Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.8 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
881.6 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 fator 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:
11.8 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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
1 000 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 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 othere 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:
DNEL (Derived No Effect Level)
Value:
3.33 mg/kg bw/day
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

Toxicity data in humans regarding FAT 41045 or FAT 41030 are unavailable. A 28-day repeated dose oral (gavage) toxicity study in the rat (OECD 407) was performed with FAT 41030 a structural analogue of FAT 41045. Both substances are very similar in their chemical structure and, as demonstrated, in a number of physicochemical properties. Therefore, the use of this study for read-across and for derivation of DNELs for FAT 41045 is considered to be appropriate.

 

In the above subacute toxicity study, FAT 41030 was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 50, 200 and 1000 mg/kg body weight/day for a period of 28 days. A control group was treated similarly with the vehicle, PEG 300, only. The groups comprised 5 animals per sex which were sacrificed after 28 days of treatment. Additional 5 rats per sex and group were used at 0 and 1000 mg/kg. These animals were treated for 28 days and then allowed a 14-day treatment-free recovery period after which they were sacrificed. Oral administration of FAT 41030 to Wistar rats at doses of 50, 200 and 1000 mg/kg/day, for 28 days was generally well tolerated and did neither produce early mortality or treatment-related signs of toxicological relevance (daily, weekly or functional observational battery) nor effects upon fore- and hindlimb grip strength or locomotor activity. Furthermore, this test revealed no effects on food consumption and body weight development, and there were no treatment-related changes in hematology parameters and no macroscopical and microscopical findings related to the administration of the test item. Test item-related findings were generally restricted to dark-red discoloration of feces and bedding in in a number of animals treated with 50, 200 or 1000 mg/kg/day and to discolorations present in the jejunum, ileum and/or caecum in a number of animals treated with 1000 mg/kg/day. These discolorations were considered to be a passive effect of the dyestuff rather than a sign of systemic toxicity and in the absence of physiological or histopathological findings considered to be of no toxicological relevance. Based on the results of this study, 50 mg/kg body weight/day of FAT 41030 was established as the no-observed-effect-level (NOEL) and 1000 mg/kg body weight/day of FAT 41030 as the no-observed-adverse-effect-level (NOAEL).

 

The oral NOAEL of 1000 mg/kg bw/day was chosen as the starting point for DNEL derivation. As there is no quantitative data available for dermal absorption of the chemical, a worst case scenario is assumed in which the absorption rate by the dermal route is considered to be the same as that by the oral route. Absorption of FAT 41045 in humans is expected to be low via the different routes - oral (10%), dermal (10%) and inhalation (10% only if exposed to dust) due to its physico-chemical properties (i.e. high molecular weight, poor water solubility and log Pow > 6.2, majority of particles > 100 µm thus belonging to the fraction non-inhalable by humans).

 

According to ECHA guidance document R.8 the oral NOAEL (1000 mg/kg bw/day) is converted to an inhalatory NOAEC Worker of 881.6 mg/m3, considering division by 0.38 m3/kg in case of 8 h exposure/day for a worker, a default factor of 50% for oral absorption divided by 100% for inhalation absorption, as well as a factor of 6.7 m3/10 m3for light weight work adjustment.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 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:
434.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral to inhation (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 fator 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:
Available data from substance fulfilling scientific principle is used
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 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:
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
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 othere 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:
DNEL (Derived No Effect Level)
Value:
1.67 mg/kg bw/day
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
Explanation for the modification of the dose descriptor starting point:
no route to route
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 othere 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:
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:
no hazard identified

Additional information - General Population

Toxicity data in humans regarding FAT 41045 or FAT 41030 are unavailable. A 28-day repeated dose oral (gavage) toxicity study in the rat (OECD 407) was performed with FAT 41030 a structural analogue of FAT 41045. Both substances are very similar in their chemical structure and, as demonstrated, in a number of physicochemical properties. Therefore, the use of this study for read-across and for derivation of DNELs for FAT 41045 is considered to be appropriate.

 

In the above subacute toxicity study, FAT 41030 was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 50, 200 and 1000 mg/kg body weight/day for a period of 28 days. A control group was treated similarly with the vehicle, PEG 300, only. The groups comprised 5 animals per sex which were sacrificed after 28 days of treatment. Additional 5 rats per sex and group were used at 0 and 1000 mg/kg. These animals were treated for 28 days and then allowed a 14-day treatment-free recovery period after which they were sacrificed. Oral administration of FAT 41030 to Wistar rats at doses of 50, 200 and 1000 mg/kg/day, for 28 days was generally well tolerated and did neither produce early mortality or treatment-related signs of toxicological relevance (daily, weekly or functional observational battery) nor effects upon fore- and hindlimb grip strength or locomotor activity. Furthermore, this test revealed no effects on food consumption and body weight development, and there were no treatment-related changes in hematology parameters and no macroscopical and microscopical findings related to the administration of the test item. Test item-related findings were generally restricted to dark-red discoloration of feces and bedding in in a number of animals treated with 50, 200 or 1000 mg/kg/day and to discolorations present in the jejunum, ileum and/or caecum in a number of animals treated with 1000 mg/kg/day. These discolorations were considered to be a passive effect of the dyestuff rather than a sign of systemic toxicity and in the absence of physiological or histopathological findings considered to be of no toxicological relevance. Based on the results of this study, 50 mg/kg body weight/day of FAT 41030 was established as the no-observed-effect-level (NOEL) and 1000 mg/kg body weight/day of FAT 41030 as the no-observed-adverse-effect-level (NOAEL).

 

The oral NOAEL of 1000 mg/kg bw/day was chosen as the starting point for DNEL derivation. As there is no quantitative data available for dermal absorption of the chemical, a worst case scenario is assumed in which the absorption rate by the dermal route is considered to be the same as that by the oral route. Absorption of FAT 41045 in humans is expected to be low via the different routes - oral (10%), dermal (10%) and inhalation (10% only if exposed to dust) due to its physico-chemical properties (i.e. high molecular weight, poor water solubility and log Pow > 6.2, majority of particles > 100 µm thus belonging to the fraction non-inhalable by humans).

 

According to ECHA guidance document R.8 the oral NOAEL (1000 mg/kg bw/day) is converted to an inhalatory NOAEC Consumer of 434.8 mg/m3, considering division by 1.15 m3/kg in case of 24 h exposure/day for general population, a default factor of 50% for oral absorption divided by 100% for inhalation absorption, as well as a factor of 6.7 m3/10 m3for light weight work adjustment.