Registration Dossier
Registration Dossier
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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.
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EC number: 701-269-3 | CAS number: -
Toxicological information
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 35.24 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:
- 1 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 881.05 mg/m³
- Explanation for the modification of the dose descriptor starting point:
In the absence of a repeated dose toxicity study conducted via the inhalation route of exposure the use of a PoD using the oral route of exposure has been employed. The NOAEL is taken from repeat dose oral toxicity studies in rats. It is assumed that oral absorption of the substance is half that of inhalation absorption.
Inhalatory N(L)OAEC = oral N(L)OAEL*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.)
= 1000 * 2.63 * 0.67 * 0.5
= 881.05 mg/m3
DNEL = PoD/AF
= 881.05/25
= 35.24 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- As the dose descriptor is the NOAEL, the default assessment factor is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- To account for using PoD taken from a subchronic study to calculate a chronic DNEL.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is usually not applied in the derivation of the inhalation DNEL.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default factor.
- AF for intraspecies differences:
- 5
- Justification:
- To account for intraspecies differences in an occupational setting.
- AF for the quality of the whole database:
- 1
- Justification:
- The database is of good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
- AF for remaining uncertainties:
- 1
- Justification:
- There are no remaining uncertainties identified therefore the default factor of 1 applies.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 35.24 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
- DNEL extrapolated from long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.35 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 15
- Dose descriptor:
- LOAEC
- AF for dose response relationship:
- 3
- Justification:
- This factor is applied because the dose-descriptor starting point is a LOAEC. At this dose level, the adverse effects were of minimal severity.
- AF for differences in duration of exposure:
- 1
- Justification:
- Local effects on the respiratory tract are related to the deposited dose per unit of surface area. Below a certain concentration the clearance capacity of the lungs is not overwhelmed and the lungs retain the ability to clear the deposited substance. Therefore, the lung effects are not suspected to worsen with increasing exposure duration.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation.
- AF for other interspecies differences:
- 1
- Justification:
- No additional assessment factor is added for interspecies extrapolation from rodent to human, since the respiratory rate of rats (0.29 m3/kg-day according to Pauluhn (2010)) leads to a greater lung tract burden as compared to humans (0.14 m3/kg-day), thus the effects observed in rats are exaggerated and provide a “built in” safety margin.
- AF for intraspecies differences:
- 5
- Justification:
- A factor of 5 is applied for worker DNELs.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study is considered as a reliable study with a klimisch score of 1.
- AF for remaining uncertainties:
- 1
- Justification:
- No other assessment factor is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.35 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 15
- DNEL extrapolated from long term DNEL
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
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:
- 8.69 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
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 434.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
In the absence of a repeated dose toxicity study conducted via the inhalation route of exposure the use of a PoD using the oral route of exposure has been employed. The NOAEL is taken from repeat dose oral toxicity studies in rats.It is assumed that oral absorption of the substance is half that of inhalation absorption.
Inhalatory N(L)OAEC = oral N(L)OAEL*(1/1.15 m3/kg bw/d)*(ABSoral/ABSinh.)
= 1000 * 0.869 * 0.5
= 434.5 mg/m3
DNEL = PoD/AF
= 434.5/50
= 8.69 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- As the dose descriptor is the NOAEL, the default assessment factor is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- To account for using PoD taken from a subchronic study to calculate a chronic DNEL.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is usually not applied in the derivation of the inhalation DNEL.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default factor.
- AF for intraspecies differences:
- 10
- Justification:
- To account for intraspecies differences.
- AF for the quality of the whole database:
- 1
- Justification:
- The database has good quality studies, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
- AF for remaining uncertainties:
- 1
- Justification:
- There are no remaining uncertainties identified therefore the default factor of 1 applies.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.69 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
- DNEL extrapolated from long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.83 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 30
- Dose descriptor:
- LOAEC
- AF for dose response relationship:
- 3
- Justification:
- This factor is applied because the dose-descriptor starting point is a LOAEC. At this dose level, the adverse effects were of minimal severity.
- AF for differences in duration of exposure:
- 1
- Justification:
- Local effects on the respiratory tract are related to the deposited dose per unit of surface area. Below a certain concentration the clearance capacity of the lungs is not overwhelmed and the lungs retain the ability to clear the deposited substance. Therefore, the lung effects are not suspected to worsen with increasing exposure duration.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for inhalation.
- AF for other interspecies differences:
- 1
- Justification:
- No additional assessment factor is added for interspecies extrapolation from rodent to human, since the respiratory rate of rats (0.29 m3/kg-day according to Pauluhn (2010)) leads to a greater lung tract burden as compared to humans (0.14 m3/kg-day); thus the effects observed in rats are exaggerated and provide a “built in” safety margin.
- AF for intraspecies differences:
- 10
- Justification:
- A factor of 10 is applied for the general population DNELs.
- AF for the quality of the whole database:
- 1
- Justification:
- The key study is considered as a reliable study with a klimisch score of 1.
- AF for remaining uncertainties:
- 1
- Justification:
- No other assessment factor is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.83 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 30
- DNEL extrapolated from long term DNEL
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
General Population - Hazard via oral 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
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
DNEL = PoD/AF
= 1000/200
= 5 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- As the dose descriptor is the NOAEL, the default assessment factor is 1.
- AF for differences in duration of exposure:
- 2
- Justification:
- To account for using PoD taken from a subchronic study to calculate a chronic DNEL.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Allometric scaling to account for differences in allometry in using the rat as a test model.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default factor.
- AF for intraspecies differences:
- 10
- Justification:
- To account for intraspecies differences.
- AF for the quality of the whole database:
- 1
- Justification:
- The database has good quality studies, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
- AF for remaining uncertainties:
- 1
- Justification:
- There are no remaining uncertainties identified therefore the default factor of 1 applies.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 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):
- 200
- DNEL extrapolated from long term DNEL
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
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.
