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EC number: 231-832-4 | CAS number: 7758-09-0
- 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
Endpoint summary
Administrative data
Description of key information
Repeated dose toxicity: Oral
A subchronic oral toxicity study with test chemical was carried out in groups of ten male and ten female 6-wk-old rats. No mortality observed and the rats appeared to be healthy throughout the study. Effects were observed in food and water consumption, opthalological and haematological effects were observed. It was concluded that in the study reported here the NOEL is lower than I00 mg /litre in the drinking-water, which is equivalent to a level lower than 10 mg /kg body weight/day and a NOAEL of 300 mg/L drnking water was observed.
Repeated dose toxicity: Inhalation
According to column 2 of Annex VIII, exposure by inhalation route is negligible on account of high boiling points (as has been informed in the boiling point that is greater than 300 °C).
Repeated dose toxicity: Dermal
The acute dermal toxicity value for test chemical is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from publication
- Qualifier:
- according to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- To determine Subchronic oral toxicity study of test chemical on Rats.
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Weanling, Wistar derived SPF-bred rats (Bor; WlSW)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Winkelmann (Institute for the Breeding of Laboratory Animals GmbH & Co. KG, Borchen, FRG).
- Females (if applicable) nulliparous and non-pregnant:yes
- Age at study initiation: 6 weeks old
- Weight at study initiation: NA
- Fasting period before study: NA
- Housing: The rats were housed under conventional conditions, in suspended stainless-steel cages fitted with a wire-mesh floor and front.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 13 days
DETAILS OF FOOD AND WATER QUALITY: All rats were fed the Institute's grain-based open-formula diet (with a nitrite and nitrate content of 2 and 140mg/kg, respectively)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): 40-70%
- Air changes (per hr): 10/hr
- Photoperiod (hrs dark / hrs light): 12hr light/dark cycles
IN-LIFE DATES: From: To: - Route of administration:
- oral: drinking water
- Details on route of administration:
- The rats received potassium nitrite in the drinking-water (tap-water; nitrite and nitrate content <0.01 and 10mg/litre, respectively) at levels of 0 (negative control), 100, 300, 1000 and 3000mg/litre.
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): Test solutions and tap-water were freshly supplied to the rats in glass bottles every day.
- Mixing appropriate amounts with (Type of food): Drinking water
- Storage temperature of food: NA
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: nitrite and nitrate content <0.01 and 10mg/litre
- Amount of vehicle (if gavage): NA
- Lot/batch no. (if required): NA
- Purity:NA
Additional information: The potassium concentrations in the nitrite solutions were equalized by adding KCl up to the K+ level of the 3000 mg KNO2/litre solution.
An additional group received drinking-water supplemented with KCl only, to achieve the same K+ concentration as that found in the 3000 mg KNO2/litre solution. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 weeks (91 days)
- Frequency of treatment:
- Everyday
- Dose / conc.:
- 0 mg/L drinking water
- Remarks:
- Negative control
- Dose / conc.:
- 100 mg/L drinking water
- Dose / conc.:
- 300 mg/L drinking water
- Dose / conc.:
- 1 000 mg/L drinking water
- Dose / conc.:
- 3 000 mg/L drinking water
- No. of animals per sex per dose:
- ten rats of each sex/group (Five treatment groups )
- Control animals:
- yes, concurrent vehicle
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes / No / Not specified
- Time schedule:
BODY WEIGHT: Yes / No / Not specified
- Time schedule for examinations: The rats were weighed at weekly intervals and were observed daily for condition and behaviour
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / Not specified
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / Not specified
- Time schedule for examinations: Food and liquid intake were measured over weekly periods throughout the study
OPHTHALMOSCOPIC EXAMINATION: Yes / No / Not specified
- Time schedule for examinations: Ophthalmoscopic observations were made in all rats of the control and top-dose groups prior to the administration of the test substances and during wk 13.
- Dose groups that were examined:
URINALYSIS: Yes / No / Not specified
- Time schedule for collection of urine: In wk 9 of treatment urine was collected over a 24-hr period from all rats, except those receiving unsupplemented tap-water
- Metabolism cages used for collection of urine: Yes It was collected in calibrated tubes under cooling on dry ice. Its volume was determined and it was examined for
creatinine and nitrite and nitrate - Sacrifice and pathology:
- Early in wk 14, the rats were killed by exsanguination from the abdominal aorta whilst under light ether anaesthesia, and a thorough autopsy was performed.
- Statistics:
- Data on body weight were evaluated by a oneway analysis of covariance, followed by Dunnett's multiple comparison tests
- Clinical signs:
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- There were no deaths and the rats appeared to be healthy throughout the study
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight was decreased at 3000 mg/l in males.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Growth and food intake were significantly decreased in the 3000-mg/litre group in males.
- Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- Food efficiency was decreased in the 3000-mg/litre group in males. (data not shown).
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Liquid intake was clearly diminished in the 3000- and the 1000-mg/litre groups of males and in the 3000-mg/litre group of females
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- Ophthalmoscopic examination did not reveal any differences between the test rats and controls that could be ascribed to treatment
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Haemoglobin concentration, packed-cell volume and erythrocyte count were slightly decreased in the males receiving 1000 and 3000mg/litre, and in the females receiving 1000 mg/litre. In females, the erythrocyte count was also decreased with a dose of 3000 mg/litre which was accompanied by increases in mean corpuscular volume and mean corpuscular haemoglobin. Methaemoglobin concentration was significantly increased with 3000mg/litre in both sexes
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- With the 3000-mg/litre treatment the plasma urea level was increased in males, while the plasma alkaline phosphatase activity was slightly decreased in both sexes, although the difference was statistically significant in females only (Table 3). There was a decrease in plasma aspartate aminotransferase in the females given 1000 and 3000 mg/litre in comparison to the KCI group, but not as compared with the controls receiving unsupplemented drinking-water
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The volume of the urine produced during 24 hr decreased with increasing nitrite levels in the drinking-water, the differences from the controls being statistically significant in males treated with 3000 mg/litre and in females treated with 300 mg/litre and above . The urine concentration test revealed an increase in the density of the urine of the animals treated with 3000mg/litre in both sexes, accompanied by a decrease in urine production in males . Excretion levels of creatinine and
nitrate did not show treatment-related differences among the groups and nitrite was not found in the urine of any of the groups. There was no evidence of
increased mutagenic activity in the urine of rats receiving 3000 mg/litre, either in the presence or in the absence of S-9 mix and fl-glucuronidase. - Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- The absolute and relative weights of the kidneys and spleen in females and the relative weight of the kidneys in males were increased in the group receiving 3000 mg/litre. The increase in the relative brain weight in males receiving 3000 mg/iitre is ascribed to the lower body weight in this group and the well-known inverse correlation between body weight and relative brain weight
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- Histopathological examination of all other organs was essentially negative.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- < 100 mg/L drinking water
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- food consumption and compound intake
- food efficiency
- haematology
- ophthalmological examination
- organ weights and organ / body weight ratios
- urinalysis
- water consumption and compound intake
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/L drinking water
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- mortality
- Dose descriptor:
- LOAEL
- Effect level:
- 1 000 mg/L drinking water
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- mortality
- Critical effects observed:
- no
- Conclusions:
- A subchronic oral toxicity study with test chemical was carried out in groups of ten male and ten female 6-wk-old rats. No mortality observed and the rats appeared to be healthy throughout the study. Effects were observed in food and water consumption, opthalological and haematological effects were observed. It was concluded that in the study reported here the NOEL is lower than I00 mg /litre in the drinking-water, which is equivalent to a level lower than 10 mg /kg body weight/day and a NOAEL of 300 mg/L drnking water was observed.
- Executive summary:
A subchronic oral toxicity study with test chemical was carried out in Wistar derieved SPF Bred rats. Groups of ten male and ten female 6-wk-old rats received test chemical in the drinking-water (tap-water) at levels of 0, 100, 300, 1000 and 3000mg/litre for a period of 13 week. The potassium concentration in the nitrite solutions was equalized by adding potassium chloride (KCL) up to the potassium level of the 3000 mg /litre solution. An additional group of ten males and ten females received drinking-water supplemented with KCI only, at an amount resulting in a potassium concentration equivalent to that of the 3000 mg /litre solution. No mortality observed and the rats appeared to be healthy throughout the study. Ophthalmoscopic examination did not reveal any differences between the test rats and controls that could be ascribed to treatment. Body weight, food intake and food efficiency were decreased at 3000-mg/litre level in males, while liquid intake was decreased in males given 1000 and 3000 mg/litre and in females given 3000 mg/litre. There was a significant increase in the methaemoglobin concentration in animals given 3000 mg/litre, while slight decreases in red blood cell variables occurred at the 1000 and 3000 mg/litre dose. No impaired renal function was observed in any of the test groups, although the relative weight of the kidneys and the plasma urea nitrogen level was increased at 3000 mg/litre. There was a slight decrease in plasma alkaline phosphatase activity at 3000 mg/litre. A small amount of nitrite was present in the saliva of the rats receiving 3000 mg/litre but there was no evidence of increased mutagenic activity in the urine of these rats. Interestingly, hypertrophy of the adrenal zone glomerulosa was observed in all test groups, the incidence and degree being dose related. It was concluded that in the study reported here the NOEL is lower than I00 mg /litre in the drinking-water, which is equivalent to a level lower than 10 mg /kg body weight/day and a NOAEL of 300 mg/L drnking water was observed.
- Endpoint:
- short-term repeated dose toxicity: oral
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because a reliable sub-chronic (90 days) or chronic toxicity study is available, conducted with an appropriate species, dosage, solvent and route of administration
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- K2
- System:
- urinary
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- exposure considerations
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Reference
Endpoint conclusion
- Quality of whole database:
- Waiver
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- exposure considerations
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Reference
Endpoint conclusion
- Quality of whole database:
- Waiver
Additional information
Data available for the target chemical was reviewed to determine the toxic nature of the test chemical upon repeated exposure. The studies are as mentioned below:
Repeated dose toxicity: Oral
A subchronic oral toxicity study with test chemical was carried out in Wistar derieved SPF Bred rats. Groups of ten male and ten female 6-wk-old rats received test chemical in the drinking-water (tap-water) at levels of 0, 100, 300, 1000 and 3000mg/litre for a period of 13 week. The potassium concentration in the nitrite solutions was equalized by adding potassium chloride (KCL) up to the potassium level of the 3000 mg /litre solution. An additional group of ten males and ten females received drinking-water supplemented with KCI only, at an amount resulting in a potassium concentration equivalent to that of the 3000 mg /litre solution. No mortality observed and the rats appeared to be healthy throughout the study. Ophthalmoscopic examination did not reveal any differences between the test rats and controls that could be ascribed to treatment. Body weight, food intake and food efficiency were decreased at 3000-mg/litre level in males, while liquid intake was decreased in males given 1000 and 3000 mg/litre and in females given 3000 mg/litre. There was a significant increase in the methaemoglobin concentration in animals given 3000 mg/litre, while slight decreases in red blood cell variables occurred at the 1000 and 3000 mg/litre dose. No impaired renal function was observed in any of the test groups, although the relative weight of the kidneys and the plasma urea nitrogen level was increased at 3000 mg/litre. There was a slight decrease in plasma alkaline phosphatase activity at 3000 mg/litre. A small amount of nitrite was present in the saliva of the rats receiving 3000 mg/litre but there was no evidence of increased mutagenic activity in the urine of these rats. Interestingly, hypertrophy of the adrenal zone glomerulosa was observed in all test groups, the incidence and degree being dose related. It was concluded that in the study reported here the NOEL is lower than I00 mg /litre in the drinking-water, which is equivalent to a level lower than 10 mg /kg body weight/day and a NOAEL of 300 mg/L drnking water was observed.
A 13 week repeated oral toxicity test was performed on Weanling Wistar derived SPF-bred rats (Bor; WlSW). A dose range of 0, 12.5, 25, 50, 100 and 3000 mg/l was admistered to nine dose groups consisting of 10 male and 10 female rats each via drinking water. There were no noticeable differences in appearance or behaviour between the treated rats and the controls during the experimental period. Body weights were significantly increased in males of the 12.5 mg KNO]litre group, which is in agreement with the higher food intake in this group. The results obtained in this study with the 100 and 3000 mg/litre levels of potassium nitrite in drinking water are comparable with those obtained at the same levels in the previous 90-day study (Til et al., 1988), although the effects on red blood cell variables at 3000 mg/litre and the incidence of hypertrophy of the zona glomerulosa of the adrenals at 100 and 3000 mg/litre were somewhat less pronounced than in the previous study at the same levels. Based on all the available data, and from the observations and conclusion, the NOAEL and LOAEL for the test chemical, was found to be 100 mg/l and 3000 mg/l, respectively.
Repeated dose toxicity: Inhalation
According to column 2 of Annex VIII, exposure by inhalation route is negligible on account of high boiling points (as has been informed in the boiling point that is greater than 300 °C).
Repeated dose toxicity: Dermal
The acute dermal toxicity value for test chemical is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.
Justification for classification or non-classification
Based on the animal data available, the test chemical is non-toxic and observed to be safe after repeated exposures. Hence, the test chemical is like to be 'unclassified' as per CLP classification.
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