Registration Dossier
Registration Dossier
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: 923-400-5 | 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:
- 17.63 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):
- 50
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 881.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No inhalation study is available. According to ECHA Guidance – Chapter R8 (p25): “in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that the end route) in the case of oral-to inhalation extrapolation”. Therefore, as no data is available on oral or inhalation absorption, the oral absorption is estimated to 50% and the inhalation absorption to 100%. The correction factor is 0.5 (50/100).
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 4
- Justification:
- OECD 422 is 6 weeks exposure
- AF for interspecies differences (allometric scaling):
- 1
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
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:
- 5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- no extrapolation NOAEL DERMAL = NOAEL ORAL
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 4
- Justification:
- OECD 422 Exposure 6 weeks.
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
2 Inhalation DNEL for long term systemic effects/Workers :
The relevant study to be selected for derivation of the DNEL is the OECD 422 combined repeated dose toxicity study with the reproduction test (2012).
Step 1) Relevant dose-descriptor:NOAEL, rat = 1000 mg/kg bw/d
Step 2) Modification of starting point:
The starting point was modified to get the correct starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:
The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans, for differences between oral absorption in rats and inhalative absorption in humans (50% and 100%, respectively), and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (1000x 1/0.38 m³/kg/d x 50%/100% x 6.7 m³/10 m³).
The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 881.6 mg/m³.
For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:
Step 3) Assessment factors:
* Interspecies: 2.5
* Intraspecies : 5(factor for workers)
* Exposure duration : 4 (subchronic to chronic exposure)
* Dose response: 1 (LOAEL > NOAEL)
* Quality of database: 1
AF total = 2.5x5x4x1x1 = 50
Step 4) DNEL calculation:
DNEL value = 881.6 / 50 = 17.61 mg/m3
DNEL Long-term Inhalation value for long term systemic effects in workers is 17.61 mg/m3
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.81 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):
- 100
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 881.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No inhalation study is available. According to ECHA Guidance – Chapter R8 (p25): “in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that the end route) in the case of oral-to inhalation extrapolation”. Therefore, as no data is available on oral or inhalation absorption, the oral absorption is estimated to 50% and the inhalation absorption to 100%. The correction factor is 0.5 (50/100)
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 4
- AF for interspecies differences (allometric scaling):
- 1
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.5 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):
- 400
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- The dermal absorption is 100% by default as no information is available of dermal absorption.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 4
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- None
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 4
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
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.
