Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive toxicity study

Data available for the read across chemicals was reviewed to determine the reproductive toxicity ofTrisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate (72214-18-7) .Based on the data available for the read across chemical, No Observed Adverse Effect Level (NOAEL) was considered to be above 940-1500mg/kg bw . Thus, comparing this value with the criteria of CLP regulationTrisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate (72214-18-7)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 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.Multigeneration toxicity study of test material was performed on male and female wistar rats.2.Reproductive and Development Toxicity Study of test material was performed in Wistar rats.

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Specific details on test material used for the study:

No data available

Species:

rat

Strain:

Wistar

Details on species / strain selection:

No data available

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

other: oral : 1.feed 2.gavage

Vehicle:

other: Study 2:1% carboxymethylcellulose in water

Details on exposure:

No data available

Details on mating procedure:

No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1.From F1 to F3 generation2.12 days (6-17 of gestation period)

Frequency of treatment:

No data available

Details on study schedule:

No data available

Remarks:

Study 10, 0.1, 1.0 or 3% (0, 50, 500,1500 mg/kg bw per day)Study 20, 100, 300 and 1000 mg/kg bw/day (0, 94, 282 or 940 mg active dye/kg bw/day)

No. of animals per sex per dose:

Study 1Total:3600 mg/kg bw: 60 male and 60 female 50 mg/kg bw : 40male and 40 female 500 mg/kg bw : 40male and 40 female 1500 mg/kg bw : 40male and 40 female After a nine-week test period, 24 males and 24 females from the control group, and 14 males and 14 females from each test group were used for teratogenicity studies; the remainder were used for the reproduction study.Study 2Total number of animals-880 mg /kg bw/day -22 female rats 94 mg /kg bw/day -22 female rats282 mg /kg bw/day -22 female rats940 mg /kg bw/day-22 female rats

Control animals:

yes

Details on study design:

No data available

Positive control:

No data available

Parental animals: Observations and examinations:

1.CAGE SIDE OBSERVATIONS: yes - Time schedule: - Cage side observations checked in table [No.?] were included. DETAILED CLINICAL OBSERVATIONS: Yes / No / No data - Time schedule: BODY WEIGHT: Yes - Time schedule for examinations: FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): - Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data WATER 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 1STANDARDISATION OF LITTERS- Performed on day 4 postpartum: [yes/no]- If yes, maximum of [...] pups/litter ([...]/sex/litter as nearly as possible); excess pups were killed and discarded. PARAMETERS EXAMINEDThe following parameters were examined in [F1 / F2 / F3] offspring:number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, were observed GROSS EXAMINATION OF DEAD PUPS:yes ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY:ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY:

Postmortem examinations (parental animals):

Study 1Postmortem examinations (Parent Animal)SACRIFICEYes, Autopsy did of parent ratsGROSS NECROPSY:No data availableHISTOPATHOLOGY / ORGAN WEIGHTS: No data availableStudy 2SACRIFICE - Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.] - Maternal animals:yes, on gestation day 21 GROSS NECROPSY - subjected to macroscopic examination,Embryonic resorptions and implantation sites was observed. HISTOPATHOLOGY / ORGAN WEIGHTS The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.

Postmortem examinations (offspring):

Study 1Postmortem examinations (offspring)SACRIFICEF1,F2, F3 pups were sacrificed.GROSS NECROPSYYesHISTOPATHOLOGY / ORGAN WEIGTHSYes

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

1.no effects observed2. Discoloured faeces were observed at 940 mg/kg bw/day.

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Description (incidence):

No mortality was observed during study

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

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

1.No treatment-related effects on reproductive function was observed 2.At the does group of 94 mg /kg bw/day one female had only embryonic resorptions.At the dose group of 282 and 940 mg /kg bw/day twoFemales were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section. These findings were considered by the study authors to be incidental as a dose relation was missing.

Dose descriptor:

NOAEL

Effect level:

> 940 - <= 1 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

reproductive performance

Remarks on result:

other: No effects on fertility was 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:

no effects observed

Description (incidence and severity):

1& 2.No significannt change were observed in treated group compare to control group.

Dermal irritation (if dermal study):

not specified

Mortality / viability:

no mortality observed

Description (incidence and severity):

2. No significant change in body weight were observed in treated group compare to control group.

Body weight and weight changes:

no effects observed

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:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not specified

Histopathological findings:

no effects observed

Description (incidence and severity):

2. No significant change was observed on external soft tissue and skeletal anomalies based in treated group compare to control group .

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

> 940 - <= 1 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

sexual maturation

mortality

body weight and weight gain

organ weights and organ / body weight ratios

Remarks on result:

other: No effects on reproductive parameters 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:

no effects observed

Dermal irritation (if dermal study):

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

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:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

1 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

sexual maturation

clinical signs

mortality

organ weights and organ / body weight ratios

Remarks on result:

other: No effects on reproductive parameters was 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 NOAEL for reproductive toxicity was considered to be above 940 – 1500 mg/kg bw/day as No effects on reproductive parameters were observed .When male and female rats were treated with Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate (72214-18-7) orally.

Executive summary:

Data available from different studies was reviewed to determine the reproductive toxicity of Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate (72214-18-7) .The studies are as mentioned below:

Study 1

A multigeneration reproductive toxicity study of test material was performed on male and female wistar rats. The test material mixed with feed in dose concentration 0, 0.1, 1.0 or 3% (0, 50, 500, 1500 mg/kg bw per day) and administered orally for three successive generations. Each generation having 60 animals of each sex in the control and 40 animals of each sex in test animals. No adverse effects were observed with respect to fertility, litter size and weight, general condition, male/female ratio, growth during lactation, survival or maturation. Autopsy of parent rats and pups at weaning did not reveal any treatment related changes in organ weights other than caecal enlargement in the 3% dose group. Gross and microscopic examination of the F3 generation at weaning did not reveal any abnormalities due to treatment and no adverse effects were seen in the teratology study. It was concluded that Brilliant Black PN did not exert any adverse effects on reproductive function of Wistar rats when fed at dietary levels up to 3% (1500 mg/kg bw per day) for three successive generations. Therefore, NOAEL was considered to be at 3% (1500 mg/kg bw per day) for F0 F1 and F2 generation .When male and female wistar rats were treated with test material orally.

Study 2

Reproductive toxicity study was observed for test material in P0 female Wistar rats ,they were  exposed at the concentration of 0, 94, 282 or 940mg /kg bw/day through  6-17of gestation period by oral (gavage).The test substance (in1%carboxymethylcellulose in water) was given daily at dose volumes of 10 ml/kg bw by oral gavage. Dams were observed daily for clinical signs, body weight and food intake recorded at designated intervals. The females were killed on gestation day 21, subjected to macroscopic examination, and foetuses were removed by Caesarean section. Common litter parameters were recorded and foetuses were sexed, weighed and submitted to external examination. About one half of the foetuses were also examined for soft tissue anomalies whereas remaining foetuses were examined for skeletal anomalies following alizarin red staining. At the does group of 94 mg /kg bw/day one female had only embryonic resorptions.At the dose group of 282 and 940 mg /kg bw/day two Females were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section. No mortality was observed. Discoloured faeces were observed at 940mg/kg bw/day. No significant changes were observed on litter parameters and fetal weight. No significant changes were observed on external soft tissue and skeletal anomalies in treated group compare to control. Therefore NOAEL was considered to be 940 mg /kg bw/day in P0 female Wistar rats, when they were exposed with test material through  6-17 of gestation period  by oral (gavage).

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Dose descriptor:

NOAEL

940 mg/kg bw/day

Study duration:

chronic

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 from different studies of test chemicals was reviewed to determine the reproductive toxicity of Trisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate (72214-18-7) .The studies are as mentioned below:

Study 1

A multigeneration reproductive toxicity study of test material was performed on male and female wistar rats. The test material mixed with feed in dose concentration 0, 0.1, 1.0 or 3% (0, 50, 500, 1500 mg/kg bw per day) and administered orally for three successive generations. Each generation having 60 animals of each sex in the control and 40 animals of each sex in test animals. No adverse effects were observed with respect to fertility, litter size and weight, general condition, male/female ratio, growth during lactation, survival or maturation. Autopsy of parent rats and pups at weaning did not reveal any treatment related changes in organ weights other than caecal enlargement in the 3% dose group. Gross and microscopic examination of the F3 generation at weaning did not reveal any abnormalities due to treatment and no adverse effects were seen in the teratology study. It was concluded that Brilliant Black PN did not exert any adverse effects on reproductive function of Wistar rats when fed at dietary levels up to 3% (1500 mg/kg bw per day) for three successive generations. Therefore, NOAEL was considered to be at 3% (1500 mg/kg bw per day) for F0 F1 and F2 generation .When male and female wistar rats were treated with test material orally.

Study 2

Reproductive toxicity study was observed for test material in P0 female Wistar rats ,they were  exposed at the concentration of 0, 94, 282 or 940mg /kg bw/day through  6-17of gestation period by oral (gavage).The test substance (in1%carboxymethylcellulose in water) was given daily at dose volumes of 10 ml/kg bw by oral gavage. Dams were observed daily for clinical signs, body weight and food intake recorded at designated intervals. The females were killed on gestation day 21, subjected to macroscopic examination, and foetuses were removed by Caesarean section. Common litter parameters were recorded and foetuses were sexed, weighed and submitted to external examination. About one half of the foetuses were also examined for soft tissue anomalies whereas remaining foetuses were examined for skeletal anomalies following alizarin red staining. At the does group of 94 mg /kg bw/day one female had only embryonic resorptions.At the dose group of 282 and 940 mg /kg bw/day two Females were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section. No mortality was observed. Discoloured faeces were observed at 940mg/kg bw/day. No significant changes were observed on litter parameters and fetal weight. No significant changes were observed on external soft tissue and skeletal anomalies in treated group compare to control. Therefore NOAEL was considered to be 940 mg /kg bw/day in P0 female Wistar rats, when they were exposed with test material through  6-17 of gestation period  by oral (gavage).

Based on the data available for the read across chemical, No Observed Adverse Effect Level (NOAEL) was considered to be above 940-1500mg/kg bw . Thus, comparing this value with the criteria of CLP regulationTrisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate (72214-18-7)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 regulationTrisodium 1-amino-4-[[3-[[4-chloro-6-[(sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate (72214-18-7)is not likely to classify as reproductive toxicant.