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EC number: 248-502-0 | CAS number: 27503-81-7
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- from October 30, 2001 to March 19, 2002
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD, Protocol of the conduct of the rodent uterotrophic assay, Draft protocol B - Immature female rats with sub-cutaneous administration (April 20, 2000).
- Principles of method if other than guideline:
- Test article were sub-cutaneously administered once per day on three consecutive days from the start of the study until either spontaneous death or scheduled sacrifice of the animals on fourth day. Clinical observations were performed daily. Body weights were determined daily. Feed intake was determined per group at termination (day 3). Gross necropsy(with uterus weights and tissue sampling) was performed on all animals at termination.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2-phenyl-1H-benzimidazole-5-sulphonic acid
- EC Number:
- 248-502-0
- EC Name:
- 2-phenyl-1H-benzimidazole-5-sulphonic acid
- Cas Number:
- 27503-81-7
- Molecular formula:
- C13H10N2O3S
- IUPAC Name:
- 2-phenyl-1H-benzimidazole-5-sulphonic acid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Experimental Animals:
The study was conducted on juvenile female rats - animals recommend in the OECD protocol for these validation studies. At the start of the study, the animals were 19 days old and had starting weights of 29 - 36 g.
SPF-bred Wistar rats of the strain HsdCpb: WU from the Harlan Winkelmann GmbH Experimental Animal Breeders in Borchen, District of Paderborn were used.The state of health of the breed is monitored and the animals spot-checked for the main specific pathogens.
The animals were transported together with foster dams from the supplier to Bayer AG. After the arrival, the animals intended for this study were acclimatized to conditions in the animal room for 3 days, until the start of the treatment. Their state of health was monitored also during this period.
Only healthy animals showing no clinical signs were used for the study. The animals were not vaccinated or treated with anti-infectives either before receipt or during toe acclimatization or treatment periods.
Housing conditions:
During the adaptation period, the animals were conventionally kept in polycarbonate cages type III (one foster dam with six or seven juvenile animals per cage). The cages were not changed during the adaptation period.
During the test period, the animals were conventionally kept in polycarbonate cages type III (three animals per cage), Low-dust wood shavings type BK 8/15 supplier: Ssniff, Spezialdiäten GmbH, Soest/ Westphalia) were used as litter. Tie wood shavings were spot-checked for contaminants levels and the records are filed at Bayer AG. The analytical results afforded no evidence for an effect on study objective.
Cages and bedding material were not changed during the test period.
The cages containing the experimental animals were placed on racks, separated by groups, in ascending animal number order. All animals taking part in this study were kept in the same animal room.
The environmental conditions in the animal room were standardized as follows:
room temperature: 22 ± 2 °C
relative humidity: approx. 55 ± 5 %
light/dark cycle: 12-hour artificial lighting
air exchange rate: approx. 10 times per hour
Diet:The animals were given "NAFAG No. 9441 Long Life W 10" (manufacturer: Eberle Nafag AG, Gossau - CH) and tap water (drinking bottles). Food and water were available for ad-libitum consumption.
Administration / exposure
- Route of administration:
- subcutaneous
- Vehicle:
- corn oil
- Details on exposure:
- Test substance were sub-cutaneously administered once per day on three consecutive days from the start of the study until either spontaneous death or scheduled sacrifice of the animals on fourth day.
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- three consecutive days
- Frequency of treatment:
- once per day
- Details on study schedule:
- Dosage Form, Doses, Study Groups
The test substance, the vehicle control, and the positive control were sub-cutaneously administered once per day on three consecutive days from the start of the study until either spontaneous death or scheduled sacrifice of the animals on fourth day.
The dose levels were chosen on basis of discussions with the sponsor and on basis of the results of a pilot study (T9071164), In this study one female rat each was treated sub-cutaneously with 1000, 500, or 200 mg/kg. At 200 mg/kg and above on the treatment area skin changes were observed, and at 500 mg/kg additionally loss of hair.
In this study not only the test item but additionally four other test compounds were investigated and compared to the same control groups. The results for each test compound will be reported separately. The dose schedule and the distribution of the control animals and animals treated with the test item by group are shown in the following table:
Group no dose No of animals Animal no.
1 0 (untreated) 6 1-6
2 0 (vehicle) 6 7-12
3 0.3 µg/kg EE 6 13-18
4 1.0 µg/kg EE 6 19-24
5 50 mg/kg test group 6 25-30
6 200 mg/kg test group 6 31-36
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 50 mg/kg bw/day
- Dose / conc.:
- 200 mg/kg bw/day
- No. of animals per sex per dose:
- 6
- Control animals:
- other: untreated and vehicle(group 1 and 2)
- Details on study design:
- Before administration, the animals were weighed, sorted according to weight, and randomly allocated to the individual groups. The randomization lists were created with a computer program.
- Positive control:
- 17a-Ethinylestradiol (Sigma, Lot 057H1178)
Examinations
- Parental animals: Observations and examinations:
- 1, General investigations
1.1.Inspection of Experimental Animals
The experimental animals were inspected at least once a day. Any clinical signs (findings) and abnormalities were recorded. Body surfaces and orifices, pos general behavior, breathing and excretory products were assessed. Findings abnormalities were recorded either using a coding system or else uncoded.
If animals become ill, they are set apart, observed more frequently and sacrificed prematurely, if death seems imminent.
1.2. Determination of Feed Consumption
The feed intake of the rats was determined per group at the end of the study on day 3. These primary data were then used to calculate the means for the feeding period, the consumption per animal/day, per group/day and per kg body weight per day. The algorithm used for calculating intake of feed is described in the Annex of the report.
1.3. Determination of Body Weight
The body weights of the individual experimental animals were determined before the beginning of the study and daily thereafter up to scheduled necropsy. - Oestrous cyclicity (parental animals):
- no data
- Sperm parameters (parental animals):
- no data
- Litter observations:
- no data
- Postmortem examinations (parental animals):
- 1. Necropsy
The animals were necropsied after exsanguination under deep ether anesthesia. Uterus and vagina of all animals were fixed in 10% neutral buffered formalin.
The fixed material was retained. Due to the request of the sponsor, histopathological investigations were not performed.
2.Organ Weights
The following exsanguinated organs of the animals sacrificed at necropsy weighed in the unfixed state:
Uterus (wet and blotted).
The uterine weights are specified in both absolute and relative terms. The relative weights were calculated by normalization to 100 g body weight (individual organ weight divided by body weight times 100). The body weight used as a basis for this calculation was determined immediately prior to necropsy of the pertinent animal. - Postmortem examinations (offspring):
- no data
- Statistics:
- The results of the animal observations, organ, body and feed weights were collected and processed on-line and off-line.
The quantitative results for individual animals were used to calculate arithmetic grThe statistical evaluation of data related to body and organ weights as well as feed intake is performed using SAS® routines.
Statistical evaluation on body weight and organ weight data are done using the Dunnet test in connection with a variance analysis. Relative organ weights are submitted to a logarythmic transformation prior to the statistical analysis.
In case of numbers of values too low to calculate test statistics this is indicated by ‘o’ or ’-’ in the tables shown in the results section and by ‘nc’ (not calculated) or ‘0’ in the tables of the Annex. The individual results listed in the Annex to this report have been rounded off. Calculation of means and variances was based in part on the non-rounded original values. Some of the values in the tables of individual body weights may be missing. This may be the consequence of a technical defect which occurred during on-line data collection or of a value which can not be listed (because of an error in weighing and a failure to meet printer format) or is unrealistic account of a weighing error and deleted. - Reproductive indices:
- no data
- Offspring viability indices:
- no data
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
Details on results (P0)
No toxicologically relevant differences in mean feed consumption per animal/day, or per kg body weight/day were detected.
No significant effect of treatment on body weights were observed.
No pathological changes were observed at 200 mg/kg bw/day test article and below. The uteri were enlarged at 0.3 and 1.0 µg/kg 17a-Ethinylestradiol.
At 200 mg/kg bw/day test article and below no effect were observed on uterine on the uterine weight.
Effect levels (P0)
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 200 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- dose received by subcutaneous injection
- Sex:
- female
- Basis for effect level:
- other: At the dose tested, no effect on uterus weight (i.e. endocrine effect) and no effect on body weight, feed consumption or signs of toxicity were observed.
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- In conclusion, no oestrogenic effects were detected at doses of 200 mg/kg bw/day of test article and below.
- Executive summary:
This study was conducted to detect estrogenic effects of the test item conformed to the OECD Validation work on in-vivo uterotrophic screening assay following repeated sub-cutaneous administration. Groups of 6 juvenile female rats of the strain HsdCpb:WU were administered test substance once a day at levels of 0 (untreated), 0 (vehicle control), 50 and 200 mg/kg body weight/day sub-cutaneously for a period of three days. Regarding state of health or general behavior of the animals, there was no difference between the untreated and treated animals of all groups. No toxicologically significant effect on feed intake, body weight and organ weight was observed.
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