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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:
11.6 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Value:
871 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
not required
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:
14 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Value:
4 200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no other uncertainties need to be concerned
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.33 mg/kg bw/day
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The inhalation route is not considered to be a relevant exposure route to human due to the physical-chemical property of substance. However, due to potential dust exposure during handling, a systemic long term inhalative DNEL was derived.

In the 28-day toxicity study, FAT 45176/A was administered to Wistar rats at doses up to and including 1000 mg/kg, there was no any test article related abnormal findings. Therefore, 1000 mg/kg FAT45176/A was established as the no-observed-adverse-effect level (NOAEL).

Based on the test results given in one-generation reproduction study conducted for read-across assessment, FAT 40558 at doses up to 1000 mg/kg did not affect the fertility or reproductive capability of male or female Sprague-Dawley rats when administered via oral gavage. FAT 45176 has the similar property, which can be considered that FAT 45176 did not cause any reproduction toxicity at the doses up to 1000 mg/kg/day.

In terms of the overview available data discussed as above, the NOAEL of 1000 mg/kg body weight/day obtained from sub-acute study was identified as the appropriate starting point for DNEL derivation.

 

As there is no quantitative data available for dermal adsorption of the substance, a worst case scenario is assumed in which the absorption rate from dermal route is considered to be same as oral route, and for both routes assumed to be 100%. Therefore, a corrected dermal NOAEL is considered to be 1000 mg/kg body weight/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.05 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Value:
307 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
not required
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:
5 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Value:
3 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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:
1.67 mg/kg bw/day
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral 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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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:
1.67 mg/kg bw/day
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

The inhalation route is not considered to be a relevant exposure route to human due to the physical-chemical property of substance. However, to assess potential dust exposure, an inhalative DNEL for systemic long-term was derived.

In the 28-day toxicity study, FAT 45176/A was administered to Wistar rats at doses up to and including 1000 mg/kg, there was no any test article related abnormal findings. Therefore, 1000 mg/kg FAT45176/A was established as the no-observed-adverse-effect level (NOAEL).

Based on the test results given in one-generation reproduction study conducted for read-across assessment, FAT 40558 at doses up to 1000 mg/kg did not affect the fertility or reproductive capability of male or female Sprague-Dawley rats when administered via oral gavage. FAT 45176 has the similar property, which can be considered that FAT 45176 did not cause any reproduction toxicity at the doses up to 1000 mg/kg/day.

In terms of the overview available data discussed as above, the NOAEL of 1000 mg/kg body weight/day obtained from the sub-acute study was identified as the basis for DNEL derivation.

 

As there is no quantitative data available for dermal adsorption of the substance, a worst case scenario is assumed in which the absorption rate from dermal route is considered to be same as oral route, and for both routes assumed to be 100%. Therefore, a corrected dermal NOAEL is considered to be 1000 mg/kg body weight/day.