Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Value:
529 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation NOAEC = 600 x (1/0.38) x (50/100) x (6.7/10) = 529 mg/m3
AF for dose response relationship:
1
Justification:
Not required. Clear NOAELs established.
AF for differences in duration of exposure:
6
Justification:
Default factor for extrapolating from subchronic to chronic duration.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required. Taken into account in conversion of oral to inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences.
AF for intraspecies differences:
5
Justification:
Default intraspecies factor for workers.
AF for the quality of the whole database:
1
Justification:
Data sufficient for tonnage.
AF for remaining uncertainties:
1
Justification:
There are 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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
3 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal NOAEL = 600 mg/kg x (50/10) = 3000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Not required. Clear NOAELs established.
AF for differences in duration of exposure:
6
Justification:
Default factor for extrapolating from subchronic to chronic duration.
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies allometric factor for extrapolating from rat to human.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences.
AF for intraspecies differences:
5
Justification:
Default intraspecies factor for workers.
AF for the quality of the whole database:
1
Justification:
Data sufficient for tonnage.
AF for remaining uncertainties:
1
Justification:
There are 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

The material was not acutely toxic via the oral or dermal route and is not anticipated to be acutely toxic via the inhalation route.

Two repeat dose toxicity studies are available: A 28 day repeat dose oral study in rats, and an OECD 421 oral study in rats. In absence of adverse effects in these studies, the NOAELs were set at the highest doses tested These NOAELs were 1000 mg/kg bw/day for parental, reproductive and developmental effects in the OECD 421 study (Petus – Árpásy, 2014; summarised at 7.8.1 and 7.8.2 (Dossier) / 5.9.1 (CSR)) and 600 mg/kg bw/day in an OECD 407 study (Lortie, 2002; Summarised at 7.5.1 (Dossier) / 5.6.1 (CSR)). In deriving the DNEL, the 600 mg/kg NOAEL is used as the OECD 407 study covers endpoints that the OECD 421 does not. The OECD 421 study gives an indication of an absence of reproductive findings and maternal toxicity at upto 1000 mg/kg bw/day.

The test material was not genotoxic, or toxic to reproduction in the OECD 421 study.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
261 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation NOAEC = 600 x (1/1.15) x (50/100) = 261 mg/m3/day
AF for dose response relationship:
1
Justification:
Not required. Clear NOAELs established.
AF for differences in duration of exposure:
6
Justification:
Default factor for extrapolating from subchronic to chronic duration.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required. Taken into account in conversion of oral to inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences.
AF for intraspecies differences:
10
Justification:
Default intraspecies factor for the general population.
AF for the quality of the whole database:
1
Justification:
Data sufficient for tonnage.
AF for remaining uncertainties:
1
Justification:
There are 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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
600
Modified dose descriptor starting point:
NOAEL
Value:
3 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal NOAEL = 600 mg/kg x (50/10) = 3000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Not required. Clear NOAELs established.
AF for differences in duration of exposure:
6
Justification:
Default factor for extrapolating from subchronic to chronic duration.
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies allometric factor for extrapolating from rat to human.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences.
AF for intraspecies differences:
10
Justification:
Default intraspecies factor for the general population.
AF for the quality of the whole database:
1
Justification:
Data sufficient for tonnage.
AF for remaining uncertainties:
1
Justification:
There are 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:
1 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation required.
AF for dose response relationship:
1
Justification:
Not required. Clear NOAELs established.
AF for differences in duration of exposure:
6
Justification:
Default factor for extrapolating from subchronic to chronic duration.
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies allometric factor for extrapolating from rat to human.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences.
AF for intraspecies differences:
10
Justification:
Default intraspecies factor for the general population.
AF for the quality of the whole database:
1
Justification:
Data sufficient for tonnage.
AF for remaining uncertainties:
1
Justification:
There are 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

The material was not acutely toxic via the oral or dermal route and is not anticipated to be acutely toxic via the inhalation route.

Two repeat dose toxicity studies are available: A 28 day repeat dose oral study in rats, and an OECD 421 oral study in rats. In absence of adverse effects in these studies, the NOAELs were set at the highest doses tested These NOAELs were 1000 mg/kg bw/day for parental, reproductive and developmental effects in the OECD 421 study (Petus – Árpásy, 2014; summarised at 7.8.1 and 7.8.2 (Dossier) / 5.9.1 (CSR)) and 600 mg/kg bw/day in an OECD 407 study (Lortie, 2002; Summarised at 7.5.1 (Dossier) / 5.6.1 (CSR)). In deriving the DNEL, the 600 mg/kg NOAEL is used as the OECD 407 study covers endpoints that the OECD 421 does not. The OECD 421 study gives an indication of an absence of reproductive findings and maternal toxicity at upto 1000 mg/kg bw/day.

The test material was not genotoxic, or toxic to reproduction in the OECD 421 study.