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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
45
Modified dose descriptor starting point:
other: NOEC
Value:
57 mg/m³
Explanation for the modification of the dose descriptor starting point:
The 5-week repeated toxicity study is well documented and supported; moreover is provides a more reliable starting point in the derivation of the DNEL.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOEC, therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied in order to consider the differences in the duration of the exposure between the sub-acute toxicity study and a chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling does not apply in case of oral-to-inhalation extrapolation from rats to humans.
AF for other interspecies differences:
2.5
Justification:
As no allometric factor has been used, an assessment factor for other interspecies differences has been chosen.
AF for intraspecies differences:
3
Justification:
Intraspecies AF for workers population, according to ECETOC guidelines.
AF for the quality of the whole database:
1
Justification:
The available data are sufficient to correctly derive the inhalation DNEL.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
7.5
Modified dose descriptor starting point:
other: NOEC
Value:
143 mg/m³
Explanation for the modification of the dose descriptor starting point:
None
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOEC, therefore the default assessment factor, as a standard procedure, is 1.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling does not apply in case of inhalation-inhalation extrapolation from rats to humans.
AF for other interspecies differences:
2.5
Justification:
As no allometric factor has been used, an assessment factor for other interspecies differences has been chosen.
AF for intraspecies differences:
3
Justification:
Intraspecies AF for workers population, according to ECETOC guidelines.
AF for the quality of the whole database:
1
Justification:
The available data are sufficient to correctly derive the inhalation DNEL.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
3
Dose descriptor starting point:
other: NOEC
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOEC, therefore the default assessment factor, as a standard procedure, is 1.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling does not apply in case of inhalation-inhalation extrapolation from rats to humans.
AF for other interspecies differences:
1
Justification:
No other assessment factor is needed for local effects.
AF for intraspecies differences:
3
Justification:
Intraspecies AF for workers population, according to ECETOC guidelines
Justification:
The available data are sufficient to correctly derive the inhalation DNEL
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Value:
64.78 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The 5-week repeated toxicity study is well documented and supported; moreover is provides a more reliable starting point in the derivation of the DNEL.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOAEL, therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied in order to consider the differences in the duration of the exposure between the oral reproductive/developmental toxicity study and a chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling for rats involves a default assessment factor of 4.
AF for other interspecies differences:
1
Justification:
An additional AF for interspecies differences is considered not necessary, because allometric scaling will be conservative enough.
AF for intraspecies differences:
3
Justification:
Intraspecies AF for workers population, according to ECETOC guidelines
AF for the quality of the whole database:
1
Justification:
The available data are sufficient to correctly derive the inhalation DNEL
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are foreseen.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Data considered in this hazard assessment derive from studies performed on sodium diisobutylnaphtalene sulphonate itself and from studies performed on similar substances, according to a read-across principle. Full justification of read-across application is provided in a separate document.

DNELs for inhalation and dermal routes of exposure have been derived. The DNEL derived for inhalation route after long term-exposure (systemic effects) has been derived from the 28-day repeated toxicity study by oral route with rats. The DNELs derived for inhalation route after short term-exposure (systemic and local effects) have been derived from the results of a 4-hour exposure study. The NO(A)EC from these inhalation studies had to be corrected into the correct starting point, considering the differences in the duration of exposure between the laboratory animals at rest and workers at light activity. A qualitative assessment has been carried out for local effect after repeated inhalation exposure.

The DNEL derived for the dermal route after long-term exposure derives from the 28-day repeated toxicity study by oral route with rats.

Where the route of exposure in the relevant toxicity study was not the same of workers, a route-to-route extrapolation has been carried out.

The correct starting points were divided by an overall assessment factor, which was a result of various consideration on uncertainties in inter-and intra-species variations, and on differences in the duration of exposure between test animals and humans. Moreover also the whole quality of the database was considered.

No DNELs were derived for local effects after long-term dermal exposure, and for systemic and local effects after short-term dermal exposure, because no hazard has been identified (i.e. the studies performed for the acute dermal toxicity endpoint, the skin irritation/corrosion endpoint and for the skin sensitization endpoint revealed no effects, and a low degree of percutaneous absorption is expected for sodium diisobutylnaphtalene sulphonate). No DNEL have been derived for the eye irritation effects, for which a qualitative approach has been followed, leading to a low hazard for this endpoint.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Value:
28 mg/m³
Explanation for the modification of the dose descriptor starting point:
The 5-week repeated toxicity study is well documented and supported; moreover is provides a more reliable starting point in the derivation of the DNEL.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOEC, therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied in order to consider the differences in the duration of the exposure between the sub-acute toxicity study and a chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling does not apply in case of inhalation-inhalation extrapolation from rats to humans.
AF for other interspecies differences:
2.5
Justification:
As no allometric factor has been used, an assessment factor for other interspecies differences has been chosen.
AF for intraspecies differences:
5
Justification:
Intraspecies AF for general population, according to ECETOC guidelines
AF for the quality of the whole database:
1
Justification:
The available data are sufficient to correctly derive the inhalation DNEL
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
other: NOEL
Value:
143 mg/m³
Explanation for the modification of the dose descriptor starting point:
None
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOEC, therefore the default assessment factor, as a standard procedure, is 1.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling does not apply in case of inhalation-inhalation extrapolation from rats to humans.
AF for other interspecies differences:
2.5
Justification:
As no allometric factor has been used, an assessment factor for other interspecies differences has been chosen.
AF for intraspecies differences:
5
Justification:
Intraspecies AF for general population, according to ECETOC guidelines.
AF for the quality of the whole database:
1
Justification:
The available data are sufficient to correctly derive the inhalation DNEL.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: NOEC
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOEC, therefore the default assessment factor, as a standard procedure, is 1.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling does not apply in case of inhalation-inhalation extrapolation from rats to humans.
AF for other interspecies differences:
1
Justification:
No other assessment factor is needed for local effects.
AF for intraspecies differences:
5
Justification:
Intraspecies AF for general population, according to ECETOC guidelines
AF for the quality of the whole database:
1
Justification:
The available data are sufficient to correctly derive the inhalation DNEL
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
64.78 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The 5-week repeated toxicity study is well documented and supported; moreover is provides a more reliable starting point in the derivation of the DNEL.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOEL, therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied in order to consider the differences in the duration of the exposure between the 28-day toxicity study and a chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling for rats involves a default assessment factor of 4.
AF for other interspecies differences:
1
Justification:
An additional AF for interspecies differences is considered not necessary, because allometric scaling will be conservative enough.
AF for intraspecies differences:
5
Justification:
Intraspecies AF for general population, according to ECETOC guidelines
AF for the quality of the whole database:
1
Justification:
The available data are sufficient to correctly derive the inhalation DNEL
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
64.78 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
None.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOAEL, therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied in order to consider the differences in the duration of the exposure between the sub-acute toxicity study and a chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling for rats involves a default assessment factor of 4.
AF for other interspecies differences:
1
Justification:
An additional AF for interspecies differences is considered not necessary, because allometric scaling will be conservative enough.
AF for intraspecies differences:
5
Justification:
Intraspecies AF for general population, according to ECETOC guidelines
AF for the quality of the whole database:
1
Justification:
The available data are sufficient to correctly derive the inhalation DNEL
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Guidelines
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
other: NOEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
None.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation was a NOAEL, therefore the default assessment factor, as a standard procedure, is 1.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling for rats involves a default assessment factor of 4.
AF for other interspecies differences:
1
Justification:
An additional AF for interspecies differences is considered not necessary, because allometric scaling will be conservative enough.
AF for intraspecies differences:
5
Justification:
Intraspecies AF for general population, according to ECETOC guidelines
AF for the quality of the whole database:
1
Justification:
The available data are sufficient to correctly derive the inhalation DNEL
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Data considered in this hazard assessment derive from studies performed on sodium diisobutylnaphtalene sulphonate itself and from studies performed on similar substances, according to a read-across principle. Full justification of read-across application is provided in a separate document.

DNELs for inhalation and dermal routes of exposure have been derived. The DNEL derived for inhalation route after long term-exposure (systemic effects) has been derived from the 28-day repeated toxicity study by oral route with rats. The DNELs derived for inhalation route after short term-exposure (systemic and local effects) have been derived from the results of a 4-hour exposure study. The NO(A)EC from these inhalation studies had to be corrected into the correct starting point, considering the differences in the duration of exposure between the laboratory animals and general population. A qualitative assessment has been carried out for local effect after repeated inhalation exposure.

The DNEL derived for the dermal route after long-term exposure derives from the 28-day repeated toxicity study by oral route with rats.

Where the route of exposure in the relevant toxicity study was not the same of workers, a route-to-route extrapolation has been carried out. 

Also DNELs for oral exposure have been derived: the DNEL for long-term exposure derived from the NOAEL determined in the 28-day repeated toxicity study by oral route with rats, while the DNEL for short-term exposure derives from the NOEL for systemic effects observed in one of the oral acute toxicity study available.

The correct starting points were divided by an overall assessment factor, which was a result of various consideration on uncertainties in inter-and intra-species variations, and on differences in the duration of exposure between test animals and humans. Moreover also the whole quality of the database was considered.

No DNELs were derived for local effects after long-term dermal exposure, and for systemic and local effects after short-term dermal exposure, because no hazard has been identified (i.e. the studies performed for the acute dermal toxicity endpoint, the skin irritation/corrosion endpoint and for the skin sensitization endpoint revealed no effects, and a low degree of percutaneous absorption is expected for sodium diisobutylnaphtalene sulphonate). No DNEL have been derived for the eye irritation effects, for which a qualitative approach has been followed, leading to a low hazard for this endpoint.

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