Registration Dossier

Administrative data

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
Dose descriptor starting point:
NOAEL
DNEL value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL 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 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 (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
Dose descriptor starting point:
NOAEL
DNEL value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL 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 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 (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The following source information was taken into account for DNEL calculation:

- A 28 day study with dietary feeding of a registered substance containing 97 -98% active ingredient was available in male rats dosed at 100, 1000 and 10000 ppm in the diet (corresponding with 7.47, 74.7 and 812 mg act.ingr./kg bw/day on average). Animals dosed at 1000 and 10000 ppm levels showed a slightly greater retardation in growth than rats at 100 ppm. Food consumption for all groups was comparable to the controls during the 28-day period. One control animal died after 4 days of feeding. Gross autopsy revealed some incidence of intestinal irritation at all levels. Various other findings were observed at necropsy, however a respiratory infection was present, therefore the interpretation of the study is difficult. The study was considered to be supporting, and further 28 -day testing was waived based on the availability of 90 -day toxicity data.

- A key 90-day study was available for the registered substance in 40 albino rats (20 males, 20 females) were fed with 1% of various test items mixed into the diet. In the same study, various members of the Sulfosuccinates Diester Group were tested (Plank et al, 1969). No significant differences in clinical blood chemistry studies and absolute organ weights have been detected, except a slight increase in SGPT (serum glutamic pyruvic transaminase) and SAP (serum alkaline phosphatase). Body weights, organ to body weight ratios, hematologic studies and urinalysis were not different between test and control animals. No deaths or abnormal behavioral reactions occurred; no gross pathological findings were noted. Administration of category members at 1% in the diet (10000 ppm equivalent to ca.750 mg act. ingr./kg body weight/day on average basis) for 90 days in rats did not result in any relevant changes in the subchronic toxicity study. The NOAEL was therefore considered to be worst case 750 mg/kg bw/day.

- The fact that no relevant target organ changes were seen up to highest concentration of 1% in diet for 90 days, allows to conclude that corresponding intake of 750 mg/kg bw is NOAEL. A justification for calculation of DNELs is attached.

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
Dose descriptor starting point:
NOAEL
DNEL value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL 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:
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 (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: E ECHA factors in combination with recent scientific literature
Overall assessment factor (AF):
56
Dose descriptor starting point:
NOAEL
DNEL value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL 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 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 (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:
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
Dose descriptor starting point:
NOAEL
DNEL value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL 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 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

The following source information was taken into account for DNEL calculation:

- A 28 day study with dietary feeding of a registered substance containing 97 -98% active ingredient was available in male rats dosed at 100, 1000 and 10000 ppm in the diet (corresponding with 7.47, 74.7 and 812 mg act.ingr./kg bw/day on average). Animals dosed at 1000 and 10000 ppm levels showed a slightly greater retardation in growth than rats at 100 ppm. Food consumption for all groups was comparable to the controls during the 28-day period. One control animal died after 4 days of feeding. Gross autopsy revealed some incidence of intestinal irritation at all levels. Various other findings were observed at necropsy, however a respiratory infection was present, therefore the interpretation of the study is difficult. The study was considered to be supporting, and further 28 -day testing was waived based on the availability of 90 -day toxicity data.

- A key 90-day study was available for the registered substance in 40 albino rats (20 males, 20 females) were fed with 1% of various test items mixed into the diet. In the same study, various members of the Sulfosuccinates Diester Group were tested (Plank et al, 1969). No significant differences in clinical blood chemistry studies and absolute organ weights have been detected, except a slight increase in SGPT (serum glutamic pyruvic transaminase) and SAP (serum alkaline phosphatase). Body weights, organ to body weight ratios, hematologic studies and urinalysis were not different between test and control animals. No deaths or abnormal behavioral reactions occurred; no gross pathological findings were noted. Administration of category members at 1% in the diet (10000 ppm equivalent to ca.750 mg act. ingr./kg body weight/day on average basis) for 90 days in rats did not result in any relevant changes in the subchronic toxicity study. The NOAEL was therefore considered to be worst case 750 mg/kg bw/day.

- The fact that no relevant target organ changes were seen up to highest concentration of 1% in diet for 90 days, allows to conclude that corresponding intake of 750 mg/kg bw is NOAEL. A justification for calculation of DNELs is attached.