Barium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive toxicity

Data available from different studies was reviewed to determine the reproductive toxicity of barium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (17852-98-1)Thus, Based on the data available from different studies , No Observed Adverse Effect Level (NOAEL) was considered to be above 1000 mg/kg bw . Thus, comparing this value with the criteria of CLP regulation barium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (17852-98-1)is 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 structurally similar chemicals

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar 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 below

Principles of method if other than guideline:

WoE report is based on two reproductive toxicity studies on rats 1.Chronic toxicity and carcinogenicity study of test material in rats.2.Reproductive and developmental toxicity study of test material was performed on charles river CD rats.

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Specific details on test material used for the study:

- Name of test material: barium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate- Molecular formula: C18H14N2O6S.Ba- Molecular weight: 521.697 g/mol- Smiles notation: [Ba+2].c1c(c(c(c2ccccc12)\N=N\c1c(cc(cc1)C)S(=O)(=O)[O-])O)C(=O)[O-]- InChl: 1S/C18H14N2O6S.Ba/c1-10-6-7-14(15(8-10)27(24,25)26)19-20-16-12-5-3-2-4-11(12)9-13(17(16)21)18(22)23;/h2-9,21H,1H3,(H,22,23)(H,24,25,26);/q;+2/p-2/b20-19+;- Substance type: Organic- Physical State: Solid

Species:

rat

Strain:

other: 1 & 2 Charies river CD®

Sex:

male/female

Details on test animals or test system and environmental conditions:

1.TEST ANIMALS- Source: Charies river Breeding Laboratories. Iac. Wilningeon - Age at study initiation: (P) x wks; (F1) x wks: P: 36 days- Weight at study initiation: (P) Males: 75-155 g, Female: 75-114 g- Fasting period before study: No data available - Housing: Animals were housed individually in hanging wire mash cages. - Diet (e.g. ad libitum): Purina Laboratory diet, ad libitum. During post weaning segment Purina Laboratory diet, Rodent Laboratory Chow@#5001 and Certified Rodent Chow were used respectively. - Water (e.g. ad libitum): Tap water, ad libitum- Acclimation period: 15 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 21.66°C- Humidity (%): 53 %- Air changes (per hr): No data available - Photoperiod (hrs dark / hrs light): 12 hr light/12hr dark 2.TEST ANIMALS- Age at study initiation: 35 days

Route of administration:

oral: feed

Type of inhalation exposure (if applicable):

not specified

Vehicle:

other: 1.Purina Laboratory diet 2.unchanged (no vehicle)

Details on exposure:

1&2 Details on exposurePREPARATION OF DOSING SOLUTIONS: test material mixed with feed DIET PREPARATION- Rate of preparation of diet (frequency): No data available - Mixing appropriate amounts with (Type of food): No data available - Storage temperature of food: No data available VEHICLE- Justification for use and choice of vehicle (if other than water): No data available - Concentration in vehicle:0,1000mg/kg bw/day - Amount of vehicle (if gavage): No data available - Lot/batch no. (if required): No data available - Purity: No data available

Details on mating procedure:

1.- M/F ratio per cage: 1:1 ratio - Length of cohabitation:7 days - Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancySperm and /or copulatory plug observed in the following morning were considered to be Day 0 of gestation. - After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available - Further matings after two unsuccessful attempts: [no / yes (explain)] No data available- After successful mating each pregnant female was caged (how):Individually - Any other deviations from standard protocol:No data available 2.- M/F ratio per cage:1:1 - Length of cohabitation: 7 days - Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:No data available - After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.No data available - Further matings after two unsuccessful attempts: [no / yes (explain)]No data available - After successful mating each pregnant female was caged (how): No data available - Any other deviations from standard protocol:No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Study 1126 week Study 29 weeks to mating and during gestational and Lactation phase (F0) or 30 months (F1)

Frequency of treatment:

Daily

Details on study schedule:

not specified

Remarks:

Study 10,0, 25, 150, or 1000 mg/kg bw/dayStudy 20,1000 mg/kg bw/day

No. of animals per sex per dose:

Study 1Total : 1300F0 generation 0 mg/kg body weight/day: 60 male, 60 Female 0 mg/kg body weight/day: 60 male, 60 Female 25 mg/kg body weight/day: 60 male, 60 Female 150 mg/kg body weight/day: 60 male, 60 Female 1000 mg/kg body weight/day: 60 male, 60 Female F1 generation 0 mg/kg body weight/day: 70 male, 70 Female 0 mg/kg body weight/day: 70 male, 70 Female 25 mg/kg body weight/day: 70 male, 70 Female 150 mg/kg body weight/day: 70 male, 70 Female 1000 mg/kg body weight/day: 70 male, 70 Female Study 2Total :520F00 mg/kg :60males and 60 females 1000mg/kg:60 male and 60 females F10 mg/kg :70males and 70 females 1000mg/kg:70 male and 70 females

Control animals:

yes, concurrent vehicle

Details on study design:

not specified

Positive control:

not specified

Parental animals: Observations and examinations:

Study 1Mortality , clinical sign, body weight, food and compound consumption, ophthalmoscopic examination, haematology, clinical chemistry, urinalysis, virology and microbiology were observed.Study 2CAGE SIDE OBSERVATIONS: Yes - Time schedule: - Cage side observations checked in table [No.?] were included. DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: BODY WEIGHT: Yes - Time schedule for examinations: FOOD 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: No data - Compound intake calculated as time-weighted averages from the consumption and body weight gain data No data WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data - Time schedule for examinations:

Oestrous cyclicity (parental animals):

Study 1:Any irregularities in the estrous cycle were investigated

Sperm parameters (parental animals):

not specified

Litter observations:

Study 1& 2:Live birth, sex, survival, body weigh, food and compound consumption, ophthalmoscopic examination, haematology, clinical chemistry, urinalysis, virology and microbiology were observed

Postmortem examinations (parental animals):

Study 1:Gross abnormalities and organ weight were examined.

Postmortem examinations (offspring):

Study 1:Gross abnormalities, organ weight and histopathology were examined.

Statistics:

Study 1: Statistically analysis were performed by using fertility indices, gestation 4, 14 and 21 day survival indices were compared by using Chi- square test and /or Fishur’s extract probability. The mean number of liveborn pups per litter and the litter mean per weight at day 0,4,14 and 21 were compared by analysis of variance (one way classification), Barletts test for homogenicty of variances and the appropriate t-test (for equal and unequal variances).For F1 rat: all pair wise statistical comparison were two tailed with the probability level for significance at 0.01. Body weight, food consumption and absolute and relative body weight were compared by analysis of variances and appropriate t-test. Data for animals with malignant tumors, with beings and all tumors combined were analyzed separately by sex. Homogenicity was analysed by cor’s test and cehan-Breslow generalized Krunkal-Wallis test. For the histopathologically proired neoplastic lesions incidencus the two control groups were tested against each other.

Reproductive indices:

Study 1:Fertility index, gestation index and effect on parturition and lactation were examined.

Offspring viability indices:

Study 1:Yes, on day 0, 4 and 14

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

2.orange discoloration of the animals and their feces

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Description (incidence):

Study 1:When treated with 150 mg/kg bw, 3 rats were died.When reated with 1000 mg/kg bw one rat died and in control 3 rats were died.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Study 1:No effect on body weight of treated rat was observed as comparable to control.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Study 1:No effect on food consumption of treated male and female rats was observed as comparable to control.

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

no effects observed

Description (incidence and severity):

Study 1:No change in treated male and female rats was observed as compared to control.

Haematological findings:

no effects observed

Description (incidence and severity):

Study 1:No change in treated male and female rats was observed as compared to control.Study 2A significant decrease in the red blood cell parameters (red blood cell count, packed cell volume and haemoglobin percent) and an increase in the reticulocyte count observed after 3, 6, 12, 18 and 24 months of treatment.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

Study 1:No effect on Clinical chemistry of treated male and female rats was observed as compared to control.

Urinalysis findings:

no effects observed

Description (incidence and severity):

Study 1:No effect on urinalysis of treated male and female rats was observed as compared to control.

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:An acceleration of testicular changes (degeneration of the testicular tubules) was observed in treated male rat, a common effect in ageing rats. However, at the termination of the study, the increased incidence was not of statistical significance.

Histopathological findings: neoplastic:

not specified

Other effects:

no effects observed

Description (incidence and severity):

Study 1Virology:No effect on virology of treated male and female rats was observed as compared to control.Microbiology:No effect on Microbiology of treated male and female rats was observed as compared to control.Study 2Compound consumption was judged to be associated with a significant increase in spleen weight, and the following non-neoplastic lesions of the spleen; extramedullary haematopoiesis, congestion, fibrosis, haemosiderosis, mesothelial hyperplasia, mesothelial cystformation, capsular fibrosis and multifocal cellular proliferations in the capsule. The accumulation of haemsiderin in some other organs of the treated rats also suggest a compound-related effect. The combination of decreased red cell parameters, reticulocytosis and haemosiderosis supports the hypothesis that there was a compound related decreased erythrocyte survival and a haematopoietic response to that decreased red cell survival.

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

Study 1:No effect on Fertility index, gestation index and effect on parturition and lactation were observed as compared to control. Study 2:There was no evidence for an impairment of reproductive functions in animals.No effect on fertility indices, gestation anomalies, viability and survival of the pups were observed in treated rats as compared to control.

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

reproductive performance

Remarks on result:

other: No effect 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

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

no mortality observed

Description (incidence and severity):

Study 1:No effect on survival of F1 offspring were observed as compared to control.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Study 1When treated with 1000 mg/kg bw, significant decrease in body weight were observed in male rat as comparable to control. When treated with 25 and 150 mg/kg bw, slightly decreased body weight was observed as comparable to control. Decrease in body weight were recovred in treated rats.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Study 1:No effect on food consumption of treated male and female offspring’s was observed as comparable to control.

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

no effects observed

Description (incidence and severity):

Study 1:No change in treated male and female offsprings rats was observed as compared to control.

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:

no effects observed

Description (incidence and severity):

Study 1:No effect on organ weight of treated male and female offspring was observed as compared to control.

Gross pathological findings:

no effects observed

Description (incidence and severity):

Study 1:No gross pathological changes were observed in treated male and female offspring as compared to control.

Histopathological findings:

no effects observed

Description (incidence and severity):

Study 1:An acceleration of testicular changes (degeneration of the testicular tubules) was observed in treated male rat, a common effect in ageing rats. However, at the termination of the study, the increased incidence was not of statistical significance.

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

viability

mortality

body weight and weight gain

food consumption and compound intake

ophthalmological examination

haematology

clinical biochemistry

urinalysis

organ weights and organ / body weight ratios

gross pathology

other: No effect observed

Remarks on result:

other: overall 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:

NOAEL was considered to be 1000 mg/kg/day for F0 generation and F1 geneartion when Charies river CD®male and female rat were exposed tobarium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate(17852-98-1) orally in feed.

Executive summary:

Data available from different studies were reviewed to determine the reproductive toxicity of barium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (17852-98-1).The studies are as mentioned below:

Study 1

In a chronic toxicity and carcinogenicity study,Charies river CD®male and female rat were exposed to test material in the concentration 0, 0, 25, 150 and 1000 mg/kg/day orally in feed. In the parental generation,3 rats were died at 150 mg/kg bw, one rat died at 1000 mg/kg bw and 3 rats were died in in control. No effect onbody weight and food consumption,ophthalmoscopic examination, haematology, clinical chemistry, urinalysis, virology and microbiologyof treated male and female rats was observed as comparable to control.Similarly, No effect on reproductive performance such as Fertility index, gestation index and effect on parturition and lactation were observed as compared to control. No effect onorgan weight and gross pathology were observed as compared to control in P and F1 generation. In addition, anacceleration of testicular changes (degeneration of the testicular tubules) was observed in treated male rat, a common effect in ageing rats. However, at the termination of the study, the increased incidence was not of statistical significance. Therefore, NOAEL was considered to be 1000 mg/kg/day for F0 generation and F1 geneartion when Charies river CD®male and female rat were exposed to test material orally in feed.

Study 2

In reproductiveand developmental toxicity study , male and femalecharles river CDrats were treated wtih test materialin dose concentration 0,1000mg/kg orally. The test material mixed with basal diets. The animals were 35 days of age when treatment was initiated.After nine weeks of treatment, the animals were mated by pairing for seven days. The effect of test material for the in-utero phase was evaluated via mortality, clinical observations, body weight, food consumption, sex ratio, pup viability data and gross necropsy observations on selected animals. Compound consumption was judged to cause orange discoloration of the animals and their feces and an enlargement of their spleens during the in-utero and chronic phases. The chronic phase revealed non-neoplastic compound related effects which included a significant decrease in the red blood cell parameters (red blood cell count, packed cell volume and haemoglobin per cent) and an increase in the reticulocyte count observed after 3, 6, 12, 18 and 24 months of treatment. Compound consumption was judged to be associated with a significant increase in spleen weight, and the following non-neoplastic lesions of the spleen; extramedullary haematopoiesis, congestion, fibrosis, haemosiderosis, mesothelial hyperplasia, mesothelial cystformation, capsular fibrosis and multifocal cellular proliferations in the capsule. The accumulation of haemsiderin in some other organs of the treated rats also suggest a compound-related effect. The combination of decreased red cell parameters, reticulocytosis and haemosiderosis supports the hypothesis that there was a compound related decreased erythrocyte survival and a haematopoietic response to that decreased red cell survival. There was no evidence for an impairment of reproductive functions in animals.No effect on fertility indices, gestation anomalies, viability and survival of the pups were observed in treated rats as compared to control.Hence,NOAEL was considered to be 1000mg/kg bw/day as no effects on reproductive and developmental parameters were observed. When male and femalecharles river CDrats were treated wtih test material orally.

Thus, Based on the data available from different studies , No Observed Adverse Effect Level (NOAEL) was considered to be above 1000 mg/kg bw . Thus, comparing this value with the criteria of CLP regulation barium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (17852-98-1)is not likely to classify as reproductive toxicant.

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 secondary source

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Data available from different studies were reviewed to determine the reproductive toxicity of barium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (17852-98-1).The studies are as mentioned below:

Study 1

In a chronic toxicity and carcinogenicity study,Charies river CD®male and female rat were exposed to test material in the concentration 0, 0, 25, 150 and 1000 mg/kg/day orally in feed. In the parental generation,3 rats were died at 150 mg/kg bw, one rat died at 1000 mg/kg bw and 3 rats were died in in control. No effect onbody weight and food consumption,ophthalmoscopic examination, haematology, clinical chemistry, urinalysis, virology and microbiologyof treated male and female rats was observed as comparable to control.Similarly, No effect on reproductive performance such as Fertility index, gestation index and effect on parturition and lactation were observed as compared to control. No effect onorgan weight and gross pathology were observed as compared to control in P and F1 generation. In addition, anacceleration of testicular changes (degeneration of the testicular tubules) was observed in treated male rat, a common effect in ageing rats. However, at the termination of the study, the increased incidence was not of statistical significance. Therefore, NOAEL was considered to be 1000 mg/kg/day for F0 generation and F1 geneartion when Charies river CD®male and female rat were exposed to test material orally in feed.

Study 2

In reproductiveand developmental toxicity study , male and femalecharles river CDrats were treated wtih test materialin dose concentration 0,1000mg/kg orally. The test material mixed with basal diets. The animals were 35 days of age when treatment was initiated.After nine weeks of treatment, the animals were mated by pairing for seven days. The effect of test material for the in-utero phase was evaluated via mortality, clinical observations, body weight, food consumption, sex ratio, pup viability data and gross necropsy observations on selected animals. Compound consumption was judged to cause orange discoloration of the animals and their feces and an enlargement of their spleens during the in-utero and chronic phases. The chronic phase revealed non-neoplastic compound related effects which included a significant decrease in the red blood cell parameters (red blood cell count, packed cell volume and haemoglobin per cent) and an increase in the reticulocyte count observed after 3, 6, 12, 18 and 24 months of treatment. Compound consumption was judged to be associated with a significant increase in spleen weight, and the following non-neoplastic lesions of the spleen; extramedullary haematopoiesis, congestion, fibrosis, haemosiderosis, mesothelial hyperplasia, mesothelial cystformation, capsular fibrosis and multifocal cellular proliferations in the capsule. The accumulation of haemsiderin in some other organs of the treated rats also suggest a compound-related effect. The combination of decreased red cell parameters, reticulocytosis and haemosiderosis supports the hypothesis that there was a compound related decreased erythrocyte survival and a haematopoietic response to that decreased red cell survival. There was no evidence for an impairment of reproductive functions in animals.No effect on fertility indices, gestation anomalies, viability and survival of the pups were observed in treated rats as compared to control.Hence,NOAEL was considered to be 1000mg/kg bw/day as no effects on reproductive and developmental parameters were observed. When male and femalecharles river CDrats were treated wtih test materialorally.

Thus, Based on the data available from different studies , No Observed Adverse Effect Level (NOAEL) was considered to be above 1000 mg/kg bw . Thus, comparing this value with the criteria of CLP regulation barium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (17852-98-1)is not likely to classify as reproductive toxicant.

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 barium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (17852-98-1)is not likely to classify as reproductive toxicant.