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:
12.5 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):
50
Modified dose descriptor starting point:
other: NAEC
Value:
625 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation should not be a preferred route for absorption. Original value is NOAEL 125 mg/Kg, subchronic study in dog by oral administration of piperazine. Allometric scaling from dog to human is 1.4. The result is multiplied by 70Kg considered as the average weight of a human being (bw) and divided by 10m3/person considered as the average volume that is breathed in 8h exposure. Conclusion [(125 mg/Kg bw /1.4)*70Kg bw]/10 m3 = 625 mg/m3 bw (NAEC)
AF for dose response relationship:
1
Justification:
not necessary
AF for differences in duration of exposure:
2
Justification:
from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Already considered (1.4)
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME
AF for intraspecies differences:
1
Justification:
Already considered (10)
AF for the quality of the whole database:
2
Justification:
The data is extrapolated from the most concerning constituent, and not calculated on the substance itself
AF for remaining uncertainties:
5
Justification:
precautionary AF to include possible contribution from other constituent
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
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:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.57 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):
350
Modified dose descriptor starting point:
NOAEL
Value:
1 250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
As reported in ECHA guideline, dermal absorption should not be higher than oral absorption
AF for dose response relationship:
1
Justification:
not necessary
AF for differences in duration of exposure:
2
Justification:
from subchronic to chronic
AF for interspecies differences (allometric scaling):
1.4
Justification:
from dog
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
2
Justification:
The data is extrapolated from the most concerning constituent, and not calculated on the substance itself
AF for remaining uncertainties:
5
Justification:
precautionary AF to include possible contribution from other constituent
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

This substance is a complex UVCB which is only partially bioavailable. DNEL for DG HF 2000 is derived from the most concerning constituent of th e soluble fraction, i.e. piperazine. This approach is derived from the NOAEL that was accepted by EMA for the use of piperazine as antihelminthic.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.25 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):
50
Modified dose descriptor starting point:
other: NAEC
Value:
312.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation should not be a preferred route for absorption. This substance is for industrial use only and handles only in controlled system. Exposure to general population has low probabilty. Original value is NOAEL 125 mg/Kg, subchronic study in dog by oral administration. Allometric scaling from dog to human is 1.4. The result is multiplied by 70Kg considered as the average weight of a human being (bw) and divided by 20m3/person considered as the average volume that is breathed for General Population. Conclusion [(125 mg/Kg bw /1.4)*70Kg bw]/0 m3 = 312.5 mg/m3 bw (NAEC)
AF for dose response relationship:
1
Justification:
Not necessary
AF for differences in duration of exposure:
2
Justification:
From subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Already considered (1.4)
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME
AF for intraspecies differences:
1
Justification:
Already considered (20)
AF for the quality of the whole database:
2
Justification:
The data is extrapolated from th emost concerning constituent and not calculated on the substance itself
AF for remaining uncertainties:
5
Justification:
Precautionary AF to include possible contribution from other constituents
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
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:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.79 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):
700
Modified dose descriptor starting point:
NOAEL
Value:
1 250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
as reported in ECHA guideline, dermal absorption should not be higher than oral absorption
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
from subchronic to chronic
AF for interspecies differences (allometric scaling):
1.4
Justification:
from dog
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
2
Justification:
The data is extrapolated from the most concerning constituent and not calculated on the substance itself
AF for remaining uncertainties:
5
Justification:
Precautionary AF to include possible contribution from other constituents
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.179 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):
700
Modified dose descriptor starting point:
NOAEL
Value:
125 mg/kg bw/day
AF for dose response relationship:
1
Justification:
not necessary
AF for differences in duration of exposure:
2
Justification:
From subchronic to chronic
AF for interspecies differences (allometric scaling):
1.4
Justification:
from dog to human
AF for other interspecies differences:
2.5
Justification:
Correction for possible differences in the ADME
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
2
Justification:
The data is extrapolated from the most concerning constituent and not measured on the substance itself
AF for remaining uncertainties:
5
Justification:
Precautionary AD to include possible contribution from other constituent
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
2 000 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not necessary
AF for dose response relationship:
1
Justification:
not necessary
AF for interspecies differences (allometric scaling):
4
Justification:
from rat
AF for other interspecies differences:
1
Justification:
not necessary
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
Test performed on the registered substance
AF for remaining uncertainties:
1
Justification:
Test performed on the registered substance. No signd of toxicity

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

This substance is a complex UVCB which is only partially bioavailable. DNEL for DG HF 2000 is derived from the most concerning constituent of th e soluble fraction, i.e. piperazine. This approach is derived from the NOAEL that was accepted by EMA for the use of piperazine as antihelminthic. Moreover, this substance is for industrial use only and no exposure to general population is expected.