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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
10 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):
20
Dose descriptor starting point:
NOAEC
Value:
408 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
204 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected for 8 h exposure, as proposed in the REACH Guidance (R.8.4.2)

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

NOAEC corrected inhalative= 408 * (6/8) * (6.7/10) =204 mg/m3
AF for dose response relationship:
1
Justification:
Default factor if a NOAEL is used as starting point.
AF for differences in duration of exposure:
2
Justification:
Use of a subchronic study as starting point for long-term systemic DNEL derivation (default assessment factor according to R8 ECHA 2012).
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling already considered during modification of the starting point.
AF for other interspecies differences:
2
Justification:
The default factor of 2.5 is reduced to 2 as the setting of the NOAEL in the 90-day inhalation study is based on a conservative approach and arguable (see endpoint summary for repeated dose toxicity).
AF for intraspecies differences:
5
Justification:
Default factor for the worker
AF for the quality of the whole database:
1
Justification:
Different inhalation studies in two species available.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC
Value:
408 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
204 mg/m³

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

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:
DNEL (Derived No Effect Level)
Value:
2.55 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):
40
Dose descriptor starting point:
NOAEL
Value:
408 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
102 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected for 24 h exposure, as proposed in the REACH Guidance (R.8.4.2)

 

NOAEC corrected inhalative= 408 * (6/24) = 102 mg/m3
AF for dose response relationship:
1
Justification:
Default factor if a NOAEL is used as starting point.
AF for differences in duration of exposure:
2
Justification:
Use of a subchronic study as starting point for long-term systemic DNEL derivation (default assessment factor according to R8 ECHA 2012).
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not necessary (NOAEL from inhalation study).
AF for other interspecies differences:
2
Justification:
The default factor of 2.5 is reduced to 2 as the setting of the NOAEL in the 90-day inhalation study is based on a conservative approach and arguable (see endpoint summary for repeated dose toxicity).
AF for intraspecies differences:
10
Justification:
Default factor for the general population
AF for the quality of the whole database:
1
Justification:
Different inhalation studies in two species available.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium 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 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

For the systemic DNELs concerning dermal and inhalation exposure the rationales are presented above.


Concerning oral short-term and long-term exposures, the DNELs are based upon the NOAEL (143 mg/kg bw/d) in the BASF subchronic drinking water study. The chronic drinking water studies which are also available do not show a decrease of the NOAEL with exposure time. Furthermore, in the course of the intravenous studies, no significant difference was seen between single administration and repeated administration; the effects observed were reversible within 30 min. Hence, the time extrapolation factor can be fixed to 1. In the light of known qualitative differences in the metabolic profiles between rodents and humans (Mraz et al., loc.cit.) a default factor of 2.5 is proposed in addition to the allometric factor of 4. (This does not necessarily mean that humans are more sensitive.) The interindividual variability towards Cyclohexanone appears to be low in the species investigated and also in human adults; however, children may be more sensitive and therefore an interspecies factor of 10 is proposed, which leads to an overall factor of 100 and oral DNELs of 1.5 mg/kg bw (acute and chronic).


For the inhalation DNELs, the calculation procedure is similar as for the workplace. However, in terms of systemic toxicity a 4 -fold higher intraspecies variability was taken into account and led to a total intraspecies factor of 10.


Similarly, also the dermal DNELs for the workplace (derived from the subacute infusion study in rats with a NOAEL of 100 mg/kg/d; see above) were divided by 4.