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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 266-257-8 | CAS number: 66215-27-8
- 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
Carcinogenicity
Administrative data
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1979/11 to 1982/06
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 982
- Report date:
- 1982
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.32 (Carcinogenicity Test)
- Deviations:
- yes
- Remarks:
- See limitations below
- Principles of method if other than guideline:
- - Seminal vesicles were not listed in the report as being taken for histopathology.
- GLP compliance:
- yes
Test material
- Reference substance name:
- N-cyclopropyl-1,3,5-triazine-2,4,6-triamine
- EC Number:
- 266-257-8
- EC Name:
- N-cyclopropyl-1,3,5-triazine-2,4,6-triamine
- Cas Number:
- 66215-27-8
- Molecular formula:
- C6H10N6
- IUPAC Name:
- N2-cyclopropyl-1,3,5-triazine-2,4,6-triamine
- Test material form:
- solid: particulate/powder
- Remarks:
- coarse cream-coloured
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 4 week old
- Source: Charles River Breeding Laboratories, Portage, Michigan
- Weight at study initiation: Male 14-31 gram, female 14-23 gram
- Housing: The mice were housed individually in hanging wire-mesh cages.
- Diet: Certified Rodent diet was available ad libitum
- Water: Water was available ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature: 21-25°C
- Humidity (%): 32-78%
- Photoperiod: 12/12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet: Diet was prepared every 4 weeks
- The appropriate amounts of the test item were each added to 500 grams of ground diet and mixed in a Hobart mixer for 5 minutes. These premixes were then added to sufficient ground diet to achieve concentrations of 50, 1000 and 3000 ppm and mixed in a twin-shell blender for 10 minutes.
Beginning week 35 and thereafter, the amount of ground diet used for the premix was increased to 2000 grams. Following the 5-minute Hobart mixing period, these premixes were then added to sufficient additional ground diet to achieve the desired concentrations and mixed in a twin-shell blender for 30 minutes.
- Storage temperature of food: Stored at room temperature
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Each lot of test diet was analyzed by Raltech Scientific Services, St. Louis, Missouri.
- Duration of treatment / exposure:
- Following 1 year of test substance administration eight mice/sex/group were sacrificed and necropsied. The remaining animals were sacrificed and necropsied after 24 months of the study.
- Frequency of treatment:
- Continuous exposure through feed.
- Post exposure period:
- Not applicable.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 3 000 ppm
- Remarks:
- High dose group, equivalent to a mean daily intake of 384 mg/kg bw/d for male and 476 mg/kg bw/d for female.
- Dose / conc.:
- 1 000 ppm
- Remarks:
- Mid dose group, equivalent to a mean daily intake of 126 mg/kg bw/d for male and 164 mg/kg bw/d for female.
- Dose / conc.:
- 50 ppm
- Remarks:
- Low dose group, equivalent to a mean daily intake of 6.5 mg/kg bw/d for male and 8.24 mg/kg bw/d for female.
- No. of animals per sex per dose:
- 68 animals/sex/dose
- Control animals:
- yes, plain diet
Examinations
- Observations and examinations performed and frequency:
- The mice were observed for appearance, behavior, overt signs of toxicity and moribundity three times daily on weekdays and twice daily on weekends and holidays. Individual detailed observations were recorded weekly. The mice were observed for mortality at least twice daily.
Individual body weights were recorded weekly the initial 13 weeks of study and bi-weekly thereafter.
Individual food (with test item) consumption was measured for 10 mice/sex/group (randomly selected) weekly the initial 13 weeks of the study and bi-weekly thereafter.
Hematological tests were performed on eight mice/sex/dose at 12 and 24 months of the study.
Hematological determinations included hemoglobin, hematocrit, erythrocyte count, total leucocyte count, platelet count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, differential leucocyte count and reticulocyte count.
- Sacrifice and pathology:
- After 12 months of dietary administration of the test item, 8 mice/sex/dose were sacrificed by carbon dioxide asphyxiation and subjected to a complete postmortem examination. After 24 months, all survivors were similarly sacrificed and examined, and examinations were performed on all animals which died spontaneously or were sacrificed extremis.
Postmortem examinations were directly supervised by a pathologist, and included the external surfaces, all orifices, the cranial cavity, carcass, and the external and cut surfaces of the brain and spinal cord. The thoracic, abdominal and pelvic cavities with their associated organs and tissues and the neck with its associated organs and tissues were examined. Any morphologic changes observed were recorded.
Weights were obtained for the liver, kidney, heart, testis and brain from animals killed at the interim and terminal sacrifices. Before weighing, the organs were trimmed free of excess fat and connective tissue. Weights were obtained for those tissue masses which were subcutaneous, solid, and could be dissected out without damaging associated tissues.
All major tissues and organs were prepared and evaluated histopathologically. - Statistics:
- Body weight gains, body weights, food consumption and hematological
parameters were compared by analysis of variance (one-way classification), Bartlett's test for homogeneity of variances and the appropriate t-test (for equal or unequal variances) as described by Steel and Torrie using Dunnett's multiple comparison tables to judge significance of differences.
All statistical analyses compared the treatment groups with the control group, by sex.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment- related differences noted in clinical condition between control and treated mice.
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- There was no clear dose-related effect on survival. However, the lowest survival was in females fed 3000 ppm cyromazine (40% compared to 51% in controls at 104 weeks).
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significantly lower body weight and body weight gains were noted for males fed 3000 ppm cyromazine throughout the study and 1000 ppm cyromazine from weeks 19 to 87. Females at these dose levels showed occasional statistically significant differences in body weight and body weight gain compared to controls. The differences at 1000 ppm were considered not to be biologically significant. Details are given below.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption was statistically significantly decreased in males treated with 1000 and 3000 ppm cyromazine throughout the study and in females fed 3000 ppm cyromazine, particularly in the first year of the study.
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related effects on the haematological parameters.
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There was no treatment-related effect on organ weights. Occasional statistically significant differences from control in absolute weights were considered to be incidental to treatment or, in the case of the liver weights in males in the 3000 ppm group, associated with the slight body weight reduction.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment-related macroscopic changes were noted at the 12 month interim examinations. At study termination, there was a slightly increased incidence of masses in the livers of treated male mice compared to controls.
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Microscopic examination revealed a variety of non-neoplastic lesions. These lesions were of a similar incidence and distribution to spontaneous lesions in CD-1 mice of a similar age.
No treatment-related non-neoplastic proliferative hepatocellular changes were observed in mice of either sex. Due to the lack of a dose response, the absence of non-neoplastic proliferative changes and absence of similar findings in female mice, the slight increase in hepatocellular neoplasms in treated groups of male mice was considered to be unrelated to the administration of cyromazine in the diet. - Histopathological findings: neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Microscopic examination revealed a variety of neoplastic lesions. Except for hepatocellular neoplasms in male mice, these lesions were of a similar incidence and distribution to spontaneous lesions in CD-1 mice of a similar age.
Several liver neoplasms (hepatocellular adenomas and carcinomas) were observed in control and treated mice. The hepatocellular adenomas were nodular growths producing compression of the surrounding hepatic parenchyma. The larger adenomas produced elevation of the surface of the liver. They were composed of enlarged well-differentiated hepatocytes which formed nodules resembling normal liver. The hepatocellular carcinomas were generally larger than the hepatocellular adenomas and produced marked compression of the adjacent parenchyma. Most of the hepatocellular carcinomas had a distinct trabecular pattern with thickened hepatic plates. The carcinomas were composed of moderately well-differentiated hepatocytes. Nuclear and cytoplasmic pleomorphism was marked and the number of mitotic figures was increased in many of the hepatocellular carcinomas.
Pulmonary metastasis was observed in one male mouse at 1000 ppm that had hepatocellular carcinoma.
Although the incidence of total liver neoplasms was slightly greater in treated groups than in the control group, there was a distinct absence of a dose-related response in the incidence of these neoplasms. The incidence of liver neoplasms in the female mice was very low and with no treatment- related increase present in the female mice.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 164 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 126 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Results are provided in the overall remarks section below.
Applicant's summary and conclusion
- Conclusions:
- Based on the results of a carcinogenicity study in mice, the NOAEL was set at 1000 ppm cyromazine (corresponding to 126 and 164 mg/kg b.w./day in males and females, respectively) based on reduced body weight gain at 3000 ppm. The study results did not indicate carcinogenic properties of Cyromazine.
- Executive summary:
Cyromazine was dietary administered to male and female CD mice at doses of 0, 50, 1000 and 3000 ppm. Eight male and 8 female mice were assigned from each group for interim clinical pathology investigations after 52 weeks of treatment. The remaining mice were kept on the study for two years. Samples from all dietary levels (including controls) were taken at intervals throughout the study and analysed to confirm concentration, stability and homogeneity.
Clinical observations, bodyweights, food consumption and haematological parameters were measured throughout the study. At the end of the scheduled period the animals were killed and subjected to a full examination post mortem. Selected organs were weighed and specified tissues were taken for subsequent histopathology examination.
There was no evidence of inflammatory, degenerative or neoplastic lesions in mice, with the exception of a slightly higher number of hepatocellular neoplasms in male mice. However, the lack of non-neoplastic proliferative lesions in the liver, the absence of a dose-related response and absence of similar changes in female mice indicates that this observation was most likely not related to treatment with the test compound.
As a result, the NOAEL was set at 1000 ppm cyromazine (corresponding to 126 and 164 mg/kg bw/day in males and females, respectively), when administered in the diet to male and female mice for a period of two years, based on reduced body weight gain at 3000 ppm. The study results did not indicate carcinogenic properties of cyromazine.
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.