Reaction products of ricinoleic acid with 2-aminoethanol and maleic acid and sodium hydrogensulfite

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

566.73 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA factors in combination with recent scientific literature

Overall assessment factor (AF):

8.4

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

4 761 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting from a key oral subchronic OECD 408 toxicity study; no repeated dose inhalation toxicity study available.

AF for dose response relationship:

1

Justification:

Different doses were tested, therefore no additional factor is used.

AF for differences in duration of exposure:

1.4

Justification:

Extrapolation from subchronic to chronic; see justification attached.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is already applied in route-to-route extrapolation

AF for other interspecies differences:

1

Justification:

No toxicodynamic differences between species; see justification attached.

AF for intraspecies differences:

2.4

Justification:

Refined assessment of population differences; see justification attached.

AF for the quality of the whole database:

1

Justification:

Results were based on key Klimisch 1-2 studies (and possible supporting studies).

AF for remaining uncertainties:

2.5

Justification:

For remaining uncertainties that would result from the above assessment factors.

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:

401.79 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA factors in combination with recent scientific literature

Overall assessment factor (AF):

33.6

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

13 500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Starting from a key oral subchronic OECD 408 toxicity study; there was no repeated-dose dermal toxicity study.

AF for dose response relationship:

1

Justification:

Different doses were tested, therefore no additional factor is used.

AF for differences in duration of exposure:

1.4

Justification:

Extrapolation from subchronic to chronic; see justification attached.

AF for interspecies differences (allometric scaling):

4

Justification:

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

AF for other interspecies differences:

1

Justification:

No toxicodynamic differences between species; see justification attached.

AF for intraspecies differences:

2.4

Justification:

Refined assessment of population differences; see justification attached.

AF for the quality of the whole database:

1

Justification:

Results were based on key Klimisch 1-2 studies (and possible supporting studies).

AF for remaining uncertainties:

2.5

Justification:

For remaining uncertainties that would result from the above assessment factors.

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 information for DNELs:

- Key data for subchronic toxicity were available from an oral 90-day repeated dose toxicity study with the read-across substance EC 939 -637 -2 or 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts'.

at dose levels of 100, 300, or 1000 mg/kg bw given to rats by daily oral administration via gavage for 90 days, followed by a 4-week recovery period. The NOAEL was 300 mg act.ingr./kg bw/day. Test-item related effects were observed at 1000 mg/kg bw, including a slight reduction in mean body weight in male and female animals, increased drinking water consumption in male and the female animals and changes in the forestomach (non-glandular part of the stomach) of almost all in the form of squamous cell hyperplasia, hyperkeratosis and sometimes submucosal mixed inflammatory cell infiltrate. The body weight and drinking water intake of all previously high-dosed animals was in the normal range during the recovery period, and no abnormalities were noted in the stomach after this recovery period. The changes in the stomach were not considered relevant for humans as humans do not have a forestomach, exposure conditions were considered to be extreme (irritating concentration daily given by bolus) and the findings were completely reversible.

-Key data for subacute toxicity were available from an oral (gavage) OECD 422 study in rats with read-across substanceEC 939 -637 -2 or 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts', at dose levels given by oral gavage of 100, 300 and 1000 mg/kg bw/day. No relevant effects were observed at 100 and 300 mg/kg bw. At the dose of 1000 mg/kg bw, decreased body weight, increased serum ALAT and decreased serum albumin, macroscopic and microscopic stomach changes and also some lung congestion were observed. NOAEL for systemic toxicity was 300 mg/kg bw/day.

- For risk assessment, the lowest NOAEL of 300 mg/kg bw in the OECD 408 study was selected as dose descriptor for calculation of long term systemic DNELS. This approach was considered conservative, Further justification of assessment factors is explained in the DNEL justification document attached to the endpoint summary.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

167.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA factors in combination with recent scientific literature

Overall assessment factor (AF):

14

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

2 348 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting from a key oral subchronic OECD 408 toxicity study; there was no repeated-dose inhalation toxicity study.

AF for dose response relationship:

1

Justification:

Different doses were tested in the various studies, therefore no additional factor is used.

AF for differences in duration of exposure:

1.4

Justification:

Extrapolation from subchronic to chronic; see justification attached.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is already applied in route-to-route extrapolation.

AF for other interspecies differences:

1

Justification:

No toxicodynamic differences between species; see justification attached.

AF for intraspecies differences:

4

Justification:

Refined assessment of population differences; see justification attached.

AF for the quality of the whole database:

1

Justification:

Results were based on key Klimisch 1-2 studies (and possible supporting studies).

AF for remaining uncertainties:

2.5

Justification:

For remaining uncertainties that would result from the above assessment factors.

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:

241.07 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA factors in combination with recent scientific literature

Overall assessment factor (AF):

56

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

13 500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Starting from a key oral subchronic OECD 408 toxicity study; there was no repeated-dose dermal toxicity study.

AF for dose response relationship:

1

Justification:

Different doses were tested, therefore no additional factor is used.

AF for differences in duration of exposure:

1.4

Justification:

Extrapolation from subchronic to chronic; see justification attached.

AF for interspecies differences (allometric scaling):

4

Justification:

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

AF for other interspecies differences:

1

Justification:

No toxicodynamic differences between species; see justification attached.

AF for intraspecies differences:

4

Justification:

Refined assessment of population differences; see justification attached.

AF for the quality of the whole database:

1

Justification:

Results were based on key Klimisch 1-2 studies (and possible supporting studies).

AF for remaining uncertainties:

2.5

Justification:

For remaining uncertainties that would result from the above assessment factors.

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:

5.36 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA factors in combination with recent scientific literature

Overall assessment factor (AF):

56

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; starting from a key oral subchronic OECD 408 toxicity study.

AF for dose response relationship:

1

Justification:

Different doses were tested, therefore no additional factor is used.

AF for differences in duration of exposure:

1.4

Justification:

Extrapolation from subchronic to chronic; see justification attached.

AF for interspecies differences (allometric scaling):

4

Justification:

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

AF for other interspecies differences:

1

Justification:

No toxicodynamic differences between speciees; see justification attached.

AF for intraspecies differences:

4

Justification:

Refined assessment of population differences; see justification attached.

AF for the quality of the whole database:

1

Justification:

Results were based on key Klimisch 1-2 studies (and possible supporting studies).

AF for remaining uncertainties:

2.5

Justification:

For remaining uncertainties that would result from the above assessment factors.

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 information for DNELs:

- Key data for subchronic toxicity were available from an oral 90-day repeated dose toxicity study with the read-across substance EC 939 -637 -2 or 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts'.

at dose levels of 100, 300, or 1000 mg/kg bw given to rats by daily oral administration via gavage for 90 days, followed by a 4-week recovery period. The NOAEL was 300 mg act.ingr./kg bw/day. Test-item related effects were observed at 1000 mg/kg bw, including a slight reduction in mean body weight in male and female animals, increased drinking water consumption in male and the female animals and changes in the forestomach (non-glandular part of the stomach) of almost all in the form of squamous cell hyperplasia, hyperkeratosis and sometimes submucosal mixed inflammatory cell infiltrate. The body weight and drinking water intake of all previously high-dosed animals was in the normal range during the recovery period, and no abnormalities were noted in the stomach after this recovery period. The changes in the stomach were not considered relevant for humans as humans do not have a forestomach, exposure conditions were considered to be extreme (irritating concentration daily given by bolus) and the findings were completely reversible.

- Key data for subacute toxicity were available from an oral (gavage) OECD 422 study in rats with read-across substance EC 939 -637 -2 or 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts', at dose levels given by oral gavage of 100, 300 and 1000 mg/kg bw/day. No relevant effects were observed at 100 and 300 mg/kg bw. At the dose of 1000 mg/kg bw, decreased body weight, increased serum ALAT and decreased serum albumin, macroscopic and microscopic stomach changes and also some lung congestion were observed. NOAEL for systemic toxicity was 300 mg/kg bw/day.

- For risk assessment, the lowest NOAEL of 300 mg/kg bw in the OECD 408 study was selected as dose descriptor for calculation of long term systemic DNELS. This approach was considered conservative, Further justification of assessment factors is explained in the DNEL justification document attached to the endpoint summary.