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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
6.88 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):
30
Modified dose descriptor starting point:
NOAEC
Value:
206.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
Conversion of the oral rat NOAEL into an inhalatory NOAEC was performed according to ECHA REACH Guidance R.8, taking into account toxicokinetic data demontrating 100% oral absorption. An assessment factor for route-to-route extrapolation is therefore not needed.
Justification:
Not applicable.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic duration in accordance with ECHA REACH Guidance R.8
AF for interspecies differences (allometric scaling):
1
Justification:
The relevant effects are found in stomach which could be regarded local effects occurring at the portal of entry. Therefore, allometric scaling factor of 1 is applied, which is in line with ECHA REACH Guidance R.8 (page 33-34).
AF for other interspecies differences:
1
Justification:
Allometric scaling and interspecies differences focus on systemic differences (toxicokinetics, dynamics & metabolic rate) between the tested species and human. As the effect as observed in the repeated dose toxicity study is primarily local (stomach), these factors are not applicable and an assessment factor of 1 is considered justified. This is supported by the ECETOC Technical Report 110 concerning the "Guidance on Assessment Factors to Derive a DNEL" of October 2010.
AF for intraspecies differences:
5
Justification:
Default for workers in accordance with ECHA REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
The quality of the database is considered to be sufficient.
Justification:
Not applicable.
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:
3.9 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):
30
Modified dose descriptor starting point:
NOAEL
Value:
117 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The dermal NOAEL was set equal to the oral NOAEL as absorption is assumed to be identical.
Justification:
Not applicable.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic duration in accordance with ECHA REACH Guidance R.8
AF for interspecies differences (allometric scaling):
1
Justification:
The relevant effects are found in stomach which could be regarded local effects occurring at the portal of entry. Therefore, allometric scaling factor of 1 is applied in accordance with ECHA REACH Guidance R.8 (page 33-34).
AF for other interspecies differences:
1
Justification:
Allometric scaling and interspecies differences focus on systemic differences (toxicokinetics, dynamics & metabolic rate) between the tested species and human. As the effect as observed in the repeated dose toxicity study is primarily local (stomach), these factors are not applicable and an assessment factor of 1 is considered justified. This is supported by the ECETOC Technical Report 110 concerning the "Guidance on Assessment Factors to Derive a DNEL" of October 2010.
AF for intraspecies differences:
5
Justification:
Default for workers in accordance with ECHA REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
The quality of the database is considered to be sufficient.
Justification:
Not applicable.
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:
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)

Additional information - workers

No repeated dose toxicity studies or repro-developmental toxicity studies are available with Bergamot oil itself. As an alternative, a weight of evidence approach was chosen based on the available studies in different species for the major constituents of Bergamot oil: d-limonene (CAS nr 5989 -27-5), linalyl acetate (CAS nr. 115-95-7) and linalool (CAS nr. 78 -70-6). Using these data results in a coverage of >80% of the composition of Bergamot oil, which ensures that the same data requirements are covered as for mono-constituent substances. Data for d-limonene and linalool are available. The data for linalool also cover linalyl acetate, as this substance is quickly metabolized to linalool and read-across is therefore justified.

The most critical NOAEL is 100 mg/kg bw/day, based on a 6-month repeated dose oral toxicity study in dogs with d-limonene (Webb, 1990). This NOAEL may not be the most appropriate value to base the DNEL on given the fact that the next dose level (1000 mg/kg bw/day) only produced effects on kidney weight which were regarded non-adverse effects. The second most critical NOAEL is 117 mg/kg bw/day, based on a 28-day oral gavage study with linalool in rats. The observed effects may be the result of bulk administration via gavage, but in the absence of definitive evidence to the contrary, these findings must be considered as treatment-related. This NOAEL of 117 mg/kg bw/day based on study with linalool in rats was taken as point of departure for derivation of the DNELs for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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):
60
Modified dose descriptor starting point:
NOAEC
Value:
101.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
Conversion of the oral rat NOAEL into an inhalatory NOAEC was performed according to ECHA REACH Guidance R.8, taking into account toxicokinetic data demontrating 100% oral absorption. An assessment factor for route-to-route extrapolation is therefore not needed.
Justification:
Not applicable.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic duration in accordance with ECHA REACH Guidance R.8
AF for interspecies differences (allometric scaling):
1
Justification:
The relevant effects are found in stomach which could be regarded local effects occurring at the portal of entry. Therefore, allometric scaling factor of 1 is applied, which is in line with ECHA REACH Guidance R.8 (page 33-34).
AF for other interspecies differences:
1
Justification:
Allometric scaling and interspecies differences focus on systemic differences (toxicokinetics, dynamics & metabolic rate) between the tested species and human. As the effect as observed in the repeated dose toxicity study is primarily local (stomach), these factors are not applicable and an assessment factor of 1 is considered justified. This is supported by the ECETOC Technical Report 110 concerning the "Guidance on Assessment Factors to Derive a DNEL" of October 2010.
AF for intraspecies differences:
10
Justification:
Default for general population in accordance with ECHA REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
The quality of the database is considered to be sufficient.
Justification:
Not applicable.
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:
1.95 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):
60
Modified dose descriptor starting point:
NOAEL
Value:
117 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The dermal NOAEL was set equal to the oral NOAEL as absorption is assumed to be identical.
Justification:
Not applicable.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic duration in accordance with ECHA REACH Guidance R.8.
AF for interspecies differences (allometric scaling):
1
Justification:
The relevant effects are found in stomach which could be regarded local effects occurring at the portal of entry. Therefore, allometric scaling factor of 1 is applied in accordance with ECHA REACH Guidance R.8 (page 33-34).
AF for other interspecies differences:
1
Justification:
Allometric scaling and interspecies differences focus on systemic differences (toxicokinetics, dynamics & metabolic rate) between the tested species and human. As the effect as observed in the repeated dose toxicity study is primarily local (stomach), these factors are not applicable and an assessment factor of 1 is considered justified. This is supported by the ECETOC Technical Report 110 concerning the "Guidance on Assessment Factors to Derive a DNEL" of October 2010.
AF for intraspecies differences:
10
Justification:
Default factor for general population in accordance with ECHA REACH Guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the database is considered to be sufficient.
Justification:
Not applicable.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.95 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):
60
Modified dose descriptor starting point:
NOAEL
Value:
117 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable as the basis for this NOAEL is an oral study.
Justification:
Not applicable.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic duration in accordance with ECHA REACH Guidance R.8.
AF for interspecies differences (allometric scaling):
1
Justification:
The relevant effects are found in stomach which could be regarded local effects occurring at the portal of entry. Therefore, allometric scaling factor of 1 is applied in accordance with ECHA REACH Guidance (page 33-34).
AF for other interspecies differences:
1
Justification:
Allometric scaling and interspecies differences focus on systemic differences (toxicokinetics, dynamics & metabolic rate) between the tested species and human. As the effect as observed in the repeated dose toxicity study is primarily local (stomach), these factors are not applicable and an assessment factor of 1 is considered justified. This is supported by the ECETOC Technical Report 110 concerning the "Guidance on Assessment Factors to Derive a DNEL" of October 2010.
AF for intraspecies differences:
10
Justification:
Default for general population in accordance with ECHA REACH Guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the database is considered to be sufficient.
Justification:
Not applicable.
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)

Additional information - General Population

No repeated dose toxicity studies or repro-/developmental toxicity studies are available with Bergamot oil itself. As an alternative, a weight of evidence approach was chosen based on the available studies in different species for the major constituents of Bergamot oil: d-Limonene (CAS nr 5989 -27-5), Linalyl acetate (CAS nr. 115-95-7) and Linalool (CAS nr. 78 -70-6). Using these data results in a coverage of >80% of the composition of Bergamot oil, which ensures that the same data requirements are covered as for mono-constituent substances. Data for d-Limonene and Linalool are available. The data for Linalool also cover Linalyl acetate, as this substance is quickly metabolized to Linalool and read-across is therefore justified.

The most critical NOAEL is 100 mg/kg bw/day, based on a 6-month repeated dose oral toxicity study in dogs with d-Limonene (Webb, 1990). This NOAEL may not be the most appropriate value to base the DNEL on given the fact that the next dose level (1000 mg/kg bw/day) only produced effects on kidney weight which were regarded non-adverse effects. The second most critical NOAEL is 117 mg/kg bw/day, based on a 28-day oral gavage study with Linalool in rats. The observed effects may be the result of bulk administration via gavage, but in the absence of definitive evidence to the contrary, these findings must be considered as treatment-related. This NOAEL of 117 mg/kg bw/day based on study with linalool in rats was taken as point of departure for derivation of the DNELs for the general population.