Registration Dossier

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
Reference
Endpoint:
sub-chronic toxicity: oral
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
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:
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 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.
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
Reference
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:
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 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.
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
Reference
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:
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 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

- 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.

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.
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
Reference
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:
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 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

- 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.

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.
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.