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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.129 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
DNEL value:
11 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
9.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 11 mg/kg/day established in the combined 28-day repeated dose toxicity study/reproductive toxicity screening study (oral route, OECD 422; Pels Rijcken, 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 9.7 mg/m³ = 11 mg/kg/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% and the bioavailability after inhalation exposure is assumed to be 100%.

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:
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:
0.037 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
DNEL value:
11 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
11 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 11 mg/kg/day established in the combined 28-day repeated dose toxicity study/ reproductive toxicity screening study (oral route, OECD 422; Pels Rijcken, 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 remains 11 mg/kg/day, as the bioavailability after oral exposure and 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:
242 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)
DNEL value:
9 075 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:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Next to the quantitative and qualitative DNELs that already have been derived for the worker population, a qualitative assessment is performed for the endpoint mutagenicity. Based on the available data it is not clear if a threshold effect for mutagenicity is concerned. In addition, in absence of a quantitative dose descriptor from an in vivo study for this endpoint, a qualitative assessment needs to be done to cover any remaining risk related to mutagenicity. As substance is classified as mutagenic category 2, it should be considered to cause high hazard

according to ECHA's Guidance on Information Requirements and Chemical Safety Assessment, Part E, Table E.3-1.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.032 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
DNEL value:
11 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
4.78 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 11 mg/kg/day established in the combined 28-day repeated dose toxicity study/reproductive toxicity screening study (oral route, OECD 422; Pels Rijcken, 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 4.78 mg/m³ = 11 mg/kg/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 was applied, as the bioavailability after oral exposure is assumed to be 50%, while the bioavailability after inhalation is assumed to be 100%.

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:
0.018 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
DNEL value:
11 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
11 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 11 mg/kg/day established in the combined 28-day repeated dose toxicity study/ reproductive toxicity screening study (oral route, OECD 422; Pels Rijcken, 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 remains 11 mg/kg/day. No correction factor is applied as bioavailability after oral exposure and 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:
0.018 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
DNEL value:
11 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:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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.

Although a qualitative assessment for mutagenicity has been performed for the worker population based on available mutagenicity data, this DNEL is not considered relevant for the population man via the environment. Therefore, this DNEL was not derived for that population.