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EC number: 203-631-1 | CAS number: 108-94-1
Toxicological Summary
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.
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