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EC number: 254-372-6 | CAS number: 39236-46-9
- 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
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: Adequately reported study performed using a standard test method: includes sufficient information to permit evaluation of developmental toxicity.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 973
- Report date:
- 1973
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- no
- Remarks:
- Pre-GLP study
- Limit test:
- no
Test material
- Reference substance name:
- N,N''-methylenebis[N'-[3-(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]urea]
- EC Number:
- 254-372-6
- EC Name:
- N,N''-methylenebis[N'-[3-(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]urea]
- Cas Number:
- 39236-46-9
- Molecular formula:
- C11H16N8O8
- IUPAC Name:
- N',N'''-methylenebis{1-[3-(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]urea}
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- Fine whte powder
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- Virgin adult females
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Daily oral administration during the dosing period.
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- Mated with young adult male mice: observation of vaginal sperm plug confirmed mating and was designated Day 0 of gestation.
- Duration of treatment / exposure:
- 10 days (gestation Days 6-15)
- Frequency of treatment:
- Once daily
- Duration of test:
- Females terminated on gestation Day 17.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
30, 95, 300 mg/kg/day
Basis:
actual ingested
- No. of animals per sex per dose:
- At least 25 females were mated and dosed in each group (25-27: pregnant and surviving to termination 20-22/group).
- Control animals:
- yes, sham-exposed
- other: positive controls, given aspirin at 150 mg/kg
Examinations
- Maternal examinations:
- On gestation Day 17 dams terminated and subjected to caesarean section. Urogenital tracts examined for abnormality.
- Ovaries and uterine content:
- Implantation and resorption sites counted, plus live and dead foetuses.
- Fetal examinations:
- Live foetuses weighed. All foetuses sexed and examined for external abnormality, then examined in detail:
- one third of each litter examined for visceral/soft tissue abnormalities (x10 magnification used to aid inspection)
- remainder processed for skeletal examination (KOH then alizarin red stain). - Statistics:
- Results tabulated/dam:
- implant sites
- resorption sites
- Live and dead foetuses
- male/female embryos
- average foetus weight/litter.
Indices calculated per group:
- live litters
- implant sites: total and average/dam
- resorptions: total number, dams with 1 or more, dams with complete resorption, % with 1 or more, % with complete resorption
- live foetuses: total and average/dam, sex ratio
- dead foetuses: total number, dams with 1 or more, dams with all dead, % with 1 or more, % with all dead
- average foetus weight.
Skeletal abnormality/variant indices:
- - Indices:
- Results tabulated/dam:
- implant sites
- resorption sites
- Live and dead foetusess
- male/female embryos
- average foetus weight/litter.
Indices calculated per group:
- live litters
- implant sites: total and average/dam
- resorptions: total number, dams with 1 or more, dams with complete resorption, % with 1 or more, % with complete resorption
- live foetuses: total and average/dam, sex ratio
- dead foetuses: total number, dams with 1 or more, dams with all dead, % with 1 or more, % with all dead
- average foetus weight.
Skeletal abnormality/variant categories (reported/group as affected foetus number and number of litters with one or more affected)
- sternebrae (incompete ossification, bipartite, extra or missing)
- ribs (fused/split, wavy, >13)
- vertebrae (incomplete ossification)
- skull (incomplete closure)
- extremities (incomplete ossification, missing)
- hyoid (missing, reduced).
Soft tissue abnormalities: none observed, so not categorised.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- not specified
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- Maternal toxic effects:no effects. Remark: No adverse reactions to treatment are reported. Bodyweight data show no effect of treatment.
Details on maternal toxic effects:
Bodyweight increase over the test period was closely similar in test groups and the sham treatment controls (51-62% increase over 17 days)
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 300 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- clinical signs
- gross pathology
- mortality
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No pattern of increased skeletal abnormality or variation was seen in test groups when compared to concurrent controls. A 28% incidence of >+13 ribs in live foetuses of the 30 mg/kg/day test group compared to 12% in controls was not considered biologically significant in the absence of a similar increase at higher test dosages.
- Visceral malformations:
- not specified
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No pattern of increased skeletal abnormality or variation was seen in test groups when compared to concurrent controls. A 28% incidence of >+13 ribs in live foetuses of the 30 mg/kg/day test group compared to 12% in controls was not considered biologically significant in the absence of a similar increase at higher test dosage.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- no effects observed
- Description (incidence and severity):
- No pattern of increased skeletal abnormality or variation was seen in test groups when compared to concurrent controls. A 28% incidence of >+13 ribs in live foetuses of the 30 mg/kg/day test group compared to 12% in controls was not considered biologically significant in the absence of a similar increase at higher test dosage.
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Maternal data
Group |
Live litters |
Mean implants/dam |
Dams with ≥1 resorption site |
Total resorptions |
Mean live foetuses/dam |
Dams with ≥1 dead foetus (% of dams) |
Mean foetal weight (g) |
Sham treated control |
20 |
12.7 |
7 |
13 |
12.0 |
1 (5%) |
0.89 |
Test: 30 mg/kg/day |
20 |
11.6 |
12 |
23 |
10.3 |
3 (14.3%) |
0.89 |
Test: 95 mg/kg/day |
20 |
12.8 |
9 |
16 |
11.9 |
2 (10.0%) |
0.87 |
Test: 300 mg/kg/day |
20 |
12.1 |
6 |
25 |
10.8 |
3 (13.6%) |
0.93 |
Aspirin positive control |
21 |
12.0 |
15 |
29 |
10.4 |
6 (27.3%) |
0.84 |
Soft tissue abnormalities: none observed.
Skeletal findings
Group |
Live foetuses examined |
Sternebrae
|
Ribs |
Vertebrae |
Skull |
Extremities |
Hyoid* |
|
Sham treated control |
167 (20) |
55 N (19) 8 B (7) 18 M (4) |
20 + (9) |
7 N (3) |
3 N (2) |
8 N (2) 1 M (1) |
23 R (10) |
|
Test: 30 mg/kg/day |
149 (20) |
49 N (17) 5 B (4) 18 M (6) |
42 + (12) |
7 N (4) |
|
8 N (4) |
19 R (11) |
|
Test: 95 mg/kg/day |
165 (20) |
75 N (19) 5 B (5) 31 M (10) |
23 + (12) |
6 N (2) |
1 N (1) |
4 N (2) |
33 R (14) |
|
Test: 300 mg/kg/day |
165 (20) |
65N (16) 7 B (5) 1 + (1) 14 M (6) |
27 + (13) |
5 N (3) |
|
8 N (4) |
17 R (11) |
|
Aspirin positive control |
158 (21) |
97 N (19) 7 B (4) 33 M (11) |
9 F (2) 1 W (1) 45 + (13) |
16 N (6) |
3 N (2) |
16 N (8) |
29 R (13) |
(n) = number of litters concerned
N = incomplete ossification(skull: incomplete closure) B = bipartite M = missing F = fused/split
+ = extra (sternebrae) or >13 (ribs) W = wavy R = reduced
* Hyoid also shown as “missing” in 22 control foetuses and up to 32, 52 and 37 test group foetuses (30, 95, 300 mg/kg/day respectively): subsequently stated to indicate lost samples, not available for inspection due to errors at necropsy
Applicant's summary and conclusion
- Conclusions:
- Oral administration of test substance at up to 300 mg/kg/day produced no evidence of teratogenic effect and no clear evidence of embryotoxicity.
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