Registration Dossier

Administrative data

Workers - 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):
150
Dose descriptor starting point:
NOAEL
DNEL value:
443.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
782.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEL = 443.7 mg/kg bw/d

This NOAEL is calculated starting from the NOAEL available from a combined repeated dose / reproductive toxicity study in rats on the read-across substance benzyl cinnamate by taking into account a correction for the molecular weight.

NOAEL (benzyl cinnamate) = 600 mg/kg bw/d

MW (benzyl cinnamate) = 238.28 g/mol

MW (ethyl cinnamate) = 176.21 g/mol

NOAEL (ethyl cinnamate) = 600 * (176.21/238.28) = 443.7 g/mol

--> 443.7 mg/kg bw/d / 0.38 m3/kg bw * 6.7 m3/ 10 m3

NOAEC = 782.3 mg/m3

AF for dose response relationship:
2
Justification:
default value for route-to-route extrapolation according to R.8.4.2.
AF for differences in duration of exposure:
6
Justification:
ECHA REACH standard AF for sub-acute to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
Not used for inhalation results
AF for other interspecies differences:
2.5
Justification:
ECHA REACH standard AF for "differences not related to calorimetric differences"
AF for intraspecies differences:
5
Justification:
default value according to R.8.4.3.1
AF for the quality of the whole database:
1
Justification:
no issues with the quality of the data base
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local 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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.479 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
Dose descriptor starting point:
NOAEL
DNEL value:
443.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
443.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL = 443.7 mg/kg bw/d

This NOAEL is calculated starting from the NOAEL available from a combined repeated dose / reproductive toxicity study in rats on the read-across substance benzyl cinnamate by taking into account a correction for the molecular weight.

NOAEL (benzyl cinnamate) = 600 mg/kg bw/d

MW (benzyl cinnamate) = 238.28 g/mol

MW (ethyl cinnamate) = 176.21 g/mol

NOAEL (ethyl cinnamate) = 600 * (176.21/238.28) = 443.7 g/mol

No specific information on dermal absorption was taken into account.

This approach starts from the assumption that dermal absorption will not be higher than oral absorption.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
ECHA REACH standard AF for sub-acute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH standard AF for rat to human extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA REACH standard AF for "differences not related to calorimetric differences"
AF for intraspecies differences:
5
Justification:
ECHA REACH standard AF for intraspecies differences to workers
AF for the quality of the whole database:
1
Justification:
no issues with the quality of the data base
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties identified
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.286 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):
300
Dose descriptor starting point:
NOAEL
DNEL value:
443.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
385.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEL = 443.7 mg/kg bw/d

This NOAEL is calculated starting from the NOAEL available from a combined repeated dose / reproductive toxicity study in rats on the read-across substance benzyl cinnamate by taking into account a correction for the molecular weight.

NOAEL (benzyl cinnamate) = 600 mg/kg bw/d

MW (benzyl cinnamate) = 238.28 g/mol

MW (ethyl cinnamate) = 176.21 g/mol

NOAEL (ethyl cinnamate) = 600 * (176.21/238.28) = 443.7 g/mol

--> 443.7 mg/kg bw/d / 1.15 m3/kg bw

NOAEC = 385.8 mg/m3

AF for dose response relationship:
2
Justification:
default value for route-to-route extrapolation according to R.8.4.2.
AF for differences in duration of exposure:
6
Justification:
ECHA REACH standard AF for sub-acute to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
not used for oral results
AF for other interspecies differences:
2.5
Justification:
differences not related to calorimetric differences
AF for intraspecies differences:
10
Justification:
default value according to R.8.4.3.1
AF for the quality of the whole database:
1
Justification:
no issues with the quality of the data base
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local 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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.74 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
Dose descriptor starting point:
NOAEL
DNEL value:
443.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
443.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL = 443.7 mg/kg bw/d

This NOAEL is calculated starting from the NOAEL available from a combined repeated dose / reproductive toxicity study in rats on the read-across substance benzyl cinnamate by taking into account a correction for the molecular weight.

NOAEL (benzyl cinnamate) = 600 mg/kg bw/d

MW (benzyl cinnamate) = 238.28 g/mol

MW (ethyl cinnamate) = 176.21 g/mol

NOAEL (ethyl cinnamate) = 600 * (176.21/238.28) = 443.7 g/mol

No specific information on dermal absorption was taken into account.

This approach starts from the assumption that dermal absorption will not be higher than oral absorption.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
ECHA REACH standard AF for sub-acute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH standard AF for rat to human extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA REACH standard AF for "differences not related to calorimetric differences"
AF for intraspecies differences:
10
Justification:
ECHA REACH default AF for the general population
AF for the quality of the whole database:
1
Justification:
no issues with the quality of the data base
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties identified
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:
0.74 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
Dose descriptor starting point:
NOAEL
DNEL value:
443.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
443.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL = 443.7 mg/kg bw/d

This NOAEL is calculated starting from the NOAEL available from a combined repeated dose / reproductive toxicity study in rats on the read-across substance benzyl cinnamate by taking into account a correction for the molecular weight.

NOAEL (benzyl cinnamate) = 600 mg/kg bw/d

MW (benzyl cinnamate) = 238.28 g/mol

MW (ethyl cinnamate) = 176.21 g/mol

NOAEL (ethyl cinnamate) = 600 * (176.21/238.28) = 443.7 g/mol

Oral absorption by rat and human are assumed to be equal.

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
ECHA REACH standard AF for sub-acute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH standard AF for rat to human extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA REACH standard AF for "differences not related to calorimetric differences"
AF for intraspecies differences:
10
Justification:
ECHA REACH standard AF for the general population
AF for the quality of the whole database:
1
Justification:
no issues with the quality of the data base
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties identified
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