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EC number: 835-272-7 | CAS number: 256374-76-2
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- January 24, 2017 to March 28, 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
- Objective of study:
- toxicokinetics
- other: The aim of this study is to summarize the hazardous information obtained so far as a safety evaluation of DAIGUARD-850 (SH-0850) and to gain its toxicokinetics-related information.
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- After peer-reviewing individual study reports and summarizing the toxicity information of the substance, its toxicokinetics-related information was extracted. All studies were conducted under GLP in accordance with OECD guidelines.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 2-({2-[(5,5-dimethyl-2-oxo-1,3,2λ⁵-dioxaphosphinan-2-yl)amino]ethyl}amino)-5,5-dimethyl-1,3,2λ⁵-dioxaphosphinan-2-one
- EC Number:
- 835-272-7
- Cas Number:
- 256374-76-2
- Molecular formula:
- C12H26N2O6P2
- IUPAC Name:
- 2-({2-[(5,5-dimethyl-2-oxo-1,3,2λ⁵-dioxaphosphinan-2-yl)amino]ethyl}amino)-5,5-dimethyl-1,3,2λ⁵-dioxaphosphinan-2-one
- Test material form:
- solid: particulate/powder
- Details on test material:
- Name
Name: Reaction products of ethane-1,2-diamine, phosphoryl=trichloride and 2,2-dimethylpropane-1,3-diol which makes N,N'-bis(5,5-dimethyl-1,3,2-dioxaphosphinane=2-oxide-2-yl)ethane-1,2-diamine as a main component
Other name: SH-0850
CAS number: 256374-76-2 (main component)
Structural formula
Molecular formula: C12H26N2O6P2 (main component)
Molecular weight: 356.29 (main component)
Provided sample
Purity of the test substance: 100%
Lot number: SK-241002
Physical-chemical properties
Solubility in water: Less than 0.03% (w/w) by visual observation
Melting point: 277 °C
Appearance at normal temperatures: White powder
Storage condition
The test substance was stored in a dark place at room temperature.
Precaution for handling
Protective gloves, mask, glasses and clothes were put on in order to avoid contacts with skin or eyes and inhalation.
Constituent 1
- Specific details on test material used for the study:
- No further details specified in the study report.
- Radiolabelling:
- no
Test animals
- Species:
- other: Various
- Details on species / strain selection:
- Information collected from several studies involoving different species and strains.
Administration / exposure
- Route of administration:
- other: Various
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- In the results of single oral, inhalation and dermal administration studies as well as repeated oral dose toxicity studies using rats, systemic toxic effects were not recognized in any of those studies, and thus the absorption of the substance was considered to be generally low. However, since the ratio of polychromatic erythrocytes to total erythrocyte counts (PCE/TE) in bone marrow revealed a dose response relationship in the mice micronucleus test, indicating that this substance was absorbed to some or a lesser extent in the oral route. In this regard, DAIGUARD-850 (SH-0850) did not show any toxic effects as shown from the results of the preliminary test for a micronucleus test using mice although the substance was absorbed orally.
- Details on distribution in tissues:
- Since the substance had a very low level of toxicity and did not have any specific target organ(s), it was considered that the substance would not occur in an extreme distribution and accumulation toward any specific organ(s).
- Details on excretion:
- No information available.
Metabolite characterisation studies
- Details on metabolites:
- No information available.
Bioaccessibility (or Bioavailability)
- Bioaccessibility (or Bioavailability) testing results:
- No information available.
Any other information on results incl. tables
Summarization of toxicity information
As for DAIGUARD-850 (SH-0850), no mortality occurred in acute oral and dermal toxicity studies in rats given up to the limit dose, and there were no clinical signs as well as no abnormalities in macroscopic observation. In an acute inhalation toxicity study, slightly laboured respiration during an exposure period and decreased body weights in the early days of post-exposure were found at the limit dose, which were slight and reversible transient changes. Here, laboured respiration observed in an acute inhalation toxicity study was considered to be a non-specific symptom brought by inhalable dusts.
In both a dermal irritation study and a skin sensitization study, neither local irritating effects nor systemic clinical signs were observed. While, in an eye irritation study, slight irritating effects on the conjunctiva were found, but disappeared within 48 hours, thus the effect was only transient.
In a 7-day repeated oral dose toxicity study with rats, there were no abnormalities in clinical signs, body weight changes or necropsy findings up to 1,000 mg/kg/day, the limit dose. Similarly, no toxic signs were revealed with no abnormalities in clinical chemistry as well as pathological examinations in 28-day and 90-day repeated oral dose toxicity studies with rats, and NOAEL of the studies were determined over 1,000 mg/kg/day. Moreover, no effects on parental systemic toxicity and on reproductive/developmental performance were noted in a reproductive/developmental screening test with rats. In addition, a dose-range finding preliminary test of a micronucleus test using mice revealed no abnormalities in clinical signs and body weight changes when they were given 2,000 mg/kg/day for two straight days.
Thus, the level of acute oral toxicity in mice was also considered to be very low. In the main test of a micronucleus test, no significant change was seen in a ratio of polychromatic erythrocytes having micronucleus (MNPCE/PCE) up to the dose of 2,000 mg/kg, indicating that DAIGUARD-850 (SH-0850) was negative for micronucleus inducing activity in mice bone marrow. However, since the ratio of polychromatic erythrocytes per total erythrocytes (PCE/TE ratio) increased in a dose-dependent manner, this was considered to be a treatment-related effect of the substance.
Outline of results of toxicity study reports for DAIGUARD-850 (SH-0850)
No. |
Study type |
Route |
Species, strain, sex |
Dose |
No. of dose |
Results |
1 |
Acute toxicity |
Oral |
Rat, Wistar, Female |
2,000 mg/kg Suspension solution in distilled water |
Single |
No abnormalities in clinical signs, body weights and necropsy findings. |
2 |
Acute toxicity |
Inhalation |
Rat, Wistar, Male/Female |
5.07 mg/L (dust, inhalable fraction: 61.4%) |
Single |
Clinical signs: Laboured respiration (during exposure), No abnormality (post-exposure), Body weight: Transiently decrease, necropsy: No abnormality |
3 |
Acute toxicity |
Dermal |
Rat, Wistar, Male/Female |
2,000 mg/kg, 24-hr occlusive application (gauze-patch moistened with water) |
Single |
No abnormality in clinical signs, local effects, body weights, necropsy findings. |
4 |
Skin irritation |
Dermal |
Rabbit, NZW, Male |
5,000 mg/animal, 4-hr occlusive application (gauze-patch moistened with water) |
Single |
No local irritative effects up to 72 hours after removal of patch. No abnormalities in systemic signs or body weights. |
5 |
Eye irritation |
Eye application |
Rabbit, NZW, Male |
100 mg/animal, placed into conjunctival sac |
Single |
Eye irritation (Conjunctival redness, chemosis, discharge), disappeared at 48 hr. No abnormalities in systemic signs or body weights. |
6 |
Skin sensitization (LLNA) |
Ear application |
Mouse, CBA/J Rj, Female |
10, 20, 50% solution (25 µl/animal) |
3 days |
SI = 0.7-1.1 vs. 15.2 (positive control, HCA), concluded as negative. No abnormalities in systemic signs and local irritating effects. |
7 |
Repeated dose toxicity |
Oral |
Rat, SD, Male/Female |
30-1,000 mg/kg/day suspension solution in distilled water |
7 days |
No abnormalities in clinical signs, body weights, organ weights and necropsy findings. |
8 |
Repeated dose toxicity (OECD TG 407) |
Oral |
Rat, SD, Male/Female |
100, 300, 1,000 mg/kg/day suspension solution in olive oil |
28 days |
No treatment-related effects in clinical signs, body weights, hematology, blood clinical chemistry, organ weights, necropsy findings, histopathological findings. NOAEL=1,000 mg/kg/day |
9 |
Repeated dose toxicity (OECD TG 408) |
Oral |
Rat, SD, Male/Female |
100, 300, 1,000 mg/kg/day suspension solution in olive oil |
90 days |
No treatment-related effects in clinical signs, body weights, ophthalmogical findings, hematology blood clinical chemistry, orgam weights, necropsy findings, histopathological findings. NOAEL = 1,000 mg/kg/day |
10 |
Reproductive/ developmental screening (OECD TG 421) |
Oral |
Rat, SD, Male/Female |
100, 300. 1,000 mg/kg/day suspension solution in olive oil |
Males: from 14 days before mating until the day before necropsy through the mating period (35 days in total) Females: from 14 days before mating until day 12 of lactation |
Parental animals: No treatment-related effect in estrous cycle, copulation index, fertility index, gestation index, number of implantation sites, delivery index, or delivery and maternal behaviour. Offspring: No treatment-related effects in sex ratio, birth index, viability index on post-natal Day 4 (PND4), or viability index on PND13, external examinations, ano-genital distance (AGD), nipple development, plasma T4 concentration on PND13 and body weight. NOAEL (parental systemic effects) = 1,000 mg/kg/day NOAL (reproductive/developmental effects) = 1,000 mg/kg/day |
11 |
Micronucleus (preliminary test) |
Oral |
Mouse, CD-1, Male/Female |
62.5-2,000 mg/kg/day suspension solution in olive oil |
2 days |
No abnormalities in clinical signs and body weights. |
Micronucleus (main test) |
Oral |
Mouse, CD-1, Male/Female |
500, 1,000, 2,000 mg/kg/day suspension solution in olive oil |
2 days |
Micronucleus induction: negative. Ratio of polychromatic erythrocytes in total erythrocytes (PCE/TE): increase in dose-dependent manner. No abnormalities in clinical signs and body weights. |
Extraction and summarization of toxicokinetics-related information
From the above toxicity results, the toxicokinetics information of DAIGUARD-850 (SH-0850) on absorption, distribution, metabolism, and excretion were extracted and summarized as described below.
a. Absorption:
In the results of single oral, inhalation and dermal administration studies as well as repeated oral dose toxicity studies using rats, systemic toxic effects were not recognized in any of those studies, and thus the absorption of the substance was considered to be generally low. However, since the ratio of polychromatic erythrocytes to total erythrocyte counts (PCE/TE) in bone marrow revealed a dose response relationship in the mice micronucleus test, indicating that this substance was absorbed to some or a lesser extent in the oral route. In this regard, DAIGUARD-850 (SH-0850) did not show any toxic effects as shown from the results of the preliminary test for a micronucleus test using mice although the substance was absorbed orally.
b. Distribution:
Since the substance had a very low level of toxicity and did not have any specific target organ(s), it was considered that the substance would not occur in an extreme distribution and accumulation toward any specific organ(s).
c. Metabolism:
No information available.
d. Excretion
No information available.
Applicant's summary and conclusion
- Conclusions:
- With reference to toxicokinetics information, the absorption of the substance was likely to be low in any of the oral, dermal or inhalation routes, but evidence of absorption of DAIGUARD-850 (SH-0850) directly in an oral route in mice was obtained from a dose-dependent increase in the ratio of polychromatic erythrocytes to total erythrocyte counts (PCE/TE ratio) in bone marrow in a mice micronucleus test. However, no toxic signs occurred in a mice micronucleus test including the preliminary one, thus there was no species difference between mice and rats from an aspect of toxicity, and it was considered that no large difference existed in the degree of oral absorption rate between the two species. Moreover, since the substance did not reveal the specific target organ toxicity in repeated dose toxicity studies with rats, it was considered that the substance would not occur in an extreme distribution and accumulation on any specific organ(s). In addition, no information was available with regard to metabolism and excretion of the substance.
- Executive summary:
DAIGUARD-850 (SH-0850) has a very low level of toxicity in acute toxicity studies in oral, inhalation and dermal routes with rats, and repeated oral dose toxicity studies up to 90 days and reproduction/developmental toxicity screening test with rats. No target organ(s) was specified in repeated dose toxicity studies.
The absorption rate ofDAIGUARD-850 (SH-0850) was likely to be poor in any oral, dermal or inhalation route. However, a dose-dependent increase in the ratio of polychromatic erythrocytes occupied in total erythrocyte counts of bone marrow was found in a mouse micronucleus test, which gave direct evidence as a toxicokinetics finding indicating that DAIGUARD-850 (SH-0850) was absorbed in an oral route in mice. But there were no toxic signs in a mouse micronucleus test including the preliminary one. It was considered, therefore, that no species difference existed between rats and mice from the aspect of toxicity, and that the degree of oral absorption appeared to be almost the same level. Further, since this substance did not show specific target organ toxicity in repeated dose toxicity studies in rats, it was considered that the substance would not occur in an extreme distribution and accumulation on any specific organ(s). In addition, no information was available with regard to metabolism and excretion of the substance.
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