Diethyl oxalate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.3 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):

75

Dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

24.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

There is no adequate experimental data on the inhalation route available. Therefore, the worker-DNEL long-term for inhalation route - systemic is derived from the NOAEL of 20 mg/kg bw/day, obtained in the key subacute oral repeated dose study in Wistar rats. The NOAECcorr. is calculated as follows:

- standard respiratory volume rat = 0.38 m³/kg/8h

- standard respiratory volume human = 6.7 m³/8h

- worker respiratory volume = 10 m³/8h

- absorption (oral, rat) = 50 %

- absorption (inhalative, human) = 100 % (default)

--> modified dose descriptor (corrected inhalatory NOAEC) = 20 mg/kg bw/day * (1/0.38 m³/kg/d) * (6.7 m³ (8h)/10 m³ (8h)) * (0.5/1) * (7 exposure days/week; rat/5 exposure days/week; worker) = 24.7 mg/m³

AF for dose response relationship:

1

Justification:

ECHA REACH Guidance (starting point for the DNEL calculation is a NOAEL)

AF for differences in duration of exposure:

6

Justification:

ECHA REACH Guidance (subacute --> chronic)

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

ECHA REACH Guidance

AF for intraspecies differences:

5

Justification:

ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

ECHA REACH Guidance (good/standard quality of the database)

AF for remaining uncertainties:

1

Justification:

ECHA REACH Guidance

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.3 mg/m³

DNEL related information

Explanation for the modification of the dose descriptor starting point:

There is no adequate experimental data on the inhalation route available. The worker-DNEL long-term for inhalation route - systemic is asumed for this exposure scenario as well.

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.06 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):

150

Dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

8.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

There is no adequate experimental data on the inhalation route available. Therefore, the general population-DNEL long-term for inhalation route - systemic is derived from the NOAEL of 20 mg/kg bw/day, obtained in the key subacute oral repeated dose study in Wistar rats. The NOAECcorr. is calculated as follows:

- standard respiratory volume rat = 1.15 m³/kg/24h

- absorption (oral, rat) = 50 %

- absorption (inhalative, human) = 100 % (default)

--> modified dose descriptor (corrected inhalatory NOAEC) = 20 mg/kg bw/day * (1/1.15 m³/kg/d) * (0.5/1) = 8.7 mg/m³

AF for dose response relationship:

1

Justification:

ECHA REACH Guidance (starting point for the DNEL calculation is a NOAEL)

AF for differences in duration of exposure:

6

Justification:

ECHA REACH Guidance (subacute --> chronic)

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

ECHA REACH Guidance

AF for intraspecies differences:

10

Justification:

ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

ECHA REACH Guidance (good/standard quality of the database)

AF for remaining uncertainties:

1

Justification:

ECHA REACH

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.033 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):

600

Dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by the dermal route.

The consumer DNEL long-term for dermal route - systemic is derived from the NOAEL of 20 mg/kg bw/day obtained in the key subacute repeated dose oral toxicity study in Wistar Han rats (Research Institute for Organic Syntheses Inc., 2011). The dermal NOAEL is calculated as follows: NOAELdermal = NOAELoral*ABSoral-rat/ABSderm-human = 20 mg/kg bw/day*(0.5/0.5) = 20 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor for remaining interspecies differences

AF for intraspecies differences:

10

Justification:

The ECHA default value for the group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.033 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):

600

Modified dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not applicable.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Default ECHA assessment factor for remaining interspecies differences

AF for intraspecies differences:

10

Justification:

The ECHA default value for the group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)