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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15 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):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
188.7 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, no inhalation study available. Corrected inhalatory NOAEC = 214 mg/kg bw/day*(1/0.38 m3/kg/day)*(50%/100%)*(6.7 m3 (8h)/10 m3 (8h)) = 188.7 mg/m3
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
no extrapolation from chronic study
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:
low hazard (no threshold derived)
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:
no hazard identified
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:
4.3 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):
50
Modified dose descriptor starting point:
NOAEL
Value:
214 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:
1
Justification:
no extrapolation from chronic study
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:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
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:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

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 chronic oral toxicity study (1-year feeding study) conducted with the substance allyl 3-cyclohexylpropionate resulting in a NOAEL > 214 mg/kg bw/day. Route-to-route (oral-inhalation) extrapolation was performed. The calculated DNEL is 15 mg/m³, applying the assessment factor of 12.5.

The long-term dermal DNEL for systemic effects is derived also on the basis of the same chronic oral toxicity study (1-year feeding 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 4.3 mg/kg bw/day, applying the assessment factor of 50.

From a skin sensitisation study it is known that allyl 3-cyclohexylpropionate shows sensitising properties. The long-term inhalation and dermal DNELs for local effects were not derived. A potency categorisation into medium hazard (> 60 % animals responding at > 1 % intradermal induction dose) 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 is no hazard identified. From the skin irritation study it is known that allyl 3-cyclohexylpropionate shows no irritating properties and therefore has a no hazard for local effects.

The acute/short term inhalation DNEL for systemic effects was not derived since insufficient data is available and an acute inhalation study will be performed.

The acute/short term dermal DNEL for systemic effects was not required, since the substance showed relatively low acute dermal toxicity and the hazard was qualified to be low.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.7 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
93 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, no inhalation study available. Corrected inhalatory NOAEC = 214 mg/kg bw/day*(1/1.15 m3/kg/day)*(50%/100%) = 93 mg/m3
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
no extrapolation from chronic study
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:
low hazard (no threshold derived)
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.1 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
Modified dose descriptor starting point:
NOAEL
Value:
214 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:
1
Justification:
no extrapolation from chronic study
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:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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:
2.1 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
Modified dose descriptor starting point:
NOAEL
Value:
214 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:
1
Justification:
no extrapolation from chronic study
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:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
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 chronic oral toxicity study (1-year feeding study) conducted with the substance allyl 3 -cyclohexylpropionate resulting in a NOAEL > 214 mg/kg bw/day. Route-to-route (oral-inhalation) extrapolation was performed. The calculated DNEL is 3.7 mg/m³, applying the assessment factor of 25.

The long-term dermal DNEL for systemic effects is derived also on the basis of the same chronic oral toxicity study (1-year feeding 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 2.1 mg/kg bw/day, applying the assessment factor of 100.

The long-term oral DNEL for systemic effects is derived by read-across from the chronic oral toxicity study (1-year feeding study) with allyl 3 -cyclohexylpropionate giving a NOAEL > 214 mg/kg bw/day. The calculated DNEL is 2.1 mg/kg bw/day, applying the assessment factor of 100.

From a skin sensitisation study is known that allyl 3-cyclohexylpropionate shows sensitising properties. The long-term inhalation and dermal DNELs for local effects were not derived. A potency categorisation into medium hazard (> 60 % animals responding at > 1 % intradermal induction dose) 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. However, the concentration of allyl 3-cyclohexylpropionate in fragranced end-products meant for end-use by the general public generally is below 1%. Therefore, no hazard was identified with regard to skin sensitisation.

The acute/short term inhalation and dermal DNELs for local effects were not derived, since there is no hazard identified. From the skin irritation study is known that allyl 3-cyclohexylpropionate shows no irritating properties and therefore has no hazard for local effects.

The acute/short term inhalation DNEL for systemic effects was not derived since insufficient data is available and an acute inhalation study will be performed.

The acute/short term oral and dermal DNELs for systemic effects were not required, since from acute oral and dermal toxicity studies the LD50 values are 380 and 1600 mg/kg bw, respectively, and the hazard could be qualified as low.