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EC number: 212-783-8 | CAS number: 868-85-9
- 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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication which meets basic scientific principles. Adopted according to OECD SIDS (public available peer reviewed source). The original source is available and has been reviewed.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Metabolism and disposition of dimethyl hydrogen phosphite in rats and mice
- Author:
- Nomeir AA, and Matthews HB
- Year:
- 1 997
- Bibliographic source:
- J Toxicol Environ Health 51: 489-501
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 2 004
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Fischer 344 rats were administered once orally 10 - 200 mg/kg 14C-labelled dimethyl phosphonate by gavage. Furthermore, rats were treated repeatedly for 5 days with an oral dose of 200 mg/kg bw 14C-labelled dimethyl phosphonate.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Dimethyl phosphonate
- EC Number:
- 212-783-8
- EC Name:
- Dimethyl phosphonate
- Cas Number:
- 868-85-9
- Molecular formula:
- C2H7O3P
- IUPAC Name:
- dimethyl phosphonate
- Details on test material:
- Name of test material (as cited in study report): dimethyl hydrogen phosphite (DMHP).
- Analytical purity: > 99%
- Radiochemical purity (if radiolabelling): 97%
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- [14C]DMHP (dimethyl hydrogen phosphite)
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories (Kingston, NY).
- Age at study initiation: 8-10 weeks old.
- Weight at study initiation: 180-220 g.
- Housing: Following dosing, the animals were housed in individual all-glass metabolism cages that allowed separate collection of urine, faeces, and exhaled radioactivity.
- Diet (e.g. ad libitum): food pellet ad libitum.
- Water (e.g. ad libitum): ad libitum.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 50 ± 10
- Photoperiod (hrs dark / hrs light): 12 / 12 hrs
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Dosing solutions were prepared by dissolving the 14C-labeled and unlabeled DMHP in corn oil.
The animals received a dosing volume of 4 mL/kg of body weight containing doses ranging from 10 to 200 mg/kg.
- Duration and frequency of treatment / exposure:
- 24 hours for single administration; 10 days after repeated administration.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Males: 10, 20, 200 mg/kg bw (single administration) and 200 mg/kg bw for 5d (repeated administration).
- No. of animals per sex per dose / concentration:
- Males: 3
- Control animals:
- no
- Positive control reference chemical:
- Not necessary
- Details on study design:
- No data
- Details on dosing and sampling:
- Expired air passed through two consecutive traps; the first contained 200 mL ethanol to collect volatile organics, and the second contained 200 mL of a mixture of ethanolamine and ethylene glycol monomethyl ether (3:7) to collect 14CO2. Urine, faeces, and trap contents were collected at selected time intervals. After preset time intervals (1-10 d), the animals were anesthetized by intraperitoneal injection of pentobarbital (80 mg/kg) and blood was collected by heart puncture. The animals were terminated by exsanguination. Radioactivity in urine and the ethanol and CO2 trap contents were determined by liquid scintillation counting using a Beckman model LS 9800 counter. Tissues were analyzed for total radioactivity by oxygen combustion of triplicate 100 mg samples to 14CO2 in Packard Tri-Carb sample oxidizer. Radioactivity was determined by liquid scintillation counting.
Faeces were extracted with methanol and the residue was air-dried, weighed, and ground to a fine powder. The extracts were counted directly. Triplicate 50 mg samples of the faecal powder were combusted.
Recovery of radioactivity from the samples oxidizer was 95-98%, while the counting efficiency was 70% for the oxidized samples and 91% for nonoxidized samples.
Calculation of the percentages of dose in each tissue was based on the actual weight of the organ and the following estimates of tissue volumes: blood, 8%, muscle, 50%, fat, 11%; and skin 16% of body weight. - Statistics:
- No data
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- DMHP was readily and near completely absorbed from the gastrointestinal tracts of rats.
- Details on distribution in tissues:
- Liver and kidneys, followed by forestomach, spleen, and lungs, contained the highest of DMHP concentration by radioactivity, while the lowest concentrations were in brain, adipose tissue, muscle, and testes. The concentrations of DMHP-derived radioactivity in tissues were approximately proportional to the dose.
- Details on excretion:
- At the doses studied, 28-38 % and 49-57% of dose were excreted in urine and as CO2 in the expired air within 24 h following administration, respectively. Elimination of labelled dose as 14CO2 continued up to approximately 12 hours following dosing. Elimination in urine continued in an almost linear fashion for up to 24 hours following dosing. Radioactivity collected in the ethanol trap and that excreted in faeces accounted for approximately 1 and 2% of dose hours, respectively, at all doses studied.
There appeared to be little or no effect of dose on the rate or route of metabolism and elimination in the dose range studied.
The effects of repeat exposure of rats to DMHP indicate that repeat administration had a little effect on metabolism to CO2 or elimination in urine.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The main metabolic pathway in rodents is demethylation to monomethyl hydrogen phosphite (MMP) and further oxidation to CO2.
Any other information on results incl. tables
Table.1 Concentrations of [14C] DMHP equivalent in tissues of male rats (as µg/g wet tissue) at 24 h following a single oral dose of 10, 100, or 200 mg/kg.
Number of daily [14C]DMHP doses |
|||
Tissue | 1 | 2 | 5 |
Blood | 36 ± 0.1 | 13 ± 1.4 | 36 ± 8 |
Liver | 8.5 ± 1.0 | 64 ± 6.4 | 165 ± 25 |
Kidney | 6.8 ± 1.3 | 59 ± 9.6 | 175 ± 40 |
Spleen | 3.9 ± 0.5 | 37 ± 3.6 | 81 ± 10 |
Lung | 3.5 ± 0.3 | 26 ± 2.7 | 70 ± 18 |
Heart | 2.1 ± 0.1 | 15 ± 1.3 | 45 ± 10 |
Skin | 1.6 ± 0.0 | 11 ± 3.3 | 42 ± 4 |
Skeletal muscle | 1.0 ± 0.1 | 6.0 ± 2.5 | 22 ± 4 |
Adipose tissue | 1.5 ± 0.1 | 7.0 ± 3.0 | 32 ± 7 |
Testes | 1.5 ± 0.2 | 12 ± 1.3 | 29 ± 3 |
Brain | 0.9 ± 0.2 | 7.0 ± 1.5 | 17 ± 3 |
Forestomach | 4.5 ± 0.7 | 40 ± 7.2 | 76 ± 7 |
Glandular stomach | 3.4 ± 0.1 | 23 ± 1.2 | 65 ± 9 |
Small intestine | 5.7 ± 0.6 | 54 ± 2.0 | 154 ± 31 |
Large intestine | 6.5 ± 4.6 | 34 ± 5.5 | 87 ± 17 |
Values are mean ± standard deviation of data from three rats
Table 2. Concentrations of [14C] DMHP equivalents in tissues of male rats (as µg/g wet/tissue) at interavals following a sinlge oral dose of 200 mg/kg.
Days following administration |
||||
Tissue | 1 | 2 | 5 | 10 |
Blood | 36 ± 8 | 22 ± 0.4 | 17 ± 1 | 13 ± 1 |
Liver | 165 ± 25 | 116 ± 8 | 69 ± 5 | 36 ± 6 |
Kidney | 175 ± 40 | 99 ± 5 | 74 ± 15 | 31 ± 2 |
Spleen | 81 ± 10 | 59 ± 3 | 47 ± 2 | 23 ± 1 |
Lung | 70 ± 18 | 52 ± 3 | 38 ± 1 | 22 ± 5 |
Heart | 45 ± 10 | 37 ± 3 | 33 ± 2 | 25 ± 4 |
Skin | 42 ± 4 | 28 ± 0 | 16 ± 10 | 15 ±1 |
Skeletal muscle | 22 ± 4 | 15 ± 2 | 17 ± 3 | 14 ± 2 |
Adipose tissue | 32 ± 7 | 16 ± 3 | 17 ± 4 | 9 ± 1 |
Testes | 29 ± 3 | 27 ± 1 | 25 ± 1 | 19 ± 1 |
Brain | 17 ± 3 | 13 ± 1 | 16 ± 1 | 13 ±1 |
Forestomach | 76 ± 7 | 69 ± 12 | 31 ± 7 | 17 ± 1 |
Glandular stomach | 65 ± 9 | 53 ± 3 | 32 ± 3 | 19 ± 1 |
Small intestine | 154 ± 31 | 82 ± 1 | 38 ± 6 | 19 ± 2 |
Large intestine | 87 ± 17 | 60 ± 4 | 36 ± 3 | 16 ± 2 |
Values are mean ± standard deviation of data from three rats.
Table 3. Concentrations of DMHP equivalents (µg/g wet tissue) in tissue of male rats following oral administration of 1, 2, or 5 daily doses of 200 mg/kg/d of [14C]DMHP.
Number of daily [14C] DMHP doses |
|||
Tissue | 1 | 2 | 5 |
Blood | 36 ± 8 | 69 ± 11 | 93 ± 4 |
Liver | 165 ± 25 | 243 ± 22 | 443 ± 29 |
Kidney | 175 ± 40 | 207 ± 63 | 343 ± 18 |
Spleen | 81 ± 10 | 121 ± 11 | 237 ± 19 |
Lung | 70 ± 18 | 107 ± 11 | 212 ± 5 |
Heart | 45 ± 4 | 70 ± 5 | 143 ± 14 |
Skin | 42 ± 4 | 69 ± 12 | 137 ± 38 |
Skeletal muscle | 22 ± 4 | 31 ± 1 | 65 ±1 |
Adipose tissue | 32 ± 7 | 54 ± 17 | 58 ± 11 |
Testes | 29 ± 3 | 48 ± 8 | 111 ± 10 |
Brain | 17 ± 3 | 28 ± 6 | 54 ± 4 |
Forestomach | 76 ± 7 | 119 ± 14 | 259 ± 47 |
Glandular stomach | 65 ± 9 | 99 ± 9 | 204 ± 7 |
Small intestine | 154 ± 31 | 188 ± 3 | 255 ± 12 |
Large intestine | 87 ± 17 | 119 ± 23 | 210 ± 25 |
Data are mean ± standard deviation of data from 3 rats at 24 hours after the last dose.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: low bioaccumulation potential based on study results.
- Executive summary:
The current study evaluates the metabolism and disposition of [14C]-dimethyl hydrogen phosphite ([14C]DMHP) in rats.
DMHP was administered by single oral dose at 10, 100, or 200 mg/kg bw and by repeated administration at 200 mg/kg bw/day for 5 days. Rats were dosed by gastric intubation. At least three animals were used for each time point
DMHP administered at a range dose of 10-200 mg/kg was readily and near completely adsorbed from the gastrointestinal tracts of rats.
DMHP-derived radioactivity was widely distributed in tissues of rats. Liver and kidneys, followed by forestomach, spleen, and lungs, contained the highest concentration by radioactivity, while the lowest concentrations were in brain, adipose tissue, muscle, and testes. The concentrations of DMHP-derived radioactivity in tissues were approximately proportional to the dose.
At the doses studied, 28-38 % and 49-57% of dose were excreted in urine and as CO2 in the expired air within 24 h following administration, respectively. Elimination of labelled dose as 14CO2 continued up to approximately 12 hours following dosing. Elimination in urine continued in an almost linear fashion for up to 24 hours following dosing. Radioactivity collected in the ethanol trap and that excreted in faeces accounted for approximately 1 and 2% of dose hours, respectively, at all doses studied.
There appeared to be little or no effect of dose on the rate or route of metabolism and elimination in the dose range studied.
The effects of repeat exposure of rats to DMHP indicate that repeat administration had little effect on metabolism to
CO2 or elimination in urine.
The main metabolic pathway in rodents is demethylation to monomethyl hydrogen phosphite (MMP) and further oxidation to CO2.
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