Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
41.2 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):
42.5
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 750 mg/m³
Explanation for the modification of the dose descriptor starting point:
NAEC: [(1000/4) x 70)/10]; NOAEL = 30 mg/kg on dog (Salvador, 2013); 4 = allometric scaling factor rat; 70 kg/bw= standard human body weight; 10 m^3/person= default human breathing volume for workers in 8 h.
AF for dose response relationship:
1
Justification:
No scaling needed
AF for differences in duration of exposure:
3.4
Justification:
ERASM Project: lower factor found based on RepDose study (factor 3.4 instead of 6 from subacute to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling needed because the starting point (NAEC) has just been corrected for the human evaluation.
AF for other interspecies differences:
2.5
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
Human Worker
AF for the quality of the whole database:
1
Justification:
GLP compliant, recent data on the registered substance
AF for remaining uncertainties:
1
Justification:
100% adsorption for inhalative route for animal and humanis assumed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
59 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):
170
Modified dose descriptor starting point:
NOAEL
DNEL value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
10% adsorption for dermal route compaired to oral route is assumed. NOAEL is corrected for route to route extrapolation
AF for dose response relationship:
1
Justification:
No scaling needed
AF for differences in duration of exposure:
3.4
Justification:
ERASM Project: lower factor found based on RepDose study (factor 3.4 instead of 6 from subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
Human worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.2 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):
85
Modified dose descriptor starting point:
other: NAEC
DNEL value:
875 mg/m³
Explanation for the modification of the dose descriptor starting point:
NAEC= ((1000 /4) x 70) /20; NOAEL = 100 mg/kg on rat (Salvador, 2013); 4 = allometric scaling factor rat; 70 kg/bw= standard human body weight; 20 m^3/person= default human breathing volume for general population 24h.
AF for dose response relationship:
1
Justification:
No scaling needed
AF for differences in duration of exposure:
3.4
Justification:
ERASM Project: lower factor found based on RepDose study (factor 3.4 instead of 6 from subacute to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling needed because the starting point (NAEC) has just been corrected for the human evaluation.
AF for other interspecies differences:
2.5
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
100% adsorption for inhalative route for animal and humanis assumed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29 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):
340
Modified dose descriptor starting point:
NOAEL
DNEL value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
10% adsorption for dermal route compaired to oral route is assumed. NOAEL is corrected for route to route extrapolation
AF for dose response relationship:
1
Justification:
No scaling needed
AF for differences in duration of exposure:
3.4
Justification:
ERASM Project: lower factor found based on RepDose study (factor 3.4 instead of 6 from subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 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):
340
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No modification necessary
AF for dose response relationship:
1
Justification:
No scaling needing
AF for differences in duration of exposure:
3.4
Justification:
ERASM Project: lower factor found based on RepDose study (factor 3.4 instead of 6 from subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
Toxicocinetic and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
100% adsorption for oral route for animal and human is assumed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population