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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:
23.5 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
DNEL value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:
No long-term inhalative toxicity data is available for FAT40863; therefore, anticipating comparable absorption by inhalative and oral route (both 10% assumed), a NOAEC corr of 1000 mg/kg/day / 0.38 m^3/kg * 6.7/10 * 10%/10% = 1763 mg/m^3 is used.
AF for dose response relationship:
1
Justification:
not required as starting point is NOAEC corr.
AF for differences in duration of exposure:
6
Justification:
default value for sub-acute study data
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
for worker, a default AF of 5 is to be used
AF for the quality of the whole database:
1
Justification:
not required, available data fulfill scientific principles
AF for remaining uncertainties:
1
Justification:
not required, 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:
medium hazard (no threshold derived)
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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal, equivalent absorption (both 10%) assumed and therefore no correction applied
AF for dose response relationship:
1
Justification:
NOAEL was used as the starting point
AF for differences in duration of exposure:
6
Justification:
based on a sub-acute study result
AF for interspecies differences (allometric scaling):
4
Justification:
rats were used in tests
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data was available
AF for intraspecies differences:
5
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
not required, available data fulfill scientific principles
AF for remaining uncertainties:
1
Justification:
not required, 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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

There is no available toxicity data concerning the test substance on humans.

In a sub-acute toxicity study, the test substance was administered daily by oral gavage to Wistar rats of both sexes at dose levels of 0, 30, 300 and 1000 mg/kg body weight/day for a period of 28 days. No adverse treatment-related effects were noted on any parameter observed during the study. 1000 mg/kg body weight/day of the test item was established as the no-observed-adverse-effect-level (NOAEL).

Another available report was conducted according to OECD guideline 421 under GLP condition. FAT 40863 A/TE was administered by daily oral gavage to male and female Wistar rats at dose levels of 100, 300 and 1000 mg/kg, also showing no adverse treatment related effects and establishing to NOAEL in this study at 1000 mg/kg bw/d too for parental toxicity and reproductive toxicity being in a good agreement with the results from the 28-day repeated dose toxicity study (see above).

Studies on acute oral and acute dermal toxicity at dosing up to 2000 mg/kg bw showed no treatment related effects and neither were effects seen on skin and eye irritation in in vitro and in vivo studies. In a LLNA study for skin sensitisation (OECD 429), skin sensitising effects were seen at 50% concentration only, whereas dosing at 25 and 10% weight/weight in distilled water showed negative results. Thus, the substance is considered a weak skin sensitiser. Three in vitro studies for mutagenicity were negative.

The toxicological data above were taken into account for DNEL derivation as described.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.8 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:
NOAEC
DNEL value:
870 mg/m³
Explanation for the modification of the dose descriptor starting point:
No long-term inhalative toxicity data is available for FAT40863; therefore, anticipating comparable absorption by inhalative and oral route (both 10% assumed), a NOAEC corr of 1000 mg/kg/day / 1.15 m^3/kg * 10%/10% = 870 mg/m^3 is used.
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 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:
not required, available data fulfill scientific principles
AF for remaining uncertainties:
1
Justification:
not required, 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:
medium hazard (no threshold derived)
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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal, equivalent absorption (both 10%) assumed and therefore no correction applied
AF for dose response relationship:
1
Justification:
NOAEL 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 were 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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
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 study
AF for interspecies differences (allometric scaling):
4
Justification:
rats were used
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 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

See description of relevant data in section on workers.