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EC number: 613-953-8 | CAS number: 66603-10-9
- 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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Remarks:
- subacute inhalation toxicity study
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 16.02.76 - 22.03.76
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 978
- Report date:
- 1978
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Test of the inhalation toxicity followed the method of KIMMERLE (H. NIESSEN, H. TIETZ, G. HECHT and G. KIMMERLE, Arch. toxicol. 20, 44, 1963)
- Version / remarks:
- Test has been performed before publication of the OECD Guidelines for the Testing of Chemicals
- Principles of method if other than guideline:
- - Principle of test: repeated daily inhalation exposure to the test substance.
- Short description of test conditions: 10 male and 10 female rats were exposed 18 times 6 hours per working day; the undiluted product (3 % aqueous K-HDO) was atomised by a continuous infusion apparatus with a constant amount of 12 ml per hour and with 600 litres pressurized air (8 atü (atü = technical atmosphere above reference level)) / hour. The animals of the control group were exposed in an equal apparatus by which 12 ml demineralised water per hour were atomized with 600 litres pressurized air (8 atü) / hour. The total test period was 4 weeks (28 days)
- Parameters analysed: body weight, clinical symptoms, clinical chemistry and haematology, pathology - GLP compliance:
- no
- Remarks:
- GLP was not mandatory at the time the study was performed
Test material
- Reference substance name:
- Cyclohexylhydroxydiazene 1-oxide, potassium salt
- EC Number:
- 613-953-8
- Cas Number:
- 66603-10-9
- Molecular formula:
- C6H11KN2O2
- IUPAC Name:
- Cyclohexylhydroxydiazene 1-oxide, potassium salt
- Test material form:
- solid: particulate/powder
- Details on test material:
- Test item: (N-Cyclohexyl-diazeniumdioxy)-potassium
IUPAC name: Cyclohexylhydroxydiazene 1-oxide, potassium salt
Chemical name: Cyclohexylhydroxydiazene 1-oxide, potassium salt; synonyma: (N-Cyclohexyl-diazeniumdioxy)-potassium, K-HDO, K-NCH, Xyligen K powder, Xyligen K
Molecular formula: C6 H11 K N2 O2
Molecular mass: 182.27
Constituent 1
- Specific details on test material used for the study:
- Nomination of test substance: Reu-E 3403 (Xyligen-K)
Formulation: 3 % aqueous solution
Chemical name: N-cyclohexyl-diazeniumdioxy-Kalium (K-HDO)
Substance number: XXV / 437
Appearance: honey-yellow liquid
Purity: technical
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: SPF-breed, Company WIGA, Sulzfeld, Germany
- Age at study initiation: 35 days
- Weight at study initiation: male rats: 90 (83-100) g / female rats: 85 (77- 91) g
- Housing: during the exposure-free time 3 or 2 rats were kept in one V2A wire cage (bottom area ca. 750 cm²) in a conventional heated and aerated room.
- Diet (e.g. ad libitum): Altromin-R of company ALTROGGE Lage/L ad libitum
- Water (e.g. ad libitum): tap water ad libitum during exposure-free time
- Acclimation period: animals were exposed in an inhalation chamber during a pre-streaming period of 5 days for 6 hours per day to a fresh-air stream of 600 litres per hour
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation chamber
- Source of air: pressurized air
- System of generating particulates/aerosols: permanent infusion apparatus
- Pressure in air chamber: 8 atü / per hour
- Air flow rate: 600 litres pressurized air per hour
- Test concentration: 20 µl Xyligen K per litre air
- Volume of test substance applied to the infusion apparatus: 12 ml
- Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- No analysis performed
- Duration of treatment / exposure:
- 18 times 6 hour per day; total test period of 4 weeks
- Frequency of treatment:
- daily during working days
Doses / concentrations
- Dose / conc.:
- 20 other: µl/L
- Remarks:
- The undiluted product (= 3 % aqueous Xyligen K) was constantly applied to the apparatus in a volume of 12 ml/ hour and atomized with 600 litres pressurized air / hour
- No. of animals per sex per dose:
- 10 animals per sex and dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- The test of the inhalation toxicity was carried out according to the method of Kimmerle (H. Niessen, H. Tietz, G. Hecht, and G. Kimmerle, Arch. toxicol. 20, 44, (1963).
After a pre-inhalation period of 5 days, during which the animals were exposed in the inhalation chambers at a time for 6 hours to a fresh air stream of 600 litres per hour, the daily (working-day) 6-hour exposure to an aqueous 3% solution of Xyligen K of totally 18 times exposures started.
The undiluted test substance (Xyligen K as 3 % aqueous solution) was administered in constant amounts of 12 ml/h (via infusion apparatus type UNITA I from B. Braun, Melsungen) and sprayed with 600 litres compressed air (8 atü)/hour into the inhalation chamber. The exposure period was 6-hours/working day.
The animals of the control group were exposed to demineralised water under the same test conditions.
A dosage of 12 ml aqueous Xyligen K solution in 600 litres air per hour amounts to a nominal concentration of 20-µg/l air or, on acceptance of a density of 1 g/ml, a value of 20 mg/l air. - Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Behaviour and appearance were controlled daily
BODY WEIGHT: Yes
- Time schedule for examinations: 2 times per week (Monday and Thursday)
MORTALITY: Yes
- Time schedule for examinations: daily
FOOD EFFICIENCY:
- Body weight gain has been determined
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 7 days before start of substance application (blood sampling 0) as well as 14 and 28 days after inhalation start (blood sampling 1 and 2) blood was collected from all animals from the retroorbital venous plexus. Blood collection occurred each between 7:00 and 11:00 a.m.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 7 days before start of substance application (blood sampling 0) as well as 14 and 28 days after inhalation start (blood sampling 1 and 2) blood was collected from all animals from the retroorbital venous plexus. Blood collection occurred each between 7:00 and 11:00 a.m.
- How many animals: all animals
- Parameters examined:
+Chemogram: sodium, potassium, carbon dioxide, chloride, calcium, inorganic phosphate, glucose, urea, total protein, total lipids, total bilirubin, creatinine
+Enzymogram: Glutamate-pyruvate-transaminase, alkaline phosphatase
+Haematogram and differential blood haemogram: Haemoglobin, erythrocytes, haematocrit, haemoglobin content of the single erythrocytes (HbE), mean cellular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), thrombocytes, leukocytes, differential blood haemogram
URINALYSIS: Yes
- Time schedule for collection of urine: 10 and 24 days after inhalation start (urine collection 1 and 2) urine was collected from all animals over night
- Parameters examined: pH-measurement, protein, glucose, urobilinogen, sediment-microscopy - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
SECTION:
- After termination of the test period, the animals were sacrificed after a fasting-period of 16 hours. Killing occurred after anaesthetising with CO2 via decapitation and bleeding. Afterwards the animals were weighed, dissected, and macroscopically evaluated. Subsequently the organs were weighed.
BODY AND ORGAN WEIGHTS:
- Parameters tested: bloodless body weight, organ weights of: heart, liver, kidneys, spleen, testis, thyroid gland, adrenal gland, lung. From this the relative organ weights (organ weight/100 g body weight) have been calculated
HISTOPATHOLOGY: Yes
The organs preserved in 4% buffered, neutral formalin solution were in part or in toto histologically processed.
Examined organs: cerebellum, cerebrum, pituitary, thyroid gland, adrenal glands, uterus, ovaries, epididymis, testis, urinary bladder, kidney, spleen, pancreas, liver, submandibular glands; colon, jejunum, ileum, duodenum, stomach, oesophagus, lung, trachea, heart. The organs of all animals of the Xyligen K test group were microscopically examined.
Methods used: hematoxylin – eosin method (all organs), Lillie's Oil Red O Method (lung, liver, kidney), PAS reaction - Other examinations:
- No other examinations performed
- Statistics:
- Mean values, standard deviation and standard error have been calculated. T-test according to Williams (body weight, organ weights). chi2 test (urinalysis)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- All control and test animals showed no toxication symptoms during the test period and were in a good physical status.
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One female of totally 20 test substance exposed animals died intercurrent during the 11th exposition without specific clinical symptoms.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Body weight gain of the test animals was unimpaired.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Comparison of the body weight gain of the male and female rats showed no significant difference between the control group and the Xyligen K test group.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Description (incidence and severity):
- Erythrocytes, haematocrit, MCV, differential blood count: unaffected
Haemoglobin: increased after blood donation 2 (females)
HbE, MCHC: decreased after blood donation 2 (males)
Leukocytes: decreased solely after blood donation 1 (males) - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- – Sodium, potassium, CO2, urea, total protein were not influenced
– Chloride: solely increased after blood donation 1 (males)
– Calcium: solely decreased after blood donation 1 (males)
– Anorg. phosphyte: increased after blood donation 2 (males)
– Glucose: increased solely after blood donation 1 (females)
– Total lipids: decreased after blood donation 2 (males)
– Bilirubin: increased solely after blood donation 1 (males and females)
– Creatinine: increased (females) and decreased (males), respectively after blood donation 2
Enzymes:
- Glutamate-pyruvate-transaminase: unaffected
- Alkaline phosphatase: increased after blood donation 2 (males) - Description (incidence and severity):
- PH, protein, glucose, urobilinogen: unaffected
Sediment: after urine donation 2, increase of round epithelia (males) and increase of leucocytes (females), respectively - Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- See haematological findings
- Description (incidence and severity):
- Absolute organ weights:
– Liver weight of the male animals of test group 1 was reduced (S ≥ 99 %).
Relative organ weights:
– reduced relative liver weights of the male animals of test group 1 (S ≥ 95 %)
– increased relative weights of adrenal glands and thyroid glands of the male animals (S ≥ 95 %) - Description (incidence and severity):
- Gross and histopathology:
The animals of the control- and the test group showed, caused by death, changes of the heart and the lungs, thereunder erythrodiapedesis, blood aspiration, and dystelectasis as well as rat-specific lymphocytic focal-like predominant peribronchial lungs- and liver infiltrates. In addition, hydrometra was seen several times on female animals. Several female animals of both test groups showed a slight extra-marrow haemopoiesis.
The male animals of the substance-treated group showed a slight increase of the foam cells in the lung. The female animals showed a slight fatty metamorphosis of liver. Three female rats had focal-like liver necrosis. The intercurrent after 15 days perished female rat of the test substance-treated group showed hyperaemia of the lung, liver, adrenal glands, and the hypophysis as well as tubolonephrosis and a slight vacuolisation of the adrenal glands (Zona fasciculata).
Valuation of the findings:
Histological focal like liver necrosis was primarily seen on 3 female animals as well as a slight increase of foam cells in the lungs of active-exposed male animals. In addition, a slight decrease of the absolute and the relative liver weights were seen on male animals of the active exposed dose group. A coherency with the application of the active cannot be ruled out, even though at least the histological liver changes are single findings. - Neuropathological findings:
- not examined
- Description (incidence and severity):
- see above
- Description (incidence and severity):
- see above
- Other effects:
- no effects observed
- Description (incidence and severity):
- No signs of intolerance or intoxication after an exposure period of 4 weeks (6 /day) observed.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Remarks on result:
- other: see remarks
- Remarks:
- a detailed description of the results is given in the summary below
Target system / organ toxicity
- Key result
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- No clinical signs of intoxication or incompatibility observed during and after eposure.
- Executive summary:
Xyligen K has been tested in a subacute inhalation test with rats as 3 % aqueous solution in a nominal concentration of 20 µl/l air (equivalent to 0.6 mg Xyligen K/l air). For control, rats have been exposed under identical test conditions to the solvent (demineralised water).
The test period was 4 weeks with working-daily 6-hours exposure.
No clinical signs of intoxication or incompatibility have been seen during and after the single expositions. Body weight gain of the animals was not affected.
One female of totally 20 test substance exposed animals died intercurrent during the 11th exposition without specific clinical symptoms.
Regarding the clinical chemistry and the haematology only male animals showed a decrease of the blood total lipid values as well as an increase of the activity of the alkaline phosphatase. The urine sediment of the male animals showed an increase of the round epithelia. The urine sediment of the female animals showed an increase of the leucocytes. A clear test substance induced change cannot be stated because of the lack of adequate clinical and additional clinical-chemistry findings, respectively.
Regarding gross-pathology a significant decrease of the relative and absolute liver weights of the substance treated male animals has been seen.
The histopathological examination showed focal-like liver necrosis for 3 substance treated female animals as well as a slight increase of the foam cells in the lungs of male animals.
A coherency with the application of the active ingredient cannot be ruled out although, at least the liver changes, were single findings.
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