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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 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:
LOAEC
Value:
8.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose the default respiratory volume for the rat corresponding to the daily duration of human exposure is considered in the first step, followed by a correction for the difference between respiratory rates of workers under standard conditions and under light activity in the second step. LAECcorr_inh = oral LOAEL (5) x 1/0.38 m3/kg bw x 6.7 m3/10 m3 = 8.8 mg/m3. Oral absorption in rats in humans is assumed to be 100% and inhalation absorption in humans is assumed to be 100%. Therefore, LAECcorr_inh = 8.8 x 1 = 8.8 mg/m3.
AF for dose response relationship:
3
Justification:
Default factor for LOAEC, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.17 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:
LOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assuming that oral absorption in rats is 100% and that dermal absorption in humans is 10%. Therefore dose descriptor after route to route extrapolation is 5 x 100/10 = 50 mg/kg bw/day. As stated in ECHA Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance , a default value of 100% skin absorption is generally used unless molecular mass is above 500 and log P is outside the range [-1, 4], in which case a value of 10% skin absorption is chosen. The test substance has a molecular mass > 500 and a log Pow > 6.2. In addition, there was no evidence of significant toxic effects in the acute dermal acute toxicity study. Therefore it is considered appropriate to use a dermal absorption factor of 10%.
AF for dose response relationship:
3
Justification:
Default factor for LOAEL, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.03 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:
LOAEC
Value:
4.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose, the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hrs exposure of general public). LAECcorr_inh = oral LOAEL (5) x 1/1.15 m3/kg bw = 4.3 mg/m3. Oral absorption in rats in humans is assumed to be 100% and inhalation absorption in humans is assumed to be 100%. Therefore, NAECcorr_inh = 4.3 x 1 = 4.3 mg/m3
AF for dose response relationship:
3
Justification:
Default factor for LOAEC, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.083 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:
LOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assuming that oral absorption in rats is 100% and that dermal absorption in humans is 10%. Therefore dose descriptor after route to route extrapolation is 5 x 100/10 = 50 mg/kg bw/day. As stated in ECHA Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance , a default value of 100% skin absorption is generally used unless molecular mass is above 500 and log P is outside the range [-1, 4], in which case a value of 10% skin absorption is chosen. The test substance has a molecular mass > 500 and a log Pow > 6.2. In addition, there was no evidence of significant toxic effects in the acute dermal acute toxicity study. Therefore it is considered appropriate to use a dermal absorption factor of 10%.
AF for dose response relationship:
3
Justification:
Default factor for LOAEL, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.008 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:
LOAEL
Value:
5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required.
AF for dose response relationship:
3
Justification:
Default factor for LOAEL, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

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