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EC number: 617-116-8 | CAS number: 80573-04-2
- 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

Carcinogenicity
Administrative data
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- Unnamed
- Year:
- 2 000
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No guideline is specified in the report.
- GLP compliance:
- no
Test material
- Reference substance name:
- Benzoic acid, 5-[(1E)-[4-[[(2-carboxyethyl)amino]carbonyl]phenyl]azo]-2- hydroxy-, disodium salt, dihydrate
- Cas Number:
- 150399-21-6
- Molecular formula:
- C17H13N3O6Na2 . 2H2O
- IUPAC Name:
- Benzoic acid, 5-[(1E)-[4-[[(2-carboxyethyl)amino]carbonyl]phenyl]azo]-2- hydroxy-, disodium salt, dihydrate
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Crl:CD (SD) BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 42 days old
- Weight at study initiation: Males: 157 - 253 g; Females: 134 - 203 g
Administration / exposure
- Route of administration:
- oral: feed
- Duration of treatment / exposure:
- 104 weeks
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 120 mg/kg bw/day
- Dose / conc.:
- 600 mg/kg bw/day
- Dose / conc.:
- 2 000 mg/kg bw/day
- No. of animals per sex per dose:
- 60 animals per sex per dose group
- Control animals:
- yes, plain diet
- Details on study design:
- Dose selection was based on 14-day palatability oral (diet) study in SD rats in which the highest tested dose (2000 mg/kg bw/day) was the no effect dose. The Sponsor selected 2000 mg/kg/day as the high dose level in the study since it is the maximum feasible dose which can be given via the diet.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly during the first 16 weeks of treatment and thereafter at 4 week intervals.
FOOD CONSUMPTION:
- Time schedule: Weekly during the first 16 weeks of treatment and thereafter at 4 week intervals.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Just before sacrifice (from vena cava)
- Parameters: Differential leucocyte count
URINALYSIS: Yes
- Time schedule for collection of urine: Weeks 2, 23, 50, 75 and 100 (24 hour urine samples) - Sacrifice and pathology:
- At the end of the treatment period, all animals were sacrificed and subjected to complete necropsy and histopathological examinations on all tissues from the control and high dose groups, animals died/ killed during the study period, all gross lesions and adrenal and kidneys from all animals.
- Statistics:
- Kaplan-Meier technique and log-rank tests were used to analyse intercurrent mortality and survival rate. The Sponsor used two sided chi-squared test, apirwise comparisons and IARC annex for the analysis of tumour incidence.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- Treatment had no significant effect on intercurrent mortality rates. At termination survival rates were comparable in all groups (30 - 47% in males and 22 - 45% in females).
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- At the end of the treatment period, absolute body weights in low, mid and high dose treated females were about 5%, 14% and 19% lower than the combined control body weights. At the end of the treatment period, the absolute body weights in high dose treated males were about 17% lower than the combined control values.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- The compound consumptions were within 2% of the intended doses (male: low dose = 120.3 ± 3.6 mg/kg bw/day, mid dose = 601.6 ± 18.0 mg/kg bw/day and high dose = 2001.8 ± 70.1 mg/kg bw/day; female: low dose = 120.5 ± 5.2 mg/kg bw/day, mid dose = 603.0 ± 27.7 mg/kg bw/day and high dose = 2008.4 ± 84.0 mg/kg bw/day).
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Haematological findings:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Distention of the caecum in high dose treated males (control 1 = 2/60, control 2 = 1/60, low dose = 1/60, mid dose = 3/60 and high dose = 38/60) and females (control 1 = 1/60, control 2 = 1/60, low dose = 0/60, mid dose = 1/60 and high dose = 24/60) were seen. Additionally, in high dose treated males, significantincrease in renal pelvic dilatation (control 1 = 4/60, control 2 = 2/60, low dose = 3/60, mid dose = 2/60 and high dose = 11/60) and distention of urinary bladder (control 1 = 5/60, control 2 = 5/60, low dose = 2/60, mid dose = 4/60 and high dose = 13/60) were also seen.
- Description (incidence and severity):
- Increased incidences of renal pelvic mineralisation, tubular dilatation and urothelial hyperplasia were seen in the mid and high dose treated males. In high dose treated males there was also an increased incidence of hydronephrosis, urinary bladder distention, cystitis and prostatitis.
- Histopathological findings: neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Significant increase in the incidence of benign pheochromocytoma in adrenal was seen in high dose treated male rats (control 1 = 13.3%, control 2 = 6.7%, low dose = 13.3%, mid dose = 15% and high dose = 30%, p<0.001 [trend test], pairwise: control 1 vs high dose; p = 0.003 and control 2 vs high dose; p = 0.001). However, rate of incidence of benign pheochromocytoma in adrenal of high dose treated males (30%) was within laboratory historical control incidence rate (10 - 46%). Hence, the test substance has no carcinogenic potential in SD rats.
- Details on results:
- The highest tested dose is the maximum tolerated dose since at this dose level body weight in males and females were 17% and 19% lower than the control body weights respectively. Hence dose selection was appropriate.
Treatment had no significant effect on intercurrent mortality rates. Survival rates at the end of the treatment period were comparable in all groups.
Increased incidences of renal pelvic mineralisation, tubular dilatation and urothelial hyperplasia were seen in mid and high dose treated males. In high dose treated males there was also an increased incidence of hydronephrosis, urinary bladder distention, cystitis and prostatitis. Significant increase in the incidence of benign pheochromocytoma in adrenal was seen in high dose treated male rats (control 1 = 13.3%, control 2 = 6.7%, low dose = 13.3%, mid dose = 15% and high dose = 30%, p<0.001 [trend test], pairwise: control 1 vs high dose; p = 0.003 and control 2 vs high dose; p = 0.001). However, rate of incidence of benign pheochromocytoma in adrenal of high dose treated males (30%) was within laboratory historical control incidence rate (10 - 46%). No other treated related neoplastic findings were evident in the study. Hence, the test substance has no carcinogenic potential in SD rats.
Effect levels
- Dose descriptor:
- dose level: Maximum tolerated dose
- Effect level:
- 2 000 mg/kg bw/day
- Sex:
- male/female
- Remarks on result:
- not determinable due to adverse toxic effects at highest dose / concentration tested
- Remarks:
- No evidence of carcinogenic potential
Target system / organ toxicity
- Critical effects observed:
- no
Any other information on results incl. tables
Toxicokinetic data:
The urinary excretion of BSZ was very low (0.063 - 1.15% of the dose) as compared to total 5 -ASA (~0.96% to 30.1%) and NASA (4.6 - 14.14%). The urinary excretion of 4 -ABA and NABA was ~0.314 - 7.66% and 0.58 - 4.09% of the dose, respectively.
Applicant's summary and conclusion
- Conclusions:
- Balsalazide has no carcinogenic potential in rats.
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