Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.5 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:
The equivalent rat inhalation NOAEC was derived using route-to-route extrapolation, based on assumption of 100% absorption after ingestion and inhalation.
AF for dose response relationship:
1
Justification:
Default AF
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic extrapolation
Justification:
AF not required
AF for other interspecies differences:
2.5
Justification:
For remaining differences
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
Default AF
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:
3.33 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation based on assumed equivalence for oral and dermal absorption.
AF for dose response relationship:
1
Justification:
Default AF
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining differences
AF for intraspecies differences:
5
Justification:
Default AF for workers
AF for the quality of the whole database:
1
Justification:
Default AF
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:
low hazard (no threshold derived)

Additional information - workers

Acute Toxicity

A DNEL for acute toxicity need only be derived if an acute hazard leading to acute toxicity (e. g. classified under CLP) has been identified and there is a potential for high peak exposures. If no hazard has been identified then a DNEL for acute toxicity is unnecessary as the long-term DNEL will be sufficient to ensure that adverse effects do no occur. Polysulfides, di-tert-nonyl is neither acutely toxic nor is it an irritant (eye, skin or respiratory tract) and therefore no acute DNELs (systemic or local) have been calculated.

Long-term Systemic Toxicity

The available data indicate a NOAEL of 1000 mg/kg bw/day for Polysulfides, di-tert-nonyl, based on a 4 week oral toxicity study (Elf Aquitaine Production, 1995) in rats administered di-tert-dodecyl polysulfide (TPS 32), a structural analogue of Polysulfides, di-tert-nonyl.

Inhalation DNEL (systemic)

Dose descriptor

The rat 4 -week oral NOAEL of 1000 mg/kg bw/d will be used as the starting point.

Modification of dose descriptor

The equivalent rat inhalation NOAEC will be derived using route-to-route extrapolation, based on assumption of 100% absorption after ingestion and inhalation.

The inhalatory NOAEC may be calculated as follows:

NOAECinhalation = NOAELoral x 1/sRVrat x ABSoral-rat/ABSinh-human x sRVhuman/wRVhuman

= 1000 x 1/0.38 x 100/100 x 6.7/10

= 1763 mg/m3 (4 -week duration of exposure)

Assessment factors (ECHA, Guidance Chapter R8, Table R8-6, November 2012)

Uncertainty

AF (ECHA)

Justification

Interspecies differences

2.5

remaining differences

Intraspecies differences

5

default AF for workers

Differences in duration of exposure

6

sub-acute to chronic extrapolation

Dose response and endpoint specific/severity issues

1

default AF

Quality of database

1

default AF

Overall AF

75

 

DNEL Worker long-term inhal-systemic = 1763/75 = 23.5 mg/m3

Dermal DNEL (systemic)

Dose descriptor

The rat 4 -week oral NOAEL of 1000 mg/kg bw/d will be used as the starting point.

Modification of dose descriptor

The equivalent dermal NOAEL will be derived using route-to-route extrapolation, based on assumption of 100% absorption after ingestion and 100% after skin contact.

The dermal NOAEL may be calculated as follows:

NOAELdermal = NOAELoral x ABSoral-rat/ABSdermal-human

= 1000 x 100/100

= 1000 mg/kg bwt/d (4 -week duration of exposure)

Assessment factors (ECHA, Guidance Chapter R8, Table R8-6, November 2012)

Uncertainty

AF (ECHA)

Justification

Interspecies differences

4.0

2.5

Allometric scaling for rat

For remaining differences

Intraspecies differences

5

default AF for workers

Differences in duration of exposure

6

sub-acute to chronic extrapolation

Dose response and endpoint specific/severity issues

1

default AF

Quality of database

1

default AF

Overall AF

300

DNEL Worker long-term dermal-systemic = 1000 / 300 = 3.33 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.8 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:
870 mg/m³
Explanation for the modification of the dose descriptor starting point:
route to route extrapolation based on assumption of equivalent absorption (100%) by inhalation and dermal routes.
AF for dose response relationship:
1
Justification:
default AF
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic extrapolation
Justification:
AF not required.
AF for other interspecies differences:
2.5
Justification:
default for remaining differences
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default AF
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:
1.66 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation base don assumption of equivalent absorption (100%) by dermal nd oral routes
AF for dose response relationship:
1
Justification:
default AF
AF for differences in duration of exposure:
6
Justification:
subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default AF
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:
1.66 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
route to route extrapolation not used - base don repeat dose oral study
AF for dose response relationship:
1
Justification:
default AF
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat
AF for other interspecies differences:
2.5
Justification:
default for remaining differences
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default AF
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:
low hazard (no threshold derived)

Additional information - General Population

Acute Toxicity

A DNEL for acute toxicity need only be derived if an acute hazard leading to acute toxicity (e. g. classified under CLP) has been identified and there is a potential for high peak exposures. If no hazard has been identified then a DNEL for acute toxicity is unnecessary as the long-term DNEL will be sufficient to ensure that adverse effects do no occur. Polysulfides, di-tert-nonyl is neither acutely toxic nor is it an irritant (eye, skin or respiratory tract) and therefore no acute DNELs (systemic or local) have been calculated.

Long-term Systemic Toxicity

The available data indicate a NOAEL of 1000 mg/kg bw/day for Polysulfides, di-tert-nonyl, based on a 4 week oral toxicity study (Elf Aquitaine Production, 1995) in rats administered di-tert-dodecyl polysulfide (TPS 32), a structural analogue of Polysulfides, di-tert-nonyl.

Inhalation DNEL (systemic)

Dose descriptor

The rat 4 -week oral NOAEL of 1000 mg/kg bw/d will be used as the starting point.

Modification of dose descriptor

The equivalent rat inhalation NOAEC will be derived using route-to-route extrapolation, based on 100% absorption after ingestion and inhalation.

The inhalatory NOAEC may be calculated as follows:

NOAECinhalation = NOAELoral x 1/sRVrat x ABSoral-rat/ABSinh-human

= 1000 x 1/1.15 x 100/100

= 870 mg/m3(4 -week duration of exposure)

Assessment factors (ECHA, ECHA Guidance Chapter R8, Table R8-6, November 2012)

Uncertainty

AF (ECHA)

Justification

Interspecies differences

2.5

remaining differences

Intraspecies differences

10

default AF for general population

Differences in duration of exposure

6

sub-acute to chronic extrapolation

Dose response and endpoint specific/severity issues

1

default AF

Quality of database

1

default AF

Overall AF

150

 

DNEL General Population long-term inhal-systemic = 870/150 = 5.8 mg/m3

Dermal DNEL (systemic)

Dose descriptor

The rat 4 -week oral NOAEL of 1000 mg/kg bw/d will be used as the starting point.

Modification of dose descriptor

The equivalent dermal NOAEL will be derived using route-to-route extrapolation, based on assumption of 100% absorption after ingestion and 100% after skin contact.

The dermal NOAEL may be calculated as follows:

NOAELdermal = NOAELoral x ABSoral-rat/ABSdermal-human

= 1000 x 100/100

= 1000 mg/kg bwt/d (4 -week duration of exposure)

Assessment factors (ECHA, ECHA Guidance Chapter R8, Table R8-6, November 2012)

Uncertainty

AF (ECHA)

Justification

Interspecies differences

4.0

2.5

Allometric scaling for rat

For remaining differences

Intraspecies differences

10

default AF for general population

Differences in duration of exposure

6

sub-acute to chronic extrapolation

Dose response and endpoint specific/severity issues

1

default AF

Quality of database

1

default AF

Overall AF

600

DNEL General Population long-term dermal-systemic = 1000 / 600 = 1.66 mg/kg bw/day

Oral DNEL (systemic)

Dose descriptor

The rat 4 -week oral NOAEL of 1000 mg/kg bw/d will be used as the starting point.

Modification of dose descriptor

The equivalent dermal NOAEL will be derived using route-to-route extrapolation, based on assumption of 100% absorption after ingestion by both humans and rats.

The oral NOAEL may be calculated as follows:

NOAELoral = NOAELoral x ABSoral-rat/ABSoral-human

= 1000 x 100/100

= 1000 mg/kg bwt/d (4 -week duration of exposure)

Assessment factors (ECHA, ECHA Guidance Chapter R8, Table R8-6, November 2012)

Uncertainty

AF (ECHA)

Justification

Interspecies differences

4.0

2.5

Allometric scaling for rat

For remaining differences

Intraspecies differences

10

default AF for general population

Differences in duration of exposure

6

sub-acute to chronic extrapolation

Dose response and endpoint specific/severity issues

1

default AF

Quality of database

1

default AF

Overall AF

600

DNEL General Population long-term oral systemic = 1000 / 600 = 1.66 mg/kg bw/day