Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.03 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor:
LOAEC
AF for dose response relationship:
3
Justification:
Conversion from LOAEC to NOAEC
AF for differences in duration of exposure:
1
Justification:
due to local effects in lung, seen in chronic as well as subchronic studies
AF for interspecies differences (allometric scaling):
1
Justification:
derived from inhalation study
AF for other interspecies differences:
1
Justification:
remaining differences not given since similar effects were observed in monkeys and rats
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
DNEL derived from guideline study RL 1
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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:
12.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route-to-route extrapolation is conducted in accordance with ECHA Practical Guide 14, Table 2 for route to route extrapolation by applying the following equation: Dermal NOAEL = (oral NOAEL)*( ABSoral/ABSdermal). Based on the inorganic nature of the substance, its molecular weight of ca. 1120-18165 g/mol and is insolubility in n-octanol, dermal absorption is considered to be lower than oral absorption. A default value of 10% dermal absorption is taken as a sufficiently conservative estimate. Hence, dermal NOAEL = [corrected NOAEL] *( ABSoral/ABSdermal) = (250 mg/kg bw/day)*(100/10) = 2500 mg/kg bw/day
AF for dose response relationship:
1
Justification:
DNEL is based on NOAEL
AF for differences in duration of exposure:
2
Justification:
DNEL is based on a 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
DNEL is based on study conducted in rats
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
2
Justification:
DNEL is based on read-across from a structural analogue
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.015 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
Dose descriptor:
LOAEC
AF for dose response relationship:
3
Justification:
Conversion from LOAEC to NOAEC
AF for differences in duration of exposure:
1
Justification:
due to local effects in lung seen in chronic as well as subchronic studies
AF for interspecies differences (allometric scaling):
1
Justification:
derived from inhalation study
AF for other interspecies differences:
1
Justification:
remaining differences not given since similar effects were observed in monkey and rats
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
DNEL derived from guideline study RL1
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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:
6.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route-to-route extrapolation is conducted in accordance with ECHA Practical Guide 14, Table 2 for route to route extrapolation by applying the following equation: Dermal NOAEL = (oral NOAEL)*( ABSoral/ABSdermal). Based on the inorganic nature of the substance, its molecular weight of ca. 1120-18165 g/mol and is insolubility in n-octanol, dermal absorption is considered to be lower than oral absorption. A default value of 10% dermal absorption is taken as a sufficiently conservative estimate. Hence, dermal NOAEL = [corrected NOAEL] *( ABSoral/ABSdermal) = (250 mg/kg bw/day)*(100/10) = 2500 mg/kg bw/day
AF for dose response relationship:
1
Justification:
DNEL is based on NOAEL
AF for differences in duration of exposure:
2
Justification:
DNEL is based on a 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
DNEL is based on study conducted with rats
AF for other interspecies differences:
2.5
Justification:
remaining differenes
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
2
Justification:
DNEL is based on a read-across from a structural analogue
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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:
0.625 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
AF for dose response relationship:
1
Justification:
DNEL is based on NOAEL
AF for differences in duration of exposure:
2
Justification:
DNEL is based on a 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
DNEL is based on study conducted with rats
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
2
Justification:
DNEL is based on read-across from structural analogue
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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