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EC number: 209-502-6 | CAS number: 583-39-1
- 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:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from peer- reviewed journal
Data source
Reference
- Reference Type:
- publication
- Title:
- The Adverse Effects of Oral test chemical on Pregnant Rats and Their Fetuses
- Author:
- Tetsuo Yamano,et.al
- Year:
- 1 995
- Bibliographic source:
- Fundamental and Applied Toxicology (1995)
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- The adverse effects of test chemical on pregnant Wistar rats were examined.
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- not specified
Test material
- Reference substance name:
- Benzimidazole-2-thiol
- EC Number:
- 209-502-6
- EC Name:
- Benzimidazole-2-thiol
- Cas Number:
- 583-39-1
- Molecular formula:
- C7H6N2S
- IUPAC Name:
- 1H-benzimidazole-2-thiol
- Details on test material:
- - Name of test material : 2-Mercaptobenzimidazole
- Substance type: Organic
- Physical state: Solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- not specified
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: CLEA Japan Inc. (Tokyo, Japan)
- Age at study initiation: Four-week-old
- Housing: Housed individually in stainless steel cages
- Diet (e.g. ad libitum): Feed (NMF, Oriental Yeast Co., Ltd., Tokyo, Japan) ; ad libitum
- Water (e.g. ad libitum): Tap water; ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C
- Humidity (%):60 ± 10%
- Photoperiod (hrs dark / hrs light): Dark period from 7:00 PM to 7:00 AM
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on exposure:
- not specified
- Details on mating procedure:
- - Impregnation procedure: [artificial insemination / purchased timed pregnant / cohoused]: cohoused
- If cohoused:
- M/F ratio per cage: females were individually paired overnight with a male of similar age.
- Length of cohabitation: overnight
- Further matings after two unsuccessful attempts: no
- Verification of same strain and source of both sexes: no
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: The day upon which sperm was found in vaginal smears was designated as Day 0 of gestation. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 11 days
- Frequency of treatment:
- Daily
- Details on study schedule:
- 20 days of gestation
Doses / concentrationsopen allclose all
- Remarks:
- 0,2.5,5,10,20,40 and 60 mg/kg bw for dose finding study
- Remarks:
- 0.3.3,10,30 mg/kg bw for teratogenicity study
- No. of animals per sex per dose:
- Dose-finding study:
Mated (pregnant) rats were assigned to seven groups of five or six animals each.
Teratology study:
Mated (pregnant) rats were divided into four groups of 20 rats each. - Control animals:
- yes
- Details on study design:
- Dose-finding study:
Mated rats were assigned to seven groups of five or six animals each. They were treated by gavage with 2-MBI in oIive oil at 0, 2.5, 5, 10, 20, 40, and 60 mg/kg/day in a volume of 5 ml/kg from Days 7 through 17 of gestation. The animals were weighed and food consumpiion was measured each day; general condition and behavior were also observed. On Day 20 of gestation, the animaIs were killed under diethylether anesthesia, laparotomy was performed, and the maternal thymus and the gravid uterus were weighed. The position and number of live and dead fetuses, including resorbed fetuses, and the number of corpora lutea were recorded. Live fetuses were weighed, sexed, and gross deformities noted. Only one dam treated with 60 mg/kg of test chemical survived; viscera ot the fetuses were examined.
Teratology study:
Dose levels of 0, 3.3, 10, and 30 mg/kg/day in a volume of 5 ml/kg were selected based upon the results of the dose-finding study.
The dose-finding study revealed that 60 mg/kg was toxic to both fetuses and dams when given throughout the period of organogenesis (Days 7-17 of gestation).Therefo re, when mated (pregnant) rats were dosed with 60 mg/kg of test chemical it was given upon 3 or 4 consecutive days at different periods during organogenesis (Days 7— 10, 11 —14, and I 5—17 of gestation). The other procedures were the same as described here. - Positive control:
- not specified
Examinations
- Parental animals: Observations and examinations:
- BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
OTHER:
GENERAL CONDITION AND BEHAVIOUR: Yes
ORGAN WEIGHT:
Maternal thymus, thyroid gland, and gravid uterus were weighed. - Oestrous cyclicity (parental animals):
- The uterine content was examined after termination: Yes
Examinations included:
- Number of early resorptions: Yes
- Number of corpora lutea were recorded. - Sperm parameters (parental animals):
- not specified
- Litter observations:
- The position and number of live and dead fetuses, including resorbed fetuses were recorded. Live fetuses were weighed, sexed, and gross deformities noted.
- Postmortem examinations (parental animals):
- GROSS NECROPSY
- Uteri was examined grossly. - Postmortem examinations (offspring):
- GROSS NECROPSY
- Fetuses were examined grossly.
- Gross necropsy consisted of Visceral and Skeletal observation. - Statistics:
- Data from the dose-finding and teratology studies in which animals were treated with ≤30 mg/kg of test chemical were analyzed by Dunnett’s multiple comparison method in a parametric or nonpararnetric manner.
- Reproductive indices:
- not specified
- Offspring viability indices:
- not specified
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- 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:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
Details on results (P0)
Teratology study: All dams survived.
Dose-finding study: Four of five rats treated with 60 mg/kg dose and one of six rats treated with 40 mg/kg died.
Body weight:
Teratology study: Substantial decrease in body weight gain was observed in all three groups.
Dose-finding study: In pregnant rats, the maternal weight gain was decreased at a 40 and a 20 mg/kg of test chemical , respectively.
Food consumption:
Teratology study: Substantial decrease in food consumption was observed in all three groups.
Dose-finding study: In pregnant rats, the food consumption was decreased at a 40 and a 20 mg/kg of test chemical , respectively.
Organ weight: Thymus weight was decreased even at the lowest dose of 3.3 mg/kg whereas treatment with 10 and 30 mg/kg of test chemical resulted in increased thyroid weight.
Reproductive performance:
No effects on reproduction of treated female rats were observed
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 30 < mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- mortality
- body weight and weight gain
- food consumption and compound intake
- reproductive performance
- Remarks on result:
- other: No effects on reproductive performance
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- Live fetuses was observed.
- Body weight and weight changes:
- effects observed, treatment-related
- 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 specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Details on results (F1)
Fetal body weights significantly decreased only in the litters of dams dosed with 10 mg/kg or higher dose
Gross pathology:
Visceral variations consisting of unilateral or bilateral kinked ureter and / or dilated renal pelvis were noted in 20.5% of fetuses at 10 mg/kg and in 47.6% of the fetuses at 30 mg/kg.
Skeletal variations, unilateral or bilateral rudimentary lumbar ribs, were observed in 22.2% of the fetuses at 30 mg/kg.
The degree of ossification was significantly reduced in the litters of dams treated with ≥ 10 mg/kg of test chemical
Dose-finding study
All fetuses from dams treated with daily doses upto 40 mg/kg body weight, all parameters with respect to fetuses were unaffected.
Only rudimentary lumbar ribs were observed when the treatment period with 60 mg/kg was shortened to Gestation days 7-10, while kinked ureter and dialated renal pelvis were observed only following treatment with 60 mg/kg on days 15-17. Finally , dilated lateral ventricles and cleft palate were observed only in the litters f dams treated with 60 mg/kg on Days 11-14; these anomalies were not observed at lower doses of the chemical.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 30 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- viability
- mortality
- body weight and weight gain
- gross pathology
- other: No adverse effects observed on
- Remarks on result:
- other: Fetal body weights significantly decreased only in the litters of dams dosed with 10 mg/kg or higher dose
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 30 mg/kg bw when Wistar female rat were treated with test chemical orally by gavage from day 7 to 17.
- Executive summary:
In a reproductive toxicity study, Wistar female rat were treated with test chemical in the concentration of 0,2.5,5,10,20,40 and 60 mg/kg bw for dose finding study and 0.3.3,10,30 mg/kg bw for teratogenicity study orally by gavage in olive oil from day 7 to 17. Four of five rats treated with 60 mg/kg of test chemical and one of six rats treated with 40 mg/kg died in Dose-finding study and all dams survived in main study. The maternal weight gain was decreased at a 40 and a 20 mg/kg of test chemical respectively in dose-finding study Substantial decrease in body weight gain was observed in all three groups in Teratology study. Food consumption was decreased at a 40 and a 20 mg/kg of test chemical , respectively in dose-finding study and Substantial decrease in food consumption was observed in all three groups in teratology study. Thymus weight was decreased even at the lowest dose of 3.3 mg/kg whereas treatment with 10 and 30 mg/kg of test chemical resulted in increased thyroid weight. No effete on reproduction of treated female rats were observed as compared to control. In addition,All fetuses from dams treated with daily doses upto 40 mg/kg body weight, all parameters with respect to fetuses were unaffected in Dose-finding study. Only rudimentary lumbar ribs were observed when the treatment period with 60 mg/kg was shortened to Gestation days 7-10, while kinked ureter and dialated renal pelvis were observed only following treatment with 60 mg/kg on days 15-17. Finally, dilated lateral ventricles and cleft palate were observed only in the litters f dams treated with 60 mg/kg on Days 11-14; these anomalies were not observed at lower doses of the chemical. Significantly decreased only in the litters of dams dosed with 10 mg/kg or higher of test chemical . Visceral variations consisting of unilateral or bilateral kinked ureter and / or dilated renal pelvis were noted in 20.5% of fetuses at 10 mg/kg and in 47.6% of the fetuses at 30 mg/kg. Skeletal variations, unilateral or bilateral rudimentary lumbar ribs, were observed in 22.2% of the fetuses at 30 mg/kg were observed. The degree of ossification was significantly reduced in the litters of dams treated with ≥ 10 mg/kg of test chemical in main study. Therefore, NOAEL was considered to be 30 mg/kg bw when Wistar female rat were treated with test chemical orally by gavage from day 7 to 17.
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