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EC number: 458-880-0 | 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
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics, other
- Type of information:
- other: expert statement
- Adequacy of study:
- supporting study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: No studies are available on adsorption, distribution, metabolism and excretion of NA-70. Predictions were made based on physical-chemical properties and results of toxicological studies performed with NA-70.
- Executive summary:
ADK STABNA-70is the lithium salt of2,4,8,10-tetra(tert-butyl)-6-hydroxy-12H-dibenzo[d,g] [1.3.2]-dioxaphosphocin 6-oxidebelonging to the class of cyclic diarylphosphoric acid esters. In the table below, some physical-chemical properties of NA-70 are given:
Endpoint
Molecular weight
493 Da
Water solubility
390 mg/L at 20 °C, pH 6
Fat solubility
< 2.5 mg/100g standard fat at 37°C.
Boiling point
Decomposes before boiling, decomposition starts above 160 °C.
Log Pow
2.5 at 22.5 °C
Vapour pressure
3.37 x 10-5Pa at 25 °C.
The available physico-chemical information of the substance has been evaluated and used to derive the qualitative toxicokinetic behaviour of NA-70. In addition, information obtained in different studies performed with the read-across source substance NA-11 was used in the assessment of toxico-kinetic properties (see the attached data review).
The ECHA “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance 2017” document[1]provides guidance, which physico-chemical properties commonly determine dermal, oral and respiratory absorption, distribution, metabolism and elimination of substances.
Oral absorption
NA-70, the lithium salt of an organic molecule, has a molecular weight of 493 Da and the following physical-chemical properties: moderate water solubility of 0.39 g/L (at 20°C), partition coefficient Log Pow = 2.5 at pH 6. These properties favour absorption after oral exposure[1]. In the repeat oral dose toxicity study the substance was absorbed since systemic toxicity was observed, including increased liver weight and effects on liver enzymes (ALP, ALT, AST).
With the read-across substance NA-11 (differing only in the cation, sodium instead of lithium), repeated dose oral toxicity tests were performed via gavage and via dosing by feed. After gavage dosing, microscopic effects were observed in liver and bile duct that were not detected after dosing via feed at comparable dose level. Since NA-11 has high cytotoxic activity, irritation of liver and bile duct after bolus dosing indicates fast absorption of NA-11 after oral dosing leading to high concentrations in the respective tissues. The same fast absorption can be expected after oral dosing of NA-70.
Dermal absorption
The above given physical-chemical properties of NA-70 could be favourable for dermal uptake. However, based on the molecular weight of 493 Da dermal absorption may already be limited due to the size of the molecules. No dermal effects were observed in skin irritation and skin sensitization tests.
Respiratory absorption - Inhalation
The partition coefficient Log Pow = 2.5 and the moderate water solubility of 0.39 g/L (at 20°C) of NA-70 are favourable for absorption directly across the respiratory tract epithelium by passive diffusion[1]. In view of the very low volatility of NA-70 (vapourpressure of3.37 x 10-5Paat 25°C) exposure to the vapour form will be limited. With regard to the large proportion of inhalable particles (25% with a diameter < 10 µm) exposure to dust of NA-70 has to be avoided. NA-70 was acutely toxic by inhalation in rats. However, inhalation toxicity rather likely was due to the high cytotoxic activity of NA-70 because the systemic exposure leading to lethality was much lower than 2000 mg/kg body weight, a dose level that was not lethal after oral dosing.
Distribution
No information on distribution of the substance in different tissues is available. Based on the histopathologic findings in the bile duct of rats and in the gall bladder of dogs after bolus dosing of NA-11, rapid elimination of systemically available NA-11 is rather likely leading to high concentrations of the cytotoxic substance in the respective tissues causing irritation.
Metabolism
The cyclic diarylphosphoric acid ester very likely is not metabolised since it proved to be stable against hydrolysis at pH values between 4 and 9 as well as in digestive simulant containing phosphatases. Also in environmental studies, no microbial degradation was observed. Disruption of the gut (faecal) microbiome by orally dosed NA-11 and hyperplasia of the intestinal epithelium after oral dosing of a similar substance (T-186) provide further evidence that the substance is not metabolized and thus keeps its cytotoxic and antimicrobial activity during passage through the intestines.
Excretion
From the observations summarised in the Chapters on distribution and metabolism, biliary excretion of the cyclic diarylphosphoric acid ester is the likely way of elimination of systemic exposure.
Bioaccumulation potential
Based on the physical-chemical properties, i.e. low fat solubility ( < 2.5 mg/100g standard fat at 37°C) and log Pow < 3, bioaccumulation is unlikely.
Reference
[1] European Chemicals Agency.,Guidance on information requirements and chemical safety assessment: chapter R.7c : endpoint specific guidance.LU: Publications Office, 2017.
Reference
Description of key information
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 100
- Absorption rate - dermal (%):
- 50
- Absorption rate - inhalation (%):
- 100
Additional information
ADK STABNA-70is the lithium salt of2,4,8,10-tetra(tert-butyl)-6-hydroxy-12H-dibenzo[d,g] [1.3.2]-dioxaphosphocin 6-oxidebelonging to the class of cyclic diarylphosphoric acid esters. In the table below, some physical-chemical properties of NA-70 are given:
Endpoint |
|
Molecular weight |
493 Da |
Water solubility |
390 mg/L at 20 °C, pH 6 |
Fat solubility |
< 2.5 mg/100g standard fat at 37°C. |
Boiling point |
Decomposes before boiling, decomposition starts above 160 °C. |
Log Pow |
2.5 at 22.5 °C |
Vapour pressure |
3.37 x 10-5Pa at 25 °C. |
The available physico-chemical information of the substance has been evaluated and used to derive the qualitative toxicokinetic behaviour of NA-70. In addition, information obtained in different studies performed with the read-across source substance NA-11 was used in the assessment of toxico-kinetic properties (see the attached data review).
The ECHA “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance 2017” document[1]provides guidance, which physico-chemical properties commonly determine dermal, oral and respiratory absorption, distribution, metabolism and elimination of substances.
Oral absorption
NA-70, the lithium salt of an organic molecule, has a molecular weight of 493 Da and the following physical-chemical properties: moderate water solubility of 0.39 g/L (at 20°C), partition coefficient Log Pow = 2.5 at pH 6. These properties favour absorption after oral exposure[1]. In the repeat oral dose toxicity study the substance was absorbed since systemic toxicity was observed, including increased liver weight and effects on liver enzymes (ALP, ALT, AST).
With the read-across substance NA-11 (differing only in the cation, sodium instead of lithium), repeated dose oral toxicity tests were performed via gavage and via dosing by feed. After gavage dosing, microscopic effects were observed in liver and bile duct that were not detected after dosing via feed at comparable dose level. Since NA-11 has high cytotoxic activity, irritation of liver and bile duct after bolus dosing indicates fast absorption of NA-11 after oral dosing leading to high concentrations in the respective tissues. The same fast absorption can be expected after oral dosing of NA-70.
Dermal absorption
The above given physical-chemical properties of NA-70 could be favourable for dermal uptake. However, based on the molecular weight of 493 Da dermal absorption may already be limited due to the size of the molecules. No dermal effects were observed in skin irritation and skin sensitization tests.
Respiratory absorption - Inhalation
The partition coefficient Log Pow = 2.5 and the moderate water solubility of 0.39 g/L (at 20°C) of NA-70 are favourable for absorption directly across the respiratory tract epithelium by passive diffusion[1]. In view of the very low volatility of NA-70 (vapourpressure of3.37 x 10-5Paat 25°C) exposure to the vapour form will be limited. With regard to the large proportion of inhalable particles (25% with a diameter < 10 µm) exposure to dust of NA-70 has to be avoided. NA-70 was acutely toxic by inhalation in rats. However, inhalation toxicity rather likely was due to the high cytotoxic activity of NA-70 because the systemic exposure leading to lethality was much lower than 2000 mg/kg body weight, a dose level that was not lethal after oral dosing.
Distribution
No information on distribution of the substance in different tissues is available. Based on the histopathologic findings in the bile duct of rats and in the gall bladder of dogs after bolus dosing of NA-11, rapid elimination of systemically available NA-11 is rather likely leading to high concentrations of the cytotoxic substance in the respective tissues causing irritation.
Metabolism
The cyclic diarylphosphoric acid ester very likely is not metabolised since it proved to be stable against hydrolysis at pH values between 4 and 9 as well as in digestive simulant containing phosphatases. Also in environmental studies, no microbial degradation was observed. Disruption of the gut (faecal) microbiome by orally dosed NA-11 and hyperplasia of the intestinal epithelium after oral dosing of a similar substance (T-186) provide further evidence that the substance is not metabolized and thus keeps its cytotoxic and antimicrobial activity during passage through the intestines.
Excretion
From the observations summarised in the Chapters on distribution and metabolism, biliary excretion of the cyclic diarylphosphoric acid ester is the likely way of elimination of systemic exposure.
Bioaccumulation potential
Based on the physical-chemical properties, i.e. low fat solubility ( < 2.5 mg/100g standard fat at 37°C) and log Pow < 3, bioaccumulation is unlikely.
Reference
[1] European Chemicals Agency.,Guidance on information requirements and chemical safety assessment: chapter R.7c : endpoint specific guidance.LU: Publications Office, 2017.
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