Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
55 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
55 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
833 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
500 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
500 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Route-to-route extrapolation

A route-to route extrapolation is necessary for the long-term systemic dermal DNEL for the general population and workers.

For both oral and dermal absorption, 100% is assumed based on a toxicokinetic assessment (Pelgrom, 2010).

 

Derivation of DNELs

The DNELs for human exposure are derived according to the guidance developed by ECETOC (2010).

Since no local effects were observed after acute dermal exposure to Polyglycerol-3, no acute local DNEL for dermal exposure is considered applicable. However, considering the systemic and local effects seen after 13-week inhalation exposure to glycerol, derivation of an acute inhalation DNELs for systemic and local effects might be considered. Since no acute toxicity was observed in any of the available tests and due to the low vapor pressure of the substance, no acute inhalation DNELs are derived.


The following DNELs will be derived:

 

Systemic:

Long-term oral general population (from 2-years diet study in rats)

Long-term inhalation general population (from 13 week inhalation study)

Long-term inhalation workers (from 13 week inhalation study)

Long-term dermal general population (from 2-year diet study in rats)

Long-term dermal general workers (from 2-year diet study in rats)

 

Local:

Long-term inhalation general population (from 13-week inhalation study in rats)

Long-term inhalation workers (from 13-week inhalation study in rats)

 

Long-term oral, systemic effects

General population

Starting point: NOAEL of ≥ 10000 mg/kg bw/day from an oral chronic toxicity study in rats.

 Safety factors:

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 5

-      Exposure duration: 1 (assuming chronic exposure of the general population)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 20

Based on the above, the long-term DNEL for systemic effects after oral exposure of the general population is 500 mg/kg bw/day (35000 mg/day).

 

Long-term inhalation, systemic effects

Worker

Starting point: NOAEC of ≥ 0.66 mg/L from a 13-week inhalation study in rats (exposure 6 hours/day, 5 days/week). 0.66 mg/L is equivalent to 660 mg/m3.

Corrected inhalatory NOAEC = 660 * 6h/8h * 6.7 m3/10 m3= 332 mg/m3.

 Safety factors:

-      Interspecies extrapolation: 1 (not applicable for inhalation route)

-      Intraspecies extrapolation: 3

-      Exposure duration: 2 (assuming chronic worker exposure)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 6

Based on the above, the long-term DNEL for systemic effects after inhalation worker exposure is 55 mg/m3.

General population

Starting point: NOAEC of ≥ 0.66 mg/L from a 13-week inhalation study in rats (exposure 6 hours/day, 5 days/week). 0.66 mg/L is equivalent to 660 mg/m3.

Corrected inhalatory NOAEC = 660 * 6h/24h * 5/7 = 117 mg/m3

 Safety factors:

-      Interspecies extrapolation: 1 (not applicable for inhalation route)

-      Intraspecies extrapolation: 5

-      Exposure duration: 2 (assuming chronic exposure of the general population)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 10

Based on the above, the long-term DNEL for systemic effects after inhalation exposure of the general population is 12 mg/m3.

 

Long-term inhalation, local effects

Worker

Starting point: NOAEC of 0.165 mg/L from a 13-week inhalation study in rats (exposure 6 hours/day, 5 days/week). 0.165 mg/L is equivalent to 165 mg/m3.

Corrected inhalatory NOAEC = 165 mg/m3(no time scaling and no correction for ventilation rate are considered necessary for local effects).

Safety factors:

-      Interspecies extrapolation: 1 (not applicable for local effects)

-      Intraspecies extrapolation: 3

-      Exposure duration: 1 (not applicable for local effects)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 3

Based on the above, the long-term DNEL for local effects after inhalation worker exposure is 55 mg/m3.

 

General population

Starting point: NOAEC of 0.165 mg/L from a 13-week inhalation study in rats (exposure 6 hours/day, 5 days/week). 0.165 mg/L is equivalent to 165 mg/m3.

Corrected inhalatory NOAEC = 165 mg/m3(no time scaling and no correction for ventilation rate are considered necessary for local effects).

Safety factors:

-      Interspecies extrapolation: 1 (not applicable local effects)

-      Intraspecies extrapolation: 5

-      Exposure duration: 1 (not applicable for local effects)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 5

Based on the above, the long-term DNEL for local effects after inhalation exposure of the general population is 33 mg/m3.

 

Long-term dermal, systemic effects

Worker

Starting point: NOAEL of ≥ 10000 mg/kg bw/day from an oral chronic toxicity study in rats.

 

Corrected dermal NOAEL = 10000 x 100/100 = 10000 mg/kg bw/day

 Safety factors:

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 3

-      Exposure duration: 1

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 12

Based on the above, the long-term DNEL for systemic effects after dermal worker exposure is 833 mg/kg bw/day (58333 mg/day).

 

General population

Starting point: NOAEL of ≥ 10000 mg/kg bw/day from an oral chronic toxicity study in rats.

 Corrected dermal NOAEL = 10000 x 100/100 = 10000 mg/kg bw/day

 Safety factors:

-      Extrapolation oral to dermal: 1

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 5

-      Exposure duration: 1

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 20

Based on the above, the long-term DNEL for systemic effects after dermal exposure of the general population is 500 mg/kg bw/day (35000 mg/day).