Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
98 mg/m³
DNEL related information
Overall assessment factor (AF):
18
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
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:
28 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Additional information - workers

Long-term exposure - systemic effects

An oral subacute toxicity gavage study with a NOAEL of > 1000 mg/kg/day was available.

 

- Dermal DNEL for long-term exposure - systemic effects

 

For the determination of the dermal DNEL, the NOAEL of 1000 mg/kg bw/day of the rat oral subacute repeated dose study was used.

 

Due to the very low water solubility below 1 mg/L and the absence of skin irritating and sensitizing effects as well as the dermal toxicity data did indicate very low dermal absorption. Therefore, absorption difference was assessed to 50 % comparing the dermal to the oral route. Accordingly, for dermal exposure the corrected starting point was calculated as 2000 mg/kg body weight / day. Using the overall assessment factor of 72, including assessment factors for interspecies extrapolation of 4 (allometric scaling rat to human), intraspecies extrapolation of 3 for worker according to ECETOC 2003, exposure duration of 6 (sub-acute to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (Worker) for dermal exposure was calculated as follows: 2000 mg/kg/day/ (4*3*6*1*1*1) = 27.78 mg/kg body weight /day.

 

- Inhalation DNEL for short-term exposure - systemic effects

 

Based on the same oral subacute study, the endpoint specific DNEL for inhalation repeated-dose toxicity for workers was calculated using a route to route extrapolation.

 

The conversion of the rat oral NOAEL of 1000 mg/kg bw/day to a corrected inhalatory human NOAEL was based on the different respiratory volume of the rat (0.38 m³/kg/day and the different rate during light activity at work (10 m³) and standard conditions (6.7 m³).

 

Corrected NOAEL = 1000 mg/kg * 1/0.38 m³/kg/day * 6.7 m³ (8h) / 10 m³ (8h) = 1763.2 mg/m³/day. Using the overall assessment factor of 18, including assessment factors for intraspecies extrapolation of 3 for worker according to ECETOC 2003, exposure duration of 6 (sub-acute to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (Worker) for inhalative exposure was calculated as follows: 1763.2 mg/m³/ (3*6*1*1*1) = 97.95 mg/m³.

The general exposure limit for inhalable dust is applied for local effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 mg/m³
DNEL related information
Overall assessment factor (AF):
30
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
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 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
120
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:
6 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Long-term exposure - systemic effects

 

No adverse effects were observed in any study. Based on the available data, the endpoint-specific dermal DNEL was calculated using a No-(Adverse)-Effect-Level of > 1000 mg/kg/day determined in an oral subacute toxicity gavage study.

 

- Oral DNEL for long-term exposure - systemic effects

 

Based on the NOAEL of 1000 mg/kg bw/day of the rat oral subacute study, the endpoint specific DNEL for oral repeated-dose toxicity for general population was calculated using the overall assessment factor of 120, including assessment factors for interspecies extrapolation of 4 (allometric scaling rat to human), intraspecies extrapolation of 5 for general polpulation according to ECETOC 2003, exposure duration of 6 (sub-acute to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (General population) for oral exposure as follows: 1000 mg/kg/day/ (4*5*6*1*1*1) = 8.33 mg/kg body weight /day.

 

 

- Dermal DNEL for long-term exposure - systemic effects

 

For the determination of the dermal DNEL, the NOAEL of 1000 mg/kg bw/day of the same rat oral subacute repeated dose study was used.

 

Due to the very low water solubility below 1 mg/L and the failure of skin irritating and sensitizing effects as well as the dermal toxicity data did indicate very low dermal absorption. Therefore, absorption difference was assessed to 50 % comparing the dermal to the oral route. Accordingly, for dermal exposure the corrected starting point was calculated as 2000 mg/kg body weight / day. Using the overall assessment factor of 120, including assessment factors for interspecies extrapolation of 4 (allometric scaling rat to human), intraspecies extrapolation of 5 for general population according to ECETOC 2003, exposure duration of 6 (sub-acute to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (general population) for dermal exposure was calculated as follows: 2000 mg/kg/day/ (4*5*6*1*1*1) = 16.67 mg/kg body weight /day.

 

 - Inhalation DNEL for short-term exposure - systemic effects

 

Based on the same oral subacute study, the endpoint specific DNEL for inhalation repeated-dose toxicity for workers was calculated using a route to route extrapolation.

 

The conversion of the rat oral NOAEL of 1000 mg/kg bw/day to a corrected inhalatory human NOAEL was based on the different respiratory volume of the rat (0.38 m³/kg/day and the different rate during light activity at work (10 m³) and standard conditions (6.7 m³).

 

Corrected NOAEL = 1000 mg/kg * 1/0.38 m³/kg/day * 6.7 m³ (8h) / 10 m³ (8h) = 869.6 mg/m³/day. Using the overall assessment factor of 30, including assessment factors for intraspecies extrapolation of 5 for general population according to ECETOC 2003, exposure duration of 6 (sub-acute to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (general population) for inhalative exposure was calculated as follows: 869.6 mg/m³/ (5*6*1*1*1) = 28.99 mg/m³.

The general exposure limit for inhalable dust of 3mg/m3 for the respirable fraction is applied to prevent from local dust overload effects.