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Workers - Hazard via inhalation route

Systemic effects

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

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21.3 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
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Starting point: NOAEL 256 mg/kg bw/day from a chronic oral study in rats.

Route-to-route extrapolation

For the derivation of the DNELs:

Long-term – dermal, systemic effects

Long-term – inhalation, systemic effects

Route-to-route extrapolation has been performed. In absence of relevant data, only differences between the different routes as determined by the assumed percentages of absorption into the systemic circulation could be accounted for (see toxicokinetic assessment).

Absorption oral (rat) = Absorption oral (human) = 50%

Absorption dermal (human) = 50%

Absorption inhalation (human) = 50%

 

The DNELs for human exposure are derived according to the ECETOC guidance (final draft).

Dermal DNEL

Route-to-route extrapolation:

Dermal NOAEL = oral NOAEL * ABSoral-rat/ABSderm-human = 256 * 50/50 = 256 mg/kg bw

Safety factors:

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 3

-      Exposure duration: 1 (assuming chronic worker exposure)

-      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 21.3 mg/kg bw/day.

Inhalation DNEL

Route-to-route extrapolation:

Inhalation NOAEL = oral NOAEL * ABSoral-rat/ABSinh-human = 256 * 50/50 = 256 mg/kg bw

Corrected inhalatory NOAEC = 256 * 1/0.38 * 6.7 m3/10 m3= 451 mg/m3

Safety factors:

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 3

-      Exposure duration: 1 (assuming chronic worker exposure)

-      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 inhalation exposure of the worker, is set at 37.6 mg/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.8 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
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.8 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
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Starting point: NOAEL 256 mg/kg bw/day from a chronic oral study in rats.

Route-to-route extrapolation

For the derivation of the DNELs:

Long-term – dermal, systemic effects

Long-term – inhalation, systemic effects

Route-to-route extrapolation has been performed. In absence of relevant data, only differences between the different routes as determined by the assumed percentages of absorption into the systemic circulation could be accounted for (see toxicokinetic assessment).

Absorption oral (rat) = Absorption oral (human) = 50%

Absorption dermal (human) = 50%

Absorption inhalation (human) = 50%

 

The DNELs for human exposure are derived according to the ECETOC guidance (final draft).

Oral DNEL

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 12.8 mg/kg bw/d.

Dermal DNEL

Route-to-route extrapolation:

Dermal NOAEL = oral NOAEL * ABSoral-rat/ABSderm-human = 256 * 50/50 = 256 mg/kg bw

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 dermal exposure of the general population is set at 12.8 mg/kg bw/day.

Inhalation DNEL

Route-to-route extrapolation:

Inhalation NOAEL = oral NOAEL * ABSoral-rat/ABSinh-human = 256 * 50/50 = 256 mg/kg bw

Corrected inhalatory NOAEC = 256 * 1/1.15 = 223 mg/m3

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 inhalation exposure of the general population is set at 11.1 mg/m3.