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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEC
Value:
3 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
1.51 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an inhalation NOAEC observed in a subacute inhalation
study (OECD 412, 2001). The NOAEC is corrected to account for differences between experimental and human exposure conditions. It is further corrected for the difference between respiratory rates under
standard conditions and under conditions of light activity (sRV human versus wRV).

NOAECcorr = NOAEC * (6 h per day/8 h per day) * (6.7 m³ (8 h)/10 m³ (8 h))

NOAECcorr = 3 mg/m³ * 0.75 * 0.67 = 1.51 mg/m³

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEC.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a 28-day inhalation study with rats (exposed 6 h/day).
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies differences were taken into account for the conversion of the rat NOAEC into a modified human NOAEC considering allometric scaling for the respiratory volumes (modification of the dose descriptor starting point). Thus, no additional AF is applicable.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default AF for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.53 µg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
187.5
Dose descriptor:
NOAEC
Value:
0.1 mg/m³
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEC.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a 28-day inhalation study with rats (exposed 6 h/day).
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies differences were taken into account for the conversion of the rat NOAEC into a modified human NOAEC considering allometric scaling for the respiratory volumes (modification of the dose descriptor starting point). Thus, no additional AF is applicable.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default AF for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
2.5
Justification:
Default AF according to ECHA REACH Guidance for effects on the respiratory tract and given that there could be significant quantitative differences in deposition, airflow patterns, clearance rates and protective mechanisms between humans and animals.
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.78 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
180
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
140 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on a dermal NOAEL observed in a 21-day dermal study in rabbits (key, 1989). The exposure duration in this study was 6h/day for 21 days (7 days per week). Therefore, a correction of this NOAEL to account for differences in exposure frequency in the study compared to that for workers (5 days/week) is needed.

NOAELcorr = NOAEL*(7/5)

NOAELcorr = 100*(7/5) = 140 mg/kg bw/day


AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute dermal study.
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default AF for rabbits according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default AF for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium 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:
3.55 µg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEC
Value:
3 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
0.53 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on a NOAEC observed in a subacute inhalation study (OECD 412, 2001). The NOAEC is corrected to account for differences between experimental conditions (6 h/day) and general population exposure conditions (24 h/day), as well as differences in experimental exposure frequency (5 days/week) and general population exposure frequency (7 days/week).


NOAECcorr = NOAEC*(6/24)*(5/7)
NOAECcorr = 3 mg/m³ * 0.25 * 0.71 = 0.53 mg/m³

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEC.
AF for differences in duration of exposure:
6
Justification:
The dose descriptor starting point is based on a NOAEC.
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling already included in ECHA starting point derivation method; no further factor required.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.27 µg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
375
Dose descriptor:
NOAEC
Value:
0.1 mg/m³
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEC.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute inhalation study.
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
2.5
Justification:
Default AF according to ECHA REACH Guidance for effects on the respiratory tract and given that there could be significant quantitative differences in deposition, airflow patterns, clearance rates and protective mechanisms between humans and animals.
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.278 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
360
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on a dermal NOAEL observed in a 21-day dermal study in rabbits (key, 1989). The exposure duration in this study was 6h/day for 21 days (7 days per week). Therefore, a correction of this NOAEL to account for differences in exposure frequency in the study compared to that for the general population (7 days/week) is not needed.


AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a subacute (21-day) dermal study
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default AF for rabbit according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.006 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
0.56 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of the starting point needed.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population