Fatty acids, C18-unsatd, dimers, hydrogenated, diisopropyl esters

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

43.64 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

Modified dose descriptor starting point:

NOAEC

Value:

1 090.9 mg/m³

Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 618.75 mg/kg bw/day*(1/0.38 m³/kg bw/day)*(1/1)*0.67 = 1090.9 mg/m³. It is assumed that oral absorption rate is 100% of that of inhalation absorption. ABSoral-rat=oral absorption rate in rats, ABSinh-human=inhalation absorption rate in humans.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL

AF for differences in duration of exposure:

2

Justification:

The DNEL is based on a subchronic study

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

5

Justification:

Default AF for workers

AF for the quality of the whole database:

1

Justification:

DNEL is based on a high quality study

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

61.88 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

Modified dose descriptor starting point:

NOAEL

Value:

6 187.5 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NOAELcorr = NOAELoral*(ABSoral-rat/ABSder-human) = 618.75 mg/kg bw/day*(1/0.1) = 6187.5 mg/kg bw/day. Regarding molecular weight, log Pow and water solubility, the dermal absorption was judged to be negligible (see section 7.1 dermal absorption). Therefore, assuming a dermal absorption of 10% displays a sufficient conservative approach.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL

AF for differences in duration of exposure:

2

Justification:

The DNEL is based on a subchronic study

AF for interspecies differences (allometric scaling):

4

Justification:

Default AF for rat

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

5

Justification:

Default AF for workers

AF for the quality of the whole database:

1

Justification:

DNEL is based on a high quality study

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

no hazard identified

Additional information - workers

Dermal DNEL worker:

 

The calculation of the dermal DNEL was based on the subchronic (90-day) oral NOAEL derived at of 125 mg/kg bw/day in rats for 2-ethylhexanol. This corresponds to a subchronic NAEL for Fatty acids, C18-unsatd., dimers, hydrogenated, diisopropyl esters of 618.75 mg/kg bw/day, as corrected for the molecular weight ratio using a correction factor of 4.95 for calculations (645.06/130.23 ~ 4.95) (see IUCLID section 7.5, repeated dose toxicity).

 

Assessment factors were applied according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, November 2012.

 

Based on molecular weight, log Pow and water solubility, the dermal absorption was judged to be negligible (see section 7.1 dermal absorption). Therefore, assuming a dermal absorption of 10% is considered to be a sufficient conservative approach. (Route to route extrapolation: NOAELcorr-dermal (oral to dermal): 618.75 mg/kg bw/day, divided by 0.1 = 6187.5 mg/kg bw/day).

 

Inhalation DNEL worker:

 

The calculation of the inhalation DNEL was based on the subchronic (90-day) oral NOAEL derived at 125 mg/kg bw/day in rats for 2-ethylhexanol. Route to route extrapolation: NOAECcorr-inhal (oral to inhal): 618.75 mg/kg/day, divided by 0.38 m³/kg/day multiplied with factor 0.67 = 1090.9 mg/m³/day.

 

Assessment factors were applied according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, November 2012.

 

The available 90-day vapour inhalation study with 2-ethylhexanol (Klimisch, 1998) was not taken into consideration for derivation of inhalation DNEL, as the inhalation exposure to a vapour of 2-ethylhexanol should not be directly compared with an inhalation exposure to an aerosol (droplets) of Fatty acids, C18-unsatd., dimers, diisopropyl esters. Therefore, the route to route extrapolation from the subchronic oral study on 2-ethylhexanol was judged to be more adequate.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.76 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

Modified dose descriptor starting point:

NOAEC

Value:

538.04 mg/m³

Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral*(1/1.15 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)= 618.75 mg/kg bw/day*(1/1.15 m³/kg bw/day) = 538.04 mg/m³. It is assumed that oral absorption rate is 100% of that of inhalation absorption. ABSoral-rat=oral absorption rate in rats, ABSinh-human=inhalation absorption rate in humans.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL

AF for differences in duration of exposure:

2

Justification:

The DNEL is based on a subchronic study

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

10

Justification:

Default AF for general population

AF for the quality of the whole database:

1

Justification:

DNEL is based on a high quality study

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

30.94 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

Modified dose descriptor starting point:

NOAEL

Value:

6 187.5 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NOAELcorr = NOAELoral*(ABSoral-rat/ABSder-human) = 618.75 mg/kg bw/day*(1/0.1) = 6187.5 mg/kg bw/day. Regarding molecular weight, log Pow and water solubility, the dermal absorption was judged to be negligible (see section 7.1 dermal absorption). Therefore, assuming a dermal absorption of 10% displays a sufficient conservative approach.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL

AF for differences in duration of exposure:

2

Justification:

The DNEL is based on a subchronic study

AF for interspecies differences (allometric scaling):

4

Justification:

Default AF for rat

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

10

Justification:

Default AF for general population

AF for the quality of the whole database:

1

Justification:

DNEL is based on a high quality study

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

3.09 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

Modified dose descriptor starting point:

NOAEL

Value:

618.75 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral*(ABSoral-rat/ABSoral-human) = 618.75 mg/kg bw/day*(1/1) = 618.75 mg/kg bw/day. It is assumed that oral absorption rate in rats and human is 100%. ABSoral-rat = ABSoral-human.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL

AF for differences in duration of exposure:

2

Justification:

The DNEL is based on a subchronic study

AF for interspecies differences (allometric scaling):

4

Justification:

Default AF for rat

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

10

Justification:

Default AF for general population

AF for the quality of the whole database:

1

Justification:

DNEL is based on a high quality study

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Dermal DNEL consumer:

The calculation of the dermal DNEL was based on the subchronic (90-day) oral NOAEL derived at of 125 mg/kg bw/day in rats for 2-ethylhexanol. This corresponds to a subchronic NAEL for Fatty acids, C18-unsatd., dimers, hydrogenated, diisopropyl esters of 618.75 mg/kg bw/day, as corrected for the molecular weight ratio using a correction factor of 4.95 for calculations (645.06/130.23 ~ 4.95) (see IUCLID section 7.5, repeated dose toxicity).

 

Assessment factors were applied according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, November 2012.

 

Based on molecular weight, log Pow and water solubility, the dermal absorption was judged to be negligible (see section 7.1 dermal absorption). Therefore, assuming a dermal absorption of 10% is considered to be a sufficient conservative approach. (Route to route extrapolation: NOAELcorr-dermal (oral to dermal): 618.75 mg/kg bw/day, divided by 0.1 = 6187.5 mg/kg bw/day).

 

Inhalation DNEL consumer:

 

The calculation of the inhalation DNEL was based on the subchronic (90-day) oral NOAEL derived at 125 mg/kg bw/day in rats for 2-ethylhexanol. Route to route extrapolation: NOAECcorr-inhal (oral to inhal): 618.75 mg/kg/day divided by 1.15 = 538.04 mg/m³/day.

 

Assessment factors were applied according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, November 2012.

 

The available 90-day vapour inhalation study with 2-ethylhexanol (Klimisch, 1998) was not taken into consideration for derivation of inhalation DNEL, as the inhalation exposure to a vapour of 2-ethylhexanol should not be directly compared with an inhalation exposure to an aerosol (droplets) of Fatty acids, C18-unsatd., dimers, diisopropyl esters. Therefore, the route to route extrapolation from the subchronic oral study on 2-ethylhexanol was judged to be more adequate.

 

Oral DNEL consumer:

 

The calculation of the oral DNEL was based on the subchronic (90-day) oral NOAEL derived at 125 mg/kg bw/day in rats for 2-ethylhexanol. This corresponds to a subchronic NAEL for Fatty acids, C18-unsatd., dimers, hydrogenated, diisopropyl esters of 618.75 mg/kg bw/day, as corrected for the molecular weight ratio using a correction factor of 4.95 for calculations (645.06/130.23 ~ 4.95) (see IUCLID section 7.5, repeated dose toxicity).

 

Assessment factors were applied according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, November 2012.