Propionaldehyde, reaction product with formaldehyde

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.7 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

DNEL value:

316 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

DNEL value:

278.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point for 8 hours of exposure was calculated according to Ref Figure R.8-3:

Corrected inhalatory NOEC =oral NOEL * (1 / sRV, rat) * (ABSoral, rat / ABSinh-human) * (sRVhuman / wRV)

Where

- sRV, rat = standard Respiratory Volume, rat =m3/kg for 8 hours

- ABS = absorption

- ABSoral, rat / ABSinh-human = 1 / 2 (default factor for extrapolation from oral to inhalation)

- sRVhuman = standard Respiratory Volume, human = 6.7 m3/person for 8 hours

- wRV = standard Respiratory Volume, worker = 10 m3/person for 8 hours

Therefore the dose descriptor starting point is:

316 mg/kg bw * (1 /m3/kg bw) * 1/2 * (6.7 m3 / 10 m3) = 278.6 mg/m3

AF for dose response relationship:

1

Justification:

Assessment factor for dose response (starting point is a NOAEL)

AF for differences in duration of exposure:

6

Justification:

Assessment factors for exposure duration (sub-acute to chronic study)

AF for interspecies differences (allometric scaling):

1

Justification:

No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC

AF for other interspecies differences:

2.5

Justification:

Assessment factors for remaining non-metabolic differences

AF for intraspecies differences:

5

Justification:

Assessment factors for workers

AF for the quality of the whole database:

1

Justification:

Good quality study

AF for remaining uncertainties:

1

Justification:

No additional factors are required

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

70.5 mg/m³

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

125

Dose descriptor starting point:

other: LD50

DNEL value:

5 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

DNEL value:

8 816 mg/m³

Explanation for the modification of the dose descriptor starting point:

No acute inhalation study is available. Therefore the data of the acute oral toxicity study are used: LD50 oral, rat >5000 mg/kg bw.

The dose descriptor starting point for 4 hours of exposure was calculated according to Ref Figure R.8-3:

Corrected inhalatory NOEC =

= oral NOEL * (1 / sRV, rat) * (ABSoral, rat / ABSinh-human) * (sRVhuman / wRV)

Where

- sRV, rat = standard Respiratory Volume, rat =m3/kg bw for 4 hours

- ABS = absorption

- ABSoral, rat / ABSinh-human = 1 / 2 (default factor for extrapolation from oral to inhalation)

- sRVhuman = standard Respiratory Volume, human =m3/person for 4 hours

- wRV = standard Respiratory Volume, worker = 5 m3/person for 4 hours

Therefore the dose descriptor starting point is:

5000 mg/kg bw * (1 / 0,19 m3/kg bw) * 1/2 * (3.35 m3 / 5 m3) = 8816 mg/m3

AF for dose response relationship:

10

Justification:

As some transient signs of toxicity were noted at that dose, a factor of 10 is therefore applied to cover the ratio of LD50/NOAEC

AF for interspecies differences (allometric scaling):

1

Justification:

No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC

AF for other interspecies differences:

2.5

Justification:

Assessment factors for remaining non-metabolic differences

AF for intraspecies differences:

5

Justification:

Assessment factors for workers

AF for the quality of the whole database:

1

Justification:

Good quality study

AF for remaining uncertainties:

1

Justification:

No additional factors are required

Local effects

Long term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.1 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):

300

Dose descriptor starting point:

NOAEL

DNEL value:

316 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

DNEL value:

316 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The dermal absorption is considered to be generally lower than the oral absorption. As a worst case it is therefore assumed that the NOAELdermal = NOAELoral.

AF for dose response relationship:

1

Justification:

Assessment factor for dose-response (starting point is a NOAEL)

AF for differences in duration of exposure:

6

Justification:

Assessment factors for exposure duration (sub-acute to chronic study)

AF for interspecies differences (allometric scaling):

4

Justification:

Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)

AF for other interspecies differences:

2.5

Justification:

Assessment factors for remaining non-metabolic differences

AF for intraspecies differences:

5

Justification:

Assessment factors for workers

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Justification:

No additional factors are required

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

40 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEL

DNEL value:

2 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

DNEL value:

2 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not required; as acute dermal study was available.

AF for dose response relationship:

1

Justification:

As no toxic signs were noted at the LD50, dermal, the dermal LD50 is considered to be also the NOAEL, dermal. A factor of 1 is therefore applied to cover the ratio of LD50/NOAEL.

AF for interspecies differences (allometric scaling):

4

Justification:

Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)

AF for other interspecies differences:

2.5

Justification:

Assessment factor for any remaining non-metabolic differences

AF for intraspecies differences:

5

Justification:

Assessment factor for workers

AF for the quality of the whole database:

1

Justification:

Good quality study

AF for remaining uncertainties:

1

Justification:

No additional assessment factors are required

Local effects

Long term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

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:

0.92 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

DNEL value:

316 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

DNEL value:

137.4 mg/m³

Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point:

The dose descriptor starting point for 24 hours of exposure was calculated according to Ref Figure R.8-3:

Corrected inhalatory NOEC= oral NOEL * (1 / sRV, rat) * (ABSoral, rat / ABSinh-human)

Where

- sRV, rat = standard Respiratory Volume, rat =m3/kg for 24 hours)

- ABS = absorption

- ABSoral, rat / ABSinh-human = 1 / 2 (default factor for extrapolation from oral to inhalation)

Therefore the starting dose descriptor is:

316 mg/kg bw * (1 /m3/kg bw) * 1/2 = 137.4 mg/m3

AF for dose response relationship:

1

Justification:

Assessment factor for dose response (starting point is a NOAEL)

AF for differences in duration of exposure:

6

Justification:

Assessment factors for exposure duration (sub-acute to chronic study)

AF for interspecies differences (allometric scaling):

1

Justification:

No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC

AF for other interspecies differences:

2.5

Justification:

Assessment factor for any remaining non-metabolic differences

AF for intraspecies differences:

10

Justification:

Assessment factor for general population

AF for the quality of the whole database:

1

Justification:

Good quality study

AF for remaining uncertainties:

1

Justification:

No additional assessment factors are required

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

21.1 mg/m³

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

250

Dose descriptor starting point:

other: LD50

DNEL value:

5 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

DNEL value:

5 263 mg/m³

Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point:

No acute inhalation study is available. Therefore the data of the acute oral toxicity study are used: LD50 oral, rat >5000 mg/kg bw.

The dose descriptor starting point for 4 hours of exposure was calculated according to Ref Figure R.8-3:

Corrected inhalatory NOEC= oral NOEL * (1 / sRV, rat) * (ABSoral, rat / ABSinh-human)

Where

- sRV, rat = standard Respiratory Volume, rat =m3/kg bw for 4 hours

- ABS = absorption

- ABSoral, rat / ABSinh-human = 1 / 2 (default factor for extrapolation from oral to inhalation)

Therefore the starting dose descriptor is:

5000 mg/kg bw * (1 /m3/kg bw) * 1/2 = 5263 mg/m3

AF for dose response relationship:

10

Justification:

As some transient signs of toxicity were noted at that dose, a factor of 10 is therefore applied to cover the ratio of LD50/NOAEC

AF for interspecies differences (allometric scaling):

1

Justification:

No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC)

AF for other interspecies differences:

2.5

Justification:

Assessment factors for remaining non-metabolic differences

AF for intraspecies differences:

10

Justification:

Assessment factors for general population

AF for the quality of the whole database:

1

Justification:

Good quality study

AF for remaining uncertainties:

1

Justification:

No additional factors are required

Local effects

Long term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.5 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):

600

Dose descriptor starting point:

NOAEL

DNEL value:

316 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

DNEL value:

316 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The dermal absorption is considered to be generally lower than the oral absorption. As a worst case it is therefore assumed that the NOAELdermal = NOAELoral.

AF for dose response relationship:

1

Justification:

Assessment factor fior dose-response (starting point is a NOAEL)

AF for differences in duration of exposure:

6

Justification:

Assessment factors for exposure duration (sub-acute to chronic study)

AF for interspecies differences (allometric scaling):

4

Justification:

Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)

AF for other interspecies differences:

2.5

Justification:

Assessment factors for remaining non-metabolic differences

AF for intraspecies differences:

10

Justification:

Assessment factors for general population

AF for the quality of the whole database:

1

Justification:

Good quality study

AF for remaining uncertainties:

1

Justification:

No additional factors are required

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEL

DNEL value:

2 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

DNEL value:

2 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not required; as an acute dermal study was available

AF for dose response relationship:

1

Justification:

As no toxic signs were noted at the LD50, dermal, the dermal LD50 is considered to be also the NOAEL, dermal. A factor of 1 is therefore applied to cover the ratio of LD50/NOAEL.

AF for interspecies differences (allometric scaling):

4

Justification:

Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)

AF for other interspecies differences:

2.5

Justification:

Assessment factor for any remaining non-metabolic differences

AF for intraspecies differences:

10

Justification:

Assessment factor for general population

AF for the quality of the whole database:

1

Justification:

Good quality study

AF for remaining uncertainties:

1

Justification:

No additional assessment factors are required

Local effects

Long term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Most sensitive endpoint:

acute toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.5 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):

600

Dose descriptor starting point:

NOAEL

DNEL value:

316 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

DNEL value:

316 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not required; as an repeated dose oral toxicity study was available

AF for dose response relationship:

1

Justification:

Assessment factor for dose-response (starting point is a NOAEL)

AF for differences in duration of exposure:

6

Justification:

Assessment factors for exposure duration (sub-acute to chronic study)

AF for interspecies differences (allometric scaling):

4

Justification:

Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)

AF for other interspecies differences:

2.5

Justification:

Assessment factor for any remaining non-metabolic differences

AF for intraspecies differences:

10

Justification:

Assessment factor for general population

AF for the quality of the whole database:

1

Justification:

Good quality study

AF for remaining uncertainties:

1

Justification:

No additional assessment factors are required

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1 000

Dose descriptor starting point:

other: LD50

DNEL value:

5 000 mg/kg bw/day

Modified dose descriptor starting point:

other: LD50

DNEL value:

5 000 mg/kg bw/day

AF for dose response relationship:

10

Justification:

As some transient signs of toxicity were noted at that dose, a factor of 10 is therefore applied to cover the ratio of LD50/NOAEC

AF for interspecies differences (allometric scaling):

4

Justification:

Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)

AF for other interspecies differences:

2.5

Justification:

Assessment factor for any remaining non-metabolic differences

AF for intraspecies differences:

10

Justification:

Assessment factor for general population

AF for the quality of the whole database:

1

Justification:

Good quality study

AF for remaining uncertainties:

1

Justification:

No additional assessment factors are required

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified