Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.141 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
10.58 mg/m³
Explanation for the modification of the dose descriptor starting point:

A developmental NOAEL of 3 mg/kg/day established in the combined 28-day repeated dose toxicity study/reproductive toxicity screening study (oral route, OECD 422; van Otterdijk, 2017) 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 NOAEC is 10.58 mg/m³ = 3 mg/kg/day x 1/0.38 m³/kg/day x 0.67 x 2. 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 2 is applied as bioavailability after oral exposure is assumed to be 100% and the bioavailability after inhalation exposure is assumed to be 50%.

AF for dose response relationship:
1
Justification:
NOAEL 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):
1
Justification:
included in the 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:
0.02 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A developmental NOAEL of 3 mg/kg/day established in the combined 28 -day repeated dose toxicity study/reproductive toxicity screening study (oral route, OECD 422; van Otterdijk, 2017) 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 3 mg/kg/day x 2 = 6 mg/kg/day. A correction factor of 2 is applied as bioavailability after oral exposure is assumed to be 100% and the bioavailability after dermal exposure is assumed to be 50%.

AF for dose response relationship:
1
Justification:
starting point NOAEL
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:
DNEL (Derived No Effect Level)
Value:
8 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Dose descriptor:
other: LOAEL (expressed in µg/cm²)
Value:
300 µg/m³
AF for dose response relationship:
3
Justification:
LOAEL used as starting point
AF for differences in duration of exposure:
1
Justification:
time-scaling is not appropriate when the toxic effect is mainly driven by the exposure concentration
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for local effects
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
for 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:
high hazard (no threshold derived)

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:
0.035 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
5.22 mg/m³
Explanation for the modification of the dose descriptor starting point:

A developmental NOAEL of 3 mg/kg/day established in the combined 28-day repeated dose toxicity study/reproductive toxicity screening study (oral route, OECD 422; van Otterdijk, 2017) 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 NOAEC is 5.22 mg/m³ = 3 mg/kg/day x 1/1.15 m³/kg/day x 2. 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 2 is applied as bioavailability after oral exposure is assumed to be 100% and the bioavailability after inhalation exposure is assumed to be 50%.

AF for dose response relationship:
1
Justification:
NOAEL 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):
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:
0.01 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A developmental NOAEL of 3 mg/kg/day established in the combined 28-day repeated dose toxicity study/reproductive toxicity screening study (oral route, OECD 422; van Otterdijk, 2017) 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 3 mg/kg/day x 2 = 6 mg/kg/day. A correction factor of 2 is applied as bioavailability after oral exposure is assumed to be 100% and the bioavailability after dermal exposure is assumed to be 50%.

AF for dose response relationship:
1
Justification:
NOAEL 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:
0.005 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
3 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL 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:
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:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

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.