Eugenol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

21.2 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:

265 mg/m³

Explanation for the modification of the dose descriptor starting point:

For potential inhalation exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. The NOAEL from the rat carcinogenicity study, 300 mg/kg bw/day, was selected as the relevant starting point for DNEL derivation. Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested on page 19 of Guidance Document, Chapter R.8 (2010). To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8-h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8-h exposure period). Thus, the corrected dose descriptor for inhalation is 300 x (1/0.38) x0.67 x (1/2) = 265 mg/m3 for workers.

AF for dose response relationship:

1

Justification:

Starting point is a NOAEL

AF for differences in duration of exposure:

1

Justification:

DNEL is based on a 2-year rodent study

AF for interspecies differences (allometric scaling):

1

Justification:

Not applicable for inhalation route

AF for other interspecies differences:

2.5

Justification:

Toxicodynamic and toxicokinetic remaining differencies

AF for intraspecies differences:

5

Justification:

Standard AF for Workers

AF for the quality of the whole database:

1

Justification:

Appropriate database

AF for remaining uncertainties:

1

Justification:

None

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6 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:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. In the absence of reliable data and on the assumption that, in general, dermal absorption will not be higher than oral absorption, no additional factor was introduced.

AF for dose response relationship:

1

Justification:

Starting point is a NOAEL

AF for differences in duration of exposure:

1

Justification:

DNEL is based on a 2-year rodent study

AF for interspecies differences (allometric scaling):

4

Justification:

Standard AF for rats

AF for other interspecies differences:

2.5

Justification:

Toxicodynamic and toxicokinetic remaining differencies

AF for intraspecies differences:

5

Justification:

Standard AF for Workers

AF for the quality of the whole database:

1

Justification:

Appropriate database

AF for remaining uncertainties:

1

Justification:

None

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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:

low hazard (no threshold derived)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.22 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:

130 mg/m³

Explanation for the modification of the dose descriptor starting point:

For potential inhalation exposure, route-to-route extrapolation from the oral NOAEL value was performed. In the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions have to be made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested on page 19 of Guidance Document, Chapter R.8 (2010). Finally, to convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24 h). Thus, the corrected dose descriptor for inhalation is: 300 x (1/1.15) x (1/2) = 130 mg/3 for the general population.

AF for dose response relationship:

1

Justification:

Starting point is a NOAEL

AF for differences in duration of exposure:

1

Justification:

DNEL is based on a 2-year rodent study

AF for interspecies differences (allometric scaling):

1

Justification:

Not applicable for inhalation route

AF for other interspecies differences:

2.5

Justification:

Toxicodynamic and toxicokinetic remaining differencies

AF for intraspecies differences:

10

Justification:

Standard AF for General Population

AF for the quality of the whole database:

1

Justification:

Appropriate database

AF for remaining uncertainties:

1

Justification:

None

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

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):

100

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. In the absence of reliable data and on the assumption that, in general, dermal absorption will not be higher than oral absorption, no additional factor was introduced.

AF for dose response relationship:

1

Justification:

Starting point is a NOAEL

AF for differences in duration of exposure:

1

Justification:

DNEL is based on a 2-year rodent study

AF for interspecies differences (allometric scaling):

4

Justification:

Standard AF for rats

AF for other interspecies differences:

2.5

Justification:

Toxicodynamic and toxicokinetic remaining differencies

AF for intraspecies differences:

10

Justification:

Standard AF for General Population

AF for the quality of the whole database:

1

Justification:

Appropriate database

AF for remaining uncertainties:

1

Justification:

None

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

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):

100

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation needed

AF for dose response relationship:

1

Justification:

Starting point is a NOAEL

AF for differences in duration of exposure:

1

Justification:

DNEL is based on a 2-year rodent study

AF for interspecies differences (allometric scaling):

4

Justification:

Standard AF for rats

AF for other interspecies differences:

2.5

Justification:

Toxicodynamic and toxicokinetic remaining differencies

AF for intraspecies differences:

10

Justification:

Standard AF for General Population

AF for the quality of the whole database:

1

Justification:

Appropriate database

AF for remaining uncertainties:

1

Justification:

None

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)