Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.23 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:
190 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
167.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long term toxicity studies via the inhalation route are available for the test substance. Route-to-route extrapolation is performed.

The NOAEL (oral route) observed in the repeated dose toxicity study of Harlan Laboratories Ltd. (2013) was used to derive a DNEL long-term, systemic effects via the inhalation route. This study was performed with the read-across substance 1-methylpiperazine according to OECD guideline 422 and in compliance with GLP. The No Observed Adverse Effect Level (NOAEL) was considered to be 190 mg/kg bw/day. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point is 167.2 mg/m³ (= 190 mg/kg bw/d x 1/(0.38 m³/kg bw/d) x 6.7 m³/10 m³ x 0.5). The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure of workers). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). In addition, the NOAEL needed to be divided by 2 as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point, no additional assessment factor is required.
AF for differences in duration of exposure:
6
Justification:
Difference in duration, subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
already included in determination of modified dose descriptor
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
0.63 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
Modified dose descriptor starting point:
NOAEL
Value:
190 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term dermal toxicity studies are available for the test substance. Route-to-route extrapolation is performed.

The NOAEL (oral route) observed in the repeated dose toxicity study of Harlan Laboratories Ltd. (2013) was used to derive a DNEL long-term, systemic effects via the dermal route. This study was performed with the read-across substance 1 -methylpiperazine according to OECD guideline 422 and in compliance with GLP.The No Observed Adverse Effect Level (NOAEL) was considered to be 190 mg/kg bw/day. After route-to-route extrapolation (oral to dermal) the dose descriptor starting point is190 mg/kg bw/day as no additional factor should be applied (it is assumed that there is no differences between dermal and oral absorption; See toxicokinetic assessment).

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point, no additional assessment factor is required.
AF for differences in duration of exposure:
6
Justification:
Difference in duration subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rats to humans
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

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

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:
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:
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

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
DNEL related information
Justification:
remaining differences
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

No consumer use is expected, so no hazard assessment for the general population is required.