Registration Dossier

Diss Factsheets

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:
no hazard identified
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:
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:
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:
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

Route-to-route extrapolation

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 toxicokinectic assessment.

 

Derivation of DNELs

The DNELs for human exposure are derived according to the ECETOC guidance (Technical Report No. 110, October 2010).

Long-term dermal, systemic effects

Worker

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

 

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 set at 833 mg/kg bw/day.

 

Long-term inhalation, systemic effects

Worker

Starting point: NOAEC of ≥ 662 mg/m3 from a 13 -week inhalation study in rats (exposure 6 hours/day, 5 days/week).

Corrected inhalatory NOAEC = 662 * 6h/8h * 6.7 m3/10 m3= 333 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 set at 55 mg/m3.

Long-term inhalation, local effects

Worker

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

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 set at 55 mg/m3.

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:
no hazard identified
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:
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:
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:
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:
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:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Route-to-route extrapolation

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 toxicokinectic assessment.

 

Derivation of DNELs

The DNELs for human exposure are derived according to the ECETOC guidance (Technical Report No. 110, October 2010)

 

Long-term oral, systemic effects

General population

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

 

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 set at 500 mg/kg bw/day.

 

Long-term inhalation, systemic effects

General population

Starting point: NOAEC of ≥ 662 mg/m3 from a 13-week inhalation study in rats (exposure 6 hours/day, 5 days/week) with glycerol.

Corrected inhalatory NOAEC = 662 * 6h/24h * 5/7 = 118 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 set at 12 mg/m3.

 

Long-term inhalation, local effects

General population

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

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 set at 33 mg/m3.

 

 

Long-term dermal, systemic effects

General population

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

 

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 set at 500 mg/kg bw/day.