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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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1978
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- The study was performed as part of the data-set for an Active Substance dossier submitted under Reg. (EC) No 1107/2009.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 978
- Report date:
- 1978
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The study was not performed based on specific guideline.
The excretion and tissue distribution of cyromazine was investigated in two male and one female rats administered a single oral dose of radiolabeled cyromazine. Exhaled volatile metabolites were collected from one rat of each sex. All test animals were housed singly in metal metabolism cages for 72 hours, post dosing, for the collection of urine and faeces.
At termination several tissues (brain, fat, heart, kidneys, liver, lungs, muscle, ovaries, spleen, testes and whole blood) were taken for the measurement of radioactivity present. - GLP compliance:
- no
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
- Details on test material:
- [U-ring-14C]-N-cyclopropyl-1,3,5-triazine -2,4,6-triamine
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- other: Charles River white rats
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
Weight: approximately 170 g each
Housing: One female and two male rates were kept in individual Roth metabolism cages. One female and two male rates were kept in metal cages. Each glass cage was fitted with a dry ice-acetone trap to collect volatiles and a second trap containing 100 ml of 2N NaOH to absorb respiratory CO2.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- carbowaxe
- Remarks:
- Aqueous Carbowax 400 formulation (1:1 v/v)
- Details on exposure:
- The rats were dosed orally one time with 0.1 mg of [U-14C triazine]-Cyromazine in 1.0 ml of solution. The dose rate was 0.5 mg/kg (equivalent to 5 ppm in feed).
- Duration and frequency of treatment / exposure:
- Single oral dose
Doses / concentrations
- Dose / conc.:
- 0.5 mg/kg diet
- Remarks:
- Dose rate equivalent to 5 ppm feed
- No. of animals per sex per dose / concentration:
- Two male and one female rats got a single dose
- Control animals:
- no
- Details on study design:
- The excretion and tissue distribution of radioactivity was investigated in two male and one female rats administered a single oral dose of 0.5 mg [U-14C triazine]- cyromazine/kg. Exhaled volatile metabolites were collected from one rat of each sex housed individually in glass metabolism cages. All test animals were housed singly in metal metabolism cages for 72 hours, post dosing, for the collection of urine and faeces.
Then, test rats were terminated and a several tissues (including brain, fat, heart, kidneys, liver, lungs, muscle, ovaries, spleen, testes and whole blood) were taken for the measurement of radioactivity present. All samples were analysed for radioactivity by liquid scintillation counting either directly or following sample oxidation. Metabolite profiles in excreta were investigated either by thin layer chromatography or by an Aminex A-5 cation exchange column. - Details on dosing and sampling:
- Exhaled volatile metabolites were collected from one rat of each sex housed individually in glass metabolism cages. All test animals were housed singly in metal metabolism cages for 72 hours, post dosing, for the daily collection of urine and faeces.
Results and discussion
- Preliminary studies:
- No preliminary study was conducted.
Main ADME resultsopen allclose all
- Type:
- metabolism
- Results:
- Unchanged parent compound was dominant in urine (ca.80%), 3 minor metabolites each of which represented less than 5% of the given dose. Faecal metabolite profile similar to urine.
- Type:
- distribution
- Results:
- Three days after oral dosing, tissue residues were very low, with <0.007 ppm in the liver and <0.003 ppm in all other tissues.
- Type:
- excretion
- Results:
- 97% of the administered dose was excreted within 24 hours, predominantly via the kidneys
- Type:
- absorption
- Results:
- appeared to be almost complete
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- The predominant route of excretion was via the kidneys, with approximately 94% or more of the dose excreted in urine. Faecal elimination accounted for just 4% and 1% of the administered dose in males and the female respectively.
- Details on distribution in tissues:
- Three days after oral dosing, tissue residues were very low, with <0.007 ppm in the liver and <0.003 ppm in all other tissues.
- Details on excretion:
- The predominant route of excretion was via the kidneys, with approximately 94% or more of the dose excreted in urine. Faecal elimination accounted for just 4% and 1% of the administered dose in males and the female respectively. Virtually, no radioactivity was recovered from exhaled air.
Metabolite characterisation studies
- Metabolites identified:
- not specified
- Details on metabolites:
- Urine contained predominantly the unchanged parent compound, which accounted for approximately 80% of the administered dose and 3 minor metabolites each of which represented less than 5% of the administered dose. Faecal metabolite profiles appeared similar to urine, but because of the low levels of faecal radioactivity, it was not possible to confirm that the metabolites corresponded to those excreted in urine.
Quantitatively determination whether the triazine ring remained intact for urine radioactivity was not possible.
Any other information on results incl. tables
Table 1: Mean recovered radioactivity over 72 hours following a single oral dose of 0.5 mg [U-14C triazine]-cyromazine/kg in rats
Sample | % of administered radioactivity | |
Male (n=2) | Female (n=1) | |
Urine | ||
0-24 hours | 93.8 | 96.6 |
24-48 hours | <0.3 | 0.5 |
48-72 hours | <0.2 | 0.3 |
Sub-total | 93.8 | 97.4 |
Faeces | ||
0-24 hours | 3.8 | 0.6 |
24-48 hours | <0.1 | 0.4 |
48-72 hours | <0.1 | <0.1 |
Sub-total | 3.8 | 1.0 |
|
|
|
Cage wash | <0.1 | <0.1 |
Volatile metabolites | <0.1 | <0.1 |
Exhaled carbon dioxide | <0.1 | <0.1 |
Tissues | <0.1 | <0.1 |
Blood | <0.1 | <0.1 |
Intestinal tract | <0.1 | <0.1 |
Total recovery |
97.5 |
98.4 |
Table 2: Tissue residues (ppm) 72 hours following a single oral dose of 0.5 mg [U-14C triazine]- cyromazine/kg in rats
Tissue Sample | ppm (µg radiolabeled cyromazine/mg tissue) | |
Male (n=2) | Female (n=1) | |
Blood | <0.002 | <0.002 |
Liver | <0.007 | <0.007 |
Kidneys | <0.002 | <0.002 |
Spleen | <0.002 | <0.002 |
Heart | <0.003 | <0.003 |
Brain | <0.002 | <0.002 |
Ovaries | - | <0.003 |
Testes | <0.003 | - |
Muscle | <0.003 | <0.003 |
Fat | <0.002 | <0.002 |
Table 3: Distribution characteristics of [U-14C triazine]- cyromazine and its metabolites (0-24 hours)
characterization | Percent of Dose | ||
A.TLC | Urine | Feces** | Total |
Cyromazine | 82.5 | - | 82.5 |
Metabolite A* | 3.2 | - | 3.2 |
Metabolite B* | 5.5 | - | 5.5 |
Metabolite C* | 4.6 | - | 4.6 |
B. Aminex A-5 |
|
|
|
Cyromazine | 79.2 | <0.1 | 79.2 |
Metabolite 1 | 2.2 | <0.1 | 2.3 |
Metabolite 2 | 3.0 | 0.1 | 3.1 |
Metabolite 3 | 5.3 | 4.1 | 9.4 |
* It could not be determined if Metabolites A, B, and C, separated on TLC, corresponded to Metabolites 1, 2 and 3, separated on Aminex A-5, because of the low amounts of radioactivity.
** Small amounts of radioactivity in the feces extract did not allow for seperation on TLC plates because of overloading with co- extractants.
Applicant's summary and conclusion
- Conclusions:
- A single oral dose of 0.5 mg/kg of [U-14C triazine]-cyromazine was almost quantitatively absorbed and rapidly excreted, almost exclusively in the urine. Greater than 97% of the dose was eliminated within 24 hours post dosing while, tissue residues were very low 72 hours after dosing. Cyromazine was poorly metabolised as greater than 80% of the dose was excreted unchanged; there were 3 minor metabolites detected in excreta, each representing less than 5% of the dose.
- Executive summary:
Three rats were given a single dose of [U-14C triazine]-Cyromazine at a rate of 0.5 mg/kg (equivalent to 5 ppm in the food). Overall recovery was 97.8%. Most of the radioactive dose was excreted in the urine (95%) with a small amount in the feaces (2.8%). Volatiles and respiratory CO2 contained less than 0.1% of the dose. Tissues, cage wash, and intestinal tract contained less than 0.1% of the dose.
Tissue levels were low. Radioactivity equivalent to [U-14C triazine]-Cyromazine in all tissues analysed and blood was less than 0.01 ppm. Rats metabolized the test material slowly to three minor metabolites. These metabolites in urine and feces accounted for 14.8% and unmetabolized test material accounted for 79.2% of the total radioactive dose. The conversion of urine radioactivity to cyanuric acid using nitric acid gave non-reproducable recoveries. Similar results were obtained using standard test material. This methodology cannot quantitatively determine whether the triazine ring remains intact for urine radioactivity. Based on only a small amount of 14CO2, the triazine ring is probably intact for all metabolites of the test material.
When dosed orally, the rat was found to rapidly absorb and excrete the test material with minor metabolism. Because of the apparent low lipid solubility of this polar compound, there was little observed tissue retention.
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