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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.35 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:
other: NOEC
Value:
176.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation is an unlikely but possible route for exposure to the substance in regular use. According to ECHA guidance document the oral NOEL (50 mg/kg bw/d) is converted to an inhalatory NOEC Worker as follows: 50 mg/kg bw /d / 0.38 m3/kg/d * 6.7 m3/10m3 * 100/50 = 176.3 mg/m3, whereas the first factor accounts for different respiratory volume from rats to humans, the second factor considers light weight activity respiratory volume increase by workers and the third factor takes account of an anticipated lower absorption via inhalative route compared to oral route (i.e. 100% for oral absorption, and 50% for inhalation).
AF for dose response relationship:
1
Justification:
NOEC 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:
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:
DNEL (Derived No Effect Level)
Value:
2.35 mg/m³
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:
3.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
other: NOEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOEL from a subacute dermal toxicity study with rats (1000 mg/kg bw) forms the basis for the derivation of the DNEL systemic for dermal exposure and thus no route-to-route extrapolation is required.
AF for dose response relationship:
1
Justification:
NOEL 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):
4
Justification:
rats are used
AF for other interspecies differences:
2.5
Justification:
no other substance-specific effects are available
AF for intraspecies differences:
5
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
Available data fulfill the scientific requirements
AF for remaining uncertainties:
1
Justification:
no other uncertainties need to be considered.
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

In the available sub-acute toxicity study, FAT 20'306 was administered daily by gavage to SPF-bred Wistar rats of both sexes at dose levels of 0, 50, 200 and 1000 mg/kg body weight/day for a period of 28 days. Based upon the results obtained in this study, the "no-observed-effect level" of FAT 20'306 was considered to be 50 mg/kg body weight for male and female rats when administered orally by gavage under the conditions described in this study.

FAT 20306 is expected to be absorbed in human via different routes - oral, dermal and inhalation route due to the physico-chemical properties (i.e., relatively high molecular weight, high water solubility, particle size: 22.9 μm (50%), low Log Pow). A worst case scenario is assumed in which the absorption rate from dermal route is considered to be 50%, for oral route 100% and for inhalative route 50%. Therefore, NOELcorr for the dermal route is 100 mg/kg bw/day.

According to ECHA guidance document the oral NOEL is converted to an inhalatory NOECWorker of 176.3 mg/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 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:
other: NOEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation is an unlikely but possible route for exposure to the substance in regular use. According to ECHA guidance document the oral NOEL (50 mg/kg bw/d) is converted to an inhalatory NOEC Worker as follows: 50 mg/kg bw /d / 1.15 m3/kg/d * 100/50 = 87.0 mg/m3, whereas the first factor accounts for different respiratory volume from rats to humans and the second factor considers an anticipated higher absorption via inhalative route compared to oral route (i.e. 100% for oral absorption, and 50% for inhalation).
AF for dose response relationship:
1
Justification:
NOEC is used as the starting point
AF for differences in duration of exposure:
6
Justification:
based on the sub-acute study
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not applied for derivation of inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
no other substance-specific effects 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 fulfill the scientific requirments
AF for remaining uncertainties:
1
Justification:
no other uncertainties needed to be considered.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 mg/m³
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:
1.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
other: NOEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOEL from a subacute dermal toxicity study with rats (1000 mg/kg bw forms the basis for the derivation of the DNEL systemic for dermal exposure and thus no route-to-route extrapolation is required.
AF for dose response relationship:
1
Justification:
NOEL is used as starting point
AF for differences in duration of exposure:
6
Justification:
based on the subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
rats are used
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 fulfill the scientific requirements
AF for remaining uncertainties:
1
Justification:
no other uncertainties need to be considered
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:
83.3 µg/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:
other: NOEL
Value:
50 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:
NOEL 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):
4
Justification:
rats are used
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data are availalbe
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
available data fulfill the scientific principles
AF for remaining uncertainties:
1
Justification:
no other uncertainties need to be considered
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
83.3 µg/kg bw/day
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

In an available sub-acute toxicity study, FAT 20306 was administered daily by gavage to SPF-bred Wistar rats of both sexes at dose levels of 0, 50, 200 and 1000 mg/kg body weight/day for a period of 28 days. Based upon the results obtained in this study, the "no-observed-effect level" of FAT 20306 was considered to be 50 mg/kg body weight for male and female rats when administered orally by gavage under the conditions described in this study. This study forms the basis for derivation of inhalation and oral DNELs.

Additionally, a subacute study by dermal application to rats is available with doses applied of 0, 40, 200, and 1000 mg/kg bw. No significant effects were observed in this study and thus the NOEL was set to 1000 mg/kg bw/d. This NOEL is used for derivation of dermal DNELs accordingly.

FAT 20306 is expected to be absorbed in human via different routes - oral, dermal and inhalation route due to the physico-chemical properties (i.e., relatively high molecular weight, high water solubility, particle size: 22.9 μm (50%), low Log Pow).

A worst case scenario is assumed in which the absorption rate from dermal route is considered to be 50%, for oral route 100% and for inhalative route 50%. Therefore, NOELcorr for the inhalation route is 100 mg/kg bw/day, based on the NOEL resulting from the subacute oral study and the corresponding NOEC is 176.3 for workers accordingly.

According to ECHA guidance document the oral NOEL is converted to an inhalatory NOECConsumer of 87.0 mg/m3.