Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.73 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance, ECETOC Guidance
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
LOAEC
DNEL value:
52.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
Oral to Inhalation extrapolation: oral LOAEL (60mg/kg bw/d) * (1 / sRVrat (0.384)) * (ABSoral-rat (1) / ABSinh-human (2)) * (sRVhuman (6.7) / wRV (10)) = inhal LOAEC = 52.3 mg/m3; Note: rat and human bioavailability via inhalation presumed equal; time-scaling not applicable
AF for dose response relationship:
1
Justification:
Default for LOAEC to NOAEC
AF for differences in duration of exposure:
4
Justification:
47 day study exposure duration. Study part way between subacute (AF 6) and sub-chronic (AF 2)”
AF for interspecies differences (allometric scaling):
1
Justification:
Default; AS included via adjustments for respiratory volume (standard rat to human and worker)”
AF for other interspecies differences:
1
Justification:
ECETOC default.
AF for intraspecies differences:
3
Justification:
ECETOC default.
AF for the quality of the whole database:
2
Justification:
Limited nature of the ZMTI repeated dose data base
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.64 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance, ECETOC Guidance.
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
DNEL value:
37 mg/m³
Explanation for the modification of the dose descriptor starting point:
inhal LC0 (2120 mg/m3) * (initial AF (50)) * (1 / sRVrat (0.384)) * (ABSoral-rat (1) / ABSinh-human (2)) * (adj for time-scaling (1)) * (sRVhuman (6.7) / wRV (10)) = inhal NOAEC = 37.0 mg/m3; Note: rat and human bioavailability via inhalation presumed equal .
AF for dose response relationship:
1
Justification:
Default, standard OECD 403/GLP study; initial AF of 50 applied to account for LC0 to NOAEC extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
Default; AS included via adjustments for respiratory volume (standard rat to human and worker).
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
3
Justification:
ECETOC default
AF for the quality of the whole database:
2
Justification:
Limited nature of the ZMTI acute toxicity data base
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.21 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guideline, ECETOC Guideline
Overall assessment factor (AF):
288
Dose descriptor starting point:
NOAEL
Modified dose descriptor starting point:
NOAEL
DNEL value:
60 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Oral to dermal extrapolation: oral LOAEL (60mg/kg bw/d) = dermal LOAEL (60 mg/kg bw/day); Note: rat and human bioavailability via dermal contact presumed equal; ABSoral-rat = ABSderm-human; adjustments for time-scaling and respiratory volume not applicable
AF for dose response relationship:
3
Justification:
Default for LOAEL to NOAEL
AF for differences in duration of exposure:
4
Justification:
47 day study exposure duration. Study part way between subacute (AF 6) and sub-chronic (AF 2)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value
AF for other interspecies differences:
1
Justification:
ECETOC Guideline
AF for intraspecies differences:
3
Justification:
ECETOC Guideline
AF for the quality of the whole database:
2
Justification:
Limited nature of the ZMTI repeated dose data base
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Justification:
ECETOC default
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

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:
0.22 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance, ECETOC Guidance
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
LOAEC
DNEL value:
26 mg/m³
Explanation for the modification of the dose descriptor starting point:
Oral to Inhalation extrapolation: oral LOAEL (60mg/kg bw/d) * (1 / sRVrat (1.152)) * (ABSoral-rat (1) / ABSinh-human (2)) = inhal LOAEC (26.0 mg/m3; Note: rat and human bioavailability via inhalation presumed equal; time-scaling not applicable; standard respiratory volume assumed (no further adjustment needed)
AF for dose response relationship:
3
Justification:
Default for LOAEC to NOAEC
AF for differences in duration of exposure:
4
Justification:
47 day study exposure duration. Study part way between subacute (AF 6) and sub-chronic (AF 2)
AF for interspecies differences (allometric scaling):
1
Justification:
Default; AS included via adjustments for rat to human standard respiratory volume
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
5
Justification:
ECETOC default
AF for the quality of the whole database:
2
Justification:
Limited nature of the ZMTI repeated dose data base
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.391 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance, ECETOC Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
18.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
Justification for route to route extrapolation: inhal LC0 (2120 mg/m3) * (initial AF (50)) * (1 / sRVrat (1.152)) * (ABSoral-rat (1) / ABSinh-human (2)) * (adj for time-scaling (1)) = inhal NOAEC (18.4 mg/m3); Note: rat and human bioavailability via inhalation presumed equal; standard respiratory volume assumed (no further adjustment needed)
AF for dose response relationship:
1
Justification:
Default, standard OECD 403/GLP study; initial AF of 50 applied to account for LC0 to NOAEC extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
Default; AS included via adjustments for rat to human standard respiratory volume
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
5
Justification:
ECETOC default
AF for the quality of the whole database:
2
Justification:
Limited nature of the ZMTI acute toxicity data base
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.13 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance, ECETOC Guidance
Overall assessment factor (AF):
480
Modified dose descriptor starting point:
LOAEL
DNEL value:
60 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Justification for route to route extrapolation: Oral to dermal extrapolation: oral LOAEL (60mg/kg bw/d) = dermal LOAEL (60 mg/kg bw/day); Note: rat and human bioavailability via dermal contact presumed equal; ABSoral-rat = ABSderm-human; adjustments for time-scaling and respiratory volume not applicable
AF for dose response relationship:
3
Justification:
Default for LOAEL to NOAEL
AF for differences in duration of exposure:
4
Justification:
47 day study exposure duration. Study part way between subacute (AF 6) and sub-chronic (AF 2)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
5
Justification:
ECETOC default
AF for the quality of the whole database:
2
Justification:
Limited nature of the ZMTI repeated dose data base
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.13 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance, ECETOC Guidance
Overall assessment factor (AF):
480
Modified dose descriptor starting point:
LOAEL
DNEL value:
60 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation; Note: rat and human bioavailability via oral contact presumed equal; ABSoral-rat = ABSoral-human; adjustments for time-scaling and respiratory volume not applicable
AF for dose response relationship:
3
Justification:
Default for LOAEL to NOAEL
AF for differences in duration of exposure:
4
Justification:
47 day study exposure duration. Study part way between subacute (AF 6) and sub-chronic (AF 2)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value
AF for other interspecies differences:
1
Justification:
ECETOC default
AF for intraspecies differences:
5
Justification:
ECETOC default
AF for the quality of the whole database:
2
Justification:
Limited nature of the ZMTI repeated dose data base
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