Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.52 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:
264.47 mg/m³
Explanation for the modification of the dose descriptor starting point:

Long term exposure – inhalation systemicDose description modification - Guidance [1. Appendix R8-1] was followed for route to route extrapolation as no relevant dose descriptor were available for inhalation exposure. As noted in R.8.4.2, as no information regarding inhalation absorption is available, a worse case scenario that 100% of the dose will be absorbed via the inhalation route. The dose descriptor was modified to take into account an 8 hour exposure and the respiratory volume corrected for light work.

 NOAECcorr = NOAEL *1 / rat resp. volume * oral / inhalation absorption * human resting resp. volume / worker resp. volume

 NOAECcorr(general) = 150 mg/kg/bw *(1 / 0.38) * (100% (default) / 100%(default)) * 6.7 m3 (8hr) / 10 m3 (8hr) = 264.47 mg/m3

 Assessment factors -Default assessment factors [1. R-8.4.3.3.] were applied.

Assessment factor = Interspecies * Intraspecies * Exposure duration * Dose-response * Quality of whole database

Assessment factor (general) = 2.5 * 5 * 6 * 1 * 1 = 75

 DNEL derivation - DNEL = NOAELcorr / Assessment factor

 DNEL = 264.47 mg/kg bw/day / 75 = 3.52 mg/kg bw/day

AF for dose response relationship:
1
Justification:
No issues
AF for differences in duration of exposure:
6
Justification:
Subacute to chromic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
Justification:
No issues
AF for remaining uncertainties:
1
Justification:
No issues
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:
3.3 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):
75
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long term exposure –dermal systemic -

NOAELcorr = NOAEL/Allometric scaling*(ABS oral rat / ABS derm rat) * (ABS derm rat / ABS derm human)

 NOAELcorr (general) = 150mg/kg bw/4 * (100% (default) / 15% (default)) * (100% (default) / 100% (default)) = 250mg/kg bw

 Assessment factors - Default assessment factors [1. R-8.4.3.3.] were applied.

Assessment factor = Interspecies * Intraspecies * Exposure duration * Dose-response * Quality of whole database

Assessment factor (general) = 2.5 * 5 * 6 * 1 * 1 = 75

 DNEL derivation - DNEL = NOAELcorr / Assessment factor

 DNEL = 250 mg/kg bw/day / 75 = 3.3 mg/kg bw/day

AF for dose response relationship:
1
Justification:
No issues
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
6
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
Justification:
no issues
AF for remaining uncertainties:
1
Justification:
No issues
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:
low hazard (no threshold derived)

Additional information - workers

Wear eye protection

General Population - Hazard via inhalation route

Systemic 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

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:
hazard unknown but no further hazard information necessary as no exposure expected
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:
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 for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

The substance is consumed in the manufacture of a pharmaceutical product and the substance is not exposed to the general population