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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
47 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:
3 526 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation is a likely route for exposure to the substance in regular use. According to ECHA guidance document the oral NOAEL (1000 mg/kg bw/d, derived from the oral OECD407 study) is converted to an inhalatory NOAEC Worker as follows: 1000 mg/kg bw /d / 0.38 m3/kg/d * 6.7 m3/10m3 * 20/10 = 3526 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 higher absorption via inhalative route compared to oral route (i.e. 20% for oral absorption, and 10% for inhalation).
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:
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:
47 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:
6.67 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
As there is no direct information regarding dermal route for the substance, a worst case scenario is assumed in which the absorption rate via dermal route is considered to be 10% and the absorption by oral route 20% according to TK assessment. Thus, the NOAEL from the OECD 407 study being 1000 mg/kg bw/d * 20/10 = 2000 mg/kg bw/d is used accordingly.
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 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

There is no available toxicity data concerning test substance on human.

In the sub-acute toxicity study, test article was administered daily by oral 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. No adverse treatment-related effects were noted on any parameter observed during the study, except of discoloration of urine and slightly higher bilirubin concentrations, considered being treatment related but not of toxicological significance. 1000 mg/kg body weight/day of the test item was established as the no-observed-adverse-effect-level (NOAEL).

FAT40549 is expected to be absorbed in human via different routes - oral, dermal and inhalation route due to the physico-chemical properties (i.e., high molecular weight, highly water solubility, particle size is 66 µm (D50 value), low Log Pow).

As there is no direct information of dermal route for substance, a worst case scenario is assumed in which the absorption rate via dermal route is considered being 10% and the absorption rate by as oral route being 20%. Therefore, NOAELcorr for the dermal route is 2000 mg/kg bw/day. According to ECHA guidance document the oral NOAEL is converted to an inhalation NOAECworker of 3526 mg/m3 (0.38 m3/kg in case of 8 h exposure/d for worker), a factor of 6.7 m3/10m3 taking account of light work activities and a default factor of 2 was assumed in the case of oral-to-inhalation extrapolation (i.e. 20% for oral absorption, and 10% for inhalation).

General Population - 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
1 739 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation is a likely route for exposure to the substance in regular use. According to ECHA guidance document the oral NOAEL (1000 mg/kg bw/d, derived from the OECD 407 study) is converted to an inhalatory NOAEC General Population as follows: 1000 mg/kg bw /d / 1.15 m3/kg/d * 20/10 = 1739 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 oral route compared to inhalation route (i.e. 2% for oral absorption, and 10% for inhalation).
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:
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:
11.6 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:
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):
600
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A worst case scenario is assumed in which the absorption rate from dermal route is considered 10% an for oral route 20%. Hence, the NOAEL is corrected by a factor of 2.
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 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:
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
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 are 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:
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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There is no available toxicity data concerning test substance on human.

In the sub-acute toxicity study, test article was administered daily by oral 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. No treatment-related effects were noted on any parameter observed during the study, except of discoloration of urine and slightly increased bilirubin levels, considered being treatment related but not of toxicological significance. 1000 mg/kg body weight/day of the test item was established as the no-observed-adverse-effect-level (NOAEL).

FAT40549 is expected to be absorbed in human via different routes - oral, dermal and inhalation route due to the physico-chemical properties (i.e., high molecular weight, highly water solubility, particle size is 66 µm on average, low Log Pow).

As there is no direct information of dermal route for substance, a worst case scenario is assumed in which the absorption rate via dermal route is considered to be 10% and for oral route assumed to be 20%. Therefore, NOAELcorr for the dermal route is 2000 mg/kg bw/day. According to ECHA guidance document the oral NOAEL is converted to an inhalation NOAEC general population of 1739 mg/m3 (1.15 m3/kg in case of 24 h exposure/d for general population), and a default factor of 2 was assumed in the case of oral-to-inhalation extrapolation (i.e. 20% for oral absorption, and 10% for inhalation).