Registration Dossier
Registration Dossier
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EC number: 212-449-1 | CAS number: 818-08-6
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 49.33 µg/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:
- 3 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 3.7 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The NOAEL from the study according to OECD Guideline 422 has been modified accounting for the standard respiratory volume for rats (8 h) of 0.38 m3/kg bw, the standard respiratory volume for human under normal conditions (8 h) of 6.7 m3/person and under light activity of 10 m3/person (default weight of 70 kg) and absorption (assumption according to ECHA Guidance R.8: 50% absorbed oral, 100 % absorbed via inhalation; factor: 1/2). In addition, since the study is performed at 7 days/week, while the exposure of workers is 5 days/week, the NOAEL is also corrected by the factor of 1.4 (7/5). The resulting corrected NOAEC is the following:
3 mg/kg bw/day*(1/0.38)*(6.7/10)*(1/2)*1.4 = 3.7 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- Default as starting point is a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- Default for sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Default as allometric scaling is already included in corrected starting point
- AF for other interspecies differences:
- 2.5
- Justification:
- Default for remaining interspecies differences
- AF for intraspecies differences:
- 5
- Justification:
- Default for workers
- AF for the quality of the whole database:
- 1
- Justification:
- The database is of good quality
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 49.33 µg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
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:
- 28 µg/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:
- 3 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 8.4 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The NOAEL from the study according to OECD Guideline 422 has been modified accounting for the difference in exposure for workers and test animals and the absorption rates. Since the study is performed at 7 days/week, while the exposure of workers is 5 days/week, the NOAEL is corrected by the factor of 1.4 (7/5). The dermal absorption considered to be 50% (please refer to Section 7.1). The resulting corrected NOAEL is the following:
3 mg/kg bw/day * (100%/50%) * 1.4 = 8.4 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Default as starting point is a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- Default for sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default for rats
- AF for other interspecies differences:
- 2.5
- Justification:
- Default for remaining interspecies differences
- AF for intraspecies differences:
- 5
- Justification:
- Default for workers
- AF for the quality of the whole database:
- 1
- Justification:
- The database is of good quality
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
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:
- low hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.67 µg/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:
- 3 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 1.3 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The NOAEL from the study according to OECD Guideline 422 has been modified accounting for the standard respiratory volume for rats (24 h) of 1.15 m³/kg bw and the oral and inhalative absorption (assumption according to ECHA Guidance R.8: 50% absorbed oral, 100 % absorbed via inhalation; factor: 1/2). The resulting corrected NOAEC is the following:
3 mg/kg bw/day*(1/1.15)*(1/2) = 1.3 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- Default as starting point is a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- Default for sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Default as allometric scaling is already included in corrected starting point
- AF for other interspecies differences:
- 2.5
- Justification:
- Default for remaining interspecies differences
- AF for intraspecies differences:
- 10
- Justification:
- Default for general population
- AF for the quality of the whole database:
- 1
- Justification:
- The database is of good quality
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.67 µg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
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:
- 10 µg/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:
- 3 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 6 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The NOAEL from the study according to OECD Guideline 422 has been modified accounting for the absorption rates. The dermal absorption is considered to be 50 % (See section 7.1). The resulting corrected NOAEL is the following:
3 mg/kg bw/day (100%/50%) = 6 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Default as starting point is a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- Default for sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default for rats
- AF for other interspecies differences:
- 2.5
- Justification:
- Default for remaining interspecies differences
- AF for intraspecies differences:
- 10
- Justification:
- Default for general population
- AF for the quality of the whole database:
- 1
- Justification:
- The database is of good quality
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
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:
- low hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 5 µg/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:
- 3 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 3 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No correction of the NOAEL from the study according to OECD Guideline 422 was neccessary. The oral absorption of rats is considered to be equal to the oral absorption of humans.
- AF for dose response relationship:
- 1
- Justification:
- Default as starting point is a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- Default for sub-acute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default for rats
- AF for other interspecies differences:
- 2.5
- Justification:
- Default for remaining interspecies differences
- AF for intraspecies differences:
- 10
- Justification:
- Default for general population
- AF for the quality of the whole database:
- 1
- Justification:
- The database is of good quality
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 5 µg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium 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.
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