Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
28 µg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25 000
Dose descriptor starting point:
T25
Value:
675 mg/m³
Modified dose descriptor starting point:
T25
Value:
688.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Due to different exposure conditions in the animal experiment and at the workplace both time scaling and a modification due to different respiratory volumes have to be applied according to the REACH guidance R.8. Differences between occupational and lifetime exposition have also been included:

(6h/8h) * (6.7m³/10m³) * (5d/5d) * (52wk/48wk) * (75yr/40yr) = 1.02


AF for dose response relationship:
1
Justification:
No AF is applied for non-treshold effects
AF for differences in duration of exposure:
1
Justification:
No AF is applied for non-treshold effects
AF for interspecies differences (allometric scaling):
1
Justification:
According to the REACH guidance R.8 an assessment factor for allometric scaling is not needed here because the dose unit of the dose descriptor is expressed as concentration.
AF for other interspecies differences:
1
Justification:
No AF is applied for non-treshold effects
AF for intraspecies differences:
1
Justification:
No AF is applied for non-treshold effects
AF for the quality of the whole database:
1
Justification:
good quality of database is given
AF for remaining uncertainties:
1
Justification:
The dose response curve is linear. Therefore no separate assessment factor is needed.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor:
NOAEC
Value:
10.8 mg/m³
AF for dose response relationship:
1
Justification:
The starting point for the DNEL was a NOAEC.
AF for differences in duration of exposure:
1
Justification:
Data indicate that incidence and severity of the degenerative changes of the olfactory epithelium depend rather on the air concentration of butanone oxime than on the duration of repeated exposure. In this case, an assessment factor is not justified.
AF for interspecies differences (allometric scaling):
2.5
Justification:
According to the REACH guidance R.8 no assessment factor for allometric scaling is applied because degeneration of the olfactory epithelium is a local adverse health effect. However, a default factor of 2.5 for remaining differences is applied because no substance specific data are available for an adjustment.
AF for other interspecies differences:
1
Justification:
AF not used for inhalation route.
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
A factor of 1 can be supported because of the extensive toxicological database available on the test material and the consistency in responses observed.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
4 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1
Dose descriptor starting point:
T25
Value:
675 mg/m³
Modified dose descriptor starting point:
T25
Value:
4 µg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For extrapolation of the inhalation to dermal DMEL it was necessary to apply modifications for the respiratory rate:

28 µg/m³ * 10 m³/day / 70 kg bw = 4 µg/kg bw/day

Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information

Local effects

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

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:
DMEL (Derived Minimum Effect Level)
Value:
4.82 µg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25 000
Dose descriptor starting point:
T25
Value:
675 mg/m³
Modified dose descriptor starting point:
T25
Value:
120.52 mg/m³
Explanation for the modification of the dose descriptor starting point:

Due to different exposure conditions in the animal experiment and general population the following corrections apply:

(6h/24h) * (5d/7d) * 675 mg/m³ = 120.52 mg/m³

AF for dose response relationship:
1
Justification:
No AF is applied for non-treshold effects
AF for differences in duration of exposure:
1
Justification:
No AF is applied for non-treshold effects
AF for interspecies differences (allometric scaling):
1
Justification:
According to the REACH guidance R.8 an assessment factor for allometric scaling is not needed here because the dose unit of the dose descriptor is expressed as concentration.
AF for other interspecies differences:
1
Justification:
No AF is applied for non-treshold effects
AF for intraspecies differences:
1
Justification:
No AF is applied for non-treshold effects
AF for the quality of the whole database:
1
Justification:
good quality of data base is given
AF for remaining uncertainties:
1
Justification:
The dose curve is linear. Therefore no separate assessment factor is needed.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.43 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor:
NOAEC
Value:
10.8 mg/m³
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEC
AF for differences in duration of exposure:
1
Justification:
Data indicate that incidence and severity of the degenerative changes of the olfactory epithelium depend rather on the air concentration of butanone oxime than on the duration of repeated exposure. In this case, an assessment factor is not justified.
AF for interspecies differences (allometric scaling):
1
Justification:
not relevant for inhalation study
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
based on good quality data base
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
1.6 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population