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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.165 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
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
12.34 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral * (1 / 0.38 m³/kg bw/day) * (ABSoral-rat / ABSinh-human) * (6.7 m³ (8h) / 10 m³ (8h)) * (7 days exposure rat / 5 exposure worker) = 10 mg/kg bw/day*(1 / 0.38 m³/kg bw/day)*(0.5 / 1)*0.67*1.4 = 12.34 mg/m³.

It is assumed that oral absorption rate is 50% of that of inhalation absorption.

ABSoral-rat = oral absorption rate in rats, ABSinh-human = inhalation absorption rate in humans.

AF for dose response relationship:
1
Justification:
ECHA default value: The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default value for extrapolation from subacute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default value (no allometric scaling needs to be applied for route-to-route extrapolation from the oral to the inhalation route).
AF for other interspecies differences:
2.5
Justification:
ECHA default value.
AF for intraspecies differences:
5
Justification:
ECHA default value for the worker.
AF for the quality of the whole database:
1
Justification:
DNEL calculation is based on a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.47 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
Dose descriptor starting point:
NOAEL
Value:
10 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:

NOAELcorr = NOAELoral * (ABSoral-rat / ABSdermal-human) * (7 day exposure rat / 5 days exposure worker) = 10 mg/kg bw/day * (100%/10%) * 1.4 = 140 mg/kg bw/day.

ABSoral-rat = oral absorption rate in rats, ABSdermal-human = dermal absorption rate in humans.

The test substance has a logPow of 5.814 and a calculated flux of 0.00394 µg/cm²/h (DERMWIN). According to Kroes et al. (Food Chem Toxicol 45, 2533–62, 2007) a dermal absorption rate of 10% can be assumed if the flux is below 0.1 µg/cm²/h. It is therefore assumed that the dermal absorption rate is 10% of the oral absorption rate.

AF for dose response relationship:
1
Justification:
ECHA default value: The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default value for extrapolation from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default value for the rat.
AF for other interspecies differences:
2.5
Justification:
ECHA default value.
AF for intraspecies differences:
5
Justification:
ECHA default value for the worker.
AF for the quality of the whole database:
1
Justification:
DNEL calculation is based on a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.029 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
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
4.35 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral * (1 / 1.15 m³/kg bw/day) * (ABSoral-ra t/ ABSinh-human) = 10 mg/kg bw/day * (1 / 1.15 m³/kg bw/day) * (0.5 / 1) * = 4.35 mg/m³.

It is assumed that oral absorption rate is 50% of that of inhalation absorption.

ABSoral-rat=oral absorption rate in rats, ABSinh-human=inhalation absorption rate in humans.

AF for dose response relationship:
1
Justification:
ECHA default value: The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default value for extrapolation from subacute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default value (no allometric scaling needs to be applied for route-to-route extrapolation from the oral to the inhalation route).
AF for other interspecies differences:
2.5
Justification:
ECHA default value.
AF for intraspecies differences:
10
Justification:
ECHA default value for the general population.
AF for the quality of the whole database:
1
Justification:
DNEL calculation is based on a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - 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):
600
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAELcorr = NOAELoral * (ABSoral-rat / ABSdermal-human) = 10 mg/kg bw/day * (100% / 10%) = 100 mg/kg bw/day.

ABSoral-rat=oral absorption rate in rats, ABSdermal-human=dermal absorption rate in humans.

The test substance has a logPow of 5.814 and a calculated flux of 0.00394 µg/cm²/h (DERMWIN). According to Kroes et al. (Food Chem Toxicol 45, 2533–62, 2007) a dermal absorption rate of 10% can be assumed if the flux is below 0.1 µg/cm²/h. It is therefore assumed that the dermal absorption rate is 10% of the oral absorption rate.

AF for dose response relationship:
1
Justification:
ECHA default value: The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default value for extrapolation from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default value for the rat.
AF for other interspecies differences:
2.5
Justification:
ECHA default value
AF for intraspecies differences:
10
Justification:
ECHA default value for the general population.
AF for the quality of the whole database:
1
Justification:
DNEL calculation is based on a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
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:
0.017 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
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 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:
ECHA default value: The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default value for extrapolation from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default value for the rat.
AF for other interspecies differences:
2.5
Justification:
ECHA default value
AF for intraspecies differences:
10
Justification:
ECHA default value for the general population.
AF for the quality of the whole database:
1
Justification:
DNEL calculation is based on a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
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