Registration Dossier
Registration Dossier
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: 230-625-6 | CAS number: 7226-23-5
- 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP and guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- testing lab.
- Limit test:
- no
Test material
- Reference substance name:
- Tetrahydro-1,3-dimethyl-1H-pyrimidin-2-one
- EC Number:
- 230-625-6
- EC Name:
- Tetrahydro-1,3-dimethyl-1H-pyrimidin-2-one
- Cas Number:
- 7226-23-5
- Molecular formula:
- C6H12N2O
- IUPAC Name:
- tetrahydro-1,3-dimethyl-1H-pyrimidin-2-one
- Test material form:
- other: liquid
- Details on test material:
- Name of the test substance used in the study report: N,N'Dimethylpropylene Urea
Purity: 99.7%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- Acclimatization: 10 days minimum prior to pairing with evaluation of health
Age at pairing: 11 weeks minimum
Body weights: 183 - 243 g
Identification: individual animal number tattooed on the pinnae
The animals were housed under standard laboratory conditions: air-conditioning with 10-15 air changes per hour; the environment monitored continuously with hourly recordings of temperature (22 ± 3°C) and relative humidity (40-70%), 12 hours artificial fluorescent light / 12 hours dark with background music played at a centrally defined bw volume for at least 8 hours during the light period.
The animals were housed individually in Makrolon cages with wire mesh tops and standardized granulated softwood bedding.
Pelleted standard Kliba 3433 rat/mouse maintenance diet and tap water in bottles were available ad libitum.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- The mixtures of the test article and vehicle were prepared daily before administration.
The test substance was weighed into a glass beaker on a tared precision balance and die vehicle added (w/v). The mixtures were prepared using a magnetic stirrer. During die daily administration period, homogeneity was maintained using a magnetic stirrer. - Details on mating procedure:
- After acclimatization, the females were housed with the males (one male one female) in special automatic mating cages, i.e. with synchronized timing to initiate the nightly mating period, until evidence of copulation was observed. This system reduced the variation in the copulation times of the different females. The females were removed and housed individually if: a) the daily vaginal smear was sperm-positive or b) a copulation plug was observed. This day was designated day 0 post coitum. The male rats used for mating were in the possession of RCC. The fertility of these males was proved and was continuously controlled.
- Duration of treatment / exposure:
- day 6 - day 20 post coitum
- Frequency of treatment:
- once daily
- Duration of test:
- until day 21 post coitum
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 5, 15, and 60 mg/kg bw
Basis:
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- The rat is a suitable rodent species for development toxicity studies. The oral route is one possible route of test article exposure. Dose levels were selected, in conjunction with the Sponsor, based on the results of a previous dose range-finding study performed with the test substance.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
POST-MORTEM EXAMINATIONS: Yes - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
- Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: Yes - Statistics:
- The following statistical methods were used to analyze body weights, food consumption, reproduction and skeletal examination data:
- Means and standard deviation of various data were calculated and included in the report.
- The Dunnett many-one t-test, based on a pooled variance estimate, was used for intergroup comparisons (i.e. single treatment groups against the Control group).
- The Steel test (many-one rank test) was applied when the data could not be assumed to follow a normal distribution.
- Fisher's Exact test for 2x2 tables was applied if the variables could be dichotomized without loss of information.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Details on maternal toxic effects:
All females survived until scheduled necropsy. No test article-related clinical signs were observed during the course of the study.
Mean food consumption was slightly reduced in the females of the 60 mg/kg body weight group (between 6.5 and 9.4%) when compared with the control group. This reduction is considered to be due to the test article administration.
The body weight, the body weight gain, and the body weight gain corrected for the uterus weight were slightly reduced in the females of the 60 mg/kg body weight group. When compared with the control group mean body weight on day 21 p.c. was 4.3% lower, and body weight gain between days 6 to 21 p.c. was 12.2% lower (86 g gain versus 98 g for control).
The mean gravid uterus weights of the females treated with 60 mg/kg body weight of the test article was slightly reduced. This reduction was considered to be the consequence of the marginally reduced fetal body and placental weights in this group.
No macroscopical changes were observed in any female during necropsy.
There were no differences noted between control and test article treated groups which indicated an embryotoxic effect.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 15 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
The sex ratios of fetuses in the vehicle control group and in the dose groups were within the normal range of variation for fetuses of this rat strain.
Mean placental weights, calculated on a litter basis, were slightly lower than for the control in the 15 and 60 mg/kg groups (4.7 and 7.0%, respectively), but statistical significance occurred only at 60 mg/kg. lt is possible that this difference in the 60 mg/kg group was associated with the slight reduction in fetal body weight seen at this dosage.
Mean female fetal body weight, assessed on a litter basis, was slightly reduced (4.3%) in the 60 mg/kg group compared with the control group, and the difference was statistically significant. Mean fetal body weight values (litter basis) for males (4.1%) and overall (4.2%), were also slightly lower than for the control group. There were no statistically significant effect on fetal body weights in the 5 and 15 mg/kg groups.
There were no fetuses with changes considered to warrant classification as a malformation.
No visceral variations were observed for fetuses in any group.
Less common skeletal variations occurred in the fetal skeletons of single fetuses in the 5 and 15 mg/kg groups. One fetus of the 5 mg/kg group and one fetus of the 15 mg/kg had bilateral wavy ribs. No association with the test-article was considered to be indicated. Analysis of other skeletal variations on an individual basis showed isolated statistically significant differences in all groups receiving the test article, caused by lower or higher stages
of development. These findings in the 5, 15 or 60 mg/kg groups were considered incidental as a dose dependency was not evident for the statistical significances when calculation was performed on a litter basis. The examination of the cartilage did not reveal differences between control or test article treated groups.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- > 60 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Under die conditions of this study, the oral administration (by gavage) of the test substance to mated female Wistar rats caused only slight adverse effects on the maternal food cansumption and body weight as well as an the placental weights and the fetal body weights at the highest dose level (60 mg/kg). There were no test substance-related influences on other gestational parameters or any signs af teratagenicity up to and including the highest dose level (60 mg/kg).
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.
