Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
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: 947-147-5 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.29 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:
- NOAEC
- Value:
- 1.29 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 1.29 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 110 mg/kg bw/day from the oral rat repeated dose and reproductive/developmental screening study (OECD TG 422) conducted using the substance, the Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate. A long-term systemic inhalation DNEL is derived from the oral NOAEL of 110 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 50% that of the inhalation rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for workers is derived as: oral NOAEL x (1/0.38 m3/kg/day) x (6.7 m3/10m3 (8 h)) x (% oral absorption/ % inhalation absorption) = 110 mg/kg bw/day x (1/0.38) x 0.67 x (50/100) = 96.97 mg/m3.
- AF for dose response relationship:
- 1
- Justification:
- Default value; the starting value is derived from a NOAEL.
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value to cover extrapolation from a sub-acute study to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- An assessment factor for allometric scaling is not required: allometric differences are already accounted for in the derivation of the corrected (inhalation) starting point.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value
- AF for intraspecies differences:
- 5
- Justification:
- Default value for workers
- AF for the quality of the whole database:
- 1
- Justification:
- Default value: a good quality database is available for the substance
- AF for remaining uncertainties:
- 1
- Justification:
- Default value: there are no significant remaining uncertainties
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:
- 0.37 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:
- 0.37 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 0.37 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 110 mg/kg bw/day from the oral rat repeated dose and reproductive/developmental screening study (OECD TG 422) conducted using the substance, the Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate. A long-term systemic dermal DNEL is derived from the oral NOAEL of 110 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 110 mg/kg bw/day x (50/50) = 110 mg/kg bw/day.
- AF for dose response relationship:
- 1
- Justification:
- Default value: the starting point is derived from a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value to take account extrapolation from a sub-acute study to chronic exposure
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value: the starting point is derived from a rat study
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value
- AF for intraspecies differences:
- 5
- Justification:
- Default value for workers.
- AF for the quality of the whole database:
- 1
- Justification:
- Default value: a good quality database is available.
- AF for remaining uncertainties:
- 1
- Justification:
- Default value: there are no significant remaining undertainties.
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:
- low hazard (no threshold derived)
Additional information - workers
The Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate is of low acute oral toxicity; the acute oral LD50 was found to be >2000 mg/kg in an fixed dose procedure study (OECD TG 420). By inference, the acute dermal and inhalation toxicity of the substance is expected to be low.
The substance was not determined to be irritating or corrosive to the skin in vitro using the EPISKIN Reconstructed Human EpiDermis Model (OECD TG 439) or the EPIDERM Skin Corrosion Test (OECD TG 431).
Regarding the eye irritation potential of the substance, inconclusive results were obtained in vitro using the Bovine Corneal Opacity and Permeability (BCOP) assay (OECD TG 437). In a precautionary approach, the substance has been classified in Category 2 for eye irritation according to Regulation (EC) 1272/2008, pending further investigations.
The skin sensitization potential of the substance has been assessed using a battery of in vitro assays which respectively assessed three key events associated with the skin sensitization adverse outcomes pathway. Taking into account respective negative results in a Direct Peptide Reactivity Assay (DPRA; OECD TG 442c) and a Human Cell Line Activation Test (h-CLAT; OECD 442E) and a positive result in a ARE-Nrf2 Luciferase assay (OECD TG 442D), in a weight of evidence evaluation of the predictive properties of the respective tests, the substance is not regarded as having skin sensitization potential overall.
The substance has not been found be genotoxic in bacterial or mammalian cell systems in vitro based on findings reported in a reverse bacterial mutation assay (OECD TG 471), a chromosome aberration test (OECD TG 473) or a mammalian gene mutation assay (OECD TG 490). Based on these findings, in vivo genotoxicity tests are not required.
The sub-acute repeated oral dose toxicity of the substance has been investigated a screening repeated dose, reproductive and developmental toxicity study (OECD TG 422), in which rats were treated as doses of 0, 35, 110 and 300 mg/kg bw/day for at least 5 consecutive weeks. The critical effects observed were general systemic toxicity characterized by adverse histopathological findings in the kidneys and forestomach at the highest dose: 300 mg/kg bw/day. Based on these findings, the NOAEL for general systemic toxicity following sub-acute oral exposures was determined to 110 mg/kg bw/day. No reproductive or developmental toxicity was observed in the study and the NOAEL for these effects was determined to be 300 mg/kg bw/day (i.e. the highest dose tested). No treatment-related effects on parameters relevant to endocrine disruption were observed.
Worker DNEL derivation
Inhalation DNELs
Systemic inhalation DNELs
The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 110 mg/kg bw/day from the oral rat repeated dose and reproductive developmental screening study (OECD TG 422) conducted using the substance, the Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate. A long-term systemic inhalation DNEL is derived from the oral NOAEL of 110 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 50% that of the inhalation rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for workers is derived as: oral NOAEL x (1/0.38 m3/kg/day) x (6.7 m3/10m3 (8 h)) x (% oral absorption/ % inhalation absorption) = 110 mg/kg bw/day x (1/0.38) x 0.67 x (50/100) = 96.97 mg/m3.
The following assessment factors have been used in accordance with REACH guidance: Intraspecies: a default value of 2.5 (remaining differences) is proposed (the application of a factor for allometric scaling is not required for the inhalation route); Interspecies: a default value of 5 is proposed for workers; Exposure duration: a default value of 6 is proposed for extrapolation from a sub-acute study to chronic exposure (this represents a conservative approach, as the data indicate low toxicity following single and repeated exposures); Dose-response: a default value of 1 is proposed as, based on the available data, the substance is of low toxicity; Quality of the data base: a default value of 1 is proposed An overall assessment factor of 75 for long-term inhalational effects is therefore calculated for workers.
Applying the assessment factor of 75 to the corrected inhalation NOAEC of 96.97 mg/m3 gives an inhalation DNEL value of 1.29 mg/m3 for long-term systemic effects.
A DNEL for acute systemic inhalation has not been derived – the substance has low acute toxicity.
Local inhalation DNELs
DNEL values for local inhalation effects are not derived. No data are available regarding local respiratory effects. The Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate is not a skin irritant or sensitiser but is an eye irritant. However relevant dose-response data are not available and a quantitative dose descriptor cannot be determined. Absence of route specific information is justified based on conditions of use and qualitative risk characterisation (See section 9 and 10). Exposure should be avoided by the use of appropriate protective equipment.
Dermal DNELs
Systemic dermal DNELs
The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 110 mg/kg bw/day from the oral rat repeated dose and reproductive developmental screening study (OECD TG 422) conducted using the substance, the Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate. A long-term systemic dermal DNEL is derived from the oral NOAEL of 110 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 110 mg/kg bw/day x (50/50) = 110 mg/kg bw/day.
The following assessment factors have been used in accordance with REACH guidance: Intraspecies: default values of 4 (allometric scaling: rat) and 2.5 (remaining differences) are proposed. Interspecies: a default value of 5 is proposed for workers; Exposure duration: a default value of 6 is proposed for extrapolation from a sub-acute study to chronic exposure (this represents a conservative approach, as the data indicate low toxicity following single and repeated exposures); Dose-response: a default value of 1 is proposed as, based on the available data, the substance is of low toxicity; Quality of the data base: a default value of 1 is proposed
Applying the assessment factor of 300 to the dermal equivalent NOAEL of 110 mg/kg bw/day gives a dermal DNEL of 0.37mg/kg bw/day for long-term systemic dermal effects.
A DNEL for acute systemic inhalation has not been derived – the substance has low acute toxicity.
Local dermal DNELs
The Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate is not a skin irritant or sensitiser; therefore local effects are not predicted. Local dermal DNEsL are not proposed in the absence of any identified hazard.
Hazard for the eyes
In a study to assess the eye irritation potential of the substance, the findings were inconclusive. Since the substance is not irritating or corrosive to the skin, a precautionary approach has been taken to classify the substance in Category 2 for eye irritation (H319: “Causes serious eye irritation”) according to Regulation (EC) 1272/2008. Studies to further investigate the eye irritation potential of the substance are on-going. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk characterization (Version 3.0, May 2016; ECHA Guidance IR&CSA, Part E) Table E3-1, “low hazard” is assigned to the substance in respect of irritation effects to the eyes and a qualitative risk characterisation is required in respect of this endpoint.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.32 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:
- NOAEC
- Value:
- 0.32 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 0.32 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 110 mg/kg bw/day from the oral rat repeated dose and reproductive/developmental screening study (OECD TG 422) conducted using the substance, the Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate. A long-term systemic inhalation DNEL is derived from the oral NOAEL of 110 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 50% that of the inhalation rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for the general population is derived as: oral NOAEL x (1/1.15) x (% oral absorption/ % inhalation absorption) = 110 mg/kg bw/day x (1/1.15) x (50/100) = 47.83 mg/m3.
- AF for dose response relationship:
- 1
- Justification:
- Default value; the starting point is derived from a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value to cover extrapolation from a sub-acute to a chronic study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- An assessment factor for allometric scaling is not required: allometric differences are already accounted for in the derivation of the corrected (inhalation) starting point.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value
- AF for intraspecies differences:
- 10
- Justification:
- Default value for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- Default value: a good quality database is available for the substance.
- AF for remaining uncertainties:
- 1
- Justification:
- Default value: there are no significant remaining differences.
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:
- 0.18 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:
- 0.18 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 0.18 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 110 mg/kg bw/day from the oral rat repeated dose and reproductive/developmental screening study (OECD TG 422) conducted using the substance, the Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate. A long-term systemic dermal DNEL is derived from the oral NOAEL of 110 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 110 mg/kg bw/day x (50/50) = 110 mg/kg bw/day.
- AF for dose response relationship:
- 1
- Justification:
- Default value: the starting point is derived from a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value to take into account extrapolation from a sub-acute study to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value: the starting point is derived from a rat study.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value
- AF for intraspecies differences:
- 10
- Justification:
- Default value for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- Default value: a good quality database is available.
- AF for remaining uncertainties:
- 1
- Justification:
- Default value: there are no significant remaining uncertainties.
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:
- 0.18 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:
- 0.18 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 0.18 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 110 mg/kg bw/day from the oral rat repeated dose and reproductive/developmental screening study (OECD TG 422) conducted using the substance, the Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate.
- AF for dose response relationship:
- 1
- Justification:
- Default value: the starting point is derived from a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value to take into account extrapolation from a sub-acute study to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value: the starting point is derived from a rat study.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value
- AF for intraspecies differences:
- 10
- Justification:
- Default value for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- Default value: a good quality database is available.
- AF for remaining uncertainties:
- 1
- Justification:
- Default value: there are no significant remaining uncertainties
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
General population DNEL derivation
Inhalation DNELs
Systemic inhalation DNELs
The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 110 mg/kg bw/day from the oral rat repeated dose and reproductive developmental screening study (OECD TG 422) conducted using the substance, the Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate. A long-term systemic inhalation DNEL is derived from the oral NOAEL of 110 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 50% that of the inhalation rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for the general population is derived as: oral NOAEL x (1/1.15 x (% oral absorption/ % inhalation absorption) = 110 mg/kg bw/day x (1/1.15 x (50/100) = 47.83 mg/m3.
The following assessment factors have been used in accordance with REACH guidance: Intraspecies: a default value of 2.5 (remaining differences) is proposed (the application of a factor for allometric scaling is not required for the inhalation route); Interspecies: a default value of 10 is proposed for the general population; Exposure duration: a default value of 6 is proposed for extrapolation from a sub-acute study to chronic exposure (this represents a conservative approach, as the data indicate low toxicity following single and repeated exposures); Dose-response: a default value of 1 is proposed as, based on the available data, the substance is of low toxicity; Quality of the data base: a default value of 1 is proposed An overall assessment factor of 150 for long-term inhalational effects is therefore calculated for the general population.
Applying the assessment factor of 150 to the corrected inhalation NOAEC of 47.83 mg/m3 gives an inhalation DNEL value of 0.32 mg/m3 for long-term systemic effects.
A DNEL for acute systemic inhalation has not been derived – the substance has low acute toxicity.
Local inhalation DNELs
DNEL values for local inhalation effects are not derived. No data are available regarding local respiratory effects. The Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate is not a skin irritant or sensitiser but is an eye irritant. However relevant dose-response data are not available and a quantitative dose descriptor cannot be determined. Inhalation exposures are not relevant to the general population.
Dermal DNELs
Systemic dermal DNELs
The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 110 mg/kg bw/day from the oral rat repeated dose and reproductive developmental screening study (OECD TG 422) conducted using the substance, the Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate. A long-term systemic dermal DNEL is derived from the oral NOAEL of 110 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 110 mg/kg bw/day x (50/50) = 110 mg/kg bw/day.
The following assessment factors have been used in accordance with REACH guidance: Intraspecies: default values of 4 (allometric scaling: rat) and 2.5 (remaining differences) are proposed. Interspecies: a default value of 10 is proposed for the general population; Exposure duration: a default value of 6 is proposed for extrapolation from a sub-acute study to chronic exposure (this represents a conservative approach, as the data indicate low toxicity following single and repeated exposures); Dose-response: a default value of 1 is proposed as, based on the available data, the substance is of low toxicity; Quality of the data base: a default value of 1 is proposed
Applying the assessment factor of 600 to the dermal equivalent NOAEL of 110 mg/kg bw/day gives a dermal DNEL of 0.18 mg/kg bw/day for long-term systemic dermal effects.
A DNEL for acute systemic inhalation has not been derived – the substance has low acute toxicity.
Local dermal DNELs
The Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate is not a skin irritant or sensitiser; therefore local effects are not predicted. Local dermal DNELs are not proposed in the absence of any identified hazard.
Oral DNELs
A DNEL of 0.18 mg/kg bw has been derived for the long-term oral systemic toxicity of the substance based on an oral NOAEL of 110 mg/kg bw/day derived from a sub-acute rate oral toxicity study and the application of a total assessment factor of 600.
No hazard has been identified with respect to eye irritation in the general population since no opportunities for exposure will arise during the intended uses of the substance.
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.