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EC number: 258-904-8 | CAS number: 53988-10-6
- 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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: sufficient documented and scientifically acceptable
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Toxicity study of a rubber antioxidant, mixture of 2-mercaptomethylbenzimidazoles, by repeated oral administration to rats
- Author:
- Saitoh M, Umemura T, Kawasaki Y, Momma Y, Matsushima Y, Sakemi K, Isama K, Kitajima S, Ogawa Y, Hasegawa R, Suzuki T, Hayashi M, Inoue T, Ohno Y, Sofuni T, Kurokawa Y, Tsuda M
- Year:
- 1 999
- Bibliographic source:
- Food Chem Toxicol 37, 777-787
Materials and methods
- Principles of method if other than guideline:
- Male and female rats were treated with MMBIs (2-mercaptomethylbenzimidazoles (a 1:1 mixture of 4-methyl and 5-methyl isomers, MMBIs) by gavage at doses 0 (corn oil), 4, 20 and 100 mg/kg for 28 consecutive days followed by a 2-week recovery period for the control and highest dose groups. Body weight and food consumption, clinical signs, organ weights, clinical biochemistry and hematological parameters including clotting times and micronuclei induction in bone marrow erythropoeitic cells were recorded and a histopathological examination was conducted.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione
- EC Number:
- 258-904-8
- EC Name:
- 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione
- Cas Number:
- 53988-10-6
- Molecular formula:
- C8H8N2S
- IUPAC Name:
- 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione
- Details on test material:
- 2-Methylmercaptobenzimidazoles (MMBIs, CAS no 53988-10-6, a 1:1 mixture of 2-mercapto-4-methylbenzimidazole, CAS no 27231-33-0 and 2-mercapto-5-methylbenzimidazole, 27231-36-3, mol.wt 164.23 were obtained from Ouchi Shinko Chemical Ind. Ltd (Osaka, Japan)
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 2, 10, 25, 50, 100, or 150 mg/kg
Basis:
other: nominal
- No. of animals per sex per dose:
- 5 male and 5 female rats/group
- Control animals:
- yes, concurrent vehicle
Results and discussion
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- organ weights and organ / body weight ratios
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- organ weights and organ / body weight ratios
Target system / organ toxicity
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 100 mg/kg bw/day (nominal)
- System:
- other: organ weights and organ/body weight ratios of liver and thyroid.
- Organ:
- kidney
- liver
- thyroid gland
- Treatment related:
- yes
- Dose response relationship:
- yes
Any other information on results incl. tables
In a subacute oral toxicity study with MB2 (2-mercaptomethylbenzimidazole; also named MMBI; 1:1 mixture of 4-ethyl and 5-methyl isomers) male and female rats were treated by gavage at doses of 0 (corn oil), 4, 20 and 100 mg/kg bw/day for 28 consecutive days followed by a 2-week recovery period for the control and highest dose groups. Body weight and food consumption, clinical signs, organ weights, clinical biochemistry and haematological parameters including clotting times, and micronuclei induction in bone marrow erytropoetic cells, and histopathology were examined (Saitoh et al., 1999).
“Relative organ weights of lung, liver and kidney, and serum cholesterol and phospholipid significantly increased in male rats treated with MMBIs at doses of 20 and 100 mg/kg. Males rats administered 100 mg/kg MMBIs exhibited a 1.8 fold increase in thyroid weight associated with histopathological changes but not altered serum thyroid hormone levels. Female rats administered 100 mg MMBIs/kg exhibited significant increases of liver and kidney weights, and serum cholesterol level. No-observed-effect levels for male and female rats were found to be 4 and 20 mg/kg, respectively, in this subacute oral toxicity study”.
Relative lung, liver and kidney weights were significantly increased in male rats treated with 20 mg/kg bw/day. However, absolute lung, liver and kidney weights in male rats were not increased significantly in male rats treated with 20 mg/kg bw/day. The increase in relative organ weights is slight and not evident in the recovery groups at 100 mg/kg bw/day. There is no correlate with histopathology finding in lung, liver and kidneys up to the highest dose of 100 mg/kg bw/day. The effects seen in relative organ weights at 20 mg/kg bw/day are regarded as secondary effects due to the slightly (2.4%) decreased body weight.
Taking the above information into account, the relative organ weight effects at 20 mg/kg bw/day are not considered adverse and the NOAEL for male rats is concluded to be 20 mg/kg bw/day.
In female rats relative and absolute organ weights of lung, liver and kidney were not increased at a dose of 20 mg/kg bw/day.
Therefore, the NOAEL for males and females is 20 mg/kg bw/day.
The PL (phospholipid) level was statistically increased in male rats only at 100 mg/kg bw/day and no effect was observed in female rats at any dose.
A slight but significant higher T-CHO (total cholesterol) level was observed in male rats at doses of 20 mg/kg bw/day and 100 mg/kg bw/day. The increase was approx. 25% and 50 %, respectively. In female rats the T-CHO level was increased at 100 mg/kg bw/day (approx. 25%) only andno significant increase in T-CHO level was observed in female rats at 20 mg/kg bw/day and below.Increased cholesterol levels in this study are accompanied by an increase of liver weights in male and female rats. The increase of cholesterol is interconnected with an increase of the liver weights. The increase of the liver weights is dose dependent and a result of the exposure of the rats to the test substance. Liver weight changes in repeated dose studies in mammalians are often caused by liver enzyme induction. An important function of the liver is to produce and clear cholesterol in the body. If the liver is not working properly, it can cause cholesterol to build up in the body.
In the subacute study by Saitoh et al. (1999), the T-CHO values were only slightly increased in male rats at 20 mg/kg bw/day. The effect was reversible in the recovery group at 100 mg/kg bw/day; the T-CHO values in the control and the 100 mg/kg bw/day groups were similar and there were no significant differences in liver or thyroid weights in the control and the 100 mg/kg bw/day groups. These data indicate, that the elevated cholesterol levels at 20 mg/kg bw/day are adaptive and should be considered non-adverse.
Applicant's summary and conclusion
- Conclusions:
- The NOEL (no-observed-effect level) for male and female rats are 4 and 20 mg/kg bw/day, respectively. The NOAEL (no-observed-adverse-effect level) for male and female rats are concluded to be 20 mg/kg bw/day.
- Executive summary:
In a subacute oral toxicity study with MB2 (2-mercaptomethylbenzimidazole; also named MMBI; 1:1 mixture of 4-ethyl and 5-methyl isomers) male and female rats were treated by gavage at doses of 0 (corn oil), 4, 20 and 100 mg/kg bw/day for 28 consecutive days followed by a 2-week recovery period for the control and highest dose groups. Body weight and food consumption, clinical signs, organ weights, clinical biochemistry and haematological parameters including clotting times, and micronuclei induction in bone marrow erytropoetic cells, and histopathology were examined (Saitoh et al., 1999).
“Relative organ weights of lung, liver and kidney, and serum cholesterol and phospholipid significantly increased in male rats treated with MMBIs at doses of 20 and 100 mg/kg. Males rats administered 100 mg/kg MMBIs exhibited a 1.8 fold increase in thyroid weight associated with histopathological changes but not altered serum thyroid hormone levels. Female rats administered 100 mg MMBIs/kg exhibited significant increases of liver and kidney weights, and serum cholesterol level. No-observed-effect levels for male and female rats were found to be 4 and 20 mg/kg, respectively, in this subacute oral toxicity study”.
Relative lung, liver and kidney weights were significantly increased in male rats treated with 20 mg/kg bw/day. However, absolute lung, liver and kidney weights in male rats were not increased significantly in male rats treated with 20 mg/kg bw/day. The increase in relative organ weights is slight and not evident in the recovery groups at 100 mg/kg bw/day. There is no correlate with histopathology finding in lung, liver and kidneys up to the highest dose of 100 mg/kg bw/day. The effects seen in relative organ weights at 20 mg/kg bw/day are regarded as secondary effects due to the slightly (2.4%) decreased body weight.
Taking the above information into account, the relative organ weight effects at 20 mg/kg bw/day are not considered adverse and the NOAEL for male rats is concluded to be 20 mg/kg bw/day.
In female rats relative and absolute organ weights of lung, liver and kidney were not increased at a dose of 20 mg/kg bw/day.
Therefore, the NOAEL for males and females is 20 mg/kg bw/day.
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