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

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive toxicity study

The data available for Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (28901-96-4 )and its read across substances was reviewed to determine the reproductive toxicity. NOAEL was considered to be 1000mg /kg bw/day for reproductive toxicity, when female rats were exposed with Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) 28901-96-4 orally.Thus, comparing this value with the criteria ofCLP regulation Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) 28901-96-4 )not likely to classify as reproductive toxicant.

 

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

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:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

WoE report is based on two reproductive toxicity studies on rats.1.&2.Reproductive toxicity study of test material was performed on male and female rats.

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Species:

rat

Strain:

Sprague-Dawley

Remarks:

(Crj: CD (SD) IGS, SPF)

Details on species / strain selection:

No data available

Sex:

male/female

Details on test animals or test system and environmental conditions:

Study 1Details on test animalTEST 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).Study 2Details on test animals and env. conditions- TEST ANIMALS- Source: Charles River Japan Co., Ltd.- Age at study initiation: 10 weeks - Weight at study initiation: 372.3 g (338to 397 g) for males and 232.6 g (202 to 252 g) for females.- Fasting period before study:- Housing: bracket-type metallic wire mesh floor cage(260 W × 380 D × 180 H, mm). However, from the 17th day of pregnancy, a stainless steel saucer covered with a laboratory animal floorcovering (White Flake, Nippon Charles River Co., Ltd.) was used instead of a metal mesh floor.- Use of restrainers for preventing ingestion (if dermal): yes/no- Diet (e.g. ad libitum): solid feed (CRF-1, Oriental Yeast Industry Co., Ltd.), . ad libitum- Water (e.g. ad libitum): tap water (Sapporo municipalwater) . ad libitum- Acclimation period:14 days ENVIRONMENTAL CONDITIONS- Temperature (°C): 23 ± 3°C- Humidity (%):55 ± 10%,- Air changes (per hr): 10 to 15 times / hour- Photoperiod (hrs dark / hrs light): illumination time of 12 hours (lit from 8 am to 8 pm) ,

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Study 1Details on oral exposurePREPARATION 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 dataStudy 2.REPARATION OF DOSING SOLUTIONS:Test substance was precisely weighed and added to 0.5% carboxymethylcellulose sodium solution (0.5% CMC-Na solution, Japan Pharmacopoeia CMC-Na, MARUKAISHI PHARMACEUTICAL CO., LTD.) So as to be 0.4, 2.0 and 10.0 w / v% Purified water, Yakuhan Pharmaceutical Co., Ltd.). In addition, it was confirmed at the test facility that the preparation liquid contained the test substance at a predetermined concentration. DIET PREPARATION- Rate of preparation of diet (frequency): The diet was prepared fresh weekly.- Mixing appropriate amounts with (Type of food ):.- Storage temperature of food: No data available- Purity: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water):- Concentration in vehicle:0,40,200,1000mg/kg - Amount of vehicle (if gavage):10ml /kg - Lot/batch no. (if required):

Details on mating procedure:

Study 2- M/F ratio per cage:1:1 - Length of cohabitation: 1 days - Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy - After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. - Further matings after two unsuccessful attempts: [no / yes (explain)] - After successful mating each pregnant female was caged (how): - Any other deviations from standard protocol:

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Study 1.No, Due to the characteristics of the test substance, it was impossible to measure the concentration using the analyzer

Duration of treatment / exposure:

Study 128 days + 14 days recoveryStudy 2For the males, 46 days for the females for the females 14 days before the mating , during pregnancy period, the period up to 3 days of nursing

Frequency of treatment:

Daily

Details on study schedule:

No data available

Remarks:

Study 1Test group: 0, 100, 300 and 1000 mg / kgStudy 20, 40,200,1000mg/kg Recovery group: 0 or 1000 mg/Kg

No. of animals per sex per dose:

Study 1Total: 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 femalesStudy 2Total:960 mg/kg: 12 male and 12 females 40mg/kg: 12 male and 12 females200 mg/kg: 12 male and 12 females1000 mg/kg: 12 male and 12 females

Control animals:

yes, concurrent vehicle

Details on study design:

Study 1Details on study design- 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

Positive control:

No data available

Parental animals: Observations and examinations:

Study 1Observations and examinations performed & frequencyCAGE 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 dataStudy 2Parental animals observation and examinationsCAGE SIDE OBSERVATIONS: yes DETAILED CLINICAL OBSERVATIONS: Yes Time schedule: Daily BODY WEIGHT: YesTime schedule for examinations: All the cases were measured on 1 day of administration (before administration), 2, 5, 7, 10 and 14 days of administration, thereafter every 7 days (including the administration end date) and further on the autopsy day. FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): All the cases were measured on the same day (including the administration end date) as the body weight measurement day except for 1 day of administration (before administration), 2, 5, 7, 10 and 14 days of administration, thereafter except for the mating period. Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data availableCompound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data Time schedule for examinations: OTHER:

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

Study 2.The live fetuses were sexed, weighed and inspected for external malformations

Postmortem examinations (parental animals):

Study 1Sacrifice and pathologyGROSS 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.Study 2Postmortem examinations (Parent Animal)SACRIFICE :All the animals were sacrificed GROSS NECROPSY: yes HISTOPATHOLOGY / ORGAN WEIGHTS: yes

Postmortem examinations (offspring):

Study 2SACRIFICE: yes - These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: GROSS NECROPSY yes - Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.] HISTOPATHOLOGY / ORGAN WEIGTHS The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.

Statistics:

Study 1A 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.

Reproductive indices:

No data available

Offspring viability indices:

No data available

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Study 1.Throughout the administration period and the recovery period, no animals showing abnormality in both sexes were observed.Study 2.Blueing of feces was observed after 2 days of administration in all of the groups of 40 mg / kg or more, and the higher doses were more pronounced. No other symptoms were observed.

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Description (incidence):

Study 1.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):

Study 1.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.Study 2No significant difference was observed over the administration period compared to the control group.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Study 1.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.Study 2An increase in food intake was observed on days 10 and 21 in the 1000 mg / kg group compared to the control group, but it was judged to beintake within the usual range. There was no significant difference in the pre-pregnancy administration period compared with the control group. In the gestation period, an increase in food intake was observed on the 5th day of gestation in the 200 mg / kg group compared to the controlgroup, but it was a variation lacking dose dependency. There was no significant difference in the nursing period compared to the control group.

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):

Study 1.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):

Study 1.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):

Study 1.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

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

Study 1.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 pigmentphagocytosis 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:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

no effects observed

Description (incidence and severity):

Study 2In the female sexual cycle test, in two cases of mating failure in the control group, continuation of the estrus pause period was observed after the start of mating, but in other cases a normal sexual cycle was shown, and the pretreatment period and the sexual cycle of the administrationperiod No change was observed.

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

There was no significant difference in the number of days until copulation, mating rate and conception rate compared with the control group. In addition, 2 cases in the mating group were observed in the control group, 1 group in the infertility group, 4 groups in the 40 mg / kg group, 1group in the 200 mg / kg group and 3 groups in the 1000 mg / kg group.There were no findings suggestive of testis and epididymis associated with test substance administration, mating failure and infertility cause. On the epididymis, granuloma of the capsule was a case of 40 mg / kg group, and perivascular localized cell infiltration, mainly lymphocytes, in the interstitium was observed in a case of 200 mg / kg group.

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

haematology

clinical biochemistry

urinalysis

organ weights and organ / body weight ratios

gross pathology

histopathology: non-neoplastic

Remarks on result:

other: No effects on reproductive organ weight

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

no mortality observed

Description (incidence and severity):

There was no significant difference in neonatal survival rate compared to the control group.

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Description (incidence and severity):

Of the dead, exfoliation of the back skin was observed in one female in the 40 mg / kg group. Dermal exfoliation of the chest and abdomen was observed in one female of the control group which was sacrificed due to weakness. Among the cases of sacrifice on the 4th day of nursing, yellowing whitening of the medial right lobe of the liver was observed in one males in the control group, and one male in the 200 mg / kg group was found missing in the tail tip.No findings suggesting association with test substance administration were observed in both males and females

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

mortality

body weight and weight gain

gross pathology

other: not specified

Remarks on result:

other: No developmental toxic effects observed

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

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-) 28901-96-4 )for reproduction toxicity in test animals were considered to be 1000 mg/Kg bw/day.

Executive summary:

Data available for the target chemicals was reviewed to determine the toxic nature of the test chemical Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) 28901-96-4 ). The studies are as mentioned below:

Study 1

Reproductive organ toxicity was determined in Repeated dose subacute toxicity. 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. No effects on reproductive organ 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. Hence the No Observed Adverse Effect Level (NOAEL) for reproductive toxicity was considered to be 1000 mg/Kg bw/day when male and female rats were treated with test material orally.

Study 2

The reproductive toxicity study of test material was performed on male and femaleCrj: CD (SD) SPF. Test material soluble in0.5% carboxymethylcellulose sodium solution (0.5% CMC-Na solution )in dose concentration 0,40,200,1000 mg/kg bw given by oral gavage route to the males, 46 days and to the females 14 days before the mating , during pregnancy period, the period up to 3 days of nursing.All animals were observe forbehavior, appearance daily. Body weight measured on 1 day of administration (before administration), 2, 5, 7, 10 and 14 days of administration, thereafter every 7 days (including the administration end date) and further on the autopsy day.

No deaths were observed in rats of any groups.Blueing of feces was observed after 2 days of administration in all of the groups of 40 mg / kg or more, and the higher doses were more pronounced. No other symptoms were observed. No significant difference was observed over the administration period compared to the control group in body weight. In the female sexual cycle test, in two cases of mating failure in the control group, continuation of the estrus pause period was observed after the start of mating, but in other cases a normal sexual cycle was shown, and the pretreatment period and the sexual cycle of the administration period no change was observed. There was no significant difference in the number of days until copulation, mating rate and conception rate compared with the control group. In addition, 2 cases in the mating group were observed in the control group, 1 group in the infertility group, 4 groups in the 40 mg / kg group, 1 group in the 200 mg / kg group and 3 groups in the 1000 mg / kg group.Compared to the control group, a decrease in the total number of births was observed in the 200 mg / kg group, but it was a variation lacking dose dependence. In addition, there were significant differences in the number of pregnant lutein, number of implantation traces, implantation rate, number of surviving children at birth confirmation, delivery rate, birth rate, sex ratio, number of dead children at birth check, pregnancy period, birth rate and nursing rate Was not observed. There was no significant difference in neonatal survival rate compared to the control group. Compared to the control group, body weight gain was observed on 1 to 4 days of nursing in males and females of the 200 mg / kg group, but it was judged to be progressing weight progressing. Of the dead, exfoliation of the back skin was observed in one female in the 40 mg / kg group. Dermal exfoliation of the chest and abdomen was observed in one female of the control group which was sacrificed due to weakness. Among the cases of sacrifice on the 4th day of nursing, yellowing whitening of the medial right lobe of the liver was observed in one males in the control group, and one male in the 200 mg / kg group was found missing in the tail tip. No findings suggesting association with test substance administration were observed in both males and females. HenceNo Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 1000mg/kg bw .When male and femalerats were treated with test material orally.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is Klimicsh 2 and from authoritative database

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity study

Data available for the target chemicals was reviewed to determine the toxic nature of the test chemical Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) (28901-96-4 ). The studies are as mentioned below:

Study 1

Reproductive organ toxicity was determined in Repeated dose subacute toxicity. 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. No effects on reproductive organ 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. Hence the No Observed Adverse Effect Level (NOAEL) for reproductive toxicity was considered to be 1000 mg/Kg bw/day when male and female rats were treated with test material orally.

Study 2

The reproductive toxicity study of test material was performed on male and femaleCrj: CD (SD) SPF. Test material soluble in0.5% carboxymethylcellulose sodium solution (0.5% CMC-Na solution )in dose concentration 0,40,200,1000 mg/kg bw given by oral gavage route to the males, 46 days and to the females 14 days before the mating , during pregnancy period, the period up to 3 days of nursing.All animals were observe forbehavior, appearance daily. Body weight measured on 1 day of administration (before administration), 2, 5, 7, 10 and 14 days of administration, thereafter every 7 days (including the administration end date) and further on the autopsy day.

No deaths were observed in rats of any groups.Blueing of feces was observed after 2 days of administration in all of the groups of 40 mg / kg or more, and the higher doses were more pronounced. No other symptoms were observed. No significant difference was observed over the administration period compared to the control group in body weight. In the female sexual cycle test, in two cases of mating failure in the control group, continuation of the estrus pause period was observed after the start of mating, but in other cases a normal sexual cycle was shown, and the pretreatment period and the sexual cycle of the administration period no change was observed. There was no significant difference in the number of days until copulation, mating rate and conception rate compared with the control group. In addition, 2 cases in the mating group were observed in the control group, 1 group in the infertility group, 4 groups in the 40 mg / kg group, 1 group in the 200 mg / kg group and 3 groups in the 1000 mg / kg group.Compared to the control group, a decrease in the total number of births was observed in the 200 mg / kg group, but it was a variation lacking dose dependence. In addition, there were significant differences in the number of pregnant lutein, number of implantation traces, implantation rate, number of surviving children at birth confirmation, delivery rate, birth rate, sex ratio, number of dead children at birth check, pregnancy period, birth rate and nursing rate Was not observed. There was no significant difference in neonatal survival rate compared to the control group. Compared to the control group, body weight gain was observed on 1 to 4 days of nursing in males and females of the 200 mg / kg group, but it was judged to be progressing weight progressing. Of the dead, exfoliation of the back skin was observed in one female in the 40 mg / kg group. Dermal exfoliation of the chest and abdomen was observed in one female of the control group which was sacrificed due to weakness. Among the cases of sacrifice on the 4th day of nursing, yellowing whitening of the medial right lobe of the liver was observed in one males in the control group, and one male in the 200 mg / kg group was found missing in the tail tip. No findings suggesting association with test substance administration were observed in both males and females. HenceNo Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 1000mg/kg bw .When male and femalerats were treated with test material orally.

 Based on the data available from different studies,Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) ( 28901-96-4 )did not showedreproductive toxicityat dose concentration 1000mg/kg bw/day.Hence the test chemical is not likely to classify as a reproductive toxicant as per the criteria mentioned in CLP regulation.

 

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation Hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-) 28901-96-4 )not likely to classify as reproductive toxicant.