Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.17 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:
439.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
387.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

From an oral OECD 422 study in rats with the read-across substance AEPD, an NOAEL of 500 mg/kg bw is available. This was corrected for the MW of AMPD to 439.5 mg/kg bw. This NOAEL was converted to an inhalation NOAEC for workers via the formula:

Inhalation NOAEC = oral NOAEL * (1/0.38 m3/kg/d) * 0.67 * (ABS oral/ABS inh.). It is assumed that the oral absorption rate is 50% of the inhalation rate.

Therefore, the inhalation NOAEC = 439.5 * (1/0.38) * 0.67* (0.5/1) = 387.5 mg/m3.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute study (OECD 422) to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not applied for the derivation of the inhalation DNEL.
AF for other interspecies differences:
2.5
Justification:
Default factor according to ECHA Guidance.
AF for intraspecies differences:
5
Justification:
Default factor for workers according to ECHA Guidance.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
3.66 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:
439.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 098.75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

From an oral OECD 422 study with the read-across susbstance AEPD, an NOAEL of 500 mg/kg bw is available. This was corrected for the MW of AMPD to 439.5 mg/kg bw. This NOAEL was converted to a dermal NOAEL via the formula:

Dermal NOAEC = oral NOAEL * (ABS oral/ABS dermal). It is assumed that the dermal absorption rate is 40% of the oral absorption rate.

Therefore, the dermal NOAEC = 439.5 * (1/0.4) = 1098.75 mg/m3.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute study (OECD 422) to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for workers according to ECHA Guidance.
AF for other interspecies differences:
2.5
Justification:
Default factor for workers according to ECHA Guidance.
AF for intraspecies differences:
5
Justification:
Default factor for workers according to ECHA Guidance.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high 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:
1.274 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:
439.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
191.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

From an oral OECD 422 study in rats with the read-across substance AEPD, an NOAEL of 500 mg/kg bw is available. This was corrected for the MW of AMPD to 439.5 mg/kg bw. This NOAEL was converted to an inhalation NOAEC for the general population via the formula:

Inhalation NOAEC = oral NOAEL * (1/1.15 m3/kg/d) * (ABS oral/ABS inh.). It is assumed that the oral absorption rate is 50% of the inhalation rate.

Therefore, the inhalation NOAEC = 439.5 * (1/1.15) * (0.5/1) = 191.1 mg/m3.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute study (OECD 422) to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not applied for the derivation of the inhalation DNEL.
AF for other interspecies differences:
2.5
Justification:
Default factor according to ECHA Guidance.
AF for intraspecies differences:
10
Justification:
Default factor for the general population according to ECHA Guidance.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
1.83 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:
439.5 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
1 098.75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

From an oral OECD 422 study witht the read-across substance AEPD, an NOAEL of 500 mg/kg bw is available. This was corrected for the MW of AMPD to 439.5 mg/kg bw. This NOAEL was converted to a dermal NOAEL for the genearal population via the formula:

Dermal NOAEC = oral NOAEL * (ABS oral/ABS dermal). It is assumed that the dermal absorption rate is 40% of the oral absorption rate.

Therefore, the dermal NOAEC = 439.5 * (1/0.4) = 1098.75 mg/m3.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute study (OECD 422) to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor according to ECHA Guidance.
AF for other interspecies differences:
2.5
Justification:
Default factor according to ECHA Guidance.
AF for intraspecies differences:
10
Justification:
Default factor for the general population according to ECHA Guidance.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.733 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:
439.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

From an oral OECD 422 study in rats with the read-across substance AEPD, an NOAEL of 500 mg/kg bw is available. This was corrected for the MW of AMPD to 439.5 mg/kg bw.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute study (OECD 422) to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor according to ECHA Guidance.
AF for other interspecies differences:
2.5
Justification:
Default factor according to ECHA Guidance.
AF for intraspecies differences:
10
Justification:
Default factor for the general population according to ECHA Guidance.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population