Calcium 1,4-bis(2-ethylhexyl) bis(2-sulphosuccinate)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 416.82 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

Modified dose descriptor starting point:

NOAEC

Value:

11 901 mg/m³

Explanation for the modification of the dose descriptor starting point:

Key 90-day oral toxicity study available; no repeated dose inhalation toxicity study available.

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 toxicodyanmic differences between speices; 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). While the DNEL is based on a read across substance as the only difference is the sodium rather than the calcium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used.

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 (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

200.89 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

Modified dose descriptor starting point:

NOAEL

Value:

6 750 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Key 90-day oral toxicity study available; no repeated dose dermal toxicity study available.

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):

4

Justification:

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

AF for other interspecies differences:

1

Justification:

No toxicodyanmic differences between speices; 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). While the DNEL is based on a read across substance as the only difference is the sodium rather than the calcium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used.

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 (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

No data are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.

Repeated dose toxicity was tested in various species, including rats, dogs, rabbits and monkeys. The NOAEL of 750 mg/kg bw/day obtained in the key study in rats was confirmed to be consistent with data from docusate sodium and category members in supporting studies in rats; other data from other species were of limited reliability and relevance and therefore not taken into account.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

419.25 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

Modified dose descriptor starting point:

NOAEC

Value:

5 870 mg/m³

Explanation for the modification of the dose descriptor starting point:

Key 90-day oral toxicity study available; no repeated dose inhalation toxicity study available.

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:

NNo toxicodyanmic differences between speices; 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). While the DNEL is based on a read across substance as the only difference is the sodium rather than the calcium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used.

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 (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

120.54 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

Modified dose descriptor starting point:

NOAEL

Value:

6 750 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Key 90-day oral toxicity study available; no repeated dose dermal toxicity study available.

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):

4

Justification:

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

AF for other interspecies differences:

1

Justification:

No toxicodyanmic differences between speices; 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). While the DNEL is based on a read across substance as the only difference is the sodium rather than the calcium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used

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 (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13.39 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

Modified dose descriptor starting point:

NOAEL

Value:

750 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not applicable

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):

4

Justification:

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

AF for other interspecies differences:

1

Justification:

No toxicodyanmic differences between speices; 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). While the DNEL is based on a read across substance as the only difference is the sodium rather than the calcium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used

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:

medium hazard (no threshold derived)

Additional information - General Population

No data are available for the registered substance, however data are available for the corresponding sodium salt of the substance, docusate sodium (CAS 577-11-7). These data are used for read-across to the registered substance calcium docusate (CAS 128 -49 -4). The presence of either of the counterions sodium or calcium is not considered to have an impact on the toxicity. It is therefore considered justified to use the data of the sodium salt for read across to the calcium salt of docusate.

Repeated dose toxicity was tested in various species, including rats, dogs, rabbits and monkeys. The NOAEL of 750 mg/kg bw/day obtained in the key study in rats was confirmed to be consistent with data from docusate sodium and category members in supporting studies in rats; other data from other species were of limited reliability and relevance and therefore not taken into account.