Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
156 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA and ERASM factors
Overall assessment factor (AF):
10.2
Modified dose descriptor starting point:
NOAEC
Value:
1 587 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:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
3.4
Justification:
ERASM extrapolation factor from subacute (starting point) to chronic (end point); see also 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:
ERASM default factor for other interspecies differences.
AF for intraspecies differences:
3
Justification:
ERASM default factor for intraspecies differences.
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:
No further assessment factors are required.
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:
331 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA and ERASM factors
Overall assessment factor (AF):
40.8
Modified dose descriptor starting point:
NOAEL
Value:
13 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A key oral 90-day toxicity study is available; there was no repeated-dose dermal toxicity study.
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:
3.4
Justification:
ERASM extrapolation factor from subacute (starting point) to chronic (end point); see also justification attached..
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:
1
Justification:
ERASM default factor for other interspecies differences.
AF for intraspecies differences:
3
Justification:
ERASM default factor for intraspecies differences.
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:
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 (no further information necessary)
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

Following source data were used for DNEL calculation:

- Key data for subacute toxicity were available from an oral (gavage) OECD 422 study in rats with read-across substance '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 were observed. NOAEL for systemic toxicity was 300 mg/kg bw/day.

- Key data for subchronic toxicity was available from an oral (diet) 90-day toxicity study in rats with read-aross substance 'Aspartic acid, N-(3-carboxy-1-oxo-sulfopropyl)-N-(C16-C18 (even numbered), C18unsaturated alkyl) tetrasodium salts' dosed at 0.5, 2 and 8 (reduced to 4) g/kg bw.day. The study showed decreased body weight gain, feed consumption and food efficiency at the mid dose and high dose levels and increased SGOT and SGPT (liver enzymes) at the high dose. Further hematuria was seen in the mid and high dose rats, various organ weights were decreased (e.g. decrease in adrenal and gonadal weight in high dose groups; decrease in pituitary weight in females of high dose group) and lower urinary tract pathology was seen in 2 high dosed rats. It thus appeared that the NOEL in the rat was below 0.50 g/kg/day, however 0.5g act.ingr./kg bw/day can be considered as NOAEL.

- Taking into account both studies, the NOAEL of 300 mg/kg bw can be considered as the most conservative NOAEL. A justification for calculation of DNELs is attached.

Qualitative assessment

Only systemic long term exposure values for worker and general population were calculated, because no concrete values (like NOAEL, LOAEL etc) are available from acute or irritation studies. The study design of the test conducted assessing the acute and local toxicity does not allow in general the derivation of local or acute DNELs, as most of the tests were, for example, conducted as limit tests due to animal welfare. Therefore a qualitative risk assessment for irritation is performed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
46 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA and ERASM factors
Overall assessment factor (AF):
17
Modified dose descriptor starting point:
NOAEC
Value:
783 mg/m³
Explanation for the modification of the dose descriptor starting point:
A key oral 90-day toxicity study is available; there was no repeated-dose inhalation toxicity study.
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:
3.4
Justification:
ERASM extrapolation factor from subacute (starting point) to chronic (end point); see also 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:
ERASM default factor for other interspecies differences.
AF for intraspecies differences:
5
Justification:
ERASM default factor for intraspecies differences.
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:
No further assessment factors are required.
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:
199 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA and ERASM factors
Overall assessment factor (AF):
68
Modified dose descriptor starting point:
NOAEL
Value:
13 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A key oral 90-day toxicity study is available; there was no repeated-dose dermal toxicity study.
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:
3.4
Justification:
ERASM extrapolation factor from subacute (starting point) to chronic (end point); see also justification attached.
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:
1
Justification:
ERASM default factor for other interspecies differences.
AF for intraspecies differences:
5
Justification:
ERASM default factor for intraspecies differences.
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:
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 (no further information necessary)
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:
4.41 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA and ERASM factors
Overall assessment factor (AF):
68
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:
3.4
Justification:
ERASM extrapolation factor from subacute (starting point) to chronic (end point); see also justification attached..
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:
1
Justification:
ERASM default factor for other interspecies differences.
AF for intraspecies differences:
5
Justification:
ERASM default factor for intraspecies differences.
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:
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

Following source data were used for DNEL calculation:

- Key data for subacute toxicity were available from an oral (gavage) OECD 422 study in rats with read-across substance '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 were observed. NOAEL for systemic toxicity was 300 mg/kg bw/day.

- Key data for subchronic toxicity was available from an oral (diet) 90-day toxicity study in rats with read-aross substance 'Aspartic acid, N-(3-carboxy-1-oxo-sulfopropyl)-N-(C16-C18 (even numbered), C18unsaturated alkyl) tetrasodium salts' dosed at 0.5, 2 and 8 (reduced to 4) g/kg bw.day. The study showed decreased body weight gain, feed consumption and food efficiency at the mid dose and high dose levels and increased SGOT and SGPT (liver enzymes) at the high dose. Further hematuria was seen in the mid and high dose rats, various organ weights were decreased (e.g. decrease in adrenal and gonadal weight in high dose groups; decrease in pituitary weight in females of high dose group) and lower urinary tract pathology was seen in 2 high dosed rats. It thus appeared that the NOEL in the rat was below 0.50 g/kg/day, however 0.5g act.ingr./kg bw/day can be considered as NOAEL.

- Taking into account both studies, the NOAEL of 300 mg/kg bw can be considered as the most conservative NOAEL.A justification for calculation of DNELs is attached.

Qualitative assessment

Only systemic long term exposure values for worker and general population were calculated, because no concrete values (like NOAEL, LOAEL etc) are available from acute or irritation studies. The study design of the test conducted assessing the acute and local toxicity does not allow in general the derivation of local or acute DNELs, as most of the tests were, for example, conducted as limit tests due to animal welfare. Therefore a qualitative risk assessment for irritation is performed.