Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving

Workers - Hazard for the eyes

Additional information - workers

The worker inhalation DNEL long-term exposure, systemic effects, was calculated to be 6 mg/m3. This is consistent with the acceptable workplace exposure limit of 5 mg/M3 established by the American Council of Governmental Hygenists.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12.5
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50

General Population - Hazard for the eyes

Additional information - General Population

The general public inhalation DNEL long-term systemic exposure was calculated to be 70 mg/m3, while the oral DNEL for long-term systemic exposure was calculated to be 20 mg/kg bw/d. These DNELs compare favorably to the U.S. ATSDR intermediate-duration reference dose for the general population of 10 mg/kg bw/d, the U.S. National Research Council's lifetime oral RfD of 4 mg/kg/d, and the oral RfD of 4 mg/kg/d developed by Hardy et al. (2009) using bench mark dose modeling. While the U.S. Intgrated Risk Information System (IRIS) published an RfD of 0.007 mg/kg/d in 2008, this RfD was improperly based on Viberg et al. (2003), which is not reliable and disregarded in this assessment. To investigate the effects reported by Viberg et al. after a single dose of 20 mg/kg, a robust, guideline- and GLP-compliant developmental neurotoxicity study was performed, which demonstrated a NOAEL of 1000 mg/kg bw/day.