Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
66.7 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):
75
Modified dose descriptor starting point:
LOAEC
Value:
5 000 mg/m³
Explanation for the modification of the dose descriptor starting point:
Under the test conditions, the LOAEL for beagle dogs was considered to be 1000 mg/kg bw/day, respectively, based on the increased absolute and relative female kidney weight and relative male kidney weight. D-limonene has the same absorption rate between oral and inhalation routes (See section 7.1) therefore no correction factor was applied for differences in absorption between oral and inhalation routes. To convert the oral LOAEL into inhalatory LOAEC, a dog default respiratory volume was used corresponding to the daily duration of human exposure (sRVdog: 0.134 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8-h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8-h exposure period). Thus, the corrected dose descriptor for inhalation is: LOAEC (mg/m3) = 1000 / 0.134 x 6.7/10 = 5000 mg/m3 for workers.
AF for dose response relationship:
3
Justification:
Default factor to convert a LOAEC into a NOAEC
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for oral to inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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:
9.5 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):
105
Modified dose descriptor starting point:
LOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No additional factor is needed when performing oral to dermal extrapolation
AF for dose response relationship:
3
Justification:
Default factor to convert a LOAEL into a NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
1.4
Justification:
Allometric scaling from dog to human
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

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:
16.6 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
Modified dose descriptor starting point:
LOAEC
Value:
2 488 mg/m³
Explanation for the modification of the dose descriptor starting point:
Under the test conditions, the LOAEL for beagle dogs was considered to be 1000 mg/kg bw/day, respectively, based on the increased absolute and relative female kidney weight and relative male kidney weight. D-limonene has the same absorption rate between oral and inhalation routes (See section 7.1) therefore no correction factor was applied for differences in absorption between oral and inhalation routes. The dog Standard Respiratory Volume (SRV) for 24 h exposure is used to convert the oral LOAEL into an inhalatory LOAEC (sRVdog: 0.402 m3/kg bw/24h). The corrected starting point is thus calculated as follows: corrected inhalatory LOAEC = oral LOAEL x (1/sRVdog); thus corrected inhalation LOAEC for general population = 1000 mg/kg bw/d x (1/0.402 m3/kg bw/d) = 2488 mg/m3
AF for dose response relationship:
3
Justification:
Default factor to convert a LOAEC into a NOAEC
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for oral to inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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:
4.8 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):
210
Modified dose descriptor starting point:
LOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No additional factor is needed when performing oral to dermal extrapolation
AF for dose response relationship:
3
Justification:
Default factor to convert a LOAEL into a NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
1.4
Justification:
Allometric scaling from dog to human
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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:
4.8 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):
210
Modified dose descriptor starting point:
LOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed
AF for dose response relationship:
3
Justification:
Default factor to convert a LOAEL into a NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
1.4
Justification:
Allometric scaling from dog to human
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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