Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.48 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
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
861 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of inhalation repeated-dose toxicity studies, a DNEL for systemic effects has to be derived by route-to-route extrapolation from the no-effect levels observed in the oral repeated-dose toxicity studies.
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
6
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
68.9 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
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
861 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
28.71 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
Value:
861 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
6
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
172.26 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor starting point:
NOAEC
Value:
861 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.26 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
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
6
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19.54 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
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.14 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Dose descriptor:
NOAEC
Value:
861 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
6
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
48.85 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor starting point:
NOAEC
Value:
861 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Two oral repeated-dose toxicity studies were performed with Patchouli oil in accordance with OECD TG 407 and OECD TG 421. In the 28-day oral feeding study with rats, some adaptive changes were observed in the liver, thyroid and kidneys of male and female rats at the highest dose of 977 mg/kg bw/day, which were however not interpreted as adverse health effects. The NOAEL in the study was 977 mg/kg bw/day. In the screening study on reproductive and developmental effects, male and female rats were exposed to Patchouli oil by gavage for up to 8 weeks. Treatment-related effects in adult animals were observed at the highest dose of 810 mg/kg bw/day. This dose level also resulted in a small number of treatment related effects on offspring and post partum with an equivocal effect on the nature of som in utero parameters. The NOEL for systemic toxicity and for reproduction and offspring development in this subacute screening study on reproductive and developmental toxicity was 277 mg/kg bw/day. This dose level was used as reasonable starting point for the DNEL derivation. In the absence of inhalation and dermal repeated-dose toxicity studies, the oral NOEL of 277 mg/kg bw/day was used to derive DNELs for inhalation and dermal toxicity by route-to-route extrapolation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.83 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
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
424.78 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
6
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.99 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
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
424.78 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.08 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Dose descriptor:
NOAEC
Value:
424.78 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
6
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
42.48 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEC
Value:
424.78 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.63 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):
600
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
6
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.77 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
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.07 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
240
Dose descriptor:
NOAEC
Value:
424.78 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
6
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24.43 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEC
Value:
424.78 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.63 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):
600 400
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
6
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.77 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
Dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
977 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
1
Justification:
Default ECHA assessment
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Two oral repeated-dose toxicity studies were performed with Patchouli oil in accordance with OECD TG 407 and OECD TG 421. In the 28-day oral feeding study with rats, some adaptive changes were observed in the liver, thyroid and kidneys of male and female rats at the highest dose of 977 mg/kg bw/day, which were however not interpreted as adverse health effects. The NOAEL in the study was 977 mg/kg bw/day. In the screening study on reproductive and developmental effects, male and female rats were exposed to Patchouli oil by gavage for up to 8 weeks. Treatment-related effects in adult animals were observed at the highest dose of 810 mg/kg bw/day. This dose level also resulted in a small number of treatment related effects on offspring and post partum with an equivocal effect on the nature of som in utero parameters. The NOEL for systemic toxicity and for reproduction and offspring development in this subacute screening study on reproductive and developmental toxicity was 277 mg/kg bw/day. This dose level was used as reasonable starting point for the DNEL derivation. In the absence of inhalation and dermal repeated-dose toxicity studies, the oral NOEL of 277 mg/kg bw/day was used to derive DNELs for inhalation and dermal toxicity by route-to-route extrapolation.