Trisodium 2-[[4,5-dihydro-3-methyl-5-oxo-1-[4-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]-1H-pyrazol-4-yl]azo]naphthalene-1,5-disulphonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

The reproductive toxicity of trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)was estimated by SSS (2017) using OECD QSAR toolbox v3.3with log kow as the primary descriptor and NOAEL was estimated to be 1013.125mg/kg bw. When male and female wistar rats were exposed withtrisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)orally.

 Thus, based on the above predictions and experimental study trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)and its structurally similar read across substance No Observed Adverse Effect Level (NOAEL) was considered to be between 500mg/kg bw to 1500mg/kg bw . Thus, comparing this value with the criteria of CLP regulation trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)cannot be classified as reproductive toxicant.

 

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox v3.3 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

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 (IUPAC name): trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate
- Molecular formula: C22H17N4Na3O13S4
- Molecular weight: 742.6253 g/mol
-InChl:1S/C22H20N4O13S4.3Na/c1-13-20(22(27)26(25-13)14-5-7-15(8-6-14)40(28,29)12-11-39-43(36,37)38)24-23-18-10-9-16-17(21(18)42(33,34)35)3-2-4-19(16)41(30,31)32;;;/h2-10,20H,11-12H2,1H3,(H,30,31,32)(H,33,34,35)(H,36,37,38);;;/q;3*+1/p-3/b24-23+;;;
- Substance type: Organic

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:

oral: gavage

Vehicle:

not specified

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:

F0-males:
- for 2 weeks prior to mating, throughout mating and after mating at least until the minimum total dosing period of 28 days had been completed
F0-females:
2 weeks prior to mating, throughout mating, and pregnancy and at least up to, and including the day before sacrifice

Frequency of treatment:

once daily

Details on study schedule:

No data available

Dose / conc.:

1 013.125 mg/kg bw/day (nominal)

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

No data available

Positive control:

No data available

Parental animals: Observations and examinations:

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
- 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): Yes / No / No data
- Time schedule for examinations:

OTHER:

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

No data available

Postmortem examinations (parental animals):

No data available SACRIFICE
- Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.]
- Maternal animals: All surviving animals [describe when, e.g. after the last litter of each generation was weaned.]

GROSS NECROPSY: yes
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]

HISTOPATHOLOGY / ORGAN WEIGHTS: yes
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.

Postmortem examinations (offspring):

No data available

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

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:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Dose descriptor:

NOAEL

Effect level:

1 013.125 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

body weight and weight gain

food consumption and compound intake

gross pathology

histopathology: non-neoplastic

reproductive performance

Remarks on result:

other: No effects on reproductive performance 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

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:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 013.125 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

Remarks on result:

other: No developmental toxic effects 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

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and "u" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Vinyl Sulfones by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Schiff base formation OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, without OH or NH2 group OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Cation AND Heterocyclic compound AND Sulfonic acid derivative AND Sulfuric acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acetal by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Cation AND Heterocyclic compound AND Sulfonic acid derivative AND Sulfuric acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Tertiary aliphatic amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Amide, aliphatic attach [-C(=O)N] AND Amino, aliphatic attach [-N<] AND Amino-carbonyl compound [NCC(=O)-C] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Azomethine, aliphatic attach [-N=C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Hydrazine [>N-N<] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfate, linear [-O-SO2-O-] AND Sulfite, linear [-OS(=O)O-] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] by Organic functional groups (US EPA)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Pyrazolone AND Sulfate AND Sulfone AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Ether by Organic Functional groups

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Pyrazolone AND Sulfate AND Sulfone AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Carboxylic acid ester by Organic Functional groups

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 623 Da

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 879 Da

Conclusions:

In reproductive toxicity study, NOAEL was estimated to be 1013.125mg/kg bw. When male and female wistar rats were exposed with trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) orally.

Executive summary:

The reproductive toxicity of trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)was estimated by SSS (2017) using OECD QSAR toolbox v3.3with log kow as the primary descriptor and NOAEL was estimated to be 1013.125mg/kg bw. When male and female wistar rats were exposed withtrisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)orally

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 013.125 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

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

Additional information

Reproductive toxicity

In different studies on trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies performed on structurally similar read across substance.

The reproductive toxicity of trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)was estimated by SSS (2017) using OECD QSAR toolbox v3.3with log kow as the primary descriptor and NOAEL was estimated to be 1013.125mg/kg bw. When male and female wistar rats were exposed with trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)orally.

Further supported by   experimental study conducted byThe Joint FAO/WHO Expert Committee on Food Additives (JECFA)(Brilliant Black PN: Toxicological Evaluation of certain food additives (WHO Food additives Series 16- 1981)) on structurally similar read across substance with Brilliant Black PN (2519-30-4). A multigeneration reproductive toxicity study of Brilliant Black PN (2519-30-4) 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 Brilliant Black PN (2519-30-4) orally.

 

Also in another experimental study conducted byU.S. National Library of Medicine(HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC, 2017.)on structurally similar read across substance with 2-Naphthalenesulfonic acid, 6-hydroxy-5-[(4-sulfophenyl)azo]-, disodium salt (2783-94-0).Three generation reproductive study of 2-Naphthalenesulfonic acid, 6-hydroxy-5-[(4-sulfophenyl)azo]-, disodium salt (2783-94-0) was performed on male and female Charles River CD rats. Animals were housed individually and fed the test diet ad libitum. The test material mixed with food in dose concentration 0, 5, 50, 150 or 500 mg/kg bw/day and 10 males and 20 females/group/generation were used .Pre-Mating Exposure / Males and Females were 60 days. Clinical observations were recorded twice daily with at least 5 hours between observations. Detailed physical examinations and palpation for masses were performed weekly. Body weights and food consumption were determined weekly for the first fourteen weeks, bi-weekly for the next 12 weeks and every 4 weeks thereafter until the end of the study. The intake of the test substance was determined from body weight, food consumption and dietary concentration. Haematology tests, including haemoglobin, haematocrit, erythrocyte and total and differential leukocyte counts, and erythrocyte morphology, were conducted on ten randomly selected animals at months 3, 6, 12, 18 and 24 of the study. Necropsies were conducted on all animals dying prior to study termination, killed in a moribund condition or killed on schedule. Histological examinations were conducted on all animals from both control groups, the highest dose group (2.0 or 5.0%) from each study and also on 10 rats randomly selected from each group for an interim sacrifice at 12 months. Histology was also performed on any animal with gross lesions or masses. Also tissues examined included adrenal glands, aorta, blood smear, brain, cecum, colon, duodenum, epididymus or uterus, esophagus, eyes, femur including marrow, tissue masses, gallbladder, heart, ileum, jejunum, duodenum, kidneys, liver, lungs and bronchi, mammary gland, nerves (sciatic), ovaries, lymph nodes, pancreas, parathyroids, pituitary gland, prostrate, rectum, skin, spleen, seminal vesicles, skeletal muscle, testes with epididymides, stomach, thymus, thyroid gland including parathyroid, trachea, urinary bladder, uterus.

 At the end of study, no treatment-related effects were reported on survival. No treatment-related changes were reported at gross necropsy. Histological evaluation revealed a variety of lesions, including neoplasms, present at similar incidences in control and treated animals. The authors considered the lesions to be spontaneous and not related to administration of the test material. There were no compound related effects on fertility, gestation, pup viability or lactation indices, on reproductive organs of females, or on organ weights among parents and offspring. There were no compound related lesions in any tissue examined histologically, including kidneys and adrenal glands from parental rats or from offspring. There was no toxicity to either the F1 or F2 generation. Food consumption was similar for control and treated animals at the lower dietary levels, but was slightly higher in the high-dose study, although not statistically significant. Haematological, clinical chemistry and urinalysis parameters did not differ significantly from the controls. Necropsies at one year did not reveal any treatment-related gross or microscopic changes. Hence NOAEL was considered to be 500mg/kg bw/day for F0, F1 and F2 generation. When male and female Charles River CD rats were treated with 2-Naphthalenesulfonic acid, 6-hydroxy-5-[(4-sulfophenyl)azo]-, disodium salt (2783-94-0) orally.

    Thus, based on the above predictions and experimental study trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)and its structurally similar read across substance No Observed Adverse Effect Level (NOAEL) was considered to be between 500mg/kg bw to 1500mg/kg bw . Thus, comparing this value with the criteria of CLP regulation trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)cannot be classified as reproductive toxicant.

 

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)cannot be classified as reproductive toxicant.