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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
98.7 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
2 468.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

ECHA guidance recommends that a factor of 2 be applied when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs. However in this case we have toxicokinetic data showing greater than 90% excretion by both the oral and intravenous routes. This indicates that oral absorption was ca. 100%. Therefore a factor of 1 was applied (see discussion) as inhalation exposure cannot be higher.  Allometric scaling is applied by taking account for the different breathing rates between rats and humans, as described in ECHA technical guidance the oral NOAEL in the rat mg/kg/day *1/0.38 * 6.7/10 = mg/m3 inhalation NOAEC for workers. An additional adjust was made as recommended in ECHA guidance R8.4.3. The oral exposure for the rats was 7 days a week but inhalation exposure of workers is considered to be 5 days a week. This is adjusted by dividing the NOEC by 5/7 or 0.714286.

AF for dose response relationship:
1
Justification:
No adverse systemic effects were seen at the limit dose of 1000mg/kg used as the oral NOAEL so a factor of 1 used.
AF for differences in duration of exposure:
2
Justification:
ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already included in the route to route extrapolation from the rat oral NOAEL to the equivalent human inhalation NOAEC.
AF for other interspecies differences:
2.5
Justification:
ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied.
AF for intraspecies differences:
5
Justification:
ECHA guidance recommends a factor of 5 for intraspecies differences for workers
AF for the quality of the whole database:
1
Justification:
While the DNEL is based on a read across substance as the only difference is the sodium rather than the potassium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used.
AF for remaining uncertainties:
1
Justification:
All uncertainties are already included so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

ECHA guidance assumes that absorption for dermal exposure is the same as for oral exposure, which is a worst case assumption.

AF for dose response relationship:
1
Justification:
No adverse effects were seen at the limit dose of 750mg/kg so a factor of 1 used.
AF for differences in duration of exposure:
2
Justification:
ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA guidance recommends as factor of 4 for Allometric scaling from effects in the rat to humans, to compensate for the different metabolic rates.
AF for other interspecies differences:
2.5
Justification:
ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied.
AF for intraspecies differences:
5
Justification:
ECHA guidance recommends a factor of 5 for intraspecies differences for workers.
AF for the quality of the whole database:
1
Justification:
While the DNEL is based on a read across substance as the only difference is the sodium rather than the potassium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used.
AF for remaining uncertainties:
1
Justification:
All uncertainties are already included so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

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 (Butanedioic acid, sulfo-, 1,1-bis(2-ethylhexyl) ester sodium salt CAS No 577-11-7). These data are used for read-across to the registered substance Potassium 1,2-bis(2-ethylhexyloxycarbonyl)ethanesulphonate CAS No 7491-09-0. The substance has a pKa of 0.18 which means that it will be completely dissociated in water solutions. The presence of either of the counterions sodium or potassium 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 Potassium salt of 1,2-bis(2-ethylhexyloxycarbonyl) ethanesulphonate.

The point of departure for deriving the DNELs is the NOAEL from the 90 day rat study of 1000 mg/kg bwt/day for the read across substance docusate sodium CAS No 577-11-7. This study is new study fully compliant with the OECD Guideline and GLP. The lack of systemic toxic effects at the 1000 mg/kg bwt/day upper limit dose is consistent with other information on related anionic surfactants

There is toxicokinetic data for docusate sodium in rats which compared oral and intra-venous injection of radio labelled docusate sodium and the relevant excretion of the radioacticity. Each route of administration resulted in the excretion of over 90% of the reactivity in the urine. This indicates that there is a very high oral absorption of more than 90%. (Cytec, Kelly 1973). Due to the equivalent level of absorption indicated by the oral and intra venous routes, the oral absorption can be considered to be ca. 100%.

When extrapolating the long term inhalation DNEL from the oral NOAEL data, ECHA guidance chapter R.8: Characteristics of dose [concentration]-response for human health ECHA (2012) makes an assumption of 50% absorption by the oral route and 100% absorption by the inhalation route. This results in the oral NOAEL being halved prior to conversion to a rat NOAEC and then to the corresponding DNEL values for workers and the general population.  As docusate sodium is absorbed greater than 90% by the oral route there is no justification for applying the defaults factor of 2 when deriving the inhalation DNELs from the oral NOAEL as there cannot be any significantly higher absorption by the inhalation route. This is considered to be a sufficient substance specific justification for this adaptation of the default factor of 2 to a factor of 1.

All other assessment factors used are those recommended by the ECHA guidance reference above.

ECHA, 2012 Guidance on information requirements and chemical safety assessment. Chapter R.8 Characterisation of dose [concentration]-response for human health.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH guidance with substance specific modification
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
740.74 mg/m³
Explanation for the modification of the dose descriptor starting point:

ECHA guidance recommends that a factor of 2 be applied when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs. However in this case we have toxicokinetic data, which shows >90% excretion, by both the oral and intravenous routes. This indicates that oral absorption was ca. 100%. Therefore a factor of 1 was applied (see discussion) as inhalation exposure cannot be higher.  Allometric scaling is applied by taking account for the different breathing rates between rats and humans, as described in IUCLID Calculator the oral NOAEL in the rat mg/kg/day *1/1.35 mg/m3 inhalation NOAEC for the general population (based on 60 kg bodyweight rather than 70 kg for workers).

AF for dose response relationship:
1
Justification:
No adverse effects were seen at the limit dose of 750mg/kg used as the oral NOAEL so a factor of 1 used.
AF for differences in duration of exposure:
2
Justification:
ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already included in the route to route extrapolation from the rat oral NOAEL to the equivalent human inhalation NOAEC.
AF for other interspecies differences:
2.5
Justification:
ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied.
AF for intraspecies differences:
10
Justification:
ECHA guidance recommends a factor of 10 for intraspecies differences for the general population.
AF for the quality of the whole database:
1
Justification:
While the DNEL is based on a read across substance as the only difference is the sodium rather than the potassium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used.
AF for remaining uncertainties:
1
Justification:
All uncertainties are already included so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

ECHA guidance assumes that absorption for dermal exposure is the same as for oral exposure, which is a worst case assumption.

AF for dose response relationship:
1
Justification:
No adverse effects were seen at the limit dose of 750mg/kg used as the oral NOAEL so a factor of 1 used.
AF for differences in duration of exposure:
2
Justification:
ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA guidance recommends as factor of 4 for Allometric scaling from effects in the rat to humans, to compensate for the different metabolic rates.
AF for other interspecies differences:
2.5
Justification:
ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied..
AF for intraspecies differences:
10
Justification:
ECHA guidance recommends a factor of 10 for intraspecies differences for the general population
AF for the quality of the whole database:
1
Justification:
While the DNEL is based on a read across substance as the only difference is the sodium rather than the potassium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used.
AF for remaining uncertainties:
1
Justification:
All uncertainties are already included so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
200
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is no route to route extrapolation as the NOAEL is from an oral study in rats so no modification of the dose descriptior.

AF for dose response relationship:
1
Justification:
No adverse effects were seen at the limit dose of 750mg/kg used as the NOAEL so a factor of 1 used.
AF for differences in duration of exposure:
2
Justification:
ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 90 day study are derived using an assessment factor of 2 for extrapolation of the study duration to chronic exposure. As the NOAEL is from a 90 day study the factor of 2 was used.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA guidance recommends as factor of 4 for Allometric scaling from effects in the rat to humans, to compensate for the different metabolic rates.
AF for other interspecies differences:
2.5
Justification:
ECHA guidance recommends an additional factor of 2.5 for other interspecies differences, therefore a factor of 2.5 has been applied.
AF for intraspecies differences:
10
Justification:
ECHA guidance recommends a factor of 10 for intraspecies differences for the general population.
AF for the quality of the whole database:
1
Justification:
While the DNEL is based on a read across substance as the only difference is the sodium rather than the potassium salt both will be dissociated in the physiological environment. Therefore a factor of 1 was used.
AF for remaining uncertainties:
1
Justification:
All uncertainties are already included so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

ECHA guidance recommends that a factor of 2 be applied when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs. However in this case we have toxicokinetic data showing >90% excretion by both the oral and intravenous routes. The equivalent excretion indicates equivalent availability/absorption for oral and intra venous routes. This indicates that oral absorption was ca. 100%. Therefore a factor of 1 was applied (see discussion) as inhalation exposure cannot be higher. Allometric scaling is applied by taking account for the different breathing rates between rats and humans, as described in ECHA technical guidance the oral NOAEL in the rat mg/kg/day *1/1.35 = mg/m3for a 60 kg member of the general population as include in the IUCLID calculator.

The point of departure for deriving the DNELs is the NOAEL from the 90 day rat study of 1000 mg/kg bwt/day for the read across substance docusate sodium CAS No 577-11-7. This study is new study fully compliant with the OECD Guideline and GLP. The lack of systemic toxic effects at the 1000 mg/kg bwt/day upper limit dose is consistent with other information on related anionic surfactants.

All other assessment factors used are those recommended by the ECHA guidance reference above.

 

ECHA, 2012 Guidance on information requirements and chemical safety assessment. Chapter R.8 Characterisation of dose [concentration]-response for human health.