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EC number: 213-156-1 | CAS number: 927-62-8
- 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:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The route of exposure (i.p.) is not standard. acceptable, well-documented publication which meets basic scientific principles
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 991
Materials and methods
- Principles of method if other than guideline:
- Exploration if chronic administration of methylamines can cause reproductive toxicity using pregnant CD-1mice and CD-1 mouse embryos in culture as experimental models.
- GLP compliance:
- not specified
- Limit test:
- yes
Test material
- Reference substance name:
- Dimethylamine Hydrochloride
- IUPAC Name:
- Dimethylamine Hydrochloride
- Reference substance name:
- Dimethylammonium chloride
- EC Number:
- 208-046-5
- EC Name:
- Dimethylammonium chloride
- Cas Number:
- 506-59-2
- IUPAC Name:
- N-methylmethanaminium chloride
- Details on test material:
- CAS 506-59-2 (dimethylamine hydrochloride), purity not specified
Constituent 1
Constituent 2
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, St. Constant, Quebec
- Weight at study initiation: 20-25 g
- Housing: Plexiglas cages with heat-treated wood chip bedding
- Diet (e.g. ad libitum): laboratory mouse chow pellets ad libitum
-Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25°C
- Humidity (%):50-70%
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- other: 0,9 % saline
- Details on exposure:
- intraperitoneal injections, once a day between 8:00 and 9:00 a.m.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Details on mating procedure:
- mice bought already mated
- Duration of treatment / exposure:
- day 1-17 of gestation
- Frequency of treatment:
- daily
- Duration of test:
- until day 18 of gestation
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0.25, 1, 2.5 and 5.0 mmol/kg bw ( 11.3, 45.1, 112.7, 225.4 mg/kg bw)
Basis:
nominal conc.
- No. of animals per sex per dose:
- 6-8
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Six to eight pregnant mice were admininstered 0, 0.25, 1, 2,5 and 5.0 mmol/kg bw dimethylamine by ip injection from day 1 to 17 after mating
- Results of untreated controls of three parallel experiments (n=29) were pooled
Examinations
- Maternal examinations:
- - Maternal and fetal body weight, mortality, resorptions, litter size, and placental weight were recorded in the in-vivo part of the study
- Ovaries and uterine content:
- Examination of the uterus for obvious sign of implantations
uteri were stained in 10 % ammonium sulfide solution to identify implantation sites - Fetal examinations:
- pubs weight for each female were calculated by dividing the sum of body weights of all live pups in a litter by the number of live pubs in the litter
mean pub weight for each treatment group was based on sum of mean pup weight for each female divided by the number of females in the group
fetuses were randomly placed either in Bouin solution for visceral examination by the freehand razor sectioning technique or in 95 % ethanol for the skeletal examination by an alizarin red S staining technique. - Statistics:
- - Statistical evaluation employed Student's t-test and Bonferroni test (multiple means)
- Indices:
- no data
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Details on maternal toxic effects:
- Dimethylamine did not produce maternal toxicity at concentrations up to 2.5 mmol/kg
- Dimethylamine did not affect fetal weights although 3 of 44 dams died, due to reasons not clear.
- Dimethylamine at doses of 5 mmol/kg caused contractions of abdominal muscles in the proximity of injektion sites, these contractions lasted 2-3 min
- For evaluation the results of untreated controls of three parallel experiments (n=29) were pooled
- No dam died from dimethylamine treatment and maternal body weight development within the range of the untreated control group
- At 225.4 mg/kg bw contractions of the muscles at the injection site lasting 2-3 minutes after dosing were observed
- No significant differences between control and treated animals were observed concerning fetal body weight, mortality, resorptions , litter size, or placental weight
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- > 225.4 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- > 112.7 mg/kg bw/day
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes. Remark: at the highest concentration higher number of resorbed and dead fetuses
Details on embryotoxic / teratogenic effects:
- Dimethylamine did not have any significant effect on pregnancy outcome.
- DMA did not adversely affect fetal development in vivo.
- Number of resorbed and dead fetuses were equally distributed across all doses of DMA, but the highest dose (5 mmol/kg bw) caused a not significant increased number of dead fetuses and a signifcant higher number of resorptions.
- none of the amines (MMA, DMA, TMA) caused a significant increase in external, interna organ, or skeletal abnormalities.
- all three methylamines possess teratogenic potential in varying degrees.
- decrease of DNA, RNA, and protein after treatment of embryos with methylamines.
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
In vitro studies: all three methylamines produced concentration-dependent decreases in yolk-sac diameter, crown-rump length, head length, and fetal survival; developmental score and somite number also exhibited a similar concentration-dependent decrease.
The effect of all the three methylamines was more marked on the head length than on crown-rump length and yolk-sac diameter.
The development of yolk-sac circulation was severly affected at 0.25 mM DMA and TMA. The color of the yolk sac of DMA- and TMA-treated embryos was paler than control and there appeared to be a decrease in flow rather than vascularization.
The external appearance of embryos was not affected by low concentrations of methylamines. at higher concentrations (> 0.5 mM), there appeared to be a dispropotionate retardation in forelimb and branchial bar development relative to the development of other organs. All embryos were dorsally convex at 1 mM MMA or DMA.
The development of hearts was unaffected at concentrations up to 1 mM of all 3 methylamines and neuropores closed well up to concentrations of 0.75 mM.
All three methylamines produced concentration-dependent decreases in embryo RNA, DNA and proteins; the relative order of toxicity was the same as in vivo, namely TMA> DMA > MMA.
TABLE 2. Effects of Dimethylamine on Pregnancy Outcome in CD-1 Mice |
|||||
Variables |
Dose (mmol/kg/d, ip, d 1-17 of gestation) |
||||
0 |
0.25 |
1.0 |
2.5 |
5.0 |
|
Animals (n) |
29 |
9 |
13 |
11 |
11 |
Day 1 body weight (g) |
23.9 ± 0.1 |
22.8 ± 0.4 |
24.2 ± 0.8 |
24.7 ± 0.5 |
25.0 ± 0.5 |
Day 18 body weight (g) |
48.4 ± 1.1 |
48.9 ± 1.0 |
50.1 ± 2.2 |
50.9 ± 1.5 |
45.9 ± 2.0 |
Dams dead (n) |
0 |
0 |
2 |
0 |
1 |
Dead fetuses/litter |
0.83 ± 0.14 |
0.78 ± 0.32 |
0.63 ± 0.26 |
0.86 ± 0.4 |
1.29 ± 0.36 |
Resorptions/litter |
0.66 ± 0.13 |
0.44 ± 0.34 |
0.75 ± 0.62 |
0.57 ± 0.2 |
1.71 ± 0.68a |
Litter size (n) |
9 ± 1 |
9 ± 1 |
10 ± 1 |
10 ± 1 |
8 ± 1 |
Fetal body weight (g) |
1.4 ± 0.03 |
1.5 ± 0.05 |
1.4 ± 0.03 |
1.4 ± 0.04 |
1.4 ± 0.03 |
Placental weight (mg) |
109 ± 2 |
114 ± 4 |
114 ± 6 |
116 ± 5 |
109 ± 5 |
ARI |
1.63 ± 0.4 |
0.90 ± 0.3 |
3.1 ± 1.1 |
0.7 ± 0.2 |
2.6 ± 1.1 |
Note.Mice were killed on d 18 of gestation; fetal and placental weights represent mean of weights per litter; ARI (adverse reproductive index) represents cumulative maternal and fetal toxicity in arbitrary units. Data are mean ± SE. |
Applicant's summary and conclusion
- Conclusions:
- - The NOAEL for maternal toxicity was 225.4 mg/kg bw based on the absence of any adverse findings at this dose,
and for developmental toxicity, including teratogenicity, the NOAEL was 112.7 mg/kg bw based on the absence of any adverse findings at this dose, - Executive summary:
DMA inhibits development of mouse embryos in culture.
DMA may act as endogenous teratogens unter certain conditions.
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