Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.6 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
441 mg/m³
Explanation for the modification of the dose descriptor starting point:

8 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation, no inhalation study available. Corrected inhalatory NOAEC = 500 mg/kg bw/day*(1/0.38 m3/kg/day)*(50%/100%)*(6.7 m3 (8h)/10 m3 (8h)) = 441 mg/m³

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentrations
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
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:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

assumed that rat oral and dermal absorptions are equal to human oral and dermal absorption

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
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
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The long-term inhalation DNEL for systemic effects is derived from the sub-chronic oral toxicity study (90-day study) with a NOAEL of 500 mg/kg bw/day. Route-to-route (oral-inhalation) extrapolation was performed. The calculated DNEL is 17.6 mg/m3, applying the assessment factor of 25.

The long-term dermal DNEL for systemic effects is derived also on the basis of the sub-chronic oral toxicity study (90-day study). For the route-to-route extrapolation it was assumed that oral and dermal absorption in the rat are equal to human oral and dermal absorption. The calculated DNEL is 5 mg/kg bw/day, applying the assessment factor of 100.

The long-term inhalation and dermal DNELs for local effects were not derived, since in the skin and eye irritation studies 4-phenylbutan-2-one showed not irritating properties and no local effects were observed in the sub-chronic oral toxicity study.

The acute/short term inhalation and dermal DNELs for systemic and local effects were not assessed, since no acute inhalation study is available and 4-phenylbutan-2-one shows low acute oral and dermal toxicity when administered (oral LD50 = 3200 mg/kg bw, dermal LD50 > 5000 mg/kg bw).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.3 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:
NOAEC
Value:
217 mg/m³
Explanation for the modification of the dose descriptor starting point:

24 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation, no inhalation study available. Corrected inhalatory NOAEC = 500 mg/kg bw/day*(1/1.15 m3/kg/day)*(50%/100%) = 217 mg/m3

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentration
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
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:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

assumed that rat oral and dermal absorptions are equal to human oral and dermal absorptions

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
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:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

no route-to-route extrapolation performed

AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required
AF for remaining uncertainties:
1
Justification:
not required
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:
no hazard identified

Additional information - General Population

The long-term inhalation DNEL for systemic effects is derived on the basis of the sub-chronic oral toxicity study (90-day study) with a NOAEL of 500 mg/kg bw/day. Route-to-route (oral-inhalation) extrapolation was performed. The calculated DNEL is 4.3 mg/m3, applying the assessment factor of 50.

The long-term dermal DNEL for systemic effects is derived also on the basis of the sub-chronic oral toxicity study (90-day study). For the route-to-route (oral-dermal) extrapolation it was assumed that oral and dermal absorption in the rat are equal to human oral and dermal absorption. The calculated DNEL is 2.5 mg/kg bw/day, applying the assessment factor of 200.

The long-term oral DNEL for systemic effects is derived on the basis of the sub-chronic oral toxicity study. No route-to-route extrapolation was performed. The calculated DNEL is 2.5 mg/kg bw/day, applying the assessment factor of 200.

The long-term inhalation and dermal DNELs for local effects were not assessed, since in the skin and eye irritation studies 4-phenylbutan-2-one showed not irritating properties and no local effects were observed in the sub-chronic oral toxicity study.

The acute/short term inhalation and dermal DNELs for systemic and local effects were not assessed, since no acute inhalation study is available and 4-phenylbutan-2-one shows low acute oral and dermal toxicity (oral LD50 = 3200 mg/kg bw, dermal LD50 > 5000 mg/kg bw).