Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
DNEL value:
35.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
Selected starting point is a NOAEL of 20 mg/kg bw/day. The corrected 8 hr inhalation NOAEC for workers is NOAEL (20 mg/kg) * 1.76 mg/m3 = 35.3 mg/m3. No factor 2 route extrapolation from oral to inhalation. Kinetic studies indicate a rapid and complete absorption via oral route, and also via inhalation 100% absorption is assumed.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
3
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for workers is 3 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Selected starting point is a NOAEL of 20 mg/kg bw/day. Kinetic studies indicate a rapid and complete absorption via oral route, but dermal absorption is maximal 20%. The corrected dermal NOAEL for workers is NOAELoral (20 mg/kg) / 20% = 100 mg/kgbw/day.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling rat to human
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
3
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for workers is 3 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
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:
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:
other: ECETOC
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
17.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
Selected starting point is a NOAEL of 20 mg/kg bw/day. The corrected 8 hr inhalation NOAEC for workers is NOAEL (20 mg/kg) * 1/1.15 mg/m3 = 17.4 mg/m3. No factor 2 route extrapolation from oral to inhalation. Kinetic studies indicate a rapid and complete absorption via oral route, and also via inhalation 100% absorption is assumed.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
5
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for consumers/general population is 5 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Selected starting point is a NOAEL of 20 mg/kg bw/day. Kinetic studies indicate a rapid and complete absorption via oral route, but dermal absorption is maximal 20%. The corrected dermal NOAEL for general population is NOAELoral (20 mg/kg) / 20% = 100 mg/kgbw/day.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling rat to human
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
5
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for consumers/general population is 5 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
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:
0.5 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):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor for sub-chronic to chronic extrapolation (AF 2)
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling rat to human
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5; therefore a factor of 1 has been applied.
AF for intraspecies differences:
5
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intraspecies differences for consumers/general population is 5 (Actually considered as sufficient for the combined remaining inter-species and intra-species factors)
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties are identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

These substances are mainly applied in professional or industrial settings. Consequently, consumers/general population will generally not be exposed.