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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 221-374-3 | CAS number: 3081-01-4
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.6 mg/m³
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 37.5
- Dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 61.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
See full derivation in "additional information" - Workers
- AF for dose response relationship:
- 1
- Justification:
- default
- AF for differences in duration of exposure:
- 1
- Justification:
- As the metric used for the LOAEL was parturition, which is defined by a set period of time (parturition), there is no adjustment for duration, as the duration is always fixed.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- default (not additional allometric scaling should be applied as a correction has already been integrated in the corrected starting point)
- AF for other interspecies differences:
- 2.5
- Justification:
- default (no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans)
- AF for intraspecies differences:
- 5
- Justification:
- default (for workers)
- AF for the quality of the whole database:
- 1
- Justification:
- default (GLP guideline study of high quality)
- AF for remaining uncertainties:
- 3
- Justification:
- AF for lack of a NOAEL and having a LOAEL instead
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:
- 0.47 mg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 150
- Dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 70 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
See full derivation in "additional information" - Workers
- AF for dose response relationship:
- 1
- Justification:
- default value
- AF for differences in duration of exposure:
- 1
- Justification:
- As the metric used for the LOAEL was parturition, which is defined by a set period of time (parturitioin), there is no adjustment for duration, as the duration is always fixed.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default (for rats)
- AF for other interspecies differences:
- 2.5
- Justification:
- default (no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans)
- AF for intraspecies differences:
- 5
- Justification:
- default (for workers)
- AF for the quality of the whole database:
- 1
- Justification:
- default (GLP guideline study of high quality)
- AF for remaining uncertainties:
- 3
- Justification:
- AF for not having a NOAEL and using a LOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.35 mg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
- Dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The short term derivation used was 5x the long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Long Term DNEL Derivation for 7PPD
The starting LOAEL was 50 mg/kg/day from an OECD 421 reproductive/developmental screen. In that study, females and males were treated with 7PPD daily for 2 weeks of pre-breeding, 2 weeks of breeding followed by 21 days of gestation until parturition. The NOAEL was based on dystocia (difficult delivery) As the primary effect observed was part of gestation (parturition) no correction factors for duration of study are applied, as gestation is a fixed time period, and thus there is no adjustment for duration.
Modification of the dose descriptor:
Worker
Worker long term dermal:
LOAEL of 50 mg/kg/day. There is no bioavailability difference between animal to human oral exposures. A factor of 1.4 is applied for exposure conditions for an adjusted LOAEL = 70 mg/kg/day
Adjustment factors: 4 for allometric scaling, 2.5 for remaining interspecies, 5 for intraspecies and 3 for lack of a NOAEL.
Total Adjustment factors = 150.
As the primary effect observed was part of gestation (parturition) correction factors for duration of study are not applied, as gestation is a fixed time period, and thus there is no adjustment for duration.
Worker long term dermal DNEL= 70 mg/kg/day/150 = 0.47 mg/kg/day
Worker long term inhalation:
LOAEL of 50 mg/kg/day. ECHA default bioavailability of animal oral of 50 % to human inhalation of 100 %, = 25 mg/kg/day.
Further correction was done by dividing this value by 0.38 m3bw/8hr = 65.7, subsequent multiplication by 0.67 (respiratory volumes) and multiplication by 1.4 (exposure conditions) for an adjusted LOAEL = 61.6 mg/m3
Adjustment factors: 2.5 for remaining interspecies, 5 for intraspecies and 3 for lack of a NOAEL.
Total Adjustment factors = 37.5.
As the primary effect observed was part of gestation (parturition) correction factors for duration of study are not applied, as gestation is a fixed time period, and thus there is no adjustment for duration.
Worker long term inhalation DNEL= 61.6 mg/m3/37.5 = 1.6 mg/m3
Short Term DNEL Derivation for 7PPD
Short-Term DNEL values are derived based ECHA guidance suggesting that a five-fold difference in the short and long term DNEL is protective in the absence of other data suggesting a more restrictive need.
|
General population |
Worker |
|
Long term inhalation |
0.25 mg/m3 |
1.6mg/m3 |
|
Long term oral/dermal |
0.17 mg/kg |
0.47 mg/kg |
|
Short term oral/dermal |
0.85 mg/kg |
2.35 mg/kg |
|
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.25 mg/m³
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- LOAEC
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 18.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
See full derivation in "additional information" - General Population
- AF for dose response relationship:
- 1
- Justification:
- default
- AF for differences in duration of exposure:
- 1
- Justification:
- As the metric used for the LOAEL was parturition, which is defined by a set period of time (parturition), there is no adjustment for duration, as the duration is always fixed.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- default (not additional allometric scaling should be applied as a correction has already been integrated in the corrected starting point)
- AF for other interspecies differences:
- 2.5
- Justification:
- default (no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans)
- AF for intraspecies differences:
- 10
- Justification:
- default (for the general population)
- AF for the quality of the whole database:
- 1
- Justification:
- default (GLP guideline study of high quality)
- AF for remaining uncertainties:
- 3
- Justification:
- AF for use of a LOAEL rather than a NOAEL
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:
- 0.17 mg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 50 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
See full derivation in "additional information" - General Population
- AF for dose response relationship:
- 1
- Justification:
- default value
- AF for differences in duration of exposure:
- 1
- Justification:
- As the metric used for the LOAEL was parturition, which is defined by a set period of time (parturition), there is no adjustment for duration, as the duration is always fixed.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default (for rats)
- AF for other interspecies differences:
- 2.5
- Justification:
- default (no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans)
- AF for intraspecies differences:
- 10
- Justification:
- default (for the general population)
- AF for the quality of the whole database:
- 1
- Justification:
- default (GLP guideline study of high quality)
- AF for remaining uncertainties:
- 3
- Justification:
- AF for use of a LOAEL and not a NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.85 mg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
- Dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The short term derivation used was 5x the long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.17 mg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 50 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
See full derivation in "additional information" - General Population
- AF for dose response relationship:
- 1
- Justification:
- default value
- AF for differences in duration of exposure:
- 1
- Justification:
- As the metric used for the LOAEL was parturition, which is defined by a set period of time (parturition), there is no adjustment for duration, as the duration is always fixed.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default (for rats)
- AF for other interspecies differences:
- 2.5
- Justification:
- default (no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans)
- AF for intraspecies differences:
- 10
- Justification:
- default (for the general population)
- AF for the quality of the whole database:
- 1
- Justification:
- default (GLP guideline study of high quality)
- AF for remaining uncertainties:
- 3
- Justification:
- AF for use of LOAEL and not NOAEL
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
Long Term DNEL Derivation for 7PPD
The starting LOAEL was 50 mg/kg/day from an OECD 421 reproductive/developmental screen. In that study, females and males were treated with 7PPD daily for 2 weeks of pre-breeding, 2 weeks of breeding followed by 21 days of gestation until parturition. The NOAEL was based on dystocia (difficult delivery) As the primary effect observed was part of gestation (parturition) no correction factors for duration of study are applied, as gestation is a fixed time period, and thus there is no adjustment for duration.
Modification of the dose descriptor:
General Population
General population long-term inhalation:
LOAEL of 50 mg/kg/day * ECHA default bioavailability of animal oral of 50 % to human inhalation of 100 % = 25 mg/kg/day.
Divided by the standard respiratory volume of 1.35 m3 kg bw/24 hr = Adjusted LOAEC of 18.5 mg/m3
Adjustment factors: 2.5 for remaining interspecies, 10 for intraspecies and 3 for LOAEC in place of NOAEC.
Total Adjustment factors = 75.
As the primary effect observed was part of gestation (parturition) correction factors for duration of study are not applied, as gestation is a fixed time period, and thus there is no adjustment for duration.
General population long term inhalation DNEL= 18,5 mg/m3/75 = 0.25 mg/m3
General population long term oral/dermal:
LOAEL of 50 mg/kg/day. There is no bioavailability difference between animal to human oral exposures, so the adjusted LOAEL = 50 mg/kg/day
Adjustment factors: 4 for allometric scaling, 2.5 for remaining interspecies, 10 for intraspecies and 3 for lack of a NOAEL.
Total Adjustment factors = 300.
As the primary effect observed was part of gestation(parturition) correction factors for duration of study are not applied, as gestation is a fixed time period, and thus there is no adjustment for duration.
General population long term inhalation DNEL = 50 mg/kg/day /300 = 0.17 mg/kg/day
Short Term DNEL Derivation for 7PPD
Short-Term DNEL values are derived based ECHA guidance suggesting that a five-fold difference in the short and long term DNEL is protective in the absence of other data suggesting a more restrictive need.
|
General population |
Worker |
|
Long term inhalation |
0.25 mg/m3 |
1.6mg/m3 |
|
Long term oral/dermal |
0.17 mg/kg |
0.47 mg/kg |
|
Short term oral/dermal |
0.85 mg/kg |
2.35 mg/kg |
|
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.
