Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
28.2 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:
353 mg/m³
Explanation for the modification of the dose descriptor starting point:
using bioavailability of 100% for the oral and 100% for the inhalation route and assuming that rat oral and inhalation absorptions are equal to human oral and inhalation absorption, a NOAEC corr of 200 mg/kg/day / 0.38 m^3/kg * 6.7/10 = 353 mg/m^3 is used
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
due to chronic study data used
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
for worker, a default AF of 5 is to be used
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
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:
4 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:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
using bioavailability of 100% for the oral and 100% for the dermal route and assuming that rat oral and dermal absorptions are equal to human oral and dermal absorption, thus the corrected dermal NOAEL is 200 mg/kg/day
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
due to chronic study data used
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:
for worker, a default AF of 5 is to be used
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
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 DNEL required: short term exposure controlled by conditions for long-term

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

A chronic (2 years) and subchronic study (90-day test) following OECD guideline using cinnamaldehyde as surrogate for methyl cinnamate, both sharing the same primary metabolite cinnamic acid, with application via diet as microcapsules showed that there was no significant differences in clinical chemistry, blood sugar and cholesterol concentrations of rats, blood, urinalysis, clinico-chemical analyses, necropsies and histopathological investigations, gross pathology and histopathology compared with controls in the parameters investigated of the dose groups of 300 mg/kg in the subchronic study and 200 mg/kg bw/d in the chronic study. All values were within normal range. Furthermore, NOAEL derived from a combined subacute repeated dose/reproductive toxicity study on methyl cinnamate is 275 mg/kg bw/d (males) resp. 300 mg/kg bw/d (females), which is a good agreement with that from the 90-day and the chronic study of the surrogate substance. 

Therefore, it is concluded that a value of 200 mg/kg derived from the chronic study can be used as the starting point for DNEL derivation, supported by the fact that 275 (males) respectively 300 (females) mg/kg bw/d was the NOAEL in the subacute repeated dose toxicity study with methyl cinnamate.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.96 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:
174 mg/m³
Explanation for the modification of the dose descriptor starting point:
using bioavailability of 100% for the oral and 100% for the inhalation route and assuming that rat oral and inhalation absorptions are equal to human oral and inhalation absorption, a NOAEC corr of 200 mg/kg/day / 1.15 m^3/kg/d = 174 mg/m^3 is used
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
due to chronic study data used
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
for consumer, a default AF of 10 is to be used
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
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:
2 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:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
using bioavailability of 100% for the oral and 100% for the dermal route and assuming that rat oral and dermal absorptions are equal to human oral and dermal absorption, thus the corrected dermal NOAEL is 200 mg/kg/day
AF for dose response relationship:
1
Justification:
not required as NOAEL is used
AF for differences in duration of exposure:
1
Justification:
due to chronic study data used
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:
for consumer, a default AF of 10 is to be used
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
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:
2 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:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not applicable
AF for dose response relationship:
1
Justification:
not required as NOAEL is used
AF for differences in duration of exposure:
1
Justification:
due to chronic study data used
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:
for consumer, a default AF of 10 is to be used
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
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

A chronic (2 years) and subchronic study (90-day test)following OECD guideline using cinnamaldehyde as surrogate for methyl cinnamate, both sharing the same primary metabolite cinnamic acid, with application via diet as microcapsules showed that there was no significant differences in clinical chemistry, blood sugar and cholesterol concentrations of rats, blood, urinalysis, clinico-chemical analyses, necropsies and histopathological investigations, gross pathology and histopathology compared with controls in the parameters investigated of the dose groups of 300 mg/kg in the subchronic study and 200 mg/kg bw/d in the chronic study. All values were within normal range. Furthermore, NOAEL derived from a combined subacute repeated dose/reproductive toxicity study on methyl cinnamate is 275 mg/kg bw/d (males) resp. 300 mg/kg bw/d (females), which is a good agreement with that from the 90-day and the chronic study of the surrogate substance. 

Therefore, it is concluded that a value of 200 mg/kg derived from the chronic study can be used as the starting point for DNEL derivation, supported by the fact that 275 (males) respectively 300 (females) mg/kg bw/d was the NOAEL in the subacute repeated dose toxicity study with methyl cinnamate.