Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-)

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

The No Observed Adverse Effect Level (NOAEL) for the test chemical Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no 28901-96-4) in male and female rats is considered to be 1000 mg/Kg bw/day when they were exposed for 28-30 days.

Repeated dose toxicity: Inhalation

Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no. 28901-96-4) has very a low vapor pressure of 1.51E-026 Pa. The particle size distribution was determined to be in the range of 147 micron to 52 micron. The normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely. Therefore this end point for repeated dose toxicity by inhalation route is considered for waiver

Repeated dose toxicity: Dermal

The acute dermal toxicity value for Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no. 28901-96-4) (as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

WoE derived based on the experimental data from structurally and functionally similar read across chemicals

GLP compliance:

not specified

Limit test:

yes

Species:

rat

Strain:

other: 1. No data; 2. Speague Dawley (Crj: CD (SD) IGS, SPF)

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. TEST ANIMALS- Source: No data - Age at study initiation: No data- Weight at study initiation: No data- Fasting period before study: No data- Housing: Rats were housed under standardized conditions- Diet (e.g. ad libitum): pelleted standard diet ad libitum- Water (e.g. ad libitum): Water ad libitum- Acclimation period: No dataENVIRONMENTAL CONDITIONS- Temperature (°C): No data- Humidity (%):No data- Air changes (per hr): No data- Photoperiod (hrs dark / hrs light): No dataIN-LIFE DATES: From: To: No data2. TEST ANIMALS- Source: Charles River Japan Co., Ltd- Age at study initiation: 5 weeks- Weight at study initiation: No data- Fasting period before study: No data- Housing: The animals were raised in a barrier system breeding room. The animals were housed in a metallic front / bed network breeding cage using water washing rearing machine. The breeding cage was changed once every other week, and the feeder was changed once a week.- Diet (e.g. ad libitum): Oriental Yeast Co., Ltd. NIH release rat and mouse feed ad libitum- Water (e.g. ad libitum): Tap water ad libitum- Acclimation period: 9 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 22.3 to 23.2 ° C- Humidity (%): 53 to 71%- Air changes (per hr): 20 times per hour- Photoperiod (hrs dark / hrs light): 12 hours (7 am lights on, 7 o'clock off at 7 pm).IN-LIFE DATES: From: To: No data

Route of administration:

oral: gavage

Details on route of administration:

No data

Vehicle:

other: 1. Vehicle was used. Details are not mentioned; 2. Corn oil

Details on oral exposure:

1. PREPARATION OF DOSING SOLUTIONS: The test chemical was dissolved in appropriate vehicle to give a final dose range of 0 or 1000 mg/Kg bw/dayDIET PREPARATION- Rate of preparation of diet (frequency): No data- Mixing appropriate amounts with (Type of food): No data- Storage temperature of food: No dataVEHICLE- Justification for use and choice of vehicle (if other than water): No data- Concentration in vehicle: 1000 mg/Kg bw/day- Amount of vehicle (if gavage): 10 mL/kg- Lot/batch no. (if required): No data- Purity: No data2. PREPARATION OF DOSING SOLUTIONS: The test chemical was dissolved in corn oil at dose level of 0, 100, 300 and 1000 mg / kg. A predetermined amount of the test substance was precisely weighed for each dose and suspended in corn oil. Preparation of the administration solution was carried out once a week, and it was stored at room temperature until dosing by subdividing every 1 day.DIET PREPARATION- Rate of preparation of diet (frequency): No data- Mixing appropriate amounts with (Type of food): No data- Storage temperature of food: No dataVEHICLE- Justification for use and choice of vehicle (if other than water): No data- Concentration in vehicle: 0, 100, 300 and 1000 mg / kg- Amount of vehicle (if gavage): 0.5 mL per 100 g body weight- Lot/batch no. (if required): No data- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

1. 30 days2. 28 days + 14 days recovery period

Frequency of treatment:

1. 22 Daily doses over a period of 30 days i.e 5 times/week, 1 dose/day for 4 weeks plus Monday and Tuesday of the last week2. Daily

Remarks:

1. 0 or 1000 mg/Kg bw/day

Remarks:

2. Test group: 0, 100, 300 and 1000 mg / kgRecovery group: 0 or 1000 mg/Kg

No. of animals per sex per dose:

1. Total: 800 mg/Kg bw/day: 20 males and 20 females1000 mg/Kg bw/day: 20 males and 20 females2. Total: 30 males and 30 femalesTest group: 0 mg/Kg: 5 males and 5 females100 mg/Kg: 5 males and 5 females300 mg/Kg: 5 males and 5 females1000 mg/Kg: 5 males and 5 femalesRecovery group: 0 mg/Kg bw/day: 5 males and 5 females1000 mg/Kg bw/day: 5 males and 5 females

Control animals:

yes, concurrent vehicle

Details on study design:

1. - Dose selection rationale: The doses were selected on the basis of acute oral LD50 study. The oral LD50 value in rats was in excess of 5000 mg/Kg bw/day and no signs of toxicity were noted and hence the dose was subacute study was selected to be 1000 mg/Kg bw/day- Rationale for animal assignment (if not random): No data- Rationale for selecting satellite groups: After termination of treatment 10 females and 10 males of each group were given a 2-week recovery period, if effects had been observed or suspected in the main study.- Post-exposure recovery period in satellite groups: 2 weeks- Section schedule rationale (if not random): No data2. - Dose selection rationale: Two weeks repeated dose study for dose setting was conducted at four doses of 0, 100, 300 and 1000 mg / kg. As a result, animals showing the obesity tendency in females were observed in the 1000 mg / kg group, but obviously It was not a sign of toxicity. Therefore, as in the preliminary test, the high dose of repeated dose toxicity test for 28 days was 1000 mg / kg, and it was set to 300 mg / kg for the medium dose and 100 mg / kg for the low dose by dividing it by the common ratio 3.- Rationale for animal assignment (if not random): No data- Rationale for selecting satellite groups: No data- Post-exposure recovery period in satellite groups: No data- Section schedule rationale (if not random): No data

Positive control:

No data

Observations and examinations performed and frequency:

1. CAGE SIDE OBSERVATIONS: Yes- Time schedule: No data- Cage side observations checked in table [No.?] were included. MortalityDETAILED CLINICAL OBSERVATIONS: Yes- Time schedule: Every dayBODY WEIGHT: Yes- Time schedule for examinations: Every dayFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No dataFOOD 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 dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data- Time schedule for examinations: No dataOPHTHALMOSCOPIC EXAMINATION: No data - Time schedule for examinations: No data- Dose groups that were examined: No dataHAEMATOLOGY: Yes - Time schedule for collection of blood: At the end of treatment and recovery period- Anaesthetic used for blood collection: No data - Animals fasted: No data - How many animals: Control and test group animals- Parameters checked in table [No.?] were examined. Hematocrit, hemoglobin, erythrocytes count, total and differential leucocyte counts, median cell volume, mediancell hemoglobin, platelet count and prothrombin time. CLINICAL CHEMISTRY: Yes- Time schedule for collection of blood: At the end of treatment and recovery period- Animals fasted: No data- How many animals: Control and test group animals- Parameters checked in table [No.?] were examined. Serum alkaline phosphatase (SAP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT).URINALYSIS: Yes- Time schedule for collection of urine: At the end of treatment and recovery period- Metabolism cages used for collection of urine: Yes- Animals fasted: No data- Parameters checked in table [No.?] were examined. Volume, color, pH, specific gravity, bilirubin, quantitative glucose, quantitative protein, urobilinogen, and urea as well as analysis of the sediment.NEUROBEHAVIOURAL EXAMINATION: No data- Time schedule for examinations: No data- Dose groups that were examined: No data- Battery of functions tested: sensory activity / grip strength / motor activity / other: No dataOTHER: No data2. CAGE SIDE OBSERVATIONS: Yes- Time schedule: All animals were observed three times daily (before administration, 1 and 5 hours after administration) during the administration period- Cage side observations checked in table [No.?] were included. the presence or absence of toxic symptoms, behavior abnormalities, mortalityDETAILED CLINICAL OBSERVATIONS: No data- Time schedule: No dataBODY WEIGHT: Yes- Time schedule for examinations: once a week from the start of administration until the end of the recovery periodFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, once a week- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: YesFOOD 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 dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data- Time schedule for examinations: No dataOPHTHALMOSCOPIC EXAMINATION: No data- Time schedule for examinations: No data- Dose groups that were examined: No dataHAEMATOLOGY: Yes- Time schedule for collection of blood: at the end of the administration period and at the end of the recovery period- Anaesthetic used for blood collection: Yes, ether- Animals fasted: 16 hrs- How many animals: No data- Parameters checked in table [No.?] were examined. hematocrit value (calculated from HCT: RBC, MCV), hemoglobin amount, red blood cell count, mean red blood cell Number of platelets, number of platelets, leukocyte count, mean red blood cell hemoglobin amount, average red blood cell hemoglobin concentration. The number and the percentage of white bloodcells were measured. Furthermore, prothrombin time (, activated partial thromboplastin time and fibrinogen amount was measuredCLINICAL CHEMISTRY: Yes- Time schedule for collection of blood: at the end of the administration period and at the end of the recovery period- Animals fasted: Yes, 16 hrs- How many animals: No data- Parameters checked in table [No.?] were examined. Total protein, albumin, A / G, blood sugar, triglyceride, total cholesterol, urea, creatinine, total bilirubin, aspartateamino-transferase, alanine aminotransferase, calcium (γ-glutamyl-3-carboxy-, inorganicphosphorus, potassium and chlorineURINALYSIS: Yes- Time schedule for collection of urine: Weekly and at the end of dosing period- Metabolism cages used for collection of urine: No data- Animals fasted: No data- Parameters checked in table [No.?] were examined. urine volume and color tone were inspected using 24-hour urine, urine specific gravity was measured. Urine wascentrifuged and the sediment was stainedNEUROBEHAVIOURAL EXAMINATION: No data- Time schedule for examinations: No data- Dose groups that were examined: No data- Battery of functions tested: sensory activity / grip strength / motor activity / other: No dataOTHER: No data

Sacrifice and pathology:

1. GROSS PATHOLOGY: Yes, At the end of the treatment period or after the recovery period, each rat was examined externally and by dissection for macroscopic abnormalities. Each rat was autopsied and selected organs, including liver, kidneys, adrenals, and spleen were weighed to determine the organ weight.HISTOPATHOLOGY: Yes, At the end of the treatment period or after the recovery period selected organs, including liver, kidneys, adrenals, and spleen were submitted for histopathological examination.2. GROSS PATHOLOGY: Yes, At the end of the administration period and at the end of the recovery period, the animals were ether anesthetized, euthanasia was euthanized and pathologic dissection performed. Weight was also measured for brain, liver, kidney, adrenal gland, thymus, heart, spleen, testis, epididymis and ovary to calculate organ weight /body weight ratio. The gravimetric organ and the spinal cord, pituitary, eyeball, salivary gland (submandibular gland, sublingual gland), thyroid, parathyroid gland, lung (including injection fixation, bronchus), trachea, pancreas, stomach, small intestine , The bone marrow (femur), the aorta, the skin, the mammary gland, the lungs, the lungs, the lungs, the lungs, the lymph nodes, the colon, the seminal vesicle, the prostate, the uterus, the vagina, the bladder, the peripheral nerve (sciatic nerve).HISTOPATHOLOGY: Yes, Histopathological examination is performed on the lung (including bronchus) and liver of all animals dissected at the end of the administration period, and the thymus, heart, spleen, kidney, adrenal gland, stomach, small intestine of the control group and high dose group among the fixed organs , Colon, testis, epididymis, uterus, ovary and bone marrow (femur). Embedded in paraffin according to a conventional method, thin sectioned, stained with hematoxylin • eosin, and examined microscopically.

Other examinations:

No data

Statistics:

1. Statistical analyses were performed. Organ weights (liver, kidneys, adrenals) were subject to analysis of variance and analysis of covariance on final body weight2. A significant difference between the control group and each administration group on body weight, food intake, hematology examination value, blood biochemical examination value, urinalysis value (only urine volume and urine specific gravity), organ weight and organ weight / body weight ratio We tested. Bartlett's equidistance test was first performed. In the case of equal variance, a significant difference between the control group and each administration group was tested in Dunnett's multiple comparison test. In the case of unequal variance in the Bartlett equidistance test, a significant difference between the control group and each administration group was tested in Steel's test. The significance levels of the above quantitative values were carried out with 5 and 1% one-sided tests. In addition, Fisher's probability calculation method was used for the test of the survival rate and the pathological examination result. The results of hematology, blood biochemistry, urine and pathological examination suggested the possibility that abnormality was present in the kidney of the same individual in one male of the control group at the end of the administration period and this may affect the results of statistical analysis. As a result, the white blood cell count, neutrophil ratio, lymphocyte ratio, fibrinogen amount, urea nitrogen, creatinine, total protein, albumin, A / G, urine volume, urine specific gravity, heart weight, kidney weight, spleen weight, Kidney relative weight and spleen relative weight were excluded from statistical subjects

Clinical signs:

no effects observed

Description (incidence and severity):

2. Throughout the administration period and the recovery period, no animals showing abnormality in both sexes were observed.

Mortality:

no mortality observed

Description (incidence):

2. No mortality was observed in all test groups, including control group, in both sexes during the administration period and recovery period.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

2. In males, no difference was observed between the control group and the test substance-administered group throughout the administration period. In the recovery period 1000 mg / kg group was found to show a low value of weight gain for 2 weeks, but it was a slight change to the extent that no difference was observed between recovery 1 and 2 weeks, it was recognized during the administration period Because it is a change, it was judged to be an accidental change.In females, no difference was observed between the control group and the test substance-administered group throughout the administration period and recovery period.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

2. In males, no difference was observed between the control group and the test substance-administered group throughout the administration period and recovery period.In females, no difference was observed between the control group and the test substance-administered group throughout the administration period. In the recovery period 1000 mg / kg group recovered for 1 week for food intake and total food consumption for 2 weeks recovery, but no difference was observed at 2 weeks of recovery, it was recognized during the administration period Because it is a change, it was judged to be an accidental change.

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Description (incidence and severity):

2. In males, the neutrophil ratio was low in the 100 mg / kg group, but none of them was a change corresponding to the dose. In addition, the prothrombin time was extended in the 1000 mg / kg group.In the females, the platelet count tended to be high in the 300 mg / kg group and the fibrinogen content was high, but neither of them was a change corresponding to the dose. In addition, although the prothrombin time was shortened in the 100 mg / kg group, it was a change without toxicological significance.There was no difference in either test item between the control group and the 1000 mg / kg group in both males and females at the end of recovery period.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

2. In males, alkaline phosphatase was high in the 100 mg / kg group and blood glucose in the females was high in the 100 mg / kg group, but neither of them was a change corresponding to the dose.At the end of recovery period, in males, potassium showed low value in the 1000 mg / kg group and ALT showed high value, but since these are changes not observed at the end of the administration period, it is suggested that the relationship with the administration of the test substance There was not. In females, total cholesterol, neutral fat, total protein, albumin and calcium showed low values in the 1000 mg / kg group, but since these are changes that were not observed at the end of the administration period, administration of the test substance was not suggested to be related.

Urinalysis findings:

no effects observed

Description (incidence and severity):

2. There was no difference in either test item between the control group and the test substance-administered group in both males and females during the study period and the recovery period.

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

2. At the end of administration period, in males, there was no difference in the organ weight between the control group and the test substance administered group. In females, the thymus weight showed a high value in the 100 mg / kg group, but not the dose-dependent change. In males, the relative weight of thymus was high in the 100 mg / kg group and the liver and thymus relative weights were high in the group of 100 mg / kg in females, but none of them corresponded to the dose.At the end of recovery period, in males, the brain weight was low in the 1000 mg / kg group and the liver and kidney weights in the females were low, but since these are changes that were not observed at the end of the administration period, the test Substance. No association with administration was suggested. In male, the relative weight of spleen was high in the 1000 mg / kg group and the relative weight of liver was low in the group of 1000 mg / kg in females, but these were not observed at the end of the administration period Therefore, no association with administration of the test substance was suggested.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

2. At the end of the administration period, no autopsy findings occurred more frequently in the test substance-administered group than in the control group, but lung green spots / areas were found in one male in the 1000 mg / kg group. In addition, cysts of the pituitary gland in males, scarring of the kidneys, hypertrophy of the kidneys and luminal dilatation of the ureter showed ovarian cysts in females.At necropsy at the end of recovery period, no lesions occurred in the test substance treated group as compared with the control group, but green lesions / areas in the lung were found in one female with 1000 mg / kg group. In addition, scarring of the kidney was observed in both males and females.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

2. No findings that occurred more frequently in the test substance-administered group than in the control group were observed. In the male control group, one case of hydronephrosis was observed, and a change such as basophilization, dilatation, necrosis and inflammation of the renal tubule and an increase in the transitional epithelium were observed in association therewith. In autopsy findings, in the animals of the 1000 mg / kg group in which the green spots / areas of the lung were observed, many macrophages phagocytosed green pigment in the alveolus were observed. In addition to this one, macrophage collection in the lung was found in one case inthe 1000 mg / kg group of males and in one case in the female 100 mg / kg group, but there was no pigment phagocytosis and localized there were. In addition, liver extramedullary hematopoiesis was observed in each of 100, 300 and 1000 mg / kg male group, 1 case each in female 300 and 1000 mg / kg group, respectively, but in females control group Was also observed in one case. Besides, renal tubular basophilization in the kidneys, fatty liver, periphery fat and small granulomas and gastric glandular dilatation were observed in both sexes, but these were all slight occurrences of single occurrence.

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Details on results:

1. Clinical signs and mortality: No clinical signs of toxicity and mortality were observed.Feces were found to be blue in colourBody weight and weight gain: The body weight gain observed in test animals was in the normal range as compared to controls following treatmentFood consumption and compound intake: The food consumption in test animals was in the normal range as compared to controls following treatmentFood efficiency: No dataWater consumption and compound intake: No dataOpthalmoscopic examination: No dataHaematology: Any hematological effects observed were in the normal range as compared to controlsClinical chemistry: The clinical examinations of liver function revealed no signs of toxicity following treatment and recovery and were in the normal rangeUrinanalysisUrinanalysis effects were found to be in the normal range. Urine was found to be green-blue in colour. Urinalysis of test and control animals and all bilirubin and urobilinogen tests were negative.Neurobehaviour: No dataOrgan weights: Increased kidney weights was noted but were normal after the 2-week recovery. This effect may relate to the morphological changes of the tubules of the kidneys, which were seen at the end of the treatment period, but not after the recovery period.Gross pathology: Kidneys and intestine showed blue colourationHistopathology: Microscopic examination revealed normal changes observed if any. Other histopathological examinations of selected tissues showed no significant effects related to the treatment with these compounds.

Dose descriptor:

NOAEL

Remarks:

1./2.

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant alterations were noted at the mentioned dose level

Critical effects observed:

not specified

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for the test chemical Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no 28901-96-4) in male and female rats is considered to be 1000 mg/Kg bw/day when they were exposed for 28-30 days.

Executive summary:

Data available for the test chemicals was reviiewed to determine the toxic nature of the test chemical Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no 28901-96-4). The studiies are as mentioned below:

Repeated dose subacute toxicity study was performed to determine the toxic nature of the test chemical. The chemical was administered by oral gavage route at dose levels of 0 or 1000 mg/Kg bw/day to 20 male and 20 females rats in a standard volume of 10 mL/kg. The treatment period was followed by a 15 day recovery period. 22 daily doses were given over a period of 30 days i.e 5 times/week, 1 dose/day for 4 weeks plus Monday and Tuesday of the last week. The doses were selectedwere selected on the basis of acute oral LD50 study. The oral LD50 value in rats was in excess of 5000 mg/Kg bw/day and no signs of toxicity were noted and hence the dose was subacute study was selected to be 1000 mg/Kg bw/day. Each day, clinical signs and body weights were recorded. Food intake was determined on a weekly basis. At the end of the treatment and the recovery period, hematology, blood chemistry, and urinalysis measurements were carried out by standard methods on animals from control and test groups. At the end of the treatment period or after the recovery period, each rat was examined externally and by dissection for macroscopic abnormalities. Each rat was autopsied and selected organs, including liver, kidneys, adrenals, and spleen were submitted for histopathological examination, following determination of the organ weights. Other organ tissues were fixed in formalin and are held for reference in the archives. Appropriate statistical analyses were performed on the different measurements. No mortality or signs of toxicity were observed during the study period and food and water consumption were within the normal range following treatment with the eight selected colorants. There was evidence of absorption, based on the coloration of urine and/or tissues following treatment with Direct Blue 86. Comparison of the urinalysis of test and control animals, and all bilirubin and urobilinogen tests were negative. The clinical examinations of liver function revealed no signs of toxicity following treatment and recovery. No overall effects were observed on the hematological profiles of the test animals compared with the controls. The statistical analyses did not reveal evidence for any treatment-related effects on liver or adrenals weights. The kidney weights were increased at termination of treatment, but were normal after the 2-week recovery. This effect may relate to the morphological changes of the tubules of the kidneys, which were seen at the end of the treatment period, but not after the recovery period. Other histopathological examinations of selected tissues showed no significant effects related to the treatment. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for the test chemical in male and female rats is considered to be 1000 mg/Kg bw/day when they were exposed for 30 days.

Repeated dose subacute toxicity study was performed to determine the toxic nature of the test chemical. The study was performed using male and female Sprague Dalwey rats. The chemical was administered by oral gavage route at dose levels of 0, 100, 300 and 1000 mg / kg for 28 days. This was followed by a recovery period of 14 days at dose level of 0 or 1000 mg/Kg/day. In observation of general condition, abnormality was not observed in both males and females, and there were no death cases. As a result of measurement of body weight and food consumption, neither sex nor effect of test substance administration was observed. As a result of hematology examination, prolonging the prothrombin time observed in the 1000 mg / kg group of males was a slight change compared to the control group, and no lesion suggesting a hepatocellular disorder was also observed It was judged that there was no toxicological significance. In females, no effect of test substance administration was observed. As a result of blood biochemistry and urine test, neither sex nor effect of test substance administration was observed. As a result of organ weight measurement, neither sex nor effect of test substance administration on both actual weight and relative weight was observed. As a result of pathological examination, neither autopsy findings nor tissue findings were observed in the changes suggesting the effect of administration of the test substance at the end of the administration period. A green spot / area of the lung was observed in one group in the male 1000 mg / kg group, but histologically, many macrophages phagocytosed green pigment were observed, so that the test substance exhibiting green color was aspirated It was considered that it invaded the alveolus by, for example, and it was judged that there was no toxicological significance. Regarding the lung macrophage colonization found in the other two cases, it was considered physiologic because it was localized without pigment phagocytosis, and it was judged that there was no toxicological significance. Extrahepatic hematopoiesis of the liver found in multiple animals was judged to be a dose-independent change, not an effect of the administration of the test substance. Since hydronephrosis observed in one males in the control group is likely to be associated with blood flow disorders, metabolic disorders, inflammation and the like, it is highly probable that items which are considered to be related to renal function and those of the same group It was judged that it was appropriate to exclude items showing distinctive values from statistical objects as compared with the other 4 cases. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for the test chemical in male and female rats is found to be 1000 mg/Kg bw/day when they were exposed for 28 days.

Based on the data available for the test chemicals, the No Observed Adverse Effect Level (NOAEL) for the test chemical Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no 28901-96-4) in male and female rats is considered to be 1000 mg/Kg bw/day when they were exposed for 28-30 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is from K2 data

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Waiver

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Data available for the test chemicals was reviiewed to determine the toxic nature of the test chemical Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no 28901-96-4). The studiies are as mentioned below: Repeated dose subacute toxicity study was performed to determine the toxic nature of the test chemical. The chemical was administered by oral gavage route at dose levels of 0 or 1000 mg/Kg bw/day to 20 male and 20 females rats in a standard volume of 10 mL/kg. The treatment period was followed by a 15 day recovery period. 22 daily doses were given over a period of 30 days i.e 5 times/week, 1 dose/day for 4 weeks plus Monday and Tuesday of the last week. The doses were selectedwere selected on the basis of acute oral LD50 study. The oral LD50 value in rats was in excess of 5000 mg/Kg bw/day and no signs of toxicity were noted and hence the dose was subacute study was selected to be 1000 mg/Kg bw/day. Each day, clinical signs and body weights were recorded. Food intake was determined on a weekly basis. At the end of the treatment and the recovery period, hematology, blood chemistry, and urinalysis measurements were carried out by standard methods on animals from control and test groups. At the end of the treatment period or after the recovery period, each rat was examined externally and by dissection for macroscopic abnormalities. Each rat was autopsied and selected organs, including liver, kidneys, adrenals, and spleen were submitted for histopathological examination, following determination of the organ weights. Other organ tissues were fixed in formalin and are held for reference in the archives. Appropriate statistical analyses were performed on the different measurements. No mortality or signs of toxicity were observed during the study period and food and water consumption were within the normal range following treatment with the eight selected colorants. There was evidence of absorption, based on the coloration of urine and/or tissues following treatment with Direct Blue 86. Comparison of the urinalysis of test and control animals, and all bilirubin and urobilinogen tests were negative. The clinical examinations of liver function revealed no signs of toxicity following treatment and recovery. No overall effects were observed on the hematological profiles of the test animals compared with the controls. The statistical analyses did not reveal evidence for any treatment-related effects on liver or adrenals weights. The kidney weights were increased at termination of treatment, but were normal after the 2-week recovery. This effect may relate to the morphological changes of the tubules of the kidneys, which were seen at the end of the treatment period, but not after the recovery period. Other histopathological examinations of selected tissues showed no significant effects related to the treatment. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for the test chemical in male and female rats is considered to be 1000 mg/Kg bw/day when they were exposed for 30 days. Repeated dose subacute toxicity study was performed to determine the toxic nature of the test chemical. The study was performed using male and female Sprague Dalwey rats. The chemical was administered by oral gavage route at dose levels of 0, 100, 300 and 1000 mg / kg for 28 days. This was followed by a recovery period of 14 days at dose level of 0 or 1000 mg/Kg/day. In observation of general condition, abnormality was not observed in both males and females, and there were no death cases. As a result of measurement of body weight and food consumption, neither sex nor effect of test substance administration was observed. As a result of hematology examination, prolonging the prothrombin time observed in the 1000 mg / kg group of males was a slight change compared to the control group, and no lesion suggesting a hepatocellular disorder was also observed It was judged that there was no toxicological significance. In females, no effect of test substance administration was observed. As a result of blood biochemistry and urine test, neither sex nor effect of test substance administration was observed. As a result of organ weight measurement, neither sex nor effect of test substance administration on both actual weight and relative weight was observed. As a result of pathological examination, neither autopsy findings nor tissue findings were observed in the changes suggesting the effect of administration of the test substance at the end of the administration period. A green spot / area of the lung was observed in one group in the male 1000 mg / kg group, but histologically, many macrophages phagocytosed green pigment were observed, so that the test substance exhibiting green color was aspirated It was considered that it invaded the alveolus by, for example, and it was judged that there was no toxicological significance. Regarding the lung macrophage colonization found in the other two cases, it was considered physiologic because it was localized without pigment phagocytosis, and it was judged that there was no toxicological significance. Extrahepatic hematopoiesis of the liver found in multiple animals was judged to be a dose-independent change, not an effect of the administration of the test substance. Since hydronephrosis observed in one males in the control group is likely to be associated with blood flow disorders, metabolic disorders, inflammation and the like, it is highly probable that items which are considered to be related to renal function and those of the same group It was judged that it was appropriate to exclude items showing distinctive values from statistical objects as compared with the other 4 cases. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for the test chemical in male and female rats is found to be 1000 mg/Kg bw/day when they were exposed for 28 days. Based on the data available for the test chemicals, the No Observed Adverse Effect Level (NOAEL) for the test chemical Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no 28901-96-4) in male and female rats is considered to be 1000 mg/Kg bw/day when they were exposed for 28-30 days.

Repeated dose toxicity: Inhalation

Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no. 28901-96-4) has very a low vapor pressure of 1.51E-026 Pa. The particle size distribution was determined to be in the range of 147 micron to 52 micron. The normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely. Therefore this end point for repeated dose toxicity by inhalation route is considered for waiver

Repeated dose toxicity: Dermal

The acute dermal toxicity value for Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no. 28901-96-4) (as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.

Based on the data available for the test chemicals ans applying the weight of evidence approach, the test chemical Hydrogen [29H,31H- phthalocyanine sulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no. 28901-96-4) is not likely to be toxic as per the criteria mentioned in CMLP regulation.

Justification for classification or non-classification

Based on the data available for the test chemicals ans applying the weight of evidence approach, the test chemical Hydrogen [29H,31H-phthalocyanine sulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (CAS no. 28901-96-4) is not likely to be toxic as per the criteria mentioned in CMLP regulation.