Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.94 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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
370.3 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/ 5 days exposure) = 150 mg/kg bw/day*(1/0.38 m³/kg bw/day)*(1/1)*0.67*1.4 = 370.3 mg/m³.

It is assumed that oral absorption rate is equal of that of inhalation absorption based on the assessment of the toxikokinetic behaviour (for details refer to Section Toxicokinetics) and the similar toxicity after acute exposure via the inhalation and oral route (Acute Tox 4, H302 and H332).

ABS(oral/rat) = oral absorption rate in rats, ABS(inh./human) = inhalation absorption rate in humans.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on NOAEL
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF for workers
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:
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:
0.7 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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
210 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) = 150 mg/kg bw/day *(1/1) * 1.4 = 210 mg/kg bw/day. It is assumed that oral and dermal absorption rates are equal.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on NOAEL
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was the rat
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF for workers
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
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:
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:
0.87 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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
130.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral*(1/1.15 m³/kg bw/day (24h)) *(ABSoral-rat/ABSinh-human) = 150 mg/kg bw/day*(1/1.15 m³/kg bw/day)*(1/1) = 130.4 mg/m³.

It is assumed that oral absorption rate is equal of that of inhalation absorption based on the assessment of the toxikokinetic behaviour (for details refer to Section Toxicokinetics) and the similar toxicity after acute exposure via the inhalation and oral route (Acute Tox 4, H302 and H332).

ABS(oral/rat) = oral absorption rate in rats, ABS(inh./human) = inhalation absorption rate in humans.

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 study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
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:
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:
0.25 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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) = 150 mg/kg bw/day *(1/1) = 150 mg/kg bw/day.

It is assumed that oral and dermal absorption rates are equal.

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 study
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was the rat
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
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
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:
0.25 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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is no route to route extrapolation necessary.

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 study
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was the rat.
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value for general population
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)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population