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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
31.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
112.5
Modified dose descriptor starting point:
LOAEC
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:
8.89 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
112.5
Modified dose descriptor starting point:
LOAEL
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:
no hazard identified

Additional information - workers

There is no information on repeated dose toxicity for grapefruit oil, however, several sub-chronic repeated dose toxicity studies are available for its major constituent limonene, in different species (mouse, rat and dog). Although the most sensitive NOAEL is from the dog study, it may not be the most appropriate NOAEL to base the DNEL on, because the study design is such that the difference in concentration between the NOAEL and LOAEL is quite high (100 mg/kg bw/day and 1000 mg/kg bw/day, respectively). When the studies in other species are taken into account, the same LOAEL is observed, but, due to another study design, a higher NOAEL. In the 90-d mouse study (NTP, 1990), the LOAEL is also 1000 mg/kg bw/day, but a NOAEL of 500 mg/kg bw/day was observed. However, as the studies are performed in different species, the choice for the mouse NOAEL of 500 mg/kg bw/day is arbitrary. Furthermore, an additional dog study is available in which a LOAEL of 1000 mg/kg bw/day was observed (NOAEL 340 mg/kg bw/day), and a 90-day rat study which resulted in a LOAEL of 1200 mg/kg bw/day. Therefore, the shared LOAEL of 1000 mg/kg bw/day can be used as a starting point for the derivation of the DNEL.

As three different species support the LOAEL, interspecies differences due to allometric scaling do not have to be taken into account. Consequently, route-to route extrapolation from oral to inhalation was performed by correcting for bodyweight and respiratory volume of humans only. In accordance with the Guidance Document on Information Requirements, Chapter R8., absorption of 100% was assumed via the inhalation route, with regard to an oral absorption of 50%. Additionally, the following assessment factors were applied:

  • interspecies effects – remaining differences 2.5
  • intraspecies effects – worker 5
  • duration – subchronic to chronic 2
  • dose response – use of LOAEL 3
  • quality of the database – 1.5, based on limitations of report (publications) or limitations in experimental set-up (NTP-studies)

 

The DNELs were derived in accordance with the Guidance on Information Requirements and Chemical Safety Assessment Chapter R8.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.78 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
225
Modified dose descriptor starting point:
LOAEC
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:
4.44 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
225
Modified dose descriptor starting point:
LOAEL
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:
4.44 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
225
Modified dose descriptor starting point:
LOAEL
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

There is no information on repeated dose toxicity for grapefruit oil, however, several sub-chronic repeated dose toxicity studies are available for its major constituent limonene, in different species (mouse, rat and dog). Although the most sensitive NOAEL is from the dog study, it may not be the most appropriate NOAEL to base the DNEL on, because the study design is such that the difference in concentration between the NOAEL and LOAEL is quite high (100 mg/kg bw/day and 1000 mg/kg bw/day, respectively). When the studies in other species are taken into account, the same LOAEL is observed, but, due to another study design, a higher NOAEL. In the 90-d mouse study (NTP, 1990), the LOAEL is also 1000 mg/kg bw/day, but a NOAEL of 500 mg/kg bw/day was observed. However, as the studies are performed in different species, the choice for the mouse NOAEL of 500 mg/kg bw/day is arbitrary. Furthermore, an additional dog study is available in which a LOAEL of 1000 mg/kg bw/day was observed (NOAEL 340 mg/kg bw/day), and a 90-day rat study which resulted in a LOAEL of 1200 mg/kg bw/day. Therefore, the shared LOAEL of 1000 mg/kg bw/day can be used as a starting point for the derivation of the DNEL.

As three different species support the LOAEL, interspecies differences due to allometric scaling do not have to be taken into account. Consequently, route-to route extrapolation from oral to inhalation was performed by correcting for bodyweight and respiratory volume of humans only. In accordance with the Guidance Document on Information Requirements, Chapter R8., absorption of 100% was assumed via the inhalation route, with regard to an oral absorption of 50%. Additionally, the following assessment factors were applied:

  • interspecies effects – remaining differences 2.5
  • intraspecies effects – general population 10
  • duration – subchronic to chronic 2
  • dose response – use of LOAEL 3
  • quality of the database – 1.5, based on limitations of report (publications) or limitations in experimental set-up (NTP-studies)

The DNELs were derived in accordance with the Guidance on Information Requirements and Chemical Safety Assessment Chapter R8.