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EC number: 204-624-6 | CAS number: 123-39-7
- 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: Comparable to Guideline study with acceptable restrictions (treatment period gestation day 6-15; partly limited documentation, e.g. no details about the test substance; untreated control; no historical control data).
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 975
- Report date:
- 1975
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Principles of method if other than guideline:
- according to Guidelines for reproduction studies for safety evaluation of drugs for human use. Food and Drug Administration, Washington 1966
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- monomethylformamide
- IUPAC Name:
- monomethylformamide
- Details on test material:
- technical product
no further details
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- Source: Wiga, Sulzfeld, Germany
Only females with vaginal plug used (gestation day 0 [GD0] )
Housing conditions:
2 animals per cage
temperature 20-24°C
rel. air humidity: 50-60%
dark/light cycle: 12/12 h
certified diet and tap water ad libitum
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Constant application volume in all dose groups: 5 ml/kg bw
Dose related to the initial weight at GD0
Solutions prepared daily - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Mating with fertile, untreated males for one night; only females with vaginal plug used (gestation day 0)
- Duration of treatment / exposure:
- Gestation day (GD) 6-15
- Frequency of treatment:
- once daily
- Duration of test:
- Termination at GD20, cesarean section
Doses / concentrations
- Remarks:
- Doses / Concentrations:
22, 67, 200 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 20-24 pregnant animals
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: data from acute oral toxicity in rats
- Rationale for animal assignment: randomisation
Examinations
- Maternal examinations:
- Clinical symptoms recorded daily
Body weight measured thrice weekly - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: no data
- placenta weight of living fetuses
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- dead and living fetuses - Fetal examinations:
- weight, length, sex of fetuses
all fetuses examined for external effects
2/3 of all fetuses processed for the study of skeletal effects (Dawsen-method; Alizarin staining)
1/3 of all fetuses processed for the study of visceral effects (fixation in Bouin's solution for 2 weeks, 15 transversal sections) - Statistics:
- Analysis of variance
t-test
level of significance: p<0.05 - Indices:
- see results
- Historical control data:
- no data available
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
No clinical signs and no mortality in any treatment group except a vaginal bleeding in 6 dams of the high dose group (considered to be related to developmental toxicity, no further effects in the high dose group).
>=67 mg/kg bw/day: reduced body weight gain; considered to be related to resorption of implantations in the high dose group or reduced fetal weight at 67 mg/kg bw/day (developmental toxicity but not maternal toxicity; in the mid dose group the difference was less than 5% to the concurrent control).
No effects on body weight gain in the low dose group.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 22 mg/kg bw/day
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 67 mg/kg bw/day
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
No effects on number of implantations in any treatment group (varied between 11.10 and 11.96 implantations per dam)
200 mg/kg bw/day:
99.6% of implantations were resorbed, mainly early resoptions; only 1 fetus alive but with malformations (e.g. exencephaly & ectopia visceralis).
67 mg/kg bw/day:
no increase in dead implantations (resorptions and dead fetuses) and no effects on number of living fetuses
decrease in fetal body weight and length
decrease in placental weight
increase in variations (no details) and malformations (mainly meningocele, malformations of ribs and vertebral column; see also Table below)
22 mg/kg bw/day:
no developmental toxicity, placental weight slightly decreased although fetal weight increased (no data about historical controls; not considered by the authors to be of toxicological relevance).
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Developmental toxicity in Sprague-Dawley rats after oral application of N-methylformamide
Parameter |
Dose in mg/kg bw/day |
|||||
Control 1 |
22 |
Control 2 |
67 |
Control 3 |
200 |
|
Pregnant dams |
23 |
24 |
20 |
21 |
24 |
23 |
Placenta weight g |
0.54 |
0.52* |
0.58 |
0.42** |
0.59 |
0.32** |
Dead implantations |
6 |
9 |
7 |
12 |
11 |
265** |
living fetusus per dam |
11.70 |
11.17 |
10.75 |
10.86 |
11.50 |
0.04 |
Fetal weight in g |
3.66 |
3.82** |
3.66 |
3.21** |
3.66 |
1 male, 2.41 |
Fetal length in cm |
3.63 |
3.64 |
3.54 |
3.37** |
3.60 |
3.2 |
Fetuses with malformations in % of fetuses examined |
1.12% |
0.37% |
1.4% |
51%$ |
0.36% |
Only 1 fetus (malformed) |
*: significant, p<0.05; **: p<0.01; $: no data about significance but clear teratogenic effect
Slight but significant decrease in placenta weight at 22 mg/kg bw
Applicant's summary and conclusion
- Conclusions:
- Developmental toxicity was found in rats at dose levels without maternal toxicity; the NOAEL was 22 mg/kg bw/day, LOAEL 67 mg/kg bw/day.
- Executive summary:
Comparable to Guideline study with acceptable restrictions (treatment period gestation day 6-15; partly limited documentation, e.g. no details about the test substance; untreated control; no historical control data).
Groups of 20 -24 pregnant Sprague-Dawley rats were gavaged at gestation day (GD) 6 -15 with 22, 67, or 200 mg/kg bw/day. Concurrent controls were untreated. The study was terminated GD20. No maternal toxicity was observed in any treatment group. The reduced body weight gain in dams was considered to be related to resorption of implantations in the high dose group or the decrease in fetal weight at the mid dose level (developmental toxicity but not maternal toxicity). No effects were found on implantations, but only 1 male fetus was alive at termination in the high dose group and this one had malformations. At 67 mg/kg bw/day no increase in resorptions and dead fetuses was found, but a decrease in fetal body weight and length, and increase in variations (no details) and malformations (51% of examined fetuses with malformations) was reported. At 22 mg/kg bw/day no developmental toxicity was detected.
Conclusion: Developmental toxicity was found in rats at dose levels without maternal toxicity; the NOAEL was 22 mg/kg bw/day, LOAEL 67 mg/kg bw/day.
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