Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
2 007.2 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
1 008.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEC of 500 ppm for parental and foetotoxic effects determined over two generations in the rat 2-generation reproductive toxicity (inhalation) study was used, which corresponds to a concentration of 2007.2 mg/m3. Modification of the starting point due to the differences in respiratory volume for workers (*6.7 m3/10 m3) and the differences in the time of exposure (*6 h/8 h) yields a modified starting point of 1008.6 mg/m3.

AF for dose response relationship:
1
Justification:
Dose descriptor of starting point is NOAEC
AF for differences in duration of exposure:
2
Justification:
Default value (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
According to the ECHA guidance (Chapter R.8), allometric scaling should not be applied in cases where inhalation doses are expressed as concentrations, as these are assumed to be already scaled according to the allometric principle
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value (workers)
AF for the quality of the whole database:
1
Justification:
Starting point was a robust read-across from cyclohexanone data obtained for the inhalation route, which is considered most relevant with regards to human exposure to cyclohexanol
AF for remaining uncertainties:
1
Justification:
No further AF considered necessary
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)
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:
1.43 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
Dose descriptor starting point:
NOAEL
Value:
143 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
143 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 143 mg/kg bw/d determined in the 90-day repeated dose toxicity (oral) study in the rat was used. Modification of the starting point was not necessary on the assumption that dermal absorption will not be higher than oral absorption and on the fact that exposure time is not relevant when the toxic effects are mainly driven by the exposure concentration.

AF for dose response relationship:
1
Justification:
Starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
Default value (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default (workers)
AF for the quality of the whole database:
1
Justification:
Starting point was a robust read-across from cyclohexanone data
AF for remaining uncertainties:
1
Justification:
No further AF considered necessary
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)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
Value:
2 007.2 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
501.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEC of 500 ppm determined in the rat 2-generation reproductive toxicity (inhalation) study was used, which corresponds to a concentration of 2007.2 mg/m3. Modification of the starting point due to the differences in the time of exposure (*6 h/24 h) yields a modified starting point of 501.8 mg/m3.

AF for dose response relationship:
1
Justification:
Dose descriptor of starting point is NOAEC
AF for differences in duration of exposure:
2
Justification:
Default value (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
According to the ECHA guidance (Chapter R.8), allometric scaling should not be applied in cases where inhalation doses are expressed as concentrations, as these are assumed to be already scaled according to the allometric principle
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Starting point was a robust read-across from cyclohexanone data obtained for the inhalation route, which is considered most relevant with regards to human exposure to cyclohexanol
AF for remaining uncertainties:
1
Justification:
No further AF considered necessary
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)
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:
0.716 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
Dose descriptor starting point:
NOAEL
Value:
143 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
143 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 143 mg/kg bw/d determined in the 90-day repeated dose toxicity (oral) study in the rat was used. Modification of the starting point was not necessary on the assumption that dermal absorption will not be higher than oral absorption and the on the fact that exposure time is not relevant when the toxic effect is mainly driven by the exposure concentration.

AF for dose response relationship:
1
Justification:
Starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
Default value (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value (general population)
AF for the quality of the whole database:
1
Justification:
Starting point was a robust read-across from cyclohexanone data
AF for remaining uncertainties:
1
Justification:
No further AF considered necessary
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)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.716 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
Dose descriptor starting point:
NOAEL
Value:
143 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
143 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 143 mg/kg bw/d determined in the 90-day repeated dose toxicity (oral) study in the rat was used. Modification of the starting point was not necessary based on same route of exposure and on the fact that exposure time is not relevant when the toxic effect is mainly driven by the exposure concentration.

AF for dose response relationship:
1
Justification:
Starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
Default value (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value (general population)
AF for the quality of the whole database:
1
Justification:
Starting point was a robust read-across from cyclohexanone data
AF for remaining uncertainties:
1
Justification:
No further AF considered necessary
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population