Fatty acids, C16-18 and C18-unsatd., compds. with triethanolamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

21.2 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

75

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

1 587 mg/m³

Explanation for the modification of the dose descriptor starting point:

Key oral combined repeated dose toxicity/reproductive and developmental toxicity study is available; no repeated dose inhalation toxicity study is available. Inhalation absorption is considered 30% versus 90% oral absorption.

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):

1

Justification:

Allometric scaling is already taken into account in route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

5

Justification:

Default factor according to ECHA guidance document.

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:

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

Acute/short term exposure

Hazard assessment conclusion:

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

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

9 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

300

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

2 700 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Key oral combined repeated dose toxicity/reproductive and developmental toxicity study available; no repeated dose dermal toxicity study available. Dermal absorption is considered 10% versus 90% oral absorption as conservative approach.

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 factor according to ECHA guidance document.

AF for intraspecies differences:

5

Justification:

Default factor according to ECHA guidance document.

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:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

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

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

Source of DNEL-derivation:

In an OECD guideline 422 study, the test item was administered by oral gavage to rats at dose levels of 100, 300 or 1000 mg/kg bw/day. The application started two weeks before mating on test day one and ended on the day or one day before sacrifice. Day of sacrifice was on test days 31/32 for the male rats and on lactation day 4 or shortly thereafter for the female rats.

No premature deaths were noted. Sporadic and transient salivation and breathing sounds were noted during the pre-mating period for 2 male and 2 female animals of the intermediate and the high dose group (300 or 1000 mg test item/kg bw/day), however these changes were not considered to be adverse.

There were further no test item related changes in neurological observations (including observational screening, grip strength and locomotor activity), body weight and weight gain, food consumption, haematology, clinical biochemistry, macroscopic examination and organ weights (absolute and relative).

During microscopic examination, test item-related changes like basophilic tubules and interstitial nephritis were noted in the kidney of the male animals of the high dose group (1000 mg test item/kg bw/day).

NOAEL (no-observed-adverse-effect level) for repeated dose toxicity was 300 mg/kg bw/day in males and 1000 mg/kg bw/day in females.

The dose of 300 mg/kg bw was used as descriptor for DNEL-derivation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.22 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

150

Dose descriptor starting point:

NOAEL

Value:

300 ng/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

783 mg/m³

Explanation for the modification of the dose descriptor starting point:

Key oral combined repeated dose toxicity/reproductive and developmental toxicity study available; no repeated dose dermal toxicity study available. Inhalation absorption is considered 30% versus 90% oral absorption as conservative approach.

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):

1

Justification:

Allometric scaling factor is already taken into account in route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

10

Justification:

Default factor according to ECHA guidance document.

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:

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

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:

4.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

600

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

2 700 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Key oral combined repeated dose toxicity/reproductive and developmental toxicity study available; no repeated dose dermal toxicity study available. Inhalation absorption is considered equal to oral absorption as conservative approach.

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 factor according to ECHA guidance document.

AF for intraspecies differences:

10

Justification:

Default factor according to ECHA guidance document.

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:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

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

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:

0.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

600

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

300 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 factor according to ECHA guidance document.

AF for intraspecies differences:

10

Justification:

Default factor according to ECHA guidance document.

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:

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

Source of DNEL-derivation:

In an OECD guideline 422 study, the test item was administered by oral gavage to rats at dose levels of 100, 300 or 1000 mg/kg bw/day. The application started two weeks before mating on test day one and ended on the day or one day before sacrifice. Day of sacrifice was on test days 31/32 for the male rats and on lactation day 4 or shortly thereafter for the female rats.

No premature deaths were noted. Sporadic and transient salivation and breathing sounds were noted during the pre-mating period for 2 male and 2 female animals of the intermediate and the high dose group (300 or 1000 mg test item/kg bw/day), however these changes were not considered to be adverse.

There were further no test item related changes in neurological observations (including observational screening, grip strength and locomotor activity), body weight and weight gain, food consumption, haematology, clinical biochemistry, macroscopic examination and organ weights (absolute and relative).

During microscopic examination, test item-related changes like basophilic tubules and interstitial nephritis were noted in the kidney of the male animals of the high dose group (1000 mg test item/kg bw/day).

NOAEL (no-observed-adverse-effect level) for repeated dose toxicity was 300 mg/kg bw/day in males and 1000 mg/kg bw/day in females.

The dose of 300 mg/kg bw was used as descriptor for DNEL derivation.