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: 232-092-5 | CAS number: 7786-17-6
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.8 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:
- 139 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- NOAEL(oral) converted to NOAEC(inhal) (158 mg/kg x [1/0.38 x 50% oral absorption rat/100% inhalation absorption human x 6.7/10]) = 139 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- Justification:
- Differences in species addressed in calculation of dose descriptor starting point
- Justification:
- Differences in species addressed in calculation of dose descriptor starting point
- AF for intraspecies differences:
- 5
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for the quality of the whole database:
- 2
- Justification:
- Limited information on chronic, reproductive and developmental toxicity. (OECD 421 study on highly similar read across substance only)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
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:
- 4 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
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 790 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- NOAEL (oral) converted to NOAEL (dermal): 158 mg/kg bw/day*50% ABS (oral)/10%ABS(dermal) = 790 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- Justification:
- Differences in species addressed in calculation of dose descriptor starting point.
- AF for intraspecies differences:
- 5
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
- AF for the quality of the whole database:
- 2
- Justification:
- Limited information on chronic, reproductive and developmental toxicity. (OECD 421 study on highly similar read across substance only)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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
2,2'-methylenebis(6-nonyl-p-cresol) is not classified for skin/eye irritation or skin sensitisation and is not expected to show any local effects; DNELs for acute exposure and local effects were therefore not calculated. The substance does not possess any genotoxic potential.
The most sensitive endpoint was the NOAEL (158 mg/kg bw/day) obtained in an acceptable 90-day feeding study in rats. The study was performed in line with good scientific principles and reported to a high standard. In accordance with Klimisch (1997) the study was assigned a reliability score of 1. This NOAEL was used as the starting point for the calculation of systemic DNELs. The reproductive and developmental toxicity was investigated in a study performed in accordance with standardised guidelines OECD 421 and EPA OPPTS 870.3550 using an appropriate test material suitable for read-across to support 2,2'-methylene-bis(6-nonyl-p-cresol); this study showed no effect at the highest dose tested. Also by read-across, no evidence of carcinogenicity was seen in acceptable studies; however the highest doses tested for carcinogenicity by read-across were of the same magnitude as the key 90-day NOAEL of the test material. An additional factor of 2 for completeness of the database is therefore applied.
For the purposes of human risk assessment there is sufficient information to consider that 2,2'-methylene-bis(6-nonyl-p-cresol) would be partially absorbed (50%) by the oral route, and slowly metabolised and excreted. The consequences of slow metabolism and excretion are however adequately addressed within the NOAEL of a 90-day study. Human dermal absorption may be considered to be 10%; inhalation absorption is assumed to be complete.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.7 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:
- 69 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- NOAEL(oral) converted to NOAEC(inhal) (158 mg/kg x [1/1.15 x 50% oral absorption rat/100% inhalation absorption human) = 69 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- Justification:
- Differences in species addressed in calculation of dose descriptor starting point
- Justification:
- Differences in species addressed in calculation of dose descriptor starting point
- AF for intraspecies differences:
- 10
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for the quality of the whole database:
- 2
- Justification:
- Limited information on chronic, reproductive and developmental toxicity. (OECD 421 study on highly similar read across substance only)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
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:
- 2 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:
- 790 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- NOAEL (oral) converted to NOAEL (dermal): 158 mg/kg bw/day*50% ABS (oral)/10%ABS(dermal) = 790 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- Justification:
- Differences in species addressed in calculation of dose descriptor starting point
- AF for intraspecies differences:
- 10
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for the quality of the whole database:
- 2
- Justification:
- Limited information on chronic, reproductive and developmental toxicity. (OECD 421 study on highly similar read across substance only)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
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:
- 0.4 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:
- 158 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Assumed that the oral absorption in rat and humans is the same
- AF for dose response relationship:
- 1
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for differences in duration of exposure:
- 2
- Justification:
- Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- Justification:
- Differences in species addressed in calculation of dose descriptor starting point
- AF for intraspecies differences:
- 10
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
- AF for the quality of the whole database:
- 2
- Justification:
- Limited information on chronic, reproductive and developmental toxicity. (OECD 421 study on highly similar read across substance only)
- AF for remaining uncertainties:
- 2.5
- Justification:
- Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
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
2,2'-methylenebis(6-nonyl-p-cresol) is not classified for skin/eye irritation or skin sensitisation and is not expected to show any local effects; DNELs for acute exposure and local effects were therefore not calculated. The substance does not possess any genotoxic potential.
The most sensitive endpoint was the NOAEL (158 mg/kg bw/day) obtained in an acceptable 90-day feeding study in rats. The study was performed in line with good scientific principles and reported to a high standard. In accordance with Klimisch (1997) the study was assigned a reliability score of 1. This NOAEL was used as the starting point for the calculation of systemic DNELs. The reproductive and developmental toxicity was investigated in a study performed in accordance with standardised guidelines OECD 421 and EPA OPPTS 870.3550 using an appropriate test material suitable for read-across to support 2,2'-methylene-bis(6-nonyl-p-cresol); this study showed no effect at the highest dose tested. Also by read-across, no evidence of carcinogenicity was seen in acceptable studies; however the highest doses tested for carcinogenicity by read-across were of the same magnitude as the key 90-day NOAEL of the test material. An additional factor of 2 for completeness of the database is therefore applied.
For the purposes of human risk assessment there is sufficient information to consider that 2,2'-methylene-bis(6-nonyl-p-cresol) would be partially absorbed (50%) by the oral route, and slowly metabolised and excreted. The consequences of slow metabolism and excretion are however adequately addressed within the NOAEL of a 90-day study. Human dermal absorption may be considered to be 10%; inhalation absorption is assumed to be complete.
The same endpoint used for workers was selected for setting the long-term DNELs for the general population. The larger assessment factor for intraspecies sensitivity was considered adequately protective for the more sensitive 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.
