Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21.2 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):
25
Dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
529 mg/m³
Explanation for the modification of the dose descriptor starting point:

Standard oral to inhalation route-to-route extrapolation (According to ECHA Guidance R8):

Corrected inhalatory NOAEC = oral NOAEL x 1/standard Respiratory Volume (rat)* Absorption oral-rat/Absorption inh-human * standard Repiratory Volume (Human)/worker Respiratory Volume

Corrected inhalatory NOAEL = 600 x 1/0.38 m3/kg/day * 50/100 * 6.7 m3 (8h)/10 m3 (8h)= 529 mg/m3

AF for dose response relationship:
1
Justification:
Oral NOAEL used as a starting point
AF for differences in duration of exposure:
2
Justification:
Subchronic (OECD 408 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling used in derivation of inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Standard factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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:
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):
100
Dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Standard oral to dermal route-to-route extrapolation: no modification of the "starting point" is applied as the oral and dermal absorptions are considered equivalent.
AF for dose response relationship:
1
Justification:
Oral NOAEL used as a starting point
AF for differences in duration of exposure:
2
Justification:
Subchronic (OECD 408 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor for the rat species
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Standard factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.2 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):
50
Dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
261 mg/m³
Explanation for the modification of the dose descriptor starting point:

Standard oral to inhalation route-to-route extrapolation for consumers (according to ECHA Guidance R8):

Corrected inhalatory NOAEC = oral NOAEL * 1/standard Respiratory Volume (rat) * Absorption oral-rat/Absorption inh-humman

Corrected inhalatory NOAEC = 600 * 1/1.15 m3/kg/d * 50/100

AF for dose response relationship:
1
Justification:
Oral NOAEL used as a starting point
AF for differences in duration of exposure:
2
Justification:
Subchronic (OECD 408 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling used in derivation of inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining differences
AF for intraspecies differences:
10
Justification:
Standard factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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:
3 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Standard oral to dermal route-to-route extrapolation: no modification of the "starting point" as oral and dermal absorptions are considered equivalent.
AF for dose response relationship:
1
Justification:
Oral NOAEL used as a starting dose
AF for differences in duration of exposure:
2
Justification:
Subchronic (OECD 408) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor for the rat species
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Standard factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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:
3 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No correction is applied to the "starting point" as the oral absorption considered equivalent in rats and humans in the absence of specific absorption data
AF for dose response relationship:
1
Justification:
Oral NOAEL used as a starting dose
AF for differences in duration of exposure:
2
Justification:
Subchronic (OECD 408) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor for the rat species
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Standard factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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