Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 946-958-1 | CAS number: -
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 50.07 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:
- 710 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 625.92 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for differences in duration of exposure:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 5
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 50.07 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:
- 710 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 625.92 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 5
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 125.18 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 5
- Dose descriptor:
- NOAEC
- Value:
- 625.92 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for differences in duration of exposure:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 1
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 5
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 125.18 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 125.18
- Dose descriptor starting point:
- NOAEC
- Value:
- 625.92 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 1
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 5
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 14.2 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):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 710 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for differences in duration of exposure:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 5
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 14.2 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):
- 14.2
- Dose descriptor starting point:
- NOAEL
- Value:
- 710 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 5
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 35.5 mg/cm²
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 20
- Dose descriptor:
- NOAEC
- Value:
- 625.92 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for differences in duration of exposure:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 1
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 5
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 35.5 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:
- 625.92 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 1
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 5
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Based on the results of this combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test an parental, reproduction and developmental no-observed-adverse-effect level (NOAEL) of at least 10000 ppm for Aurantiol Pure was established, corresponding to an overall mean test item intake of 710 mg/kg bw/day for males.
No reproduction toxicity was observed up to the highest dose level tested (10000 ppm).
No treatment-related toxicologically significant changes were noted in any of the reproductive parameters investigated in this study (i.e. mating and fertility indices, precoital time, number of implantations, estrous cycle, spermatogenic profiling, and histopathological examination of reproductive organs).
No developmental toxicity was observed up to the highest dose level tested (10000 ppm).
No treatment-related changes were noted in any of the developmental parameters investigated in this study (i.e. gestation, viability and lactation indices, duration of gestation, parturition, sex ratio, maternal care and early postnatal pup development consisting of mortality, clinical signs, body weight, anogenital distance, areola/nipple retention, T4 thyroid hormone levels and macroscopic examination).
For the exposure scenarios assessment and DNELs, the male NOAEL has been chosen as the worse case parameter.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 12.35 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:
- 710 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 308.7 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for differences in duration of exposure:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 12.35 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:
- 710 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 308.7 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 30.87 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:
- 308.7 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for differences in duration of exposure:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 1
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 30.87 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:
- 308.7 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 1
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7.1 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:
- 710 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for differences in duration of exposure:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7.1 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:
- 710 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 17.75 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:
- 308.7 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for differences in duration of exposure:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 1
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 17.75 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:
- 308.7 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 1
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7.1 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:
- 710 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for differences in duration of exposure:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7.1 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:
- 710 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- ECHA default guidance
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA default guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA default guidance
- AF for intraspecies differences:
- 10
- Justification:
- ECHA default guidance
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA default guidance
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA default guidance
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Based on the results of this combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test an parental, reproduction and developmental no-observed-adverse-effect level (NOAEL) of at least 10000 ppm for Aurantiol Pure was established, corresponding to an overall mean test item intake of 710 mg/kg bw/day for males.
No reproduction toxicity was observed up to the highest dose level tested (10000 ppm).
No treatment-related toxicologically significant changes were noted in any of the reproductive parameters investigated in this study (i.e. mating and fertility indices, precoital time, number of implantations, estrous cycle, spermatogenic profiling, and histopathological examination of reproductive organs).
No developmental toxicity was observed up to the highest dose level tested (10000 ppm).
No treatment-related changes were noted in any of the developmental parameters investigated in this study (i.e. gestation, viability and lactation indices, duration of gestation, parturition, sex ratio, maternal care and early postnatal pup development consisting of mortality, clinical signs, body weight, anogenital distance, areola/nipple retention, T4 thyroid hormone levels and macroscopic examination).
For the exposure scenarios assessment and DNELs, the male NOAEL has been chosen as the worse case parameter.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
