Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 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):
12.5
Modified dose descriptor starting point:
NOAEC
DNEL value:
264.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of data on absorption, it was assumed that 50% absorption occurs by the oral route. To secure a conservative external NOAEL a maximum absorption should be assumed for the inhalation route (i.e.; 100%). To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8h exposure period). Thus, the corrected starting point for inhalation is : 300 mg/kg bw/d x 0.5 x (1/0.38 m3/kg bw/8h) x (6.7 m3 for 8h exposure /10 m3 for 8h exposure) = 264.5 mg/m3 for workers.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Toxic effects observed only during gestation phase; it is specific to gestation stage that has been assessed entirely during the study therefore long-term extrapolation is not relevant
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for oral to inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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:
6 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):
50
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No additional factor is needed when performing oral to dermal extrapolation.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Toxic effects observed only during gestation phase; it is specific to gestation stage that has been assessed entirely during the study therefore long-term extrapolation is not relevant
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling from rat to human
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.2 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
130.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of data on absorption, it was assumed that 50% absorption occurs by the oral route.To secure a conservative external NOAEL a maximum absorption should be assumed for the inhalation route (i.e.; 100%). To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/d). Thus, the corrected starting point for inhalation is : 300 mg/kg bw/d x 0.5 x (1/1.15 m3/kg bw/d) = 130.5 mg/m3
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Toxic effects observed only during gestation phase; it is specific to gestation stage that has been assessed entirely during the study therefore long-term extrapolation is not relevant
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for oral to inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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:
3 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):
25
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No additional factor is needed when performing oral to dermal extrapolation
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Toxic effects observed only during gestation phase; it is specific to gestation stage that has been assessed entirely during the study therefore long-term extrapolation is not relevant
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling from rat to human
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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:
3 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):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No additional factor is needed when performing oral to dermal extrapolation
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Toxic effects observed only during gestation phase; it is specific to gestation stage that has been assessed entirely during the study therefore long-term extrapolation is not relevant
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling from rat to human
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population