Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: scientifically acceptable study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 978
- Report date:
- 1978
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- Determination of teratogenicity of test substance after treatment of female rats from gestation day 6 to gestation day 15
- GLP compliance:
- no
- Remarks:
- well documented study
- Limit test:
- no
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): 80 021/B
No additional data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: the albino rats used in the present study were Sprague-Dawley derived (Tif/RAI) and obtained from a closed SPF breeding colony
- Age at study initiation: 2 months at the start of the study
- Weight at study initiation: means of 200 g (females)
- Housing: throughout the experiment the successfully mated were kept in groups of 5 in Macrolon cages in an air-conditioned room at a temperature
- Diet (e.g. ad libitum): the standard diet fed was Nafag No.890
- Water (e.g. ad libitum): tap water
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±0.5°C
- Humidity (%): 60±5%
- Photoperiod (hrs dark / hrs light): the room was illuminated for 10 hours daily
No additional data
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): not specified
- Concentration in vehicle: 5, 50, 100 and 125 mg/ml for the respective dose levels (100, 1000, 2000 and 2500 mg/kg)
- Amount of vehicle (if gavage): the amount of fluid administered was 20 ml/kg of body weight
- Lot/batch no. (if required): Prod. No.8322, from own stocks
- Purity: a 2% solution of a sodiiim carboxymethylcellulose was used as vehicle - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/3
- Length of cohabitation: overnight
- Further matings after two unsuccessful attempts: no; only male with proven fertility were used
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- from day 6 until day 15 of pregnancy (with the exception of the high dose group of the supplementary study, treated day only during the organogenesis from day 6 to day 10 of pregnancy; see below)
- Frequency of treatment:
- daily
- Duration of test:
- the dams were killed at day 21 of pregnancy
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 100, 1000 and 2000 mg/kg bw (first experiment; main study); 0, 2000 and 2500 mg/kg bw (second experiment; supplementary study);
Basis:
actual ingested
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
The experiment was conducted in two parts, a main study comprising a no effect dose and toxic dose levels, and a supplementary study (further evaluation of possible effect of the compound on embryonic and foetal development) in which the effects of treatment at very high doses was examined in particular.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: see below
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: general condition and symptomatology were checked daily
BODY WEIGHT: Yes
- Time schedule for examinations: weight gain was checked daily
FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes; food consumption was noted on Days 6, 11, 16 and 21 of pregnancy
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice: dams were killed by dry ice and fetuses removed by Caesarean section on day 21 of pregnancy
- Organs examined: following assessment of the dams organs, especially of the ovaries and uterus (mucosa and contents, including amniotic fluid and placentae as well as abortions and resorption sites). - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter
- Head examinations: Yes: No data - Statistics:
- t-test (no additional detail provided
- Indices:
- yes (see Table 1)
- Historical control data:
- were available
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Details on maternal toxic effects:
DETAILED CLINICAL OBSERVATIONS
- Main study: no test substance dependant adverse effects reported
- Supplementary study: no test substance dependant adverse effects reported
BODY WEIGHT
- Main study: at the 2000 mg/kg dose level dams displayed a marked reduction in body-weight gain throughout the period of treatment.
- Supplementary study: in both the dose groups feed intake and body weight were diminished during the period of treatment
FOOD CONSUMPTION
- Main study: at the 2000 mg/kg dose level dams displayed a marked reduction in feed intake throughout the period of treatment. The dams of the 1000 mg/kg dose solely showed a slight decrease in feed intake.
- Supplementary study: in both the dose groups feed intake was diminished during the period of treatment
Effect levels (maternal animals)
- Dose descriptor:
- LOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
CLINICAL SIGNS MORTALITY (Table 1)
- Main study: the rates of either implantation or embryo-lethality (resorptions) were comparable for all groups.
The average weight of the live fetuses was significantly diminished in the 1000 mg/kg and 2000 mg/kg dose groups.
- Supplementary study: the rates of either implantation or embryo-lethality (resorptions) were comparable for the three experimental groups, including the vehicle control.
The average weight of the fetuses was significantly reduced in both the dose groups.
SOFT TISSUE EXAMINATIONS
- Main study: In two fetuses of the 2000 mg/kg dose group slight edema-like changes of the subcutaneous tissue (anasarca) were detected by slicing. Two fetuses showed hypoplasia of lungs in association with dystopia cordis. The incidences concerning hydrocephaly as well as hypoplasia of lungs and anasarca were found to be not beyond the 99 % confidence limits of the vehicle control. Both, hypoplasia of lungs and anasarca, are the most frequent anomalies occurring in untreated controls.
- Supplementary study: the visceral examination of fetuses by applying the slicing technique revealed the occurrence of an internal hydrocephalus in one fetus of the 2500 mg/kg dose group. In a further fetus from another litter of this dose group hypoplasia of lungs was detected. Slight edema-like change of subcutaneous tissue was observed in one fetus of the vehicle control. Spontaneous anomalies have occurred in the cumulative of untreated controls too.
SKELETAL EXAMINATIONS (Table 1)
- Main study: The skeletal assessment did not reveal any significant deviation from the vehicle control in the 100 mg/kg dose group. In both the higher dose groups, however, skeletal maturation in the fetuses was found to be reduced; the phalangeal nuclei of fore and hind limb, the calcaneous and the 5th sternebra were affected in this respect. The incidences concerning the few skeletal anomalies observed among the fetuses of the high-dose group and listed in Table 6 are still ranging within the 99 % confidence limits of the vehicle control.
- Supplementary study: skeletal assessment revealed in both the dose groups an increase in the numbers of still unossified phalangeal nuclei of fore and hind limb and calcaneus. In the 2500 mg/kg dose group, in addition, there was an increased number of still incompletely ossified 5th stemebrae. One instance of irregularly-shaped stemebrae was detected in either the 200 mg/kg dose group or the 2500 mg/kg dose group.
HEAD EXAMINATIONS
- Main study: six fetuses from one litter of the 2000 mg/kg dose group showed slight edema of the cervical region by gross inspection. One out the 302 live fetuses of this high dose group appeared to be suspicious with regard to hydrocephaly. By applying the slicing technique an internal hydrocephalus was found in this fetus.
- Supplementary study: one fetus of the 2'500 mg/kg dose group showed hypoplasia of the lower jaw. This type of malformation was also found among two out of three mal-developed fetuses of the cumulative control
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: fetotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- > 2 500 mg/kg bw/day (actual dose received)
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Table 1: Fetus parameters at indicated experiment and dose level
Parameters |
Cumulative historic control |
Main study |
Supplementary study |
|||||
0 mg/kg |
100 mg/kg |
1000 mg/kg |
2000 mg/kg |
0 mg/kg |
2000 mg/kg |
2500 mg/kg |
||
Number of dams |
570 |
25 |
25 |
25 |
25 |
25 |
25 |
25 |
Spontaneous dam deaths |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
Number of dam with deciduomata |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1/25 |
Number of dams with implantations |
508(a) |
23 |
22 |
21 |
23 |
22/24 |
24/25 |
24/25 |
Mean number of implantations (%) |
13.56 |
13.04 |
12.45 |
12.10 |
14.39 |
13.1±1.6 |
13.9±1.2 |
13.5±1.7 |
Embryonic resorptions (%) |
7.1 |
9.0 |
9.5 |
5.1 |
7.0 |
4.7 |
9.9 |
9.9 |
Fetal resorptions (%) |
0.1 |
0 |
0 |
0 |
0.9 |
0.4 |
0.3 |
0 |
Dead fetuses (%) |
0.1 |
0 |
0 |
0 |
0.9 |
0.4 |
0.3 |
0 |
Live fetuses (%) |
92.5 |
91.0 |
90.5 |
94.9 |
91.2 |
51.1 |
51.8 |
49.0 |
Live fetuses with malformations |
8 / 6361(b) |
0 / 273 |
0 / 248 |
0 / 241 |
1 / 302(c) |
0 / 262 |
0 / 299 |
2 / 252(e) |
Weight of live fetuses (g) |
5.25±0.43 |
5.38±0.47 |
5.34±0.40 |
5.04±0.37(d) |
4.02±0.56(d) |
5.36±0.45 |
5.02±0.31(f) |
5.15±0.40(f) |
(a) One totally aborted litter included; (b) 1 Cleft palate + mandibular hypoplasia, 2 Mandibular hypoplasias, 3 Generalized oedemas and 3 "open eyes"; (c) Hydrocephalus internus (as stated by applying the slicing technique); (d) Significantly reduced when compared with the vehicle control (t test, p < 0.01); (e) Mandibular hypoplasia and Internal hydrocephaly (stated by applying the slicing technique); (f) Significantly lower than in the control group (t test, 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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.