3,3'-[(4-{(E)-[2-bromo-4-nitro-6-(trifluoromethyl)phenyl]diazenyl}phenyl)imino]dipropanenitrile

Toxicological Summary

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

Value:

1 763 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 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:

medium hazard (no threshold derived)

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 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 further uncertainties to be taken into account.

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

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 the test substance on humans.

In an available sub-acute toxicity study, FAT 41029/A 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. Oral administration of FAT 41'029/A 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 hind limb grip strength. Test item-related findings were generally restricted to only slight effects on loco motor activity at 1000 mg/kg/day. These effects were considered to be non-adverse. Based on the results of this study, 1000 mg/kg body weight/day of FAT41'029/A is the no-observed-adverse-effect-level (NOAEL).

Based on the mentioned above, it was reasonable to choose the oral NOAEL of 1000 mg/kg/day as the starting point for the purpose of DNEL derivation.

As there is no quantitative data available for dermal adsorption of the chemical, a worst case scenario is assumed in which the absorption rate from dermal route is considered to be same as oral route.

FAT41029 is expected to be absorbed in human via different routes - oral (assumed 10%), dermal (assumed 10%) and inhalation route (assumed 10% only if human is exposed in dusts directly) due to the physico-chemical properties (i.e., moderate molecular weight, poor water solubility, particle size is rather course with a mass median diameter of 236 µm, Log Pow of 3.6).

According to ECHA guidance document the oral NOAEL (1000 mg/kg bw/d) is converted to an inhalatory NOAEC_Worker of 1763 mg/m³, considering division by 0.38 m³/kg in case of 8 h exposure/d for worker as well as a factor of 6.7 m³/10 m³ for light weight work adjustment.

As the substance FAT 41029 is a weak skin sensitiser (positive in maximisation test but negative in Buehler test) a medium hazard (no threshold derived) for acute inhalation and dermal exposure is set, to be addressed qualitatively in the exposure scenarios.

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

Value:

870 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 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 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:

Available data from substance fulfilling scientific principle is used

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

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 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 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:

medium hazard (no threshold derived)

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 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 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

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

In an available sub-acute toxicity study, FAT 41029/A 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. Oral administration of FAT 41'029/A 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 hind limb grip strength. Test item-related findings were generally restricted to only slight effects on loco motor activity at 1000 mg/kg/day. These effects were considered to be non-adverse. Based on the results of this study, 1000 mg/kg body weight/day of FAT41'029/A is the no-observed-adverse-effect-level (NOAEL).

Based on the mentioned above, it was reasonable to choose the oral NOAEL of 1000 mg/kg/day as the starting point for the purpose of DNEL derivation.

As there is no quantitative data available for dermal adsorption of the chemical, a worst case scenario is assumed in which the absorption rate from dermal route is considered to be same as oral route.

FAT41029 is expected to be absorbed in human via different routes - oral (assumed 10%), dermal (assumed 10%) and inhalation route (assumed 10% only if human is exposed in dusts directly) due to the physico-chemical properties (i.e., moderate molecular weight, poor water solubility, particle size is rather course with a mass median diameter of 236 µm, Log Pow of 3.6).

According to ECHA guidance document the oral NOAEL (1000 mg/kg bw/d) is converted to an inhalatory NOAEC_Consumer of 870 mg/m³, considering division by 1.15 m³/kg in case of 24 h exposure/d for consumer.

As the substance FAT 41029 is a weak skin sensitiser (positive in maximisation test but negative in Buehler test) a medium hazard (no threshold derived) for acute inhalation and dermal exposure is set, to be addressed qualitatively in the exposure scenarios.