Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.

Diss Factsheets

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.