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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.7 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:
435.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects in workers after long-term inhalation exposure to the read-across substance, 4-methyl-4-phenylpentan-2-ol, was

derived via route-to-route extrapolation from the NOAEL obtained in the OECD Guideline 421 in rats (494.32 mg/kg bw/day). To convert the oral NOAEL in rats to an inhalation NOAEC in humans, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38m3/kg bw/8h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8h exposure period); extrapolation from 50% bioavailability oral to 100% bioavailability inhalation. Therefore, inhalatory NOAEC = oralNOAEL*(1/sRVrat 8h)*(ABSoral/ABSinh)*(sRVhuman/wRV) OR 494.32*(1/0.38)*(50/100)*(6.7/10) = 435.7.

AF for dose response relationship:
1
Justification:
not required as starting from a NOAEC
AF for differences in duration of exposure:
4
Justification:
The duration of exposure in the key study providing the point of departure NOAEL was at least 6 weeks for male rats and 7-8 weeks for female rats. These exposure durations fall between the descriptors for subchronic (90 days) and subacute (28 days) in the guidance document. That´s why a modification to the exposure duration AF was made from the conservative AF6 to AF4.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required when route to route extrapolation conducted
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker exposure
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
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.47 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:
494.32 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The No Observed Adverse Effect Level (NOAEL) used to calculate the DNEL was taken from the findings for the read across substance 4-methyl-4-phenylpentan-2-ol in a reproductive toxicity study (OECD 421) in rats. The NOAEL (No Observed Adverse Effect Level) was, therefore, determined to be 494.32 mg/kg bw/day. Based on the REACH guidance R8 page 19, a default value of 50% is assumed for dermal absorption. As oral absorption was also set at 50%, no correction of dose descriptor starting point was done.

AF for dose response relationship:
1
Justification:
not required as stating from a NOAEL
AF for differences in duration of exposure:
4
Justification:
The duration of exposure in the key study providing the point of departure NOAEL was at least 6 weeks for male rats and 7-8 weeks for female rats. These exposure durations fall between the descriptors for subchronic (90 days) and subacute (28 days) in the guidance document. That´s why a modification to the exposure duration AF was made from the conservative AF6 to AF4.
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling rat -human
AF for other interspecies differences:
2.5
Justification:
default factor
AF for intraspecies differences:
5
Justification:
factor for worker exposure
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
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The basis for the inhalation and dermal DNELs for worker exposure comes from an oral OECD 421 with the read across substance 4-methyl-4-phenylpentan-2-ol , from which a NOAEL of 400 mg/kg bw/day was identified. The NOAEL (No Observed Adverse Effect Level) of 400 mg/kg bw/day was used (taking into account the molecular weight correction between source and target substance (178.27 vs. 220.31), the NOAEL for 1,3-Dimethyl-3-phenylbutyl acetate is 494.32 mg/kg) as the basis of the DNEL calculations using appropriate assessment factors for relevant indicators including route to route extrapolation, allometric scaling, exposure duration and study length.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.15 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):
100
Modified dose descriptor starting point:
NOAEC
Value:
215 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects in general population after long-term inhalation exposure to the read-across substance, 4-methyl-4-phenylpentan-2-ol, was derived via route-to-route extrapolation from the NOAEL obtained in the OECD 421 oral repeated dose toxicity study in rats (494.32 mg/kg bw/day). To convert oral rat NOAEL into inhalatory NOAEC in humans, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24h); extrapolation from 50% bioavailability oral to 100% bioavailability inhalation. Therefore, the corrected inhalation NOAEC for general population is oral NOAEL*(1/sRVrat 24h)*(ABSoral/ABSinh) or 494.32*(1/1.15)*(50/100) = 215 mg/m3.

AF for dose response relationship:
1
Justification:
Not requiredas starting point is NOAEC
AF for differences in duration of exposure:
4
Justification:
The duration of exposure in the key study providing the point of departure NOAEL was at least 6 weeks for male rats and 7-8 weeks for female rats. These exposure durations fall between the descriptors for subchronic (90 days) and subacute (28 days) in the guidance document. That´s why a modification to the exposure duration AF was made from the conservative AF6 to AF4.
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for concentrations
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
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.23 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):
400
Modified dose descriptor starting point:
NOAEL
Value:
494.32 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects in the general population after long-term dermal exposure to the read-across substance, 4-methyl-4-phenylpentan-2-ol, was derived via route-to-route extrapolation from the NOAEL of 494.32 mg/kg bw/day obtained in the OECD 421 in rats with the read-across substance. Based on the REACH guidance R8 page 19, a default value of 50% is assumed for dermal absorption. As oral absorption was also set at 50%, no correction of dose descriptor starting point was done.

AF for dose response relationship:
1
Justification:
Not required with a starting point of NOAEL
AF for differences in duration of exposure:
4
Justification:
The duration of exposure in the key study providing the point of departure NOAEL was at least 6 weeks for male rats and 7-8 weeks for female rats. These exposure durations fall between the descriptors for subchronic (90 days) and subacute (28 days) in the guidance document. That´s why a modification to the exposure duration AF was made from the conservative AF6 to AF4.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to 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
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
1.23 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):
400
Dose descriptor starting point:
NOAEL
Value:
494.32 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As the NOAEL was taken from an oral study, no modification of the dose descriptor was performed.

AF for dose response relationship:
1
Justification:
Not required as starting point is NOAEL
AF for differences in duration of exposure:
4
Justification:
The duration of exposure in the key study providing the point of departure NOAEL was at least 6 weeks for male rats and 7-8 weeks for female rats. These exposure durations fall between the descriptors for subchronic (90 days) and subacute (28 days) in the guidance document. That´s why a modification to the exposure duration AF was made from the conservative AF6 to AF4.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to 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 basis for the inhalation, dermal and oral DNELs for general population exposure comes from an oral OECD 421 with the read across substance 4-methyl-4-phenylpentan-2-ol , from which a NOAEL of 400 mg/kg bw/day was identified. The NOAEL (No Observed Adverse Effect Level) of 400 mg/kg bw/day was used (taking into account the molecular weight correction between source and target substance (178.27 vs. 220.31), the NOAEL for 1,3-Dimethyl-3-phenylbutyl acetate is 494.32 mg/kg) as the basis of the DNEL calculations using appropriate assessment factors for relevant indicators including route to route extrapolation, allometric scaling, exposure duration and study length.