Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.059 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):
225
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
13.22 mg/m³
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 15 mg/kg bw/day, established in the 28 -day repeated dose oral toxicity study (oral route, OECD 407; Brunke et al., 2007), was used to derive a DNEL long-term, systemic effects via the inhalation route. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point LOAEC is 13.22 mg/m³ = 15 mg/kg bw/day x 1/0.38 m³/kg/day x 0.67 x 0.5. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure for workers). For workers, the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under respective conditions (6.7 m³ for base level, 10 m³ for light activity). A correction factor of 0.5 is applied as bioavailability after oral exposure is assumed to be 50%, while after inhalation it is 100%.

AF for dose response relationship:
3
Justification:
LOAEL was used as starting point
AF for differences in duration of exposure:
6
Justification:
difference in study duration subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
included in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
no need for further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for further assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.017 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):
900
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 15 mg/kg/day, established in the 28 -day repeated dose oral toxicity study (oral route, OECD 407; Brunke et al., 2007), was used to derive a DNEL long-term, systemic effects via dermal administration. After route-to-route extrapolation (oral to dermal) the dose descriptor starting point is 15 mg/kg bw/day. No correction factor for route to route extrapolation is needed as bioavailability after oral and dermal exposure is assumed to be 50%.

AF for dose response relationship:
3
Justification:
LOAEL was used as starting point
AF for differences in duration of exposure:
6
Justification:
difference in study duration subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
no need for further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for further assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.014 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):
450
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
6.52 mg/m³
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 15 mg/kg bw/day, established in the 28 -day repeated dose oral toxicity study (oral route, OECD 407; Brunke et al., 2007), was used to derive a DNEL long-term, systemic effects via the inhalation route. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point LOAEC is 6.52 mg/m³ = 15 mg/kg bw/day x 1/1.15 m³/kg/day x 0.5. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m³/kg for 24 hours exposure of general public). A correction factor of 0.5 is applied as bioavailability after oral exposure is assumed to be 50% while after inhalation it is assumed to be 100%.

AF for dose response relationship:
3
Justification:
LOAEL was used as starting point
AF for differences in duration of exposure:
6
Justification:
difference in study duration subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
included in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
no need for further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for further assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.008 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):
1 800
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The LOAEL of 15 mg/kg/day, established in the 28 -day repeated dose oral toxicity study (oral route, OECD 407; Brunke et al., 2007), was used to derive a DNEL long-term, systemic effects via dermal administration. After route-to-route extrapolation (oral to dermal) the dose descriptor starting point is 15 mg/kg bw/day No correction factor is applied as bioavailability after oral and dermal exposure is assumed to be 50%.

AF for dose response relationship:
3
Justification:
LOAEL is used as starting point
AF for differences in duration of exposure:
6
Justification:
difference in study duration subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
no need for further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for further assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.008 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):
1 800
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
AF for dose response relationship:
3
Justification:
LOAEL used as starting point
AF for differences in duration of exposure:
6
Justification:
difference in study duration subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
no need for further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for further assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

No consumer use is foreseen for this substance. However, as exposure for humans via the environment via inhalation, dermal and oral route is considered as relevant for this substance, DNELs were derived for this population.