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EC number: 204-254-5 | CAS number: 118-47-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from QSAR Toolbox 3.4.0.17
- Justification for type of information:
- QSAR prediction: migrated from IUCLID 5.6
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Principles of method if other than guideline:
- Reproduction / Developmental Toxicity Screening Test of 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid in rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data availabel
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- No data availabel
- Details on mating procedure:
- No data availabel
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
40 to 55 days
males: 2 weeks prior to mating, mating and 5 weeks post mating
females: 2 weeks prior to mating, mating, pregnancy, 4 days lactation- Frequency of treatment:
- Daily
- Details on study schedule:
- No data available
- Remarks:
- Doses / Concentrations:
860 mg/kg bw
Basis: - No. of animals per sex per dose:
- No data available
- Control animals:
- yes
- Details on study design:
- No data available
- Positive control:
- No data available
- Parental animals: Observations and examinations:
- No data available
- 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
- Postmortem examinations (offspring):
- No data available
- Statistics:
- No data available
- Offspring viability indices:
- No data available
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 860 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effect on systemic/reproductive performance/fertility
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
- Remarks on result:
- not measured/tested
- Reproductive effects observed:
- not specified
- Conclusions:
- Estimated NOAEL was considered to be 860 mg/kg bw Wistar male and female rats were treated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid orally by gavage.
- Executive summary:
Reproductive toxicity was estimated by using QSAR Toolbox version 3.4.0.17 in Wistar male and female rats trreated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid in the concentration of 860 mg/kg bw in water orally by gavage. No effect on systemic/reproductive performance/fertility was observed in treated male and femalerats. Therefore, estimated NOAEL was considered to be 860 mg/kg bw Wistar male and female rats were treated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid orally by gavage.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain
(((("a"
or "b" or "c" )
and ("d"
and (
not "e")
)
)
and "f" )
and ("g"
and "h" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as AN2 AND AN2 >> Michael addition
to activated double bonds in heterocyclic ring systems AND AN2 >>
Michael addition to activated double bonds in heterocyclic ring systems
>> Pyrazolone and Pyrazolidine Derivatives AND AN2 >> Schiff base
formation with carbonyl compounds (AN2) AND AN2 >> Schiff base formation
with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives
AND Schiff base formation AND Schiff base formation >> Schiff base on
pyrazolones and pyrazolidinones AND Schiff base formation >> Schiff base
on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones by
Protein binding by OASIS v1.4
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Acylation AND Acylation >>
Direct Acylation Involving a Leaving group AND Acylation >> Direct
Acylation Involving a Leaving group >> Acetates by Protein binding by
OECD
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Acid moiety AND Amides AND
Hydrazines by Aquatic toxicity classification by ECOSAR
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.4
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as AN2 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
and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA
intercalation >> N-Hydroxyethyl Lactams OR Non-covalent interaction >>
DNA intercalation >> Polycyclic Aromatic Hydrocarbon and
Naphthalenediimide Derivatives 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 >> Generation of ROS by
glutathione depletion (indirect) OR Radical >> Generation of ROS by
glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom 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 and Naphthalenediimide 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 ion OR SN1 >> Nucleophilic substitution on diazonium ion >>
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
and Naphthalenediimide Derivatives OR SN2 >> Alkylation, nucleophilic
substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic
substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR
SN2 >> Direct acting epoxides formed after metabolic activation OR SN2
>> Direct acting epoxides formed after metabolic activation >> Quinoline
Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR
SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes
Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon
atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon
atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives
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.1.4
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "g"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -1.91
Domain
logical expression index: "h"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 1.82
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 860 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimish 2 and from QSAR Toolbox version 3.4.0.17
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:
Data available for target 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid (118-47-8) and its read across Tartrazine (CAs no 1934-21-0) for reproductive toxicity are summarized as below
Based on prediction done by using QSAR Toolbox version 3.4.0.17 (2016), reproductive toxicity was estimated in Wistar male and female rats by using 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid in the concentration of 860 mg/kg bw in water orally by gavage. No effect on systemic/reproductive performance/fertility was observed in treated male and female rats. Therefore, estimated NOAEL was considered to be 860 mg/kg bw Wistar male and female rats were treated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid orally by gavage.
In a study conducted by Mehedi et al (2009), sub chronic toxicity was evaluated in male swiss albino mice by using Tartrazine in the concentration of 0, 0.1%, 1% and 2.5% (173.9 ±0.25, 1767.8±0.32and 5541.4±0.47 mg/kg/day ) by oral drinking water. Groups of Tartrazine treated mice, six males per dose group, were mated 1:1 with untreated females for 1 week. Females were then separated and allowed to gestate to term. For females that failed to deliver a litter, this was considered as a sign of male infertility whereas litter delivery indicated male fertility. Food and water consumption, body weight, reproductve fuction, Reproductive performance, organ weight and histopathology were observed. Decrase in food consumption and increase in water consumption were observed in 173.9, 1767.8 and 5541.4 mg/kg/day treated male rats as compared to control. Average (±SE) tartrazine intake calculated from liquid consumption, in mg kg-1day-1, was (173.9±0.25), (1767.8±0.32), (5541.4±0.47) for 0.1, 1 and 2.5% tartrazine groups, respectively. Significantly increased body weight gain was observed in 1767.8 mg/kg/day and decrease in relative testis and seminal vesicles weight in 173.9, 1767.8 and 5541.4 mg/kg/day treated male rats, but the effect were not statistically significant and no effect on absolute organ weight were observed in treated male rats as compared to control. Decreased in male mating index and body weight and litter sizes were observed in 5541.4 mg/kg/day treated male rats as compared to control. Similarly, significant decreased in Total number of spermatids count, Sperm concentration in epididymis reserves and percentage motility in 5541.4 mg/kg/day, percentage motility and Sperm concentration in epididymides in 1767.8 mg/kg/day and Sperm concentration in epididymides in 173.9 mg/kg/day treated male rats as compared to control. Sperm head (amorphous, macro-or microcephaly) and the sperm flagellum (entangled, twisted, coiled, with ANSA) morphological abnormalities and significantly affected percentage morphologically normal spermatozoa were observed in 5541.4 mg/kg/day treated male rats as compared to control. In addition, extensive disruption in semniferous tubules, widening of the interstitial spaces and loss leydig cells, Spermatogenic cells are affected and then depleted with absence of spermatozoa in the lumen at 5541.4 mg/kg/day, decreased intercellular connections and imperfect and dilation in some semniferous tubules of testis at 1767.8 mg/kg/day and emniferous tubules were not identical with conjunctive tissue dystrophy in testes at 173.9 mg/kg/day treated male rats as compared to control. Therefore NOAEL was considered to be173.9 mg/kg/day (0.1%) when swiss albino male mice treated with tartrazine orally by drinking water for 13 weeks.
In a study conducted by Colljns et al (1990), Teratogeninc potential was evaluated in Osborne-Mendel female rats by using Tartrazine in the concentration of 0, 60, 100, 200, 400, 600 and 1000 mg/kg /day orally by gavage in water. One female in 60 mg/kg body weight/day died on day 13 of gestation of gavage difficulties unrelated to dosage. No clinical sign of toxicity were observed in treated female rats as compared to control. Significant increase in food consumption at 100 mg/kg body weight/day and no effect on body weight were observed in treated female rats as compared to control. No effect on % of pregnant female, no of corpora, implantation, no of viable foetuses, 5 resorptions, early death or late deaths per litter and sex ratio of treated rats as compared to control. Similarly, no effect on foetuses viability and body weight were observed in treated rats. In addition, three hydrocephalic pups in a single litter and isolated increase in the number of litters containing foetuses with at least two types of stemebral variations in foetuses at 200 mg/kg body weight/day, significant increase in haemorrhages at 600 mg/kg body weight/day and four foetuses from three litters at 1000 mg/kg body weight/day were observed but, The incidences of foetuses with visceral variations and of litters containing those foetuses were similar in all groups. Therefore, NOAEL was considered to be 1000 mg/kg bw/day for F0 and F1 generation when Osborne-Mendel female rats were treated with Tartrazine orally by gavage for 19 days.
In a study conducted by Colljns et al (1992), Teratogeninc potential was evaluated in Osborne-Mendel female rats by using Tartrazine in the concentration of 67.4, 131.8, 292.4, 567.9 and 1064.3 mg/kg bw/day orally in water. No effect on survival and clinical sign were observed in treated rats as compared to control. No effects on body weight and food consumption of treated female rats were observed as compared to control. Nine litters were totally resorbed, but the resorptions were not related to dosage (67.4 mg/kgbw/day-1 litter; 131.8 mg/kg bw/day-3 litters; 567.9 mg/kg bw /day-2 litters and 1064.3 mg/kgbw/day-3 litters) as compared to control. Similarly, no effect on Implantation efficiency, foetal viability and foetal development were observed in treated rats. In addition, haemorrhages, one animal with exencephaly (67.4 mg/kg bw/day), one animal with an extra foetus body attached to the chest (1064.3 mg/kgbw/day) and two animals with reduced tails (0 and 131.8 mg/kg bw/day) were observed in foetuses of treated female rats. The abnormalities are not dose related and they are considered random. Significant increase in reduced ossification of the hyoid bone and two skeletal variations in 67.4 and 567.9 mg/kgbw/day are considered to be random because of the lack of dose response. Therefore, NOAEL was considered to be 1064.3 mg/kg bw/day for F0 and F1 generation when Osborne-Mendel female rats were treated with Tartrazine orally by drinking water for 19 days.
In a study conducted by Tanakaet al(2008), three-generation reproductive and neurobehavioral toxicity was evaluated in Crlj: CD1 male and female mice by using Tartrazine in the concentration of 0, 75, 225 and 675 mg/kg bw/day orally in feed. In F0 generation, No significant effect on body weight, food consumption and exploratory behaviour of treated mice were observed as compared to control. No significant effect on birth rate of offspring was observed as compared to control. In F1 generation, No significant adverse effect was observed on survival, litter size, litter weight, or sex ratio at birth. Significant increase in body weight was observed in 75, 225 and 675 mg/kg bw/day but not significant as compared to control. At 225 mg/kg bw/day, significantly accelerated swimming direction in male offspring and Surface righting in female offspring at PND 7 were observed. In male offspring, movement time (s), total distance (cm), average distance (cm) and number of turning were significantly affected at 3 weeks of age and no significant adverse effect was observed on movement activity and bodyweight of treated F1 offspring. In F2 generation, no significant adverse effects were observed on survival indices, litter size, litter weight, or sex ratio at birth as compared to control. At 75 mg/kg bw/day, significant increase in body weight of female offspring at PNDs 14 and 21, and in male offspring at PNDs 7, 14 and 21.Significant acceleration of swimming direction at PND 7 at 675 mg/kg bw/day and time taken of olfactory orientation at PND 14 and Surface righting at PND 7 in 225 mg/kg bw/day and time taken of olfactory orientation at PND 14 in 675 mg/kg bw/day were observed as compared to control. In male offspring, significant tendency to affected total distance (cm), average distance (cm) and average speed (cm/s) at 3 weeks and 8 week of age were observed at 675 mg/kg bw/day. No significant effects on reproduction were observed in treated male and female offspring were observed as compared to control. Few adverse effects on several behavioral parameters were observed in 675 mg/kg bw/day which is in excess of the ADI of tartrazine (0–7.5 mg/kg bw) unlikely to produce any adverse effects in humans. Therefore, NOAEL was considered to be 675 mg/kg bw/day for F0, F1 and F2 generation when Crlj: CD1 male and female mice were treated with Tartrazine orally in feed approx. 200 days.
Thus base on the weight of evidence for target 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid (118-47-8) and its structurally similar read across Tartrazine (CAs no 1934-21-0) is likely to classified as non hazardous as per the criteria of CLP regulation.
Short description of key information:
Estimated NOAEL was considered to be 860 mg/kg bw Wistar male and female rats
Justification for selection of Effect on fertility via oral route:
Estimated NOAEL was considered to be 860 mg/kg bw Wistar male and female rats were treated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid orally by gavage
Effects on developmental toxicity
Description of key information
Estimated NOAEL was considered to be 930 mg/kg bw Sprague-Dawley rats were treated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid orally
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from QSAR Toolbox 3.4.0.17
- Justification for type of information:
- QSAR prediction: migrated from IUCLID 5.6
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: as below
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 33.4.0.17
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- other: not applicable
- Vehicle:
- water
- Details on exposure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data available
- Details on mating procedure:
- No data available
- Duration of treatment / exposure:
- 11 days
- Frequency of treatment:
- Daily
- Duration of test:
- until gestation day 20
- No. of animals per sex per dose:
- 25 male and female
- Control animals:
- yes
- Details on study design:
- No data available
- Maternal examinations:
- No data available
- Ovaries and uterine content:
- No data available
- Fetal examinations:
- No data available
- Statistics:
- No data available
- Indices:
- No data available
- Historical control data:
- No data available
- Details on maternal toxic effects:
- Maternal toxic effects:no data
Details on maternal toxic effects:
No data available - Remarks on result:
- not measured/tested
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no data
Details on embryotoxic / teratogenic effects:
No data available - Dose descriptor:
- NOAEL
- Effect level:
- 930.167 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effect on development
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Estimated NOAEL was considered to be 930 mg/kg bw Sprague-Dawley rats were treated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid orally by gavage for 11 day
- Executive summary:
Developmental toxicity was estimated by using QSAR Toolbox version 3.4.0.17 in Sprague-Dawley rats by using 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid in the concentration of 930 mg/kg bw in water orally by gavage. No effect on development was observed in treated rats. Therefore, estimated NOAEL was considered to be 930 mg/kg bw Sprague-Dawley rats were treated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid orally by gavage for 11 day.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain
((((((("a"
or "b" or "c" )
and ("d"
and (
not "e")
)
)
and ("f"
and (
not "g")
)
)
and ("h"
and (
not "i")
)
)
and ("j"
and (
not "k")
)
)
and ("l"
and (
not "m")
)
)
and ("n"
and "o" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as AN2 AND AN2 >> Michael addition
to activated double bonds in heterocyclic ring systems AND AN2 >>
Michael addition to activated double bonds in heterocyclic ring systems
>> Pyrazolone and Pyrazolidine Derivatives AND AN2 >> Schiff base
formation with carbonyl compounds (AN2) AND AN2 >> Schiff base formation
with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives
AND Schiff base formation AND Schiff base formation >> Schiff base on
pyrazolones and pyrazolidinones AND Schiff base formation >> Schiff base
on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones by
Protein binding by OASIS v1.4
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Acylation AND Acylation >>
Direct Acylation Involving a Leaving group AND Acylation >> Direct
Acylation Involving a Leaving group >> Acetates by Protein binding by
OECD
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Acid moiety AND Amides AND
Hydrazines by Aquatic toxicity classification by ECOSAR
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.4
Domain
logical expression index: "e"
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 >> Schiff base formation by
aldehyde formed after metabolic activation OR AN2 >> Schiff base
formation by aldehyde formed after metabolic activation >> Geminal
Polyhaloalkane Derivatives 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 >> Coumarins OR Non-covalent interaction >> DNA
intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine
Side Chain OR Radical OR Radical >> Radical mechanism via ROS formation
(indirect) OR Radical >> Radical mechanism via ROS formation (indirect)
>> Coumarins OR Radical >> Radical mechanism via ROS formation
(indirect) >> Geminal Polyhaloalkane Derivatives OR SN1 OR SN1 >>
Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic
attack after carbenium ion formation >> Specific Acetate Esters OR SN2
OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR
SN2 >> Acylation involving a leaving group after metabolic activation OR
SN2 >> Acylation involving a leaving group after metabolic activation >>
Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, ring opening
SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four-
and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after
metabolic activation OR SN2 >> Direct acting epoxides formed after
metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides
formed after metabolic activation >> Quinoline Derivatives OR SN2 >>
Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic
substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >>
Nucleophilic substitution at sp3 carbon atom after thiol (glutathione)
conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after
thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR
SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated
carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.4
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OECD
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as SN1 OR SN1 >> Iminium Ion
Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >>
Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1
>> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >>
Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding
by OECD
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group 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, non cyclic structure OR Strong binder, OH group OR
Very strong binder, OH group by Estrogen Receptor Binding
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Acylation AND Acylation >>
Direct Acylation Involving a Leaving group AND Acylation >> Direct
Acylation Involving a Leaving group >> Acetates by Protein binding by
OECD
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Acylation >> Direct Acylation
Involving a Leaving group >> Anhydrides OR Michael addition OR Michael
addition >> Acid imides OR Michael addition >> Acid imides >> Acid
imides-MA OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr
>> Nucleophilic aromatic substitution >> Activated halo-benzenes by
Protein binding by OECD
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Not possible to classify
according to these rules (GSH) by Protein binding potency
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Moderately reactive (GSH) OR
Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) by Protein
binding potency
Domain
logical expression index: "n"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -4.46
Domain
logical expression index: "o"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 3.62
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 930 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Kilmish 2 and from QSAR Toolbox version 3.4.0.17
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
Developmental toxicity:
Data available for target 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid (118-47-8) and its read across Tartrazine (CAs no 1934-21-0) for developmental toxicity are summarized as below
Based on prediction done by using QSAR Toolbox version 3.4.0.17 (2016), developmental toxicity was estimated in Sprague-Dawley rats by using 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid in the concentration of 930 mg/kg bw in water orally by gavage. No effect on development was observed in treated rats. Therefore, estimated NOAEL was considered to be 930 mg/kg bw Sprague-Dawley rats were treated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid orally by gavage for 11 day.
In a study conducted by Tanakaet al(2008), three-generation reproductive and neurobehavioral toxicity was evaluated in Crlj: CD1 male and female mice by using Tartrazine in the concentration of 0, 75, 225 and 675 mg/kg bw/day orally in feed. In F0 generation, No significant effect on body weight, food consumption and exploratory behaviour of treated mice were observed as compared to control. No significant effect on birth rate of offspring was observed as compared to control. In F1 generation, No significant adverse effect was observed on survival, litter size, litter weight, or sex ratio at birth. Significant increase in body weight was observed in 75, 225 and 675 mg/kg bw/day but not significant as compared to control. At 225 mg/kg bw/day, significantly accelerated swimming direction in male offspring and Surface righting in female offspring at PND 7 were observed.
In male offspring, movement time (s), total distance (cm), average distance (cm) and number of turning were significantly affected at 3 weeks of age and no significant adverse effect was observed on movement activity and bodyweight of treated F1 offspring. In F2 generation, no significant adverse effects were observed on survival indices, litter size, litter weight, or sex ratio at birth as compared to control. At 75 mg/kg bw/day, significant increase in body weight of female offspring at PNDs 14 and 21, and in male offspring at PNDs 7, 14 and 21. Significant acceleration of swimming direction at PND 7 at 675 mg/kg bw/day and time taken of olfactory orientation at PND 14 and Surface righting at PND 7 in 225 mg/kg bw/day and time taken of olfactory orientation at PND 14 in 675 mg/kg bw/day were observed as compared to control. In male offspring, significant tendency to affected total distance (cm), average distance (cm) and average speed (cm/s) at 3 weeks and 8 week of age were observed at 675 mg/kg bw/day. No significant effects on reproduction were observed in treated male and female offspring were observed as compared to control. Few adverse effects on several behavioral parameters were observed in 675 mg/kg bw/day which is in excess of the ADI of tartrazine (0–7.5 mg/kg bw) unlikely to produce any adverse effects in humans. Therefore, NOAEL was considered to be 675 mg/kg bw/day for F0, F1 and F2 generation when Crlj: CD1 male and female mice were treated with Tartrazine orally in feed approx. 200 days.
In a study conducted by Colljns et al (1990), Teratogeninc potential was evaluated in Osborne-Mendel female rats by using Tartrazine in the concentration of 0, 60, 100, 200, 400, 600 and 1000 mg/kg /day orally by gavage in water. One female in 60 mg/kg body weight/day died on day 13 of gestation of gavage difficulties unrelated to dosage. No clinical sign of toxicity were observed in treated female rats as compared to control. Significant increase in food consumption at 100 mg/kg body weight/day and no effect on body weight were observed in treated female rats as compared to control. No effect on % of pregnant female, no of corpora, implantation, no of viable foetuses, 5 resorptions, early death or late deaths per litter and sex ratio of treated rats as compared to control. Similarly, no effect on foetuses viability and body weight were observed in treated rats. In addition, three hydrocephalic pups in a single litter and isolated increase in the number of litters containing foetuses with at least two types of stemebral variations in foetuses at 200 mg/kg body weight/day, significant increase in haemorrhages at 600 mg/kg body weight/day and four foetuses from three litters at 1000 mg/kg body weight/day were observed but, The incidences of foetuses with visceral variations and of litters containing those foetuses were similar in all groups. Therefore, NOAEL was considered to be 1000 mg/kg bw/day for F0 and F1 generation when Osborne-Mendel female rats were treated with Tartrazine orally by gavage for 19 days.
In a study conducted by Colljns et al (1992), Teratogeninc potential was evaluated in Osborne-Mendel female rats by using Tartrazine in the concentration of 67.4, 131.8, 292.4, 567.9 and 1064.3 mg/kg bw/day orally in water. No effect on survival and clinical sign were observed in treated rats as compared to control. No effects on body weight and food consumption of treated female rats were observed as compared to control. Nine litters were totally resorbed, but the resorptions were not related to dosage (67.4 mg/kgbw/day-1 litter; 131.8 mg/kg bw/day-3 litters; 567.9 mg/kg bw /day-2 litters and 1064.3 mg/kgbw/day-3 litters) as compared to control. Similarly, no effect on Implantation efficiency, foetal viability and foetal development were observed in treated rats. In addition, haemorrhages, one animal with exencephaly (67.4 mg/kg bw/day), one animal with an extra foetus body attached to the chest (1064.3 mg/kgbw/day) and two animals with reduced tails (0 and 131.8 mg/kg bw/day) were observed in foetuses of treated female rats. The abnormalities are not dose related and they are considered random. Significant increase in reduced ossification of the hyoid bone and two skeletal variations in 67.4 and 567.9 mg/kgbw/day are considered to be random because of the lack of dose response. Therefore, NOAEL was considered to be 1064.3 mg/kg bw/day for F0 and F1 generation when Osborne-Mendel female rats were treated with Tartrazine orally by drinking water for 19 days.
Thus base on the weight of evidence for target 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid (118-47-8) and its structurally similar read across Tartrazine (CAs no 1934-21-0) is likely to classified as non hazardous as per the criteria of CLP regulation.
Justification for selection of Effect on developmental toxicity: via oral route:
Estimated NOAEL was considered to be 930 mg/kg bw Sprague-Dawley rats were treated with 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid orally by gavage for 11 day.
Justification for classification or non-classification
Base on the weight of evidence for target 5-oxo-1-(4-sulphophenyl)-2-pyrazoline-3-carboxylic acid (118-47-8) and its structurally similar read across Tartrazine (CAs no 1934-21-0) is likely to classified as non hazardous for reproduction and development toxicant as per the criteria of CLP regulation.
Additional information
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