Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.59 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
DNEL value:
180 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
159 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEL(oral) converted to NOAEC(inhal) (180 mg/kg x [1/0.38 x 50% oral absorption rat/100% inhalation absorption human x 6.7/10]) = 159 mg/m3

AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Not applied as differences in the allometry are assumed to be compensated by differences in the respiration rate.
AF for other interspecies differences:
2.5
Justification:
Default value in line with Section R.8.4.3 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
4
Justification:
Limited data on the substance itself with regards to developmental and reprotoxicity
AF for remaining uncertainties:
1
Justification:
Not applied.
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:
0.9 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
400
Dose descriptor starting point:
NOAEL
DNEL value:
180 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
360 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL(oral) converted to NOAEL(dermal) (180 mg/kg x [50% oral absorption rat/25% dermal absorption humans]) = 360 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment 5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for other interspecies differences:
2.5
Justification:
Default value in line with Section R.8.4.3 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
4
Justification:
Limited data on the substance itself with regards to developmental and reprotoxicity
AF for remaining uncertainties:
1
Justification:
Not applied.
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

(z)-3-hexenyl salicylate does not show any local or acute effects and so DNELs for local and/or acute effects have not been calculated.

The available one generation reproduction study is considered as the most relevant study for the dose descriptor starting point and the NOAEL of 180 mg/kg bw/day (general parental toxicology, parental female reproduction and F1 generation development) from this study has been used as the starting point for the calculation of the systemic DNELs.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.39 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
DNEL value:
180 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
78.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEL(oral) converted to NOAEC(inhal) (180 mg/kg x [1/1.15 x 50% oral absorption rat/100% inhalation absorption human]) = 78.2 mg/m3

AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Not applied as differences in the allometry are assumed to be compensated by differences in the respiration rate.
AF for other interspecies differences:
2.5
Justification:
Default value in line with Section R.8.4.3 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
4
Justification:
Limited data on the substance itself with regards to developmental and reprotoxicity
AF for remaining uncertainties:
1
Justification:
Not applied
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:
0.45 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
800
Dose descriptor starting point:
NOAEL
DNEL value:
180 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
360 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL(oral) converted to NOAEL(dermal) (180 mg/kg x [50% oral absorption rat/25% dermal absorption humans]) = 360 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for other interspecies differences:
2.5
Justification:
Default value in line with Section R.8.4.3 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
4
Justification:
Limited data on the substance itself with regards to developmental and reprotoxicity
AF for remaining uncertainties:
1
Justification:
Not applied
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:
0.23 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
800
Dose descriptor starting point:
NOAEL
DNEL value:
180 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
180 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Same oral absorption in rat and humans

AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for other interspecies differences:
2.5
Justification:
Default value in line with Section R.8.4.3 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
4
Justification:
Limited data on the substance itself with regards to developmental and reprotoxicity
AF for remaining uncertainties:
1
Justification:
Not applied
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

(z)-3-hexenyl salicylate does not show any local or acute effects and so DNELs for local and/or acute effects have not been calculated.

The available one generation reproduction study is considered as the most relevant study for the dose descriptor starting point and the NOAEL of 180 mg/kg bw/day (general parental toxicology, parental female reproduction and F1 generation development) from this study has been used as the starting point for the calculation of the systemic DNELs.