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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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental 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 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 and their fetuses were examined.
- GLP compliance:
- not specified
- Limit test:
- no
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 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
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: 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: [yes / no (explain)]: 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. - Duration of treatment / exposure:
- 7-17 days
- Frequency of treatment:
- Daily
- Duration of test:
- 20 days of gestation
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Control group (Dose-finding study)
- Dose / conc.:
- 2.5 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 5 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 10 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 20 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 40 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 60 mg/kg bw/day
- Remarks:
- Dose-finding study
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Control group (Teratology study)
- Dose / conc.:
- 3.3 mg/kg bw/day
- Remarks:
- Teratology study
- Dose / conc.:
- 10 mg/kg bw/day
- Remarks:
- Teratology study
- Dose / conc.:
- 30 mg/kg bw/day
- Remarks:
- Teratology 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 diet hylether 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 2-MBI 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).Therefore, when mated (pregnant) rats
were dosed with 60 mg/kg of 2-MBI, 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.
Examinations
- Maternal 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. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of early resorptions: Yes - Fetal examinations:
- - Fetuses were examined grossly.
- Gross necropsy consisted of Visceral and Skeletal observation.
- The position and number of live and dead fetuses, including resorbed fetuses were recorded. Live fetuses were weighed, sexed, and gross deformities noted. - 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.
- Indices:
- not specified
- Historical control data:
- not specified
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Teratology study
All dams treated with 0, 3.3, 10 and 30 mg/kg of test chemical survived.
Dose-finding sludy
Four of five rats treated with 60 mg/kg of test chemical and one of 6 rats treated with 40 mg/kg died. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Teratology study
Substantial decrease in body weight gain was observed in all three groups.
Dose-finding sludy
In pregnant rats, the maternal weight gain was decreased at a 40 and a 20 mg/kg of test chemical espectively. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Teratology study
Substantial decrease in food consumption was observed in all three groups.
Dose-finding sludy
In pregnant rats, the food consumption was decreased at a 40 and a 20 mg/kg of test chemical , respectively. - 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
- Description (incidence and severity):
- 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.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Decreased thymus weights, increased thyroid weights, decreased body weight gain, and decreased food consumption in the treated dams were observed.Because of the severe resulting toxicity, 60 mg/kg dose could not be administered throughout the period of organogenesis (Gestetion days 7-17). Instead, the test animals were dosed for shorter periods of time, viz., Gestation Days 7-10 (17 rats), 11-14 (16 pregnant rats), or 15-17(16 pregnant rats). Even under these dosing conditions, test chemical was severely toxic to dams, as evidenced by a substantial decrease in maternal body weight gain and food consumption in all three groups and maternal death (5 out of 16 dams) in the group treated on Days 11-14 of gestation. Vaginal bleeding was observed in 10 and 2 dams in the group treated on Days 11-14 and 15-17 of gestation, respectively.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- < 3.3 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: Because of significant decrease in maternal thymus weights at this dose.
Maternal abnormalities
- Abnormalities:
- not specified
- Localisation:
- not specified
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Fetal body weights were significantly decreased only in the litters of dams dosed with 10 mg/kg or higher dose of test chemical
- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- not specified
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- 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 - Visceral malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- 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.
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Decresed fetal body weights and increased the incidence of certain anomalies of the urogenital system and of rudimentary lumbar ribs.
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 of dams treated with 60 mg/kg on Days 11-14; these anomalies were not observed at lower doses of the chemical.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 3.3 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: teratogenicity
- Remarks on result:
- other: No developmental toxic effects were observed
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The no observed adverse effect level was considered to be 3.3 mg/kg. When rats were treated with test chemical orally.
- Executive summary:
The study was designed to investigate the reproductive toxicity effects of test chemical to pregnant Wistar rats and to their fetuses by oral route. Pregnant rats were treated with test chemical at doses of 0, 3.3, 10, and 30 mg/kg during the period of organogenesis (Gestation Days 7-17). Mated (pregnant) rats were divided into four groups of 20 rats each. Treatment with 10 and 30 mg/kg of test chemical resulted in decreased thymus weights, increased thyroid weights, decreased body weight gain, and decreased food consumption in the treated dams. These dosages also reduced fetal body weights and increased the incidence of certain anomalies of the urogenital system and of rudimentry lumbar ribs. Under the conditions of the present study, The no observed adverse effect level was considered to be 3.3 mg/kg. When rats were treated with test chemical orally.
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