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: 217-288-0 | CAS number: 1800-91-5
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.11 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
- Dose descriptor starting point:
- NOAEL
- Value:
- 250 mg/kg bw/day
- Value:
- 308.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The dose descriptor used as a starting point is the NOAEL identified in the OECD422 study in rats performed by the oral route and using a route-to-route extrapolation (DNEL calculator).
Limited effects were observed in the OECD422 study in rats conducted by the oral route. The oral NOAEL was set at 250 mg/kg/day based on significant increase in liver weight and histopathology findings in the liver at the highest dose of 1000 mg/kg/day.
Corrected inhalatory NOAEC = Oral NOAEL x 1 / sRVrat x Abs (oral, rat) / Abs (inhal, human)
Default conversion and assessment factors were applied for the route-to-route extrapolation (oral to inhalation):
- in the absence of specific data, a 50% difference is considered for bioavailability between the oral and inhalation routes (default).
- correction for exposure conditions: 7 days/week for oral gavage in rats, 5 days/week for human work period.
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (DNEL calculator)
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Default (DNEL calculator)
- AF for other interspecies differences:
- 2.5
- Justification:
- Default (DNEL calculator)
- AF for intraspecies differences:
- 5
- Justification:
- Default (DNEL calculator)
- AF for the quality of the whole database:
- 1
- Justification:
- Default (DNEL calculator)
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:
- 11.7 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):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 250 mg/kg bw/day
- Value:
- 3 500 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The dermal long-term DNEL was derived using the repeated oral dose toxicity and route-to-route extrapolation according to REACH guidance R.8.
- correction for exposure conditions: 7 days/week for oral gavage in rats, 5 days/week for human work period.
- The oral to dermal route to route extrapolation considered a difference in potential absorption.
- AF for dose response relationship:
- 1
- Justification:
- Default (DNEL calculator)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (DNEL calculator)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default (DNEL calculator)
- AF for other interspecies differences:
- 2.5
- Justification:
- Default (DNEL calculator)
- AF for intraspecies differences:
- 5
- Justification:
- Default (DNEL calculator)
- AF for the quality of the whole database:
- 1
- Justification:
- Default (DNEL calculator)
- 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:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
The DNEL was derived conservatively from the mid-dose of the 28-day repeated dose toxicity study using the default assessment factors.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.72 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:
- 250 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The dose descriptor used as a starting point is the NOAEL identified in the OECD422 study in rats performed by the oral route and using a route-to-route extrapolation (DNEL calculator).
Limited effects were observed in the OECD422 study in rats conducted by the oral route. The oral NOAEL was set at 250 mg/kg/day based on significant increase in liver weight and histopathology findings in the liver at the highest dose of 1000 mg/kg/day.
Corrected inhalatory NOAEC = Oral NOAEL x 1 / sRVrat x Abs (oral, rat) / Abs (inhal, human)
Default conversion and assessment factors were applied for the route-to-route extrapolation (oral to inhalation):
- in the absence of specific data, a 50% difference is considered for bioavailability between the oral and inhalation routes (default).
- correction for exposure conditions: 1 (7 days/week for oral gavage in rats, 7 days/week for the general population).
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 6
- Justification:
- Default
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Default (inhalation)
- AF for other interspecies differences:
- 2.5
- Justification:
- Default
- AF for intraspecies differences:
- 10
- Justification:
- Default for general population
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- AF for remaining uncertainties:
- 1
- Justification:
- Default
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:
- 4.17 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:
- 250 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 2 500 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The dermal long-term DNEL was derived using the repeated oral dose toxicity and route-to-route extrapolation according to REACH guidance R.8.
- correction for exposure conditions: 7 days/week for oral gavage in rats, 7 days/week for potential exposure of the general population.
The oral to dermal route to route extrapolation considered a difference in potential absorption.
- AF for dose response relationship:
- 1
- Justification:
- Default
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (subacute study)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default
- AF for other interspecies differences:
- 2.5
- Justification:
- Default
- AF for intraspecies differences:
- 10
- Justification:
- Default (general population)
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- AF for remaining uncertainties:
- 1
- Justification:
- Default
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:
- 0.42 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:
- 250 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 250 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The oral long-term DNEL was derived using the repeated oral dose toxicity and assessment factors according to REACH guidance R.8.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- Justification:
- Default
- AF for intraspecies differences:
- 10
- Justification:
- Default
- AF for the quality of the whole database:
- 1
- Justification:
- Default
- AF for remaining uncertainties:
- 1
- Justification:
- Default
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
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.
