Registration Dossier
Registration Dossier
Diss Factsheets
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EC number: 203-614-9 | CAS number: 108-77-0
- 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, dermal: NOAEL(systemic) = 500 mg/kg bw/d, LOAEL(local) = 50 mg/kg bw /day for the rabbit, 21 d (OECD TG 410); study 83-0093-FKT
- Repeated dose toxicity, inhalative: NOAEC(systemic) = 0.25 mg/m³, NOAEC(local) = 0.05 mg/m³ for the rat, 90 d (OECD TG 413); study 94-0211-FGT
Key value for chemical safety assessment
- Toxic effect type:
- concentration-driven
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1990-03-07 to 1990-06-13
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with acceptable restrictions (e.g. non-GLP)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Version / remarks:
- as at 1987
- Deviations:
- no
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: in-house breeding colony
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 145 - 190 g (males), 120 - 160 g (females)
- Fasting period before study: none reported
- Housing: 5 per cage (suspended stainless steel wire mesh cages)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.5
- Humidity (%): 50 - 65 %
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: not applicable to vapour
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 1 m³ chamber
- Method of holding animals in test chamber: not reported
- Source and rate of air: not reported
- Method of conditioning air: not reported
- System of generating particulates/aerosols:
- vapour generation: cyanuric chloride was sublimated by leading gel dried air through glass tubes (heated to 60 - 90°C with thermostated water on the outside of the tube). The air was filtered to retain particles by plugs of silane treated glass wool. Cyanuric chloride vapour was mixed with dried heated clean air and conducted to the exposure chamber trough glass tubes covered with flexible electric heating tape.
- Temperature, humidity, pressure in air chamber: not reported
- Air flow rate: 120 liters/min
- Air change rate: 7.2 air changes /h
- Method of particle size determination: not reported
- Treatment of exhaust air: not reported
TEST ATMOSPHERE
- Brief description of analytical method used: 5 L air are passed with a flow rate of 0.5 mL/min through 2 mL of toluene in an Impinger gas washing bottle. Afterwards the volume of toluene was refilled to 2 mL. 3 µL of the resulting solution was analysed on a gas chromatography system with nitrogen/phosphorus detector (Hewlett-Packard HP5890A, capillary glass column, HP-1 5m x 0.53 mm x 2.65 µm film thickness, detection range 0.00025 - 0.025 mg/sample). Quantification was reached by comparison to dilutions from weighted amounts of cyanuric chloride dissolved in toluene.
- Samples taken from breathing zone: yes, once every 2 h - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- see above under TEST ATMOSPHERE
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- 6 hours daily, 5 times a week
- Remarks:
- Doses / Concentrations:
0.01, 0.05 and 0.25 mg/m³
Basis:
analytical conc. - No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: doses were selected on a 28 d inhalation study where a NOAEC of 0.08 mg/cbm and a LOAEC of 0.4 mg/cbm were determined
- Rationale for animal assignment: random selecting using a computerized random figure generator
- Rationale for selecting satellite groups: no satellite group
- Post-exposure recovery period in satellite groups: no satellite group - Positive control:
- none used
- Observations and examinations performed and frequency:
General:
Mortality daily; Clinical signs daily before and after exposure; Body weight at study initiation and weekly thereafter; Food consumption.
Clinical pathology:
- Blood chemistry at end of treatment period: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), sorbitol dehydrogenase (SDH),
γ-g lutamyl transpeptidase (GGT), alkaline phosphatase (ALP), ornithine carbamoyltransferase (OCT), total billirubin, total protein, albumin, blood
urea nitrogen (BUN), glucose, natrium, potassium, chloride, inorganic phosphate and calcium;
- Hematology at end of treatment period: red blood cell count (RBC), white blood cell count (WBC), hemoglobin, hematocrit value, mean
corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count, percentage of reticulocytes and differential
leukocyte count.
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
Neither cage side observations nor detailed clinical observations are detailed in the study
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
The report made no differentiation between cage side observations and detailed clinical observations
BODY WEIGHT: Yes
- Time schedule for examinations: at arrival in the test facility, on day 1 of the study and weekly thereafter
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
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: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the treatment period, in the morning
- Anaesthetic used for blood collection: Yes, ether
- Animals fasted: No
- How many animals: all
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the treatment period, in the morning
- Animals fasted: No
- How many animals: all
- Parameters checked in table 1 were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 2)
- Macroscopy: external appearance, body orifices, body cavities and their contents
HISTOPATHOLOGY: Yes (see table 2)
- Statistics:
- Bartlett’s test for homogeneity of variance, ANOVA, Dunnett’s test, Kruskal-Wallis test, Dunn’s summed rank test, Jonkheere’s test for trend and ANCOVA.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- no treatment related effects; small but significantly decrease in hemoglobin in females in the high dose group, but regarded to reflect biological variation; reduced white blood cell count in all treated male groups, but no dose dependency.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistical significant differences of glucose (males) and phosphatase (females) in the mid dose group are regarded to reflect biological variation.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- Occasional statistically significant differences were not dose dependent and regarded to be incidental.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- GROSS PATHOLOGY
- Higher incidence of yellowish exudate in noses of high dose males which was occasionally also found in control and treatment groups of males and females and are a rather common finding in Wistart rats kept at the Institute. These findings might be a result of slight infections of the respiratory tract and therefore not test item related.
HISTOPATHOLOGY: NON-NEOPLASTIC
- Slightly higher incidence of purulent inflamation of the nose combined with accumulation of neutrophils in lumen in the noses of high dose males (correlation with yellowish exudate)
- lymphocytic infiltrations in nasal mucosa in control and exposure groups
- interstitial lymphocyte infiltration in alveolar septa and foamy macrophages in the lumen of alveoli in all treated male groups without a clear dose dependency
- Higher incidence of increased cellularity of BALT in high dose males compared to control and other groups
all above mentioned findings are regarded to be a result of a slight infection of the respiratory tract, which might be slightly enhanced in the high dose group due to the irritating nature of the test item
- minimal increase in the no. of fast red (+) droplets in hepatocytes in males in the high dose male group, but the severity of this findings is not higher than in occasional findings in control animals and no degenerative changes or differences in clinical chemistry parameters of the liver are apparent - Dose descriptor:
- NOAEC
- Remarks:
- systemic
- Effect level:
- 0.25 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Value for systemic effects
- Dose descriptor:
- NOAEC
- Remarks:
- local
- Effect level:
- 0.05 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: local effects in the lung due to the corrosive action of cyanuric chloride
- Critical effects observed:
- not specified
- Conclusions:
- The present study was conducted according to the OECD guideline 413 as at 1987. Wistar rats were treated repeatedly during 90 d with cyanuric chloride via the inhalation route. No clear treatment related effect became obvious and therefore, the highest tested concentration of 0.25 mg/m³ can be regarded as a level where surely not toxicity occurs. As a LOAEL is missing this value cannot be termed a NOAEL. The true NOAEL might be even higher.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 0.25 mg/m³
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1990-03-07 to 1990-06-13
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with acceptable restrictions (e.g. non-GLP)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Version / remarks:
- as at 1987
- Deviations:
- no
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: in-house breeding colony
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 145 - 190 g (males), 120 - 160 g (females)
- Fasting period before study: none reported
- Housing: 5 per cage (suspended stainless steel wire mesh cages)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.5
- Humidity (%): 50 - 65 %
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: not applicable to vapour
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 1 m³ chamber
- Method of holding animals in test chamber: not reported
- Source and rate of air: not reported
- Method of conditioning air: not reported
- System of generating particulates/aerosols:
- vapour generation: cyanuric chloride was sublimated by leading gel dried air through glass tubes (heated to 60 - 90°C with thermostated water on the outside of the tube). The air was filtered to retain particles by plugs of silane treated glass wool. Cyanuric chloride vapour was mixed with dried heated clean air and conducted to the exposure chamber trough glass tubes covered with flexible electric heating tape.
- Temperature, humidity, pressure in air chamber: not reported
- Air flow rate: 120 liters/min
- Air change rate: 7.2 air changes /h
- Method of particle size determination: not reported
- Treatment of exhaust air: not reported
TEST ATMOSPHERE
- Brief description of analytical method used: 5 L air are passed with a flow rate of 0.5 mL/min through 2 mL of toluene in an Impinger gas washing bottle. Afterwards the volume of toluene was refilled to 2 mL. 3 µL of the resulting solution was analysed on a gas chromatography system with nitrogen/phosphorus detector (Hewlett-Packard HP5890A, capillary glass column, HP-1 5m x 0.53 mm x 2.65 µm film thickness, detection range 0.00025 - 0.025 mg/sample). Quantification was reached by comparison to dilutions from weighted amounts of cyanuric chloride dissolved in toluene.
- Samples taken from breathing zone: yes, once every 2 h - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- see above under TEST ATMOSPHERE
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- 6 hours daily, 5 times a week
- Remarks:
- Doses / Concentrations:
0.01, 0.05 and 0.25 mg/m³
Basis:
analytical conc. - No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: doses were selected on a 28 d inhalation study where a NOAEC of 0.08 mg/cbm and a LOAEC of 0.4 mg/cbm were determined
- Rationale for animal assignment: random selecting using a computerized random figure generator
- Rationale for selecting satellite groups: no satellite group
- Post-exposure recovery period in satellite groups: no satellite group - Positive control:
- none used
- Observations and examinations performed and frequency:
General:
Mortality daily; Clinical signs daily before and after exposure; Body weight at study initiation and weekly thereafter; Food consumption.
Clinical pathology:
- Blood chemistry at end of treatment period: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), sorbitol dehydrogenase (SDH),
γ-g lutamyl transpeptidase (GGT), alkaline phosphatase (ALP), ornithine carbamoyltransferase (OCT), total billirubin, total protein, albumin, blood
urea nitrogen (BUN), glucose, natrium, potassium, chloride, inorganic phosphate and calcium;
- Hematology at end of treatment period: red blood cell count (RBC), white blood cell count (WBC), hemoglobin, hematocrit value, mean
corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), platelet count, percentage of reticulocytes and differential
leukocyte count.
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
Neither cage side observations nor detailed clinical observations are detailed in the study
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
The report made no differentiation between cage side observations and detailed clinical observations
BODY WEIGHT: Yes
- Time schedule for examinations: at arrival in the test facility, on day 1 of the study and weekly thereafter
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
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: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the treatment period, in the morning
- Anaesthetic used for blood collection: Yes, ether
- Animals fasted: No
- How many animals: all
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the treatment period, in the morning
- Animals fasted: No
- How many animals: all
- Parameters checked in table 1 were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 2)
- Macroscopy: external appearance, body orifices, body cavities and their contents
HISTOPATHOLOGY: Yes (see table 2)
- Statistics:
- Bartlett’s test for homogeneity of variance, ANOVA, Dunnett’s test, Kruskal-Wallis test, Dunn’s summed rank test, Jonkheere’s test for trend and ANCOVA.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- no treatment related effects; small but significantly decrease in hemoglobin in females in the high dose group, but regarded to reflect biological variation; reduced white blood cell count in all treated male groups, but no dose dependency.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistical significant differences of glucose (males) and phosphatase (females) in the mid dose group are regarded to reflect biological variation.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- Occasional statistically significant differences were not dose dependent and regarded to be incidental.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- see details on results
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- GROSS PATHOLOGY
- Higher incidence of yellowish exudate in noses of high dose males which was occasionally also found in control and treatment groups of males and females and are a rather common finding in Wistart rats kept at the Institute. These findings might be a result of slight infections of the respiratory tract and therefore not test item related.
HISTOPATHOLOGY: NON-NEOPLASTIC
- Slightly higher incidence of purulent inflamation of the nose combined with accumulation of neutrophils in lumen in the noses of high dose males (correlation with yellowish exudate)
- lymphocytic infiltrations in nasal mucosa in control and exposure groups
- interstitial lymphocyte infiltration in alveolar septa and foamy macrophages in the lumen of alveoli in all treated male groups without a clear dose dependency
- Higher incidence of increased cellularity of BALT in high dose males compared to control and other groups
all above mentioned findings are regarded to be a result of a slight infection of the respiratory tract, which might be slightly enhanced in the high dose group due to the irritating nature of the test item
- minimal increase in the no. of fast red (+) droplets in hepatocytes in males in the high dose male group, but the severity of this findings is not higher than in occasional findings in control animals and no degenerative changes or differences in clinical chemistry parameters of the liver are apparent - Dose descriptor:
- NOAEC
- Remarks:
- systemic
- Effect level:
- 0.25 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Value for systemic effects
- Dose descriptor:
- NOAEC
- Remarks:
- local
- Effect level:
- 0.05 mg/m³ air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: local effects in the lung due to the corrosive action of cyanuric chloride
- Critical effects observed:
- not specified
- Conclusions:
- The present study was conducted according to the OECD guideline 413 as at 1987. Wistar rats were treated repeatedly during 90 d with cyanuric chloride via the inhalation route. No clear treatment related effect became obvious and therefore, the highest tested concentration of 0.25 mg/m³ can be regarded as a level where surely not toxicity occurs. As a LOAEL is missing this value cannot be termed a NOAEL. The true NOAEL might be even higher.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 0.05 mg/m³
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1983-03-08 to 1983-03-30
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with acceptable restrictions (e.g. purity of test substance not reported)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Deviations:
- no
- GLP compliance:
- no
- Remarks:
- study performed prior to implementation of GLP
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Davidson's Mill Farm; Jamesbury, NJ, U.S.A.
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: not reported
- Fasting period before study: not reported, fasting prior to collecting of blood samples
- Housing: individually, in hanging wire mesh cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 22 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): 11.3 h
- Photoperiod (hrs dark / hrs light): 12/12
- Type of coverage:
- occlusive
- Vehicle:
- other: mineral oil
- Details on exposure:
- TEST SITE
- Area of exposure: back
- % coverage: 30 % of total skin surface
- Type of wrap if used: gauze bandaging and occlusion with impervious plastic (Prime Wrap II (R)), wrapping of total application site with 3-inch wide Dermiform (R) Tape.
- Time intervals for shavings or clippings: not reported
- plastic collars (E-Jay Saf-T Shields, W.A. Butler, Inc. Columbus, Ohio, U.S.A.) were applied 1 week prior to study initiation and remained for the duration of the study
REMOVAL OF TEST SUBSTANCE
- Washing: tepid water and disposable papertowels
- Time after start of exposure: 6 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg bw
- Concentration: 0, 25, 75 and 250 mg/mL
- Constant volume or concentration used: no
- For solids, paste formed: no, suspension
VEHICLE
- Justification for use and choice of vehicle: most suitable vehicle for generation of suspensions
- Amount(s) applied (volume or weight with unit): 2 mL/kg bw
- Lot/batch no. : not reported
- Purity: not reported
USE OF RESTRAINERS FOR PREVENTING INGESTION: no, plastic collars (E-Jay Saf-T Shields, W.A. Butler, Inc. Columbus, Ohio, U.S.A.) were applied 1 week prior to study initiation and remained for the duration of the study - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 3 weeks
- Frequency of treatment:
- 5 days/week, 6 h/day
- Remarks:
- Doses / Concentrations:
0,50, 150, 500 mg/kg (m/f)
Basis:
nominal per unit body weight - No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent no treatment
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
- Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked in table 1 were included.
- Presumably further observations were conducted in addition, but they were not reported in detail
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
- no differentiation was made between cage side observation and clinical observations
- see table 1 for checked observations
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: once daily
- grading of skin reactions according to Draize score
BODY WEIGHT: Yes
- Time schedule for examinations: at study start and weekly thereafter
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No, but individual food consumption was estimated, based on visual examination of food remaining in the feeder dish
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: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: once on study day 0 and once at study day 20
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: 6 per group
- Parameters checked in table 2 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: once on study day 0 and once at study day 20
- Animals fasted: Yes
- How many animals: 6 per group
- Parameters checked in table 2 were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 3)
HISTOPATHOLOGY: Yes (see table 3) - Clinical signs:
- effects observed, treatment-related
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- occasional findings of ocular and nasal discharges in all groups except the high dose group, nasal discharge very prominent in high dose group
- other signs and findings are incidentally and scattered over the dose groups
- dermal irritation:
- no dermal irritation in the control group
- slight dermal irritation in the vehicle test group (slight erythema and slight to no edema) during the last 7 to 10 days of the study
- significant dermal irritation in the three dose groups showing dose-related progression, dermal irritation increased also with duration of the study in these dose groups (sequence: blanching, fissuring, desquamation, eschar (if present) and exfoliation (if present)
dose signs
50 mg/kg bw/day moderate to marked erythema and edema, blanching, fissuring and desquamation, plus 1/3 of the group showed eschar and exfoliation
150 mg/kg bw/day marked erythema and edema, blanching, fissuring and desquamation eschar and exfoliation
500 mg/kg bw/day marked erythema and edema, blanching, fissuring and desquamation eschar and exfoliation
- Mortality: 3 animals died
animal // dose goup // cause of death // test item related
animal 21465 // (150 mg/kg bw/day) // multifocal ulcerative dermatitis and associated debilitating effects // yes
animal 21435 // (vehicle control group) // multifocal renal and pulmonary abscessation // no
animal 21479 // (150 mg/kg bw/day) // severe hepatic necrosis and severe bronchopneumonia // no
BODY WEIGHT AND WEIGHT GAIN
- see table 4
- Body weight losses from study initiation to termination were noted for group 4 males and group 5 males and females
- Body weights of group 5 females were significantly different from both control groups at day 21 of the study
- All noted group mean body weight losses are considered biologically significant and related to the administration of the test article
FOOD CONSUMPTION
- no remarkable changes in the dietary habits of the study animals on the daily visual estimate of food remaining in the dish
HAEMATOLOGY
- No test article related values observed
- statistically significant differences from control group values were considered to be due to normal biological variability
CLINICAL CHEMISTRY
- No test article related values observed
- statistically significant differences from control group values were considered to be due to normal biological variability
URINALYSIS
- not performed
NEUROBEHAVIOUR
- not performed
ORGAN WEIGHTS
- no test article related changes observed
- occasional statistically significant changes either due to low body weights or within normal biological variability
GROSS PATHOLOGY
- no test article related changes observed
HISTOPATHOLOGY: NON-NEOPLASTIC
- all organs except skin:
- generally no test article related changes observed
- additional occasional findings in treated animals were similiar in type and frequency as in the control groups and were therefore considered to be due to normal biological variability
-skin:
- no findings in the untreated control group
- findings in the vehicle control groups included epidermal hyperkeratosis and acanthosis and follicular hyperkeratosis and acanthosis
- numerous test article related microscopic changes in the epidermis, dermis and follicles in treated skin of dosed animals:
- intraepidermal suppuration
- ulceration in the epidermis in groups 4 (mid dose) and 5 (high dose) (more prominent in group 5)
- more pronounced dermal inflammation and follicular acanthosis in dose groups compared to vehicle control
- more pronounced epidermal acanthosis and follicular hyperkeratosis (males only in groups 4 and 5)
- additional microscopic findings were considered not test item related
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
- not applicable
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- systemic effects
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no indications for systemic toxicity
- Key result
- Dose descriptor:
- LOAEL
- Remarks:
- local effects (irritation)
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: skin corrosion/irritation
- Critical effects observed:
- not specified
- Conclusions:
- Under the condition of the present study a LOAEL of 50 mg/kg bw/day could be deduced for local dermal effects. As body weight effects were clearly assigned to reduced food intake due to stress caused by repeated treatment with the corrosive substance and no other indications for systemic toxicity was observed a systemic NOAEL of 500 mg/kg bw/d can be derived.
Reference
- Table 4: Average body weights and body weight gains during 3 weeks of treatment
Dose rate [mg/kg bw/day] |
Body Weights (g) |
Total Weight Gain |
||||
Week ‑1 |
Week 1 |
Week 2 |
Week 3 |
g |
% of control |
|
Male |
||||||
0 group 1 |
2693 ± 179.7 |
2906 |
2984 |
2968 ± 331.1 |
275 |
100 |
0, vehicle group 2 |
2733 ± 263.3 |
2831 |
2929 |
2972 ± 141.2 |
239 |
87 |
Low (50) group 3 |
2686 ± 229.7 |
2723 |
2836 |
2805 ± 335.9 |
119 |
43.3 |
Mid (150) group 4 |
2672 ± 229.9 |
2676 |
2721 |
2598 ±287.4 |
- 74 |
- 23 |
High (500) group 5 |
2704 ±239.2 |
2617 |
2590 |
2521 ± 305.6 |
- 183 |
- 67 |
Female |
||||||
0 group 1 |
2819 ± 192.9 |
2986 |
3142 |
3076 ±309.0 |
257 |
100 |
0, vehicle group 2 |
2806 ±127.9 |
2989 |
3102 |
3172 ±255.0 |
366 |
142 |
Low (50) group 3 |
2799 ± 170.8 |
2809 |
2969 |
2984 ±263.6 |
185 |
72.0 |
Mid (150) group 4 |
2832 ± 178.9 |
2817 |
2962 |
2935 ±163.2 |
103 |
40.1 |
High (500) group 5 |
2821 ±226.4 |
2743 |
2778 |
2646 ±292.3 1, 4 |
175 |
- 68.1 |
1 Significantly different (p 0.05) from the control.
2 Significantly different (p 0.01) from the control.
3 Significantly different (p 0.05) from the vehicle control.
4 Significantly different (p 0.01) from the vehicle control.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rabbit
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1983-03-08 to 1983-03-30
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with acceptable restrictions (e.g. purity of test substance not reported)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Deviations:
- no
- GLP compliance:
- no
- Remarks:
- study performed prior to implementation of GLP
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Davidson's Mill Farm; Jamesbury, NJ, U.S.A.
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: not reported
- Fasting period before study: not reported, fasting prior to collecting of blood samples
- Housing: individually, in hanging wire mesh cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 22 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): 11.3 h
- Photoperiod (hrs dark / hrs light): 12/12
- Type of coverage:
- occlusive
- Vehicle:
- other: mineral oil
- Details on exposure:
- TEST SITE
- Area of exposure: back
- % coverage: 30 % of total skin surface
- Type of wrap if used: gauze bandaging and occlusion with impervious plastic (Prime Wrap II (R)), wrapping of total application site with 3-inch wide Dermiform (R) Tape.
- Time intervals for shavings or clippings: not reported
- plastic collars (E-Jay Saf-T Shields, W.A. Butler, Inc. Columbus, Ohio, U.S.A.) were applied 1 week prior to study initiation and remained for the duration of the study
REMOVAL OF TEST SUBSTANCE
- Washing: tepid water and disposable papertowels
- Time after start of exposure: 6 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg bw
- Concentration: 0, 25, 75 and 250 mg/mL
- Constant volume or concentration used: no
- For solids, paste formed: no, suspension
VEHICLE
- Justification for use and choice of vehicle: most suitable vehicle for generation of suspensions
- Amount(s) applied (volume or weight with unit): 2 mL/kg bw
- Lot/batch no. : not reported
- Purity: not reported
USE OF RESTRAINERS FOR PREVENTING INGESTION: no, plastic collars (E-Jay Saf-T Shields, W.A. Butler, Inc. Columbus, Ohio, U.S.A.) were applied 1 week prior to study initiation and remained for the duration of the study - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 3 weeks
- Frequency of treatment:
- 5 days/week, 6 h/day
- Remarks:
- Doses / Concentrations:
0,50, 150, 500 mg/kg (m/f)
Basis:
nominal per unit body weight - No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent no treatment
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
- Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked in table 1 were included.
- Presumably further observations were conducted in addition, but they were not reported in detail
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
- no differentiation was made between cage side observation and clinical observations
- see table 1 for checked observations
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: once daily
- grading of skin reactions according to Draize score
BODY WEIGHT: Yes
- Time schedule for examinations: at study start and weekly thereafter
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No, but individual food consumption was estimated, based on visual examination of food remaining in the feeder dish
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: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: once on study day 0 and once at study day 20
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: 6 per group
- Parameters checked in table 2 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: once on study day 0 and once at study day 20
- Animals fasted: Yes
- How many animals: 6 per group
- Parameters checked in table 2 were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 3)
HISTOPATHOLOGY: Yes (see table 3) - Clinical signs:
- effects observed, treatment-related
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- occasional findings of ocular and nasal discharges in all groups except the high dose group, nasal discharge very prominent in high dose group
- other signs and findings are incidentally and scattered over the dose groups
- dermal irritation:
- no dermal irritation in the control group
- slight dermal irritation in the vehicle test group (slight erythema and slight to no edema) during the last 7 to 10 days of the study
- significant dermal irritation in the three dose groups showing dose-related progression, dermal irritation increased also with duration of the study in these dose groups (sequence: blanching, fissuring, desquamation, eschar (if present) and exfoliation (if present)
dose signs
50 mg/kg bw/day moderate to marked erythema and edema, blanching, fissuring and desquamation, plus 1/3 of the group showed eschar and exfoliation
150 mg/kg bw/day marked erythema and edema, blanching, fissuring and desquamation eschar and exfoliation
500 mg/kg bw/day marked erythema and edema, blanching, fissuring and desquamation eschar and exfoliation
- Mortality: 3 animals died
animal // dose goup // cause of death // test item related
animal 21465 // (150 mg/kg bw/day) // multifocal ulcerative dermatitis and associated debilitating effects // yes
animal 21435 // (vehicle control group) // multifocal renal and pulmonary abscessation // no
animal 21479 // (150 mg/kg bw/day) // severe hepatic necrosis and severe bronchopneumonia // no
BODY WEIGHT AND WEIGHT GAIN
- see table 4
- Body weight losses from study initiation to termination were noted for group 4 males and group 5 males and females
- Body weights of group 5 females were significantly different from both control groups at day 21 of the study
- All noted group mean body weight losses are considered biologically significant and related to the administration of the test article
FOOD CONSUMPTION
- no remarkable changes in the dietary habits of the study animals on the daily visual estimate of food remaining in the dish
HAEMATOLOGY
- No test article related values observed
- statistically significant differences from control group values were considered to be due to normal biological variability
CLINICAL CHEMISTRY
- No test article related values observed
- statistically significant differences from control group values were considered to be due to normal biological variability
URINALYSIS
- not performed
NEUROBEHAVIOUR
- not performed
ORGAN WEIGHTS
- no test article related changes observed
- occasional statistically significant changes either due to low body weights or within normal biological variability
GROSS PATHOLOGY
- no test article related changes observed
HISTOPATHOLOGY: NON-NEOPLASTIC
- all organs except skin:
- generally no test article related changes observed
- additional occasional findings in treated animals were similiar in type and frequency as in the control groups and were therefore considered to be due to normal biological variability
-skin:
- no findings in the untreated control group
- findings in the vehicle control groups included epidermal hyperkeratosis and acanthosis and follicular hyperkeratosis and acanthosis
- numerous test article related microscopic changes in the epidermis, dermis and follicles in treated skin of dosed animals:
- intraepidermal suppuration
- ulceration in the epidermis in groups 4 (mid dose) and 5 (high dose) (more prominent in group 5)
- more pronounced dermal inflammation and follicular acanthosis in dose groups compared to vehicle control
- more pronounced epidermal acanthosis and follicular hyperkeratosis (males only in groups 4 and 5)
- additional microscopic findings were considered not test item related
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
- not applicable
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- systemic effects
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no indications for systemic toxicity
- Key result
- Dose descriptor:
- LOAEL
- Remarks:
- local effects (irritation)
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: skin corrosion/irritation
- Critical effects observed:
- not specified
- Conclusions:
- Under the condition of the present study a LOAEL of 50 mg/kg bw/day could be deduced for local dermal effects. As body weight effects were clearly assigned to reduced food intake due to stress caused by repeated treatment with the corrosive substance and no other indications for systemic toxicity was observed a systemic NOAEL of 500 mg/kg bw/d can be derived.
Reference
- Table 4: Average body weights and body weight gains during 3 weeks of treatment
Dose rate [mg/kg bw/day] |
Body Weights (g) |
Total Weight Gain |
||||
Week ‑1 |
Week 1 |
Week 2 |
Week 3 |
g |
% of control |
|
Male |
||||||
0 group 1 |
2693 ± 179.7 |
2906 |
2984 |
2968 ± 331.1 |
275 |
100 |
0, vehicle group 2 |
2733 ± 263.3 |
2831 |
2929 |
2972 ± 141.2 |
239 |
87 |
Low (50) group 3 |
2686 ± 229.7 |
2723 |
2836 |
2805 ± 335.9 |
119 |
43.3 |
Mid (150) group 4 |
2672 ± 229.9 |
2676 |
2721 |
2598 ±287.4 |
- 74 |
- 23 |
High (500) group 5 |
2704 ±239.2 |
2617 |
2590 |
2521 ± 305.6 |
- 183 |
- 67 |
Female |
||||||
0 group 1 |
2819 ± 192.9 |
2986 |
3142 |
3076 ±309.0 |
257 |
100 |
0, vehicle group 2 |
2806 ±127.9 |
2989 |
3102 |
3172 ±255.0 |
366 |
142 |
Low (50) group 3 |
2799 ± 170.8 |
2809 |
2969 |
2984 ±263.6 |
185 |
72.0 |
Mid (150) group 4 |
2832 ± 178.9 |
2817 |
2962 |
2935 ±163.2 |
103 |
40.1 |
High (500) group 5 |
2821 ±226.4 |
2743 |
2778 |
2646 ±292.3 1, 4 |
175 |
- 68.1 |
1 Significantly different (p 0.05) from the control.
2 Significantly different (p 0.01) from the control.
3 Significantly different (p 0.05) from the vehicle control.
4 Significantly different (p 0.01) from the vehicle control.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 50
- Study duration:
- subacute
- Species:
- rabbit
Additional information
Oral:
In a repeated dose oral toxicity study (83-0090-FKR) rats were treated on 5 consecutive days with Cyanuric chloride in mineral oil via gavage (0, 10, 20, 40, 80, 160, 320 mg/kg bw) and observed for clinical signs, weight development and overt signs of toxicity. At the end of the study animals were subjected to gross necroscopy. The administration of Cyanuric chloride at dose levels of 20, 40, 80, 160, 320 mg/kg bw caused various test article related signs, significantly decreased body weight and food consumption and macroscopic lesions in the stomach. A NOAEL for subacute oral toxicity of 10 mg/kg bw/day was deduced under the test conditions.
Published data of Jedrychowski et al., (1992) indicated systemic effects and systemic immunologic effects probably due to irritation and corrosive effects of Cyanuric chloride. Dose dependent histopathological lesions were present in the gastro-intestinal tract, liver, spleen and lung. However, the findings were due to irritation and corrosive effect of Cyanuric chloride on the mucous membranes of the gastro-intestinal tract. The reported mortality could be attributed to these effects being the consequence of corrosivity of the test substance. All in all, the study was assessed as “not reliable” (Klimisch 4) as only a short abstract without detailed reporting on investigations was available with poor quality which limits its power for chemical assessment.
Two further data sources (Clayton and Clayton_1981; The chemistry of Cyanuric chloride), both secondary literature, deduced a NOEL of 20 mg/kg bw in rats and a NOAEL of 37 mg/kg bw in rabbits, respectively.
In addition, reproductive toxicity studies after oral exposure to cyanuric chloride (83-0091-FGT, 83-0092-FGT) as well as reproductive toxicity studies to NHDT solution (2017-0020-DGR, 2017-0018-DGR, 2017-0016-DGR) did not reveal any adverse effects relevant for classification for repeated dose toxicity.
Inhalation:
In a subchronic inhalation key toxicity study (94-0211-DKT) rats were treated repeatedly during 90 d with Cyanuric chloride (5 d/wk 6h/d; 0.01, 0.05 and 0.25 mg/m³). Animals were observed for clinical signs, weight development and overt signs of toxicity. At the end of the study animals were subjected to gross necroscopy and histologic analysis as well as clinical chemistry and hematologic parameters were determined.
Findings in blood chemistry, hematology and organ weights were considered not treatment-related, since no dose-response relationship became apparent, or the observation was found only in one sex. Effects on hemoglobin, reticulocytes and young neutrophils showed a high inter-individual variance. The effects on the lower airways were attributed to a viral infection by the author of the report. The presence of yellowish exudate in females of treated and control groups, the presence of interstitial lymphocyte infiltration in alveolar septa of the lungs, and foamy macrophages in all dose groups may indicate the study was performed with non-specific-pathogen-free (SPF) rats. However, the findings in the airways seemed to be slightly enhanced in the high dose group due to the irritating nature of the test item.
As no clear treatment related effect became obvious, the highest tested concentration of 0.25 mg/m³ can be regarded as a level where surely no systemic toxicity occurs. As a systemic LOAEC is missing this value cannot be termed a systemic NOAEC. The true systemic NOAEC might be even higher. As a relation of the findings in the airways at the high conentration group to the irritating potential of the test substance cannot be excluded, a local NOAEC of 0.05 mg/m³ was established. Due to the restricted reliability and existing human data for repeated inhalation exposure with Cyanuric chloride (see chapter 7.10) the presented key study will not be used for risk assessment.
In a short abstract of a 28 days study (Rydzynski et al., 1993) a NOAEC of 0.04 mg/m³ and a LOAEC of 0.2 mg/m³ for lymphoproliferative properties was mentioned and furthermore published data (Blagodatin et al., 1968, exposure: 2.5 months high dose; 5 months low dose) indicated a NOAEL of 0.3 mg /m³ and a LOAEC of 1.88 mg/m³ for Cyanuric chlorid. Due to the insufficient documentation (“not reliable”, Klimisch 4) and the abbreviated exposure time the published data of Rydzynski et al., 1993 and Blagodatin et al., 1968 are not assignable for classification. In addition, insufficient documentation does not allow the discrimination if reported effects were due to acute corrosive effects of Cyanuric chloride or a true effect of repeated exposure which is not caused by secondary effects.
Dermal:
In a dermal toxicity key study (83-0093 -FKT) rabbits were treated repeatedly during 21 days with Cyanuric chloride in mineral oil via occlusive dermal application (5 days/weekly 6h/day; 50, 150, 500 mg/kg bw). Animals were observed for clinical signs, weight development and overt signs of toxicity. At the end of the study animals were subjected to gross necroscopy and histologic analysis as well as clinical chemistry and hematologic parameters were determined.
Generally, effects are only seen at the portal of entry based on the irritation and caustic effects of Cyanuric chloride. One animal died due to test item related effects: multifocal ulcerative dermatitis and associated debilitating effects. The following clinical signs were noted: nasal discharge in the high dose groups and significant dermal irritation in the three dose groups showing dose-related progression, dermal irritation increased also with duration of the study in these dose groups (sequence: blanching, fissuring, desquamation, eschar (if present) and exfoliation. Treatment related body weight losses were noted for mid dose males and high dose males and females. The effects were related to stress due to the irritating and corrosive action of the test item.
Correspondingly the histological examination of treatment site samples revealed epidermal hyperkeratosis and acanthosis, follicular hyperkeratosis and acanthosis in all groups treated with test substance and the vehicle control group (dose related increase). Intraepidermal suppuration, ulceration of the epidermis increased relative severity of dermal inflammation in 50, 150 and 500 mg/kg groups. For local dermal effects only a LOAEL of 50 mg/kg bw/day could be deduced. As body weight effects were assigned to a reduced food intake due to the stress of the repeated treatment with the corrosive substance the derivation of a systemic NOAEL is regarded as scientifically unjustified.
Two further published data (Blagodation_1968, The Chemistry of Cyanuric chloride) reported the effects of Cyanuric chloride after repeated dermal exposure. Blagodation_1968 indicated no systemic effects after dermal application of 200 mg/kg bw for 2-4 treatment frequency. The second published data mentioned skin irritation in succeeding doses however at gross necropsy no systemic effects of Cyanuric chloride could be detected.
Justification for selection of repeated dose toxicity via oral
route - systemic effects endpoint:
In accordance with column 2 of REACH Annex IX, the test repeated
dose toxicity after oral exposure does not need to be conducted as
repeated dose toxicity studies for inhalation and dermal exposure are
available, which represent the relevant exposure routes.
Justification for selection of repeated dose toxicity inhalation -
systemic effects endpoint:
Most reliable animal study.
Justification for selection of repeated dose toxicity inhalation -
local effects endpoint:
Most reliable animal study.
Justification for selection of repeated dose toxicity dermal -
systemic effects endpoint:
Most reliable study.
Justification for selection of repeated dose toxicity dermal - local
effects endpoint:
Most reliable study.
Justification for classification or non-classification
Classification for specific target organ toxicity-repeated exposure should be applied, if a substance has produced significant toxicity at low (Category 1) or moderate (Category 2) exposure concentrations, but secondary effects should not be included.
Severe effects such as mortalities after oral exposure to Cyanuric chloride were likely to be the consequence of corrosivity and not due to systemic toxicity after repeated exposure. As well as other reported effects were secondary nature due to the acute irritation and caustic effects of Cyanuric chloride or were of insufficient documentation and hence not suitable for assessment. Classification for acute oral toxicity Cat. 4, acute inhalation toxicity Cat.2 as well as STOT SE 3 with SCL ≥ 5% is already assigned which covers the corrosive effects.
Classification of Cyanuric chloride based on reported (local) effects due to corrosive properties lacking an organ specificity is not appropriate. Therefore, based on the available data Cyanuric chloride is not subject for classification and labeling regarding specific target organ toxicity repeated exposure according to CLP Regulation (EC) No 1272/2008.
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.

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