Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
22.3 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
1 675 mg/m³
Explanation for the modification of the dose descriptor starting point:
assuming 100% absorption via oral and 10% via inhalative route the NOAEL of 95 mg/kg bw/d from a subacute study is corrected by multiplying with 100/10 and division by 0.38 m3/kg for air consumption and multiplication with 6.7/10 for light work adjustment --> NOAECcorr = 95 mg/kg bw/d * 100/10 * 6.7/10 / 0.38 m3/kg/d = 1675 mg/m3
AF for dose response relationship:
1
Justification:
NOAEC used as starting point
AF for differences in duration of exposure:
6
Justification:
based on the subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
for worker, a default AF of 5 is to be used
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
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:
3.2 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
950 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal, assuming 100% oral absorption and 10% dermal absorption and thereby corrected by multiplying with 100/10
AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point
AF for differences in duration of exposure:
6
Justification:
based on the subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
rats are used in the animal test
AF for other interspecies differences:
2.5
Justification:
no other substance-specific information is available
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used
AF for remaining uncertainties:
1
Justification:
no other uncertainties needed to be considered.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.2 mg/kg bw/day
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:
high hazard (no threshold derived)

Additional information - workers

Due to low vapor pressure (3.3E-5 Pa at 20 °C) and high boiling point (> 50 °C), the inhalation route is not considered to be a relevant exposure route to human. However, an inhalative DNEL, long-term systemic has been derived.

It is assumed in the Toxicokinetik assessment based ona conservative approach that the absorption rate from dermal and inhalative route is considered to be 10% whereas by oral route 100% absorption is assumed. Thus the NOAEL inhalative and dermal, derived by route to route extrapolation, have been adjusted accordingly.

One GLP study following OECD guideline 422 was conducted to investigate the potential toxicity of DNNSA and identified NOAEL:

Parental NOAEL: 95 mg/kg/day

Reproduction NOAEL: at least 893 mg/kg/day

Developmental NOAEL: 298 mg/kg body weight/day.

In this study, treatment of male and female Wistar rats with di C8-C10, branched, C9 rich, alkylnaphthalene sulphonic acid (DNNSA) by oral gavage at dose levels of 95, 298, 893 mg/kg body weight/day revealed parental toxicity at 298 and 893 mg/kg body weight/day. At 95 mg/kg, no toxicologically relevant effects were noted in any of the parameters. Developmental toxicity (lower pup body weights) was observed at the high dose of 893 mg/kg. No developmental toxicity was observed for treatments of 95 and 298 mg/kg body weight/day. The NOAEL was 298 mg/kg body weight/day.No reproduction toxicity was observed for treatment up to 893 mg/kg body weight/day.

Therefore, the NOAEL of 95 mg/kg/day was selected as the basis for DNEL derivation according to the strict rule.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.5 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
826 mg/m³
Explanation for the modification of the dose descriptor starting point:
assuming 100% absorption via oral and 10% via inhalative route the NOAEL of 95 mg/kg bw/d from a subacute study is corrected by multiplying with 100/10 and by division by 1.15 m3/kg/d for air consumption --> NOAECcorr = 95 mg/kg bw/d * 100/10 / 1.15 m3/kg/d = 826 mg/m3.
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEC
AF for differences in duration of exposure:
6
Justification:
based on the subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
for general population, a default AF of 10 is to be used
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
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:
1.6 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
950 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal
AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point
AF for differences in duration of exposure:
6
Justification:
based on the subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
rats are used in the animal test
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data are available.
AF for intraspecies differences:
10
Justification:
for general population, a default factor of 10 is used.
AF for the quality of the whole database:
1
Justification:
available data from substance fulfill the scientific principles
AF for remaining uncertainties:
1
Justification:
no other uncertainties need to be considered
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 mg/kg bw/day
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:
0.16 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
95 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to route
AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point
AF for differences in duration of exposure:
6
Justification:
based on a subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
rats are used in the animal test
AF for other interspecies differences:
2.5
Justification:
no other substance-specific information are available
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
available data from substance fulfill scientific principle is used
AF for remaining uncertainties:
1
Justification:
no other uncertainties needed to be considered.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.16 mg/kg bw/day
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

Due to low vapor pressure (3.3E-5 Pa at 20 °C) and high boiling point (> 50 °C), the inhalation route is not considered to be a relevant exposure route to human. However, an inhalative DNEL for systemic long-term toxicity was derived.

It is assumed in the Toxicokinetik assessment based ona conservative approach that the absorption rate from dermal and inhalative route is considered to be 10% whereas by oral route 100% absorption is assumed. Thus the NOAEL inhalative and dermal, derived by route to route extrapolation, have been adjusted accordingly.

One GLP study following OECD guideline 422 was conducted to investigate the potential toxicity of DNNSA and identified NOAEL:

Parental NOAEL: 95 mg/kg/day

Reproduction NOAEL: at least 893 mg/kg/day

Developmental NOAEL: 298 mg/kg body weight/day.

In this study, treatment of male and female Wistar rats with di C8-C10, branched, C9 rich, alkylnaphthalene sulphonic acid (DNNSA) by oral gavage at dose levels of 95, 298, 893 mg/kg body weight/day revealed parental toxicity at 298 and 893 mg/kg body weight/day. At 95 mg/kg, no toxicologically relevant effects were noted in any of the parameters. Developmental toxicity (lower pup body weights) was observed at the high dose of 893 mg/kg. No developmental toxicity was observed for treatments of 95 and 298 mg/kg body weight/day. The NOAEL was 298 mg/kg body weight/day.No reproduction toxicity was observed for treatment up to 893 mg/kg body weight/day.

Therefore, the NOAEL of 95 mg/kg/day was selected as the basis for DNEL derivation according to the strict rule.