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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 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: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- June 2, 1989 - July 3, 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EPA-TSCA-Test Guideline "Functional Observational Battery"
- Version / remarks:
- Federal Register, Vol. 50, No. 188, September 27, 1985, pp. 39458 - 39461, amended on May 20, 1987
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EPA-TSCA Guideline "Neuropathology"
- Version / remarks:
- Vol. 52, No. 97, pp. 19081 - 19082
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
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:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Reu E 7350e
- Purity test date: N-Cyclohexyldiazeniumdioxy-potassium-hydrate powder, purity 100 % calculated as hydrate
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: before start and during test: test room temperature
- Stability under test conditions: stable
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
The test substance was weighed out and thorougly mixed with a small amount of feed in a beaker. The premix was subsequently prepared in a household mixer. A corresponding amount of feed was then added to the premix to obtain the desired concentration, and mixing was carried out for about 10 minutes in a laboratory mixer. The test substance preparations were prepared once for the whole study period.
FORM AS APPLIED IN THE TEST (if different from that of starting material)
see above
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Male and female Wistar rats from Dr. Karl Thomae GmbH, D-W7950 Biberach/Riss, FRG, which were free of signs of disease, were used for the investigations. The rats were unambiguously identified by tattoo of the respective animal number into the left ear.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, D-W7950 Biberach/Riss, FRG
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 42 days
- Weight at study initiation (mean body weight): 176 g (male), 140 g (female)
- Fasting period before study: The animals were daily fed with the test substance preparations until the start of the fasting period (withdrawal of feed) of about 16 - 20 hours before necropsy.
- Housing: During the study, the rats were housed singly in type DK III stainless steel wire cages from Becker & Co., D-W4620 Castrop-Rauxel, FRG (floor area about 800 cm²). The animals were housed in a completely air-conditioned room in which a central air-conditioner ensured temperatures in the range 20 - 24°C and relative humidities in the range 30 - 70%. The day/night rhythm was 12 hours (12 hours light from 06.00 - 18.00 h, 12 hours dark from 18.00 - 6.00 h). Deviations from these ranges did not occur. The room was completely disinfected before the start of the study. The walls were cleaned once a week and the floor twice a week, in each case using water containing 0.1 % Incidin perfect®.
- Diet: ad libitum throughout the study (acclimatisation and administration period)
- Water: ad libitum throughout the study (acclimatisation and administration period).
- Acclimation period: 7 days
DETAILS OF FOOD AND WATER QUALITY:
The feed received by the animals was Kliba rats/mice/hamsters maintenance diet, 343 meal, Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland. The feed batch used in the study was assayed for contaminants.
The drinking water was regularly assayed for contaminants by the municipal authorities of D-W6710 Frankenthal, FRG, and by the Department of Water Chemistry and Technical Services of BASF Aktiengesellschaft.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): see above
- Humidity (%): see above
- Air changes (per hr): see above
- Photoperiod (hrs dark / hrs light): see above
Administration / exposure
- Route of administration:
- oral: feed
- Details on route of administration:
- Application via diet
- Vehicle:
- other: food
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test substance was weighed out and thoroughly mixed with a small amount of feed in a beaker. The premix was subsequently prepared in a household mixer. A corresponding amount of feed was then added to the premix to obtain the desired concentration, and mixing was carried out for about 10 minutes in a laboratory mixer. The test substance preparations were prepared once for the whole study period.
The homogeneous distribution of the test substance in the feed was checked using 6 samples, which were taken at the beginning of the study, of the concentration used.
DIET PREPARATION
- Rate of preparation of diet (frequency): The test substance preparations were prepared once for the whole study period.
VEHICLE
- Justification for use and choice of vehicle (if other than water): feeding study
- Concentration in vehicle: 900 ppm corresponding to a mean daily substance intake of about 82 mg/kg body weight in the male rats and of about 90 mg/kg body weight in the female rats.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- ANALYSES OF THE TEST SUBSTANCE:
The analyses regarding the characterization of the test substance were carried out prior to the start of the study. The degree of purity of the test substance was 91% (calculated: free of water) or 100% (calculated as hydrate), respectively.
ANALYSES OF THE DOSES:
The method used for analyses of doses in the feed (extraction out of the carrier and colorimetric determination) resulted in recovery rates of less than 80% due to the poor extractability of the test substance. The analytical results for potassium hydrate can be extrapolated from the analytically verified copper values (Project No. 20C0124/88078). Therefore, all values obtained with the colorimetric determination have to be calculated with the recovery rate. The following results were obtained: The homogeneity analyses of the 900 ppm dose revealed that the test substance was homogeneously distributed in the feed and the concentration was correct. The stability analyses carried out over a period of 10 and 32 days showed that the test substance is stable for these periods: calculated with the recovery rate of the starting value, the values obtained correspond to 93% (after 10 days) and 91% (after 32 days) of the expected values. As some animals received the test substance for 36 days due to technical reasons, it was assumed, based upon the above mentioned findings, that the test substance would be stable also for 36 days in the feed.
FEED ANALYSES: :
On the basis of duration of use and the analytical findings the feed was found to be suitable. Fed. Reg. Vol. 44, No. 91 of Hay 9, 1979, p. 27354 (EPA) served as a guideline for maximum tolerable contaminants. - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily by food
Doses / concentrationsopen allclose all
- Dose / conc.:
- 900 ppm
- Remarks:
- corresponding to a mean daily substance intake of about 82 mg/kg body weight in the male rats and of about 90 mg/kg body weight in the female rats.
- Dose / conc.:
- 0 ppm
- Remarks:
- The control group (5 male and 5 female Wistar rats) of a study running in parallel(Project No. 20C0124/88078) was used.
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent no treatment
- yes, plain diet
- Details on study design:
- - Dose selection rationale: The dose was chosen on the basis of the following investigations (1, 2, 3):
1) Study of the acute toxicity of N-cyclohexyldiazeniumdioxy-potassium-hydrate on rats (BASF Aktiengesellschaft, Project No. XXV/210)
2) Study of the subchronic oral toxicity (3 months) of N-cyclohexyldiazeniumdioxy-potassium-hydrate on rats (Laboratorium fur Pharmakologie und Toxikologie, Prof. Dr.med. F. Leuschner, 1978)
3) Study of the palatability of N-cyclohexyldiazenium dioxy-potassium-hydrate on rats BASF Aktiengesellschaft
- Rationale for animal assignment (if not random): Before the start of the administration period the animals were distributed according to weight among the test group separated by sex. The randomization list was drawn up by a computer (laboratory data processing, Department of Toxicology, BASF Aktiengesellschaft). - Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: A check was made for dead or moribund animals twice a day (Mondays to Fridays) and once a day (Saturdays, Sundays and public holidays)
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: The animals were examined twice daily (Mondays to Fridays) or once a day (Saturdays, Sundays and public holidays) for any evident signs of toxicity. Once weekly they underwent an additional detailed clinical examination.
BODY WEIGHT: Yes
- Time schedule for examinations: the body weight was determined once a week and at the start of the study (day 0)
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- The feed consumption was determined once a week during the period of administration.
FOOD EFFICIENCY: Yes
- Body weight gain: has been determined
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: once a week
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: end of study (three days prior to necropsy )
- Anaesthetic used for blood collection: Not specified
- Animals fasted: No
- How many animals: 5 animals per sex and test group
- Parameters tested: Leukocytes, erythrocytes, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelets, differential blood count, reticulocytes, clotting analysis (thromboplastin time), haemoglobin derivatives (total haemoglobin, oxyhaemoglobin, carboxyhaemoglobin, methaemoglobin, content of oxygen bound to haemoglobin, oxygen saturation, reduced haemoglobin, oxygen capacity), clotting analysis (thromboplastin time)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: end of study (three days prior to necropsy )
- Animals fasted: Yes / No / Not specified
- How many animals: 5 animals per sex and test group
- Parameters tested: Enzymes: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum-gamma-glutamyltransferase
Blood chemistry: Sodium, potassium, chloride, inorganic phosphate, calcium, urea, creatinine, glucose, total bilirubin, total protein, albumin, globulins, triglycerides, cholesterol, magnesium
URINALYSIS: Yes
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Not specified
- Parameters tested: Appearance, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood, sediment
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: The observation of the neurofunction was made on all animals once prior to the start of the test substance administration, 24 hours after the first administration and on days 7, 14 and on day 27.
- Dose groups that were examined: all dose groups were examined
- Battery of functions tested: The examination of the neural functions was performed using a "functional observational battery"· which includes various parameters of sensoric and motoric functions as follows: general appearance, tremors, convulsions, piloerection, lacrimation/secretion of pigmented tears, salivation, pupil size, diarrhea, vocalization, paresis, paralysis, ataxia, body tone, posture, animal body (appearance), locomotor activity, respiration, urination, skin colour, righting reflex, behaviour, grip strength, pupillary reflex, winking reflex, vision, audition, olfaction, sensitivity of the body surface, pain perception (hot plate test), tail pinch, toe pinch, visual placing response, miscellaneous: all other visible clinical signs.
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Organs: Duodenum, jejunum, ileum, cecum, colon, rectum, liver, kidneys, brain, all gross lesions
HISTOPATHOLOGY: Yes
Organs: Duodenum, jejunum, ileum - Statistics:
- STATISTICAL EVALUATION
Clinical examinations:
The parameter substance intake was determined using the following formula:
substance intake: (FC • D) ⁄ BWX
FC: mean daily feed consumption (in g) from day X - 7 to day X
D: Dosage in ppm
BWX: Body weight on day x of the study (in g)
For the statistical evaluation of the study, means and standard deviations were calculated for the variables feed consumption, water consumption, body weight, substance intake, grip strength (fore and hind limbs) and hot-plate test for the animals, and printed out in the form of tables.
The statistical significance of the clinical data was determined by the MANN-WHITNEY-U-test.
Significances (p-markers: * for p ≤ 0.05, ** for p ≤ 0.02, *** for p ≤ 0.002) resulting from the test have been shown in the tables.
Clinical chemistry and hematology:
Mean and standard deviation were calculated for each test group and tabulated together with the individual values. Except for the differential blood count, a statistic analyses is done via the Mann-Whitney-U-test. If the results of this test are significant, p-markers (* for p ≤ 0.05, ** for p ≤ 0.02, *** for p ≤ 0.002) were printed together with the group mean in the tables.
Urinalyses:
The assessment to whether certain characteristics differed in degree in the control and test groups was carried out using the chi² test in appropriate two-by two contingency tables.
Significances which resulted from this chi² test have been indicated in the tables (* for p ≤ 0.05, ** for p ≤ 0.01).
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The only clinical finding was a discoloration of the faeces at a dose of 1500 ppm. This finding was considered to represent a chemical reaction of the test substance in the digestive tract rather than being the consequence of a toxic effect of the animals.
- Mortality:
- no mortality observed
- Description (incidence):
- No animal died intercurrently during the test period.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The body weight gain of the male and female animals of the 900 ppm group was not affected by the test substance administration when compared to the control group.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- When compared to the untreated controls (Project No.: 20C0124/88078), no substance-related effects were seen regarding the amount of feed consumed daily.
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- The amount of test substance intake (in mg) was calculated based upon the weekly determined feed consumption and the week1y determined body weight. The average daily test substance intake was for the male rats (900 ppm) about 82 mg/kg body weight. The female rats (900 ppm) had a mean daily substance intake of about 90 mg/kg body weight.
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- There were no statistically significant differences between the water consumption of the male or female animals of the 900 ppm group and the corresponding control group.
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No substance related effects were observed
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- Throughout the administration period, male and female animals (900 ppm) showed no abnormal clinical symptoms.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No substance related effects were observed
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- Neurofunctional tests:
No substance related changes of grip-strength of forelimbs, grip strength of hind limbs, or in the Hot Plate Test were seen in male and female animals of the three dose groups in comparison to the control group. The statistically significantly reduced value in the hot plate test of test group 2 (females) on day 1 can be assessed as an outlier. All other results of the “functional observational battery” also revealed no evidence that the test substance might be neurotoxic under the chosen conditions. - Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- The mean organ weights (absolute and relative) showed slight fluctuations, which did not give any indication of a relationship to the substance.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- no effects observed
- Description (incidence and severity):
- The grip strength of the fore limbs of the males was statistically significantly increased on day 14, and the grip strength of the hind limbs of the females was significantly reduced on day 1.
Both findings were assessed as being incidental and not related to the test substance administration. All other results of the “functional observational battery" also revealed no evidence that the test substance might be neurotoxic under the chosen conditions - Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 90 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- NOAEL for K-HDO > 90 mg/kg bw/day or
NOAEL for 30% K-HDO > 300 mg/kg bw day - Executive summary:
The aim of the study was to investigate the mechanistic effect of N-Cyclohexyldiazeniumdioxy-potassium-hydrate on the digestive tract after 4 weeks administration via the diet. Particular attention was paid to possible neurotoxic effects.
The oral administration of 900 ppm (mean daily substance intake of about 82 mg/kg body weight in the male rats and of about 90 mg/kg body weight in the female rats) for a period of 4 weeks caused the following substance induced changes:
-increase in magnesium in both sexes
-increase in inorganic phosphatase and calcium in the females.
-decrease in glucose and triglycerides in the females
The results of clinical examinations, neurofunctional tests, or pathological investigations did not show any substance-related changes.
There were no indications of any damage to the intestinal mucosa. In particular, there were no signs of any irritant effect.
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.