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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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Several relevant methodological deficiencies: at the commencement of the study the weights variation of animals used exceeded ± 20 per cent of the mean weight (21% in males and 33% in females); only vehicle control used; the lowest concentration showed evidence of toxicity; analytical purity was not reported; test material administration was conducted in different ways in different test groups; exposure atmospheric sampling was not conducted properly; temperature at which the test is performed was between 24-27 °C; on test day 16, four male rats of group treated with 483.1 mg/m³ were not loaded into the chamber and did not receive exposure to the test material, due to a technician error. However, according to OECD SIDS a reliability of 1 was given.
Data source
Referenceopen allclose all
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 1 982
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 2 004
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- In a 4-week study, male and female Sprague-Dawley rats (20/sex per group) inhaled 48.7, 142.1, 483.1, and 803.9 mg/m³ (12, 35, 119, and 198 ppm) dimethyl phosphonate vapour for 6 hours/day on 5 days/week.
- 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 phosphonate
- Physical state: liquid
- Analytical purity: not reported
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 28 days
- Weight at study initiation: males: 349-437g (mean 397 g); females: 187-278 (mean 239 g).
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- other: nitrogen
- Details on inhalation exposure:
- - Interim sacrifices: Five male and five female rats from each group were sacrificed 2, 4 and 6 week after commencement of exposure (exceptions: in the 119 ppm group only 8 animals were necropsied after 6 weeks; in the 198 ppm group no animals were necropsied after 4 and after 6 weeks each).
- Determination of chamber concentration: a calibration curve relating concentration to the absorption at this wavelength was prepared (calibration was carried out with dry air). One to two samples were taken daily from each exposure chamber. The exposure concentration was calculated by comparing the infrared absorption of the sample to the standard curve. - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- 6 hours/day, 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
target concentration: 0, 10 (40.6), 30 (121.8), 100 (406), 300 (1218) ppm (mg/m³) (effective inhaled concentration: 0, 12 (48. 7), 35 (142.1), 119 (483.14), 198 (803.88) ppm(mg/m³)).
Basis:
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: 4 weeks
- Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Clinical signs were performed daily; full recorded physical assessment was performed weekly.
BODY WEIGHT: Yes
- Time schedule for examinations: daily
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: every two weeks (in a pre-exposure ophthalmoscopic examination those animals that showed ocular abnomalities were discarded from study).
HAEMATOLOGY: Yes
- Time schedule for collection of blood: once in week 4.
- The following parameters were examined: haemoglobin, hematocrit, erythrocyte count, leukocyte count (total and differential), clotting time.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: once in week 4.
- The following parameters were examined: blood urea nitrogen, serum glutamic pyruvic transaminase, serum alkaline phosphatase, glucose.
URINALYSIS: Yes
- Time schedule for collection of urine: once in week 4.
- The following parameters were examined: appearance, specific gravity, occult blood, pH, protein, bilirubin, ketones, glucose.
-ORGAN WEIGHT: brain, gonads (ovary or testicle paired), heart, kidneys (right and left separately), liver, lungs, pituitary, spleen.
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes; all animals died during the study or were killed in extremis and at scheduled sacrifice respectively.
HISTOPATHOLOGY: Yes. - Other examinations:
- The reversibility of cataract formation was studied in detail.
- Statistics:
- Body weights, haematology, clinical chemistry parameters, organ weights, and organ/body weight ratios were statistically evaluated according to Snedecor, G.W. and Cochran, W.G., Statistical Methods, 6th Edition, Iowa State Univ. Press (1967), Hollander and Wolfe, Nonparametric Statistical Methods, John Wiley and Sons, New York (1973); Dunnett, C.W. J. Am. Sta. Assn., Vol. 50 (1955), Biometrics, Vol. 20 (1964).
Results and discussion
Results of examinations
- Details on results:
- TOXIC RESPONSE/EFFECTS BY DOSE LEVEL
MORTALITY AND TIME TO DEATH
At 119 ppm the number of death in week 1-4: 0, 0, 1, 2 ; at 198 ppm the number of death in week 1-4: 0, 8, 5, 11, 3. Causes of deaths may have been necrosis and acute purulent inflammation of the skin.
At 483.1 and 803.9 mg/m³ the time of death varied betwwen 7 and 26 days.
TOXIC EFFECTS
At doses >= 12 ppm (48.7 mg/m³; males and females): EYES: irritation of superficial ocular structures (associated with inflammatory changes of intraocular structures in many rats) - mucosal irritation - keratitis; KIDNEY: increased absolute and relative kidney weights.
At doese >= 35 ppm: BODY WEIGHT: reduced body weight gain; EYES (males and females): lenticular opacities, progressed to cataract; SKIN (males and females): cutaneous and mucosal irritation (increased lacrimal, nasal or buccal secretions and/or erythema, edema, loss of elasticity, fissuring, necrosis or eschar formation of the skin); nasal and ocular responses disappeared within one week; cutaneous changes were not fully reversible during the observation period.
RESPIRATORY TRACT MALE AND FEMALE
Inflammation of the anterior nares (control: 4/39; 12 ppm: 4/38; 35 ppm: 6/39; 119 ppm: 7/39; 198 ppm: 9/36) seems to be an extension of the effect on the skin >=119 ppm.
MORTALITY MALE AND FEMALE
Increased mortality. Time of death: at 119 ppm: on days 14 (1, female) and 23 (1, male); 198 ppm: on days 7 to 26 included (13, male + 14, females); BODY WEIGHT MALE AND FEMALE
Body weight losses.
CLINICAL SIGNS MALE AND FEMALES
Neurological impairment (lack of coordination, lack of grip).
SKIN MALE AND FEMALE
Dermatitis (control 12, 35, ppm: 0/40; 119 ppm: 7/39; 198 ppm: 27/36)
RESPIRATORY TRACT MALES AND FEMALES
Irritation of the respiratory tract (dry or moist rales labored or irregular breathing); changes were reversible within one to two weeks.
Inflammation of the external nares (control, 12 and 35 ppm: 0/40, 119 ppm: 5/39, 198 ppm: 22/36). At 198 ppm: red discoloration of lungs and nasal turbinates; 9 rats (4 males and 5 females) had no discernible thymus tissue.
HAEMATOLOGY
male: hematocrit and haemoglobin reduced; male and female: neutrophils increased, increased total leukocyte numbers.
CLINICAL CHEMISTRY
male: increased SGPT; male and female: decreased glucose concentration.
FERTILITY MALE
Hypospermatogenesis (control, 12, 35 ppm: 0/20, 119 ppm:3/20, 198 ppm: 4/19). In each case the content of sperm in the epididymis was below normal.
SPLEEN
hematopoiesis in the spleen (control, 12, 35, 119 ppm: each 0/40, 198 ppm: 4/18).
PROSTATE
Acute prostatitis 4/18 (low incidence of prostatitis was seen in general).
FURTHER FINDINGS
Enlarged costochondral junction (control: 1/40; 12 and 35 ppm: 0/40, 119 ppm: 6/40, 198 ppm: 2/36). Treatment relation was not studied.
OTHER EXAMINATIONS
Cataract formation and cessation was studied in animals of the 119 ppm group. Cataract formation had stopped after two weeks post-exposure and at four weeks post-exposure the formation of normal lens fibers had recommenced.
Effect levels
- Dose descriptor:
- LOAEC
- Effect level:
- 12 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: eye effects and kidney weights; 12 ppm=48.7 mg/m³
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Executive summary:
Mobil Oil Corporation (1992)
In a 4-week study, male and female Sprague-Dawley rats (20/sex per group) inhaled 48.7, 142.1, 483.1, and 803.9 mg/m³ (12, 35, 119, and 198 ppm) dimethyl phosphonate vapour for 6 hours/day on 5 days/week.
At all concentrations increased kidney weights were observed in male and female rats. Irritation of superficial ocular structures, mucosal irritation and keratitis were shown in all dose groups and in both sexes. The eye changes progressed to cataracts in dose groups of 142.1 mg/m³. At 142.1 mg/m³ cutaneous irritation was observed, the skin effects progressed to dermatitis at 483.1 mg/m³, and at 803.9 mg/m³ necrosis and acute purulent inflammation of the skin were main causes of deaths. At 142.1 mg/m³ inflammation of the anterior nares was visible in male and female rats. At 483.1 mg/m³ the external nares were affected, and at 803.9 mg/m³ red discoloration of the lungs and the nasal turbinates were observed in both sexes.
In male rats reduced body weight gains were observed at 142.1 mg/m³. In the next higher dosage (483.1 mg/m³) body weight losses and increased mortality was shown in male and female rats.
Time to death varied between 7 and 26 days at 483.1 and 803.9 mg/m³. Hypospermatogenesis was observed in male rats at lethal doses of = 483.1 mg/m³. Hematopoiesis in the spleen occurred in 4/18 female rats at 803.9 mg/m³ only and was not observed in the controls or the lower doses. No historical control data were provided.
The LOAEC derived for this study is 48.7 mg/m³ (12 ppm).
No NOAEL was achieved in this study.
This study is not reliable because several relevant methodological deficiencies: at the commencement of the study the weights variation of animals used exceeded ± 20% of the mean weight (21% in males and 33% in females); only vehicle control used; the lowest concentration should evidence of toxicity; analytical purity was not reported; test material administration was conducted in different ways in different test groups; exposure atmospheric sampling was not conducted properly; temperature at which the test is performed was between 24-27 °C; on test day 16 four male rats of group treated with 483.1 mg/m³, were not loaded into the chamber and did not receive exposure to the test material, due to a technician error.
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