Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
95 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
253.4 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
95 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
253.4 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
20
Dose descriptor starting point:
other: NOAEL

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

DNEL values for workers were calculated for dermal and inhalation routes of exposure. Penetration of FR-370 through these routes is assumed to be negligible owing to the high molecular weight above 1000g/mol, the Log Pow value above 4 and the very poor solubility in water (0.0156 mg/L), (Guidance on Information Requirements and Chemical Safety Assessment, (Chapter R.7C paragraph R.7.12).

Skin route

In addition to the above argumentation, FR-370 was found to be not irritating to skin and eye, not sensitizing to skin and showed skin LD50>2000 mg/kg bw with no systemic toxicity or any other toxicity. Therefore, it is unlikely that exposure of workers via the dermal route will be harmful. Nevertheless, in order to avoid any potential exposure, workers are instructed to wear protective gloves, body covering clothes and boots.

Inhalation route

Although FR-370 contains an inhalable fraction of particles, it is not expected to be absorbed or cause toxicity or any adverse effect via inhalation owing to its properties. In addition, the respiratory system was not found to be a target in both the 90 days oral repeated dose study or in the ADME study.

 

In summary, the above arguments indicate that the substance is unlikely to be available to workers through the dermal route or inhalation route. The risk management measures provided in Part A are sufficient for safe use by workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
47.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
126.7 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
47.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
126.7 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEC

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.79 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
40
Dose descriptor starting point:
other: NOAEL

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.79 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

DNEL values for general population were calculated for dermal and inhalation routes of exposure. Penetration of FR-370 through these routes is assumed to be negligible owing to the high molecular weight above 1000g/mol, the Log Pow value above 4 and the very poor solubility in water (0.0156 mg/L), (Guidance on Information Requirements and Chemical Safety Assessment, (Chapter R.7C paragraph R.7.12).

Oral route

The results from the ADME study and 90-day repeat dose oral toxicity study further support the above argumentation, showing very low absorption and retention of FR-370 in tissues (2%) and no systemic toxic effects above 1000mg/kg (highest dose level tested).

Skin route

FR-370 was found to be not irritating to skin and eye, not sensitizing to skin and showed skin LD50>2000 mg/kg bw with no systemic toxicity or any other toxicity. Therefore, it is unlikely that exposure of general population via the dermal route will be harmful.

Inhalation route

Although FR-370 contains an inhalable fraction of particles, it is not expected to be absorbed or cause toxicity or any adverse effect via inhalation. In addition, the respiratory system was not found to be a target in both the 90 days oral repeated dose study or in the ADME study.

In summary, the above arguments indicate that the substance is unlikely to be available forgeneral populationthrough the oral route, dermal route or inhalation route.