidance Part E Table E3-1.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

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):

50

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

435 mg/m³

Explanation for the modification of the dose descriptor starting point:

The starting point is the NOAEL of 1000 mg/kg bw/d from the rat oral 90 -day toxicity study. This starting point is corrected for the relative extent of oral absorption (default assumption, 50%) and inhalation absorption (100%) and for breathing rate (x1/1.15) to give a corrected inhalation starting point (NOAEC) of 435 mg/m3. 

AF for dose response relationship:

1

Justification:

Default factor

AF for differences in duration of exposure:

2

Justification:

Default factor for extrapolating from a subchronic study to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

Not required: already taken into account in correction of the starting point

AF for other interspecies differences:

2.5

Justification:

Default value

AF for intraspecies differences:

10

Justification:

Default value for general population

AF for the quality of the whole database:

1

Justification:

Default factor

AF for remaining uncertainties:

1

Justification:

Default factor: no significant 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:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

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):

200

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The starting point is the NOAEL of 1000 mg/kg bw/d from the rat oral 90 -day toxicity study.  In the absence of dermal absorption data, dermal absorption is assumed to be equivalent to oral absorption. The corrected dermal starting point is therefore 1000 mg/kg bw/d.

AF for dose response relationship:

1

Justification:

Default factor

AF for differences in duration of exposure:

2

Justification:

Default factor for extrapolating from subchronic study to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

Default factor (starting point is a rat study)

AF for other interspecies differences:

2.5

Justification:

Default factor

AF for intraspecies differences:

10

Justification:

Default factor for general population

AF for the quality of the whole database:

1

Justification:

Default factor

AF for remaining uncertainties:

1

Justification:

Default factor: no significant remaining uncertainty

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:

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):

200

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

other: modification not required

Explanation for the modification of the dose descriptor starting point:

The starting point is the NOAEL of 1000 mg/kg bw/d from a 90 -day rat oral toxicity study. Modification of the starting point is not required.

AF for dose response relationship:

1

Justification:

Default factor

AF for differences in duration of exposure:

2

Justification:

Default factor for extrapolating from subchronic study to chronic exposures

AF for interspecies differences (allometric scaling):

4

Justification:

Default factor (starting point is from a rat study)

AF for other interspecies differences:

2.5

Justification:

Default factor

AF for intraspecies differences:

10

Justification:

Default factor for general population

AF for the quality of the whole database:

1

Justification:

Default factor

AF for remaining uncertainties:

1

Justification:

Default factor: no significant 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:

low hazard (no threshold derived)

Additional information - General Population

General population DNELs

Inhalation DNELs

The starting point is the NOAEL of 1000 mg/kg bw/d from the rat oral 90 -day toxicity study. This starting point is corrected for the relative extent of oral absorption (default assumption, 50%) and inhalation absorption (100%) and for breathing rate (x1/1.15) to give a corrected inhalation starting point (NOAEC) of 435 mg/m3.  Individual assessment factors of 1 (for dose-response relationship), 2 (exposure duration), 1 (allometric scaling), 2.5 (other interspecies differences), 10 (intraspecies differences), 1 (database quality) and 1 (remaining uncertainties) are combined to give an overall assessment factor of 50. Applying the overall assessment factor to the corrected starting point results in a long-term systemic DNEL of 9 mg/m3.

The substance is of low systemic toxicity. No acute toxicity hazard resulting in classification has been identified, therefore a DNEL for acute systemic effects is not proposed.

No data are available for respiratory irritation; no hazard is identified therefore local inhalation DNELs are not proposed.

Dermal DNELs

The starting point is the NOAEL of 1000 mg/kg bw/d from the rat oral 90 -day toxicity study.  In the absence of dermal absorption data, dermal absorption is assumed to be equivalent to oral absorption. The corrected dermal starting point is therefore 1000 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 2 (for exposure duration), 4 (allometric scaling), 2.5 (other interspecies differences), 10 (intraspecies differences), 1 (database quality) and 1 (remaining uncertainties) are combined to give an overall assessment factor of 200. Applying the overall assessment factor to the corrected starting point results in a DNEL of 5 mg/kg bw/d. 

The substance is of low systemic toxicity. No acute toxicity hazard resulting in classification has been identified, therefore a DNEL for acute systemic effects is not proposed.

The substance is not a skin irritant or skin sensitiser; therefore local dermal DNELs are not derived.

Oral DNELs

The starting point is the NOAEL of 1000 mg/kg bw/d from a 90 -day rat oral toxicity study. Modification of the starting point is not required. Individual assessment factors of 1 (for dose-response relationship), 2 (for exposure duration), 4 (allometric scaling), 2.5 (other interspecies differences), 10 (intraspecies differences), 1 (database quality) and 1 (remaining uncertainties) are combined to give an overall assessment factor of 200. Applying the overall assessment factor to the starting point results in a DNEL of 5 mg/kg bw/d.

The substance is of low systemic toxicity. No acute toxicity hazard resulting in classification has been identified, therefore a DNEL for acute systemic effects is not proposed.

An eye irritation study indicates that the substance is an eye irritant (CLP Cat 2). Low hazard is assigned according to ECHA CSA Guidance Part E Table E3-1.