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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
Description of key information
Acute Toxicity:
Oral: LD50> 2000 mg/kg b.w. for rat (OECD 423)
Dermal: LD50> 2000 mg/kg b.w. for rat (OECD 402, 24h exposure)
Inhalation: LC50= 3110 mg/m³ for rat (OECD 403, 4 h exposure)
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
[Describe why the read-across can be performed (e.g. common functional group(s), common precursor(s)/breakdown product(s) or common mechanism(s) of action]
The two substances ADK STAB NA-11 (CAS no. 85209-91-2, EC no. 286-344-4) and ADK STAB NA-70 (CAS no. 85209-93-4, EC no. 458-880-0) have the same molecular structure, i.e. 2,4,8,10-tetra-tert-butyl-6-hydroxy-12H-dibenzo[d,g][1.3.2]-dioxaphosphocin-6-oxide. The substances only differ in the counter ion of the cyclic diarylphosphoric acid ester, i.e. sodium and lithium, respectively. Water solubility of NA-11 amounts to 1850 mg/l, that of NA-70 to 390 mg/l. Both substances dissociate at low concentration in aqueous environments.
With both substances, many toxicity studies were performed to determine their hazard potential. In short-term studies for determination of the hazard potential after single or short-term exposure, i.e. skin and eye irritation, skin sensitisation and systemic toxicity after single oral or dermal application, the two substances did not exhibit adverse effects. The LD50 after single oral or dermal exposure was > 2000 mg/kg body weight. In a study for acute inhalation toxicity performed with NA-70 (in powder form), at high concentrations acute toxicity was observed leading to classification for acute toxicity category 4.
In genetic toxicity tests, the two substances exhibited high cytotoxicity in mammalian cell cultures. Based on the results of in vitro and vivo tests, a genotoxic potential can be excluded. The results from these short-term tests confirm the expectation that the two different salts of the cyclic diarylphosphoric acid ester exhibit well comparable toxic properties.
In oral toxicity studies with repeated dosing, at high doses some toxic effects were observed with both substances. A detailed assessment of all toxicological data available on NA-11 and NA-70 and two other substances with the same chemical structure was performed. It was concluded that read-across from data obtained in studies performed with any of the substances is appropriate including the studies for reproduction and developmental toxicity performed with NA-11. See attached review.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]
See attached review.
3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]
See attached review.
4. DATA MATRIX
See attached review. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: No deaths at 2000 mg/kg bw
- Interpretation of results:
- other: LD50 > 2000 mg/kg
- Conclusions:
- No labelling regarding acute oral toxicity according to Regulation (EC) No 1272/2008 is required.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- > 2 000 mg/kg bw
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- (1981) Method B2, Commission Directive 92/69/EEC
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS: Sprague-Dawley Crl:CD® (SD) IGS BR
- Source:Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200g - 350g
- Fasting period before study: none
- Housing:in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items: wooden chew blocks
- Diet (e.g. ad libitum): ad libidtum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: min. 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation: dust
- Type of inhalation exposure:
- nose only
- Vehicle:
- clean air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany)
- Exposure chamber volume: 30 l
- Method of holding animals in test chamber: tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber
- Source of air: Compressed air, passed through a water trap and respiratory quality filters
- Method of particle size determination: Marple Personal Cascade Impactor, (Westech IS Ltd, Beds., UK); six impactor stages (9.6, 6.6, 3.5, 1.8, 0.87
and 0.33 μm cut points
- Treatment of exhaust air: passed through a scrubber trap, connected with a filter
- Samples taken from breathing zone: yes
TEST ATMOSPHERE (see Any other information on materials and methods incl. tables, table 1) - Analytical verification of test atmosphere concentrations:
- yes
- Remarks:
- gravimetric method
- Duration of exposure:
- 4 h
- Concentrations:
- see Any other information on materials and methods incl. tables, table 1
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations: hourly during exposure, at the end of exposure and 1h later. Once daily up to 14 days.
and weighing: prior to exposure on the day of treatment, days 7 and 14.
- Necropsy performed: yes (all animal, surviving, died, killed)
- Other examinations performed: clinical signs, body weight, macroscopic examination, esp. of the respiratory tract, behavioural observations - Statistics:
- LC50’s estimated by Linear Interpolation (US EPA, 1989)
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 3.11 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- see Any other information on results incl. tables, table 2
- Clinical signs:
- other: Common abnormalities:increased respiratory rate, hunched posture, pilo-erection and wet fur. Frequent instances of decreased respiratory rate, laboured respiration, noisy respiration, ataxia and red/brown staining around the head. Occasional instances of
- Body weight:
- Normal bodyweight development for all surviving animals during the study with the following exeptions:
Group 1: 1 male and 1 female showed reduced bodyweight gain or slight bodyweight loss during Week 1 but recovered to show normal development during Week 2. A further female from Group 1 showed slight bodyweight loss during Week 2.
Group 2: 5 females exhibited a reduced bodyweight gain or slight bodyweight loss during Week 1 but recovered to show normal development during Week 2. - Gross pathology:
- Macroscopic abnormalities detected amongst
- animals that survived until Day 14 at necropsy:
Lungs – enlarged, fluid filled, abnormally dark, pale patches, dark patches (in all animals of the low and mid dose groups);
- animals that died or were humanely killed during the course of the study at necropsy:
Lungs – haemorrhagic, fluid filled, abnormally dark, pale patches;
Liver – dark;
Kidneys – dark or pale;
Stomach – gaseous distension; Small Intestine – gaseous distension; Large Intestine – gaseous distension. - Interpretation of results:
- other: Acute Toxicity Inhalation Category 4, H332: [Regulation (EC) No 1272/2008]
- Conclusions:
- Acute Toxicity Inhalation Category 4, H332: [Regulation (EC) No 1272/2008]
Reference
Table 2: Mortality data
Group Number |
Mean Achieved Atmosphere Concentration (mg/L) |
|
Deaths |
|
Male |
Female |
Total |
||
1 |
1.00 |
0/5 |
0/5 |
0/10 |
2 |
1.96 |
2/5 |
0/5 |
2/10 |
3 |
5.03 |
5/5 |
5/5 |
10/10 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 3.11 mg/L
- Physical form:
- inhalation: dust / mist
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- 24 February 1987
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Sprague-Dawley origin (Crl:CD (SD) IGS BR)
- Source: Charles River (UK) Ltd., Margate, Kent, UK.
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: at least 200 g
- Housing: in solid-floor polypropylene cages furnished with woodflakes. Individual housing during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): standard laboratory rodent diet (Certified Rat and Mouse Diet (Code 5LF2))
- Water (e.g. ad libitum): drinking water
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12h/12h - Type of coverage:
- semiocclusive
- Vehicle:
- arachis oil
- Details on dermal exposure:
- back and flanks
- approximately 10% of total body surface area
- Type of wrap if used: surgical gauze semioccluded with a piece of self-adhesive bandage
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with cotton wool moistened with arachis oil BP
- Time after start of exposure: 24h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution):200 mg/ml w/v
- Constant volume or concentration used: yes
- For solids, paste formed: yes
VEHICLE
- Amount(s) applied (volume or weight with unit): 10 ml/kg - Duration of exposure:
- 24 h
- Doses:
- 2000 mg/kg
- No. of animals per sex per dose:
- 10 rats (5 of each sex)
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. After removal of dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: local dermal irritation (erythema, eschar formation, oedema formation), any other lesion or reaction (spots, scabbing) - Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- none
- Clinical signs:
- none
- Body weight:
- All animals showed expected gains in bodyweight over the study period.
- Gross pathology:
- no abnormalities
- Other findings:
- no signs of dermal irritation
- Interpretation of results:
- other: LD50 > 2000 mg/kg
- Conclusions:
- No labelling regarding acute dermal toxicity according to Regulation (EC) No 1272/2008 is required.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- > 2 000 mg/kg bw
Additional information
Justification for classification or non-classification
In both, the acute oral and the acute dermal toxicity studies with NA-70, all animals survived the limit dose of 2000 mg/kg b.w. Therefore, classification for acute oral or dermal toxicity is not required [REGULATION (EC) 1272/2008].
According to the result of the acute inhalation toxicity study, NA - 70 has to be classified as acute toxic category 4 [REGULATION (EC) 1272/2008].
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.
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