Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.37 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
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:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.417 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
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-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The DNELs for human exposure are derived according to the ECETOC guidance (final draft March 17, 2010).

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) = 100%

Long-term inhalation, systemic effects

Starting point: NOAEL 30 mg/kg bw/day from an OECD422 oral study in rats.

 

Route-to-route extrapolation:

Inhalation NOAEL = oral NOAEL * ABSoral-rat/ABSinh-human = 30 * 50/100 = 15 mg/kg bw

 

Corrected inhalatory NOAEC = 15 x 1/0.38ax 6.7/10b= 26.4 mg/m3

 

astandard respiratory volume of rats for 8 hours;bstandard human respiratory volume/respiratory volume for worker with light activity.

 

Safety factors:

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 3

-      Exposure duration: 6 (assuming chronic worker exposure)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 72

Long-term dermal, systemic effects

Starting point: NOAEL 30 mg/kg bw/day from an OECD422 oral study in rats.

 

Route-to-route extrapolation:

Dermal NOAEL = oral NOAEL * ABSoral-rat/ABSderm-human = 30* 50/50 = 30 mg/kg bw

 

Safety factors:

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 3

-      Exposure duration: 6 (assuming chronic worker exposure)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 72

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.11 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
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:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
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-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
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

The DNELs for human exposure are derived according to the ECETOC guidance (final draft March 17, 2010).

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) = 100%

Long-term dermal, systemic effects

Starting point: NOAEL 30 mg/kg bw/day from an OECD422 oral study in rats.

 

Route-to-route extrapolation:

Dermal NOAEL = oral NOAEL * ABSoral-rat/ABSderm-human = 30 * 50/50 = 30 mg/kg bw

 

Safety factors:

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 5

-      Exposure duration: 6 (assuming chronic exposure of the general population)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 120

Long-term inhalation, systemic effects

Starting point: NOAEL 30 mg/kg bw/day from an OECD422 oral study in rats

 

Route-to-route extrapolation:

Inhalation NOAEL = oral NOAEL * ABSoral-rat/ABSinh-human = 30 * 50/100 = 15 mg/kg bw

 

Corrected inhalatory NOAEC = 15 * 1/1.15a= 13.0 mg/m3

 

astandard respiratory volume of rats for 24 hours.

 

Safety factors:

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 5

-      Exposure duration: 6 (assuming chronic exposure of the general population)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 120

 

Long-term oral, systemic effects

Starting point: NOAEL 30 mg/kg bw/day from an OECD422 oral study in rats.

 

Safety factors:

-      Interspecies extrapolation: 4

-      Intraspecies extrapolation: 5

-      Exposure duration: 6 (assuming chronic exposure of the general population)

-      Dose response: 1

-      Quality of the data base: 1

Total safety factor: 120

 

Based on the above, the long-term DNEL for systemic effects after oral exposure of the general population, is set at 0.25 mg/kg bw/d.