Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.5 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):
75
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 764 mg/m³
Explanation for the modification of the dose descriptor starting point:
8 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation was considered unnecessary due to the low water solubility and low chemical reactivity of (ethoxymethoxy)cyclododecane and the bioavailability therefore not being higher than after oral ingestion, no inhalation study available. Corrected inhalatory NOAEC = 1000 mg/kg bw/day*(1/0.38 m3/kg/day)*(6.7 m3 (8h)/10 m3 (8h)) = 1764 mg/m3
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentrations
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker
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

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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 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):
300
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
assumed that rat oral and dermal absorptions are equal to human oral and dermal absorption
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for worker
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
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:
no hazard identified

Additional information - workers

The long-term inhalation DNEL for systemic effects is derived from the subacute oral toxicity study (28-day study) with a NOAEL of 1000 mg/kg bw/day. The calculated DNEL is 23.5 mg/m³, applying the assessment factor of 75.

The long-term dermal DNEL for systemic effects is derived also on the basis of the subacute oral toxicity study (28-day study). For the route-to-route extrapolation it was assumed that oral and dermal absorption in the rat are equal to human oral and dermal absorption. The calculated DNEL is 3.3 mg/kg bw/day, applying the assessment factor of 300.

From skin sensitisation study is known that (ethoxymethoxy)cyclododecane shows sensitising properties. The long-term inhalation and dermal DNELs for local effects were not derived. A potency categorisation into medium hazard (EC3 > 2 %) applies for the neat substance or mixtures containing the substance in quantities of equal to or more than 1 %, taking into account the generic concentration limits that trigger classification of a mixture as given in Table 3.4.5 of Commission Regulation (EU) No 286/2011.

The acute/short term inhalation and dermal DNELs for local effects were not derived, since there are no quantitative data available. From skin irritation study is known that (ethoxymethoxy)cyclododecane shows irritating properties and therefore has a low hazard for local effects.

The acute/short term inhalation and dermal DNELs for systemic effects were not required, since no hazard in acute oral and dermal toxicity studies were identified (oral and dermal LD50 > 5000 mg/kg bw).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.8 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):
150
Modified dose descriptor starting point:
NOAEC
DNEL value:
869.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
24 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation as considered unnecessary based upon the low water solubility and low chemical reactivity of (ethoxymethoxy)cyclododecane , no inhalation study available. Corrected inhalatory NOAEC = 1000 mg/kg bw/day*(1/1.15 m3/kg/day) = 869.6 mg/m3
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentration
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

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.67 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
assumed that rat oral and dermal absorptions are equal to human oral and dermal absorptions
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-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

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.67 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route-to-route extrapolation performed
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-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
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The long-term inhalation DNEL for systemic effects is derived from the subacute oral toxicity study (28-day study) with a NOAEL of 1000 mg/kg bw/day. The calculated DNEL is 5.8 mg/m³, applying the assessment factor of 150.

The long-term dermal DNEL for systemic effects is derived also on the basis of the subacute oral toxicity study (28-day study). For the route-to-route extrapolation it was assumed that oral and dermal absorption in the rat are equal to human oral and dermal absorption. The calculated DNEL is 1.67 mg/kg bw/day, applying the assessment factor of 600.

The long-term oral DNEL for systemic effects is derived on the basis of the subacute oral toxicity study (28-day study) with NOAEL of 1000 mg/kg bw/day. The calculated DNEL is 1.67 mg/kg bw/day, applying the assessment factor of 600.

The long-term and short term inhalation and dermal DNELs for local effects were not derived on the basis that they were considered to present no hazard.

The acute/short term inhalation, dermal and oral DNELs for systemic effects were not required, since no hazard in acute oral and dermal toxicity studies were identified (oral and dermal LD50 > 5000 mg/kg bw).