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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:
0.26 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
19.39 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral to inhalation (no direct data for inhalation route is available)
AF for dose response relationship:
1
Justification:
NOAEC is used as a starting point
AF for differences in duration of exposure:
6
Justification:
based on a 28-day study
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not applied for the derivation of inhalation DNEL.
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data are available.
AF for intraspecies differences:
5
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used.
AF for remaining uncertainties:
1
Justification:
no other uncertainties needed to be considered.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
0.37 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
110 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal (no direct data for dermal route is available); for adjustment of the NOAEL 100% oral absorption and 10% dermal absorption was assumed
AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point
AF for differences in duration of exposure:
6
Justification:
based on the 28-day toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
rats are used in the animal test
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data are available
AF for intraspecies differences:
5
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used .
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account
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:
medium hazard (no threshold derived)

Additional information - workers

Considering very low vapor pressure (4.8E-3 Pa at 20 °C) and low water solubility (125 µg/ml), the inhalation route is not considered further as exposure scenarios for the test article do not indicate inhalative exposure to be the likely route of exposure to workers in regular process. Therefore, a worst case scenario is assumed in which the inhalation absorption is considered to be the same as that of the oral absorption.

Since the water solubility is far below 1 mg/L (125 µg/ml) and the log POW values is outside the range [-1, 4], dermal uptake is likely to be low. There is no quantitative data available for dermal adsorption of test material, thus, a default value of dermal absorption rate is proposed to be 10%. (i.e. the absorption rate from dermal is assumed to be one-tenth that of oral route).

NOAEL of 11 mg/kg/day resulted from the available sub-acute oral study is selected as the basis of DNEL calculation in light of the whole toxicity database. NOAELcorr for the dermal route is 110 mg/kg.bw/day. According to ECHA guidance document the oral NOAEL is converted to an inhalative NOAECworker resulting in a NOAEC of 19.39 mg/m3 (NOAELoral / 0.38 m3/kg × 6.7 m3 (8h)/10 m3 (8h)).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.064 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):
150
Modified dose descriptor starting point:
LOAEC
Value:
9.57 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral to inhalation (no direct data for inhalation route is available)
AF for dose response relationship:
1
Justification:
NOAEC is used as the starting point
AF for differences in duration of exposure:
6
Justification:
based on the subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not applied for the derivation of inhalation DNEL.
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data are available.
AF for intraspecies differences:
10
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used .
AF for remaining uncertainties:
1
Justification:
Available data from substance fulfilling scientific principle is used .
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
0.18 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
110 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal(no direct data for dermal route is available)
AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point
AF for differences in duration of exposure:
6
Justification:
based on the sub-acute toxicity
AF for interspecies differences (allometric scaling):
4
Justification:
rats are used in the animal test
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data are available
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used .
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account
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:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
11 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation
AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point
AF for differences in duration of exposure:
6
Justification:
based on the sub-acute toxicity
AF for interspecies differences (allometric scaling):
4
Justification:
rats are used in the animal tests
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data are available
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used.
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account
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

Although the general population is not exposed to the test article as a chemical substance and consequently inhalative exposure to the substance is unlikely (vapor pressure: 4.8E-3 Pa at 20 °C), a DNEL has been derived. A worst case scenario is assumed in which the inhalation absorption is considered to be the same as that of the oral absorption.

Since the water solubility is far below 1 mg/L (125 µg/ml), log P values is outside the range [-1, 4], dermal uptake is likely to be low and there is no quantitative data available for dermal adsorption of test material, thus, a default value of dermal absorption rate is proposed to be 10%. (i.e. the absorption rate from dermal is assumed to be one-tenth that of oral route.)

According to ECHA guidance, it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly.

In this case, NOAEL of 11 mg/kg/day resulted from the available sub-acute oral study is selected as the basis of DNEL calculation in light of the whole toxicity database. NOAELcorr for the dermal route is 110 mg/kg bw/day. According to ECHA guidance document the oral NOAEL is converted to an inhalative NOAECgeneral population by dividing through 1.15 m3/kg resulting in a NOAEC of 9.57 mg/m3.