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EC number: 212-052-3 | CAS number: 756-79-6
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: scientifically acceptable publication
Data source
Reference
- Reference Type:
- publication
- Title:
- Dimethyl methyl phosphonate induction of dominant lethal mutations in male mice
- Author:
- Dunnick JK, Solleveld HA, Harris MW, Chapin R and Lamb IV JC
- Year:
- 1 984
- Bibliographic source:
- Mutation Research 138: 213-218
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- compareable rodent dominat lethal assay
- GLP compliance:
- no
- Remarks:
- well documented study
- Type of assay:
- rodent dominant lethal assay
Test material
- Reference substance name:
- Dimethyl methylphosphonate
- EC Number:
- 212-052-3
- EC Name:
- Dimethyl methylphosphonate
- Cas Number:
- 756-79-6
- Molecular formula:
- C3H9O3P
- IUPAC Name:
- dimethyl methylphosphonate
- Details on test material:
- - Name of test material (as cited in study report): dimethyl methyl phosphonate (DMMP)
- Analytical purity: >99%
- Lot/batch No.: not specified; test substance was obtained from Stauffer Chemical Company, Weslport, Connecticut
- Other: the compound was analyzed by gas chromatography, thin-layer chromatography and by infrared, ultraviolet and nuclear magnetic resonance spectroscopy
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: CB6F1 males and CD-I females
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: B6C3F, male mice were obtained from Frederick Cancer Research Center (Frederick, MD), and were 7-8 weeks of age on the first day of dosing (referred to as day 1). Female CD-I mice were obtained from Charles River Breeding Laboratories (Portage, MI)
- Age at study initiation: the animals were 9 weeks of iage when mated
- Assigned to test groups randomly: yes
- Housing: housed in solid bottom polycarbonate cages with Corn Cob bedding (Granville Milling Co., Creedmoor, NC), Male mice were housed individually (except during mating) throughout the course of the study
- Diet (e.g. ad libitum): Open formula, autoclavable, rodent diet NIH 31 laboratory feed
- Water (e.g. ad libitum): tap water
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1±1.1°C
- Humidity (%): 50±10%
- Photoperiod (hrs dark / hrs light): a 12-h fluorescent light and dark cycle was provided
No additional data provided
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: not specified
No additional data - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Animals were dosed by gavage in aqueous solutions; no additinal details provided - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 5 days per week for 13 weeks
- Post exposure period:
- The 20 male mice in groups 1, 4, and 5 which were kept for an additional 15 weeks without chemical treatment, were mated to untreated CD-I female mice at week 29 (mating trial 4, days 196-200)
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 250, 500, 1000 and 2000 mg/kg bw
Basis:
actual ingested
male animals in goups listed below
- No. of animals per sex per dose:
- (1) vehicle control (40 animals); (2). 250 mg/kg (20 animals): (3) 500 mg/kg (20 animals; (4) 1000 mg/kg (40 animals) and (5) 2000 mg/kg (40 animals)
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- none
Examinations
- Tissues and cell types examined:
- Sperm concentration and morphology, hormones and enzymes levels, dominant lethal effect
- Details of tissue and slide preparation:
- Not applicable
- Evaluation criteria:
- Significant dominant lethal effect in male mice causing an increased number of dead implants (resorptions) and a decreased number of live fetuses when male mice treated for 4, 8, or 12 weeks, were mated to untreated female mice.
- Statistics:
- Statistical analysis for differences in mean number of live and dead implants and percent dead implants was done according to the Kruskal—Wallis one-way analysis of variance by ranks and the Wilcoxon rank sum test.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- positive
- Remarks:
- increased number of dead implants (resorptions) and a decreased number of live fetuses at 2000 mg/kg bw and somewhat at 1000 mg/kg, reversible after 15 weeks recovery
- Toxicity:
- no effects
- Remarks:
- no chemically related effects observed in treated animals
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- not examined
- Additional information on results:
- MORTALITY AND CLINICAL SIGNS
All male mice dosed with 0, 250, 500, 1000 or 2000 mg/kg DMMP, S days per week for 13 weeks, survived the treatment, and no dose-related clinical signs of toxicity were seen in any groups.
BODY WEIGHT
There were no chemically related effects on total body weight
ORGAN WEIGHT
There were no chemically related effects on organ/body weight ratios for testis, epididymis, prostate, and kidney
GROSS PATHOLOGY
Gross lesions were not seen in any group.
HISTOPATHOLOGY
Microscopic examination of selected organs, including those of the genitourinary tract did not reveal any treatment-related lesions. Dose-related effects were not seen on sperm concentration, sperm morphology, cholinesterase plasma levels, or FSH or LH plasma level
OTHER
- Mating frequency: the percentage of males able to impregnate at least 1 female was equal to or greater than 85% for each treatment group. The fertilization rate (number of fertilized females/number of females mated X 100) was equal to or greater than 85% in all groups of mice during the 4 mating trials, with the exception of the 250-mg/kg group at mating trial 1 where the fertilization rate was 75%. Chemical treatment had no effect on the fertilization rate (Table 1).
- Fertility: mating of control male B6C3F, mice to CD-1 females gave a reproducible number of live fetuses per female and a low background frequency of resorptions. The average number of live fetuses per female in the vehicle control group for mating trials 1-4, was 11.8, 10.3, 11.2 and 11.1, respectively. The average number of resorptions per female in the vehicle control group was 0.6, 1.0, 0.8 and 0.4 for mating trials 1-4. These mating trials occurred when male mice were 11-36 weeks of age and there were no age-related effects on fertility of the male mouse during this time period.
Test substance treatment of male mice at 2000 mg/kg for 4, 8, or 12 weeks decreased the average number of live fetuses per female and increased the average number of dead implants (resorptions) per female. The resorptions were primarily early resorptions. An increase in the number of dead implants was seen in the l000 mg/kg group in mating trials 1 and 3, but not at mating trial 2. The dominant lethal index was increased in the 2000 mg/kg group in mating trials 1-3 (40, 37, 44%, respectively), and in the 1000 mg/kg groups in mating trials 1 and 3 (12 and 13%, respectively). After a 15-week recovery period the percent dead implants in the 1000 and 2000 mg/kg groups returned to a rate comparable to that in the control groups (Table 1)
Any other information on results incl. tables
Table 1: Dominant lethal test with B6C3F1 male mice treated with test substance and mated to intreated CD-1 female mice (a)
Evaluated parameters |
Test substance dose (mg/kg bw per day) |
||||
0 |
250 |
500 |
1000 |
2000 |
|
1. Mating after 4 weeks of treatment |
|||||
Males with pregnant females (%) |
100% (20/20) |
85% (17/20) |
100% (20/20) |
100% (20/20) |
95% (19/20) |
Mean fertilization rate (b) |
85% (34/40) |
75% (30/40) |
88% (35/40) |
85% (34/40) |
85% (34/40) |
Mean live implants/female (c) |
11.9±0.3 |
12.2±0.3 |
11.4±0.4 |
10.4±0.5* |
7.2±0.6** |
Mean dead implants/female (c) |
0.6±0.2 |
0.8±0.2 |
1.1±0.2* |
1.6±0.3** |
3.2±0.4** |
Mean percentage of dead implants/female (in %) (d) |
5.3±1.3 |
5.8±1.2 |
9.6±1.4* |
13.4±2.2** |
30.9±4.2** |
Mean percentage of dominant lethal mutations (in %) (e) |
- |
-3 |
4 |
12* |
40** |
2. Mating after 8 weeks of treatment |
|||||
Males with pregnant females (%) |
100% (20/20) |
100% (20/20) |
100% (20/20) |
100% (20/20) |
100% (20/20) |
Mean fertilization rate (b) |
88% (34/40) |
90% (36/40) |
88% (34/40) |
95% (38/40) |
92% (37/40) |
Mean live implants/female (c) |
10.3±0.5 |
11.4±0.5 |
11.2±0.4 |
10.5±0.5 |
6.5±0.4** |
Mean dead implants/female (c) |
1.1±0.2 |
0.7±0.1 |
0.7±0.2 |
1.1±0.2 |
3.7±0.3** |
Mean percentage of dead implants/female (in %) (d) |
9.8±2.1 |
6.5±1.4 |
6.1±1.6 |
10.1±1.7 |
34.6±3.2** |
Mean percentage of dominant lethal mutations (in %) (e) |
- |
-10 |
-8 |
-2 |
37** |
3. Mating after 12 weeks of treatment |
|||||
Males with pregnant females (%) |
100% (40/20) |
95% (20/20) |
100% (20/20) |
100% (20/20) |
95% (38/40) |
Mean fertilization rate (b) |
94% (74/80) |
92% (37/40) |
90% (36/40) |
88% (34/40) |
89% (71/80) |
Mean live implants/female (c) |
11.2±0.4 |
10.9±0.5 |
11.1±0.6 |
9.7±0.5** |
6.3±0.3** |
Mean dead implants/female (c) |
0.8±0.1 |
0.8±0.3 |
0.8±0.2 |
1.7±0.3** |
4.7±0.2** |
Mean percentage of dead implants/female (in %) (d) |
8.3±1.5 |
8.3±2.9 |
6.6±1.8 |
15.3±2.7** |
44.2±2.3** |
Mean percentage of dominant lethal mutations (in %) (e) |
- |
3 |
1 |
13** |
44** |
4. Mating after 15 weeks of recovery |
|||||
Males with pregnant females (%) |
100% (20/20) |
- |
- |
100% (20/20) |
100% (20/20) |
Mean fertilization rate (b) |
90% (36/40) |
- |
- |
92% (37/40) |
95% (71/80) |
Mean live implants/female (c) |
11.1±0.4 |
- |
- |
11.4±0.3 |
11.1±0.4 |
Mean dead implants/female (c) |
0.4±0.1 |
- |
- |
0.5±0.1 |
0.7±0.1 |
Mean percentage of dead implants/female (in %) (d) |
5.0±1.6 |
- |
- |
4.5±1.1 |
6.2±1.4 |
Mean percentage of dominant lethal mutations (in %) (e) |
- |
- |
- |
-3 |
0 |
(a)20 males in each group, each male mated to 2 females except in the third mating trial where there were 40 males in the control and 2000 mg/kg groups; (b)Fertilization rate(number of fertilized females/number of females mated x 100); (c)% resorptions = (total dead implants/total dead and live implants)x100; (d)Mean±SE; (e)Percentage of induced dominant lethal mutations was calculated as: % dominant lethal mutations = (1-average living implants in test group/average living implants in control groupx100); *P<0.05; **P<0.01 |
Applicant's summary and conclusion
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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