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EC number: 202-607-8 | CAS number: 97-77-8
- 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
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- Endpoint summary
- Stability
- Biodegradation
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- 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
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- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
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- Additional toxicological data

Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08 Jul - 9 Nov 1987
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 987
- Report date:
- 1987
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- adopted in 2014
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 84-2
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Thiram
- EC Number:
- 205-286-2
- EC Name:
- Thiram
- Cas Number:
- 137-26-8
- Molecular formula:
- C6H12N2S4
- IUPAC Name:
- tetramethylthiuram disulfide
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratory, Kingston, NY, USA
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: 27.1 - 35.9 g (males), 23.8 - 30.7 g (females)
- Assigned to test groups randomly: yes
- Housing: up to 5 per cage in plastic autoclavable cages with wire lids
- Diet:certified laboratory rodent chow, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26.67
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 20 Jul 1987 1987 To: 15 Oct 1987
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- CMC (carboxymethyl cellulose), 1%
- Justification for choice of solvent/vehicle: toxicity profile in animals
- Concentration of test material in vehicle: 3.8, 18.9 and 37.7 for the low, mid and high dose, respectively
- Volume administered: 10 mL/kg bw
- Lot/batch no.: 7-2-87 - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The dosing solutions were prepared freshly and based on the most recently measured body weight (directly before injection).
- Duration of treatment / exposure:
- single dose
- Frequency of treatment:
- single dose
- Post exposure period:
- 24, 48 and 72 h
Doses / concentrationsopen allclose all
- Dose / conc.:
- 38 mg/kg bw/day
- Dose / conc.:
- 189 mg/kg bw/day
- Dose / conc.:
- 377 mg/kg bw/day
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- triethylenemelamine
- Route of administration: IP injection
- Doses / concentrations: 0.25 mg/kg bw
- Vehicle: water
Examinations
- Tissues and cell types examined:
- Bone marrow from femur was prepared.
- Details of tissue and slide preparation:
- Toxicits test: A toxicity test was conducted with 6 groups of five male and five female rats each. Animals were observed after dose administration and daily thereafter for 7 days for clinical signs of chemical effect. Body weights were recorded prior to dose administration and 1 and 3 days after dose administration
TREATMENT AND SAMPLING TIMES: Animals were observed after dosing for clinical signs. At the scheduled time of sacrifice, 5 mice/sex were sacrificed by CO2 asphyxiation. Immediately following sacrifice, the femurs were exposed, cut just about the knee and the bone marrow was aspired into a syringe containing fetal bovine serum. The bone marrow cells were transferred to a capped centrifuge tube containing approximately 1 mL FBS. The bone marrow cells were pelleted by centrifugation.
DETAILS OF SLIDE PREPARATION: After centrifugation, the pellet was were resuspended by aspiration with a capillary pipet and a small drop of bone marrow suspension was spread onto a clean glass slide. Two to four slides were prepared from each animal. The slides were fixed in methanol stained with May-Gruenwald-Giemsa and permanently mounted.
METHOD OF ANALYSIS: Using medium magnification, an area of acceptable quality was selected such that the cells were well spread and stained. Using oil immersion, 1000 polychromatic erythrocytes were scored for the presence of micronuclei. The proportion of polychromatic erythrocytes to total erythrocytes and the number of micronucleated normocytes in the field of 1000 polychromatic erythrocytes were also enumerated.
- Evaluation criteria:
- The test article is considered to induce a positive response if a treatment—related increase in micronucleated polychromatic erythrocytes is observed relative to the vehicle control (P<0.05, Kastenbaum—Bowman Tables) . The positive response must be dose—dependent or must be observed at a single dose level at adjacent sacrifice times. If a single treatment group is significantly elevated at one sacrifice time, the assay is considered a suspect or unconfirmed positive and a repeat assay will be recommended.
The mean incidence of micronucleated polychromatic erythrocytes must not exceed 5/1000 polychromatic erythrocytes in the negative (vehicle) control. The incidence of micronucleated polychromatic erythrocytes in the positive control group must be statistically significantly increased relative to the negative control (P<0.05, Kastenbaum—Bowman Tables) . - Statistics:
- The incidence of micronucleated polychromatic erythrocytes per 1000 polychromatic erythrocytes was presented for each animal and treatment group.
Statistical significance was determined using the Kastenbaum—Bowman tables which were based on the binomial distribution.
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF TOXICITY STUDY
- Dose range: 200 - 1000 mg/kg bw
- Results: Deaths were observed in all test article—treated groups, with 1, 6, 9, 7 and 9 deaths occurring at dose groups of 200, 400, 600, 800 and 1000 mg/kg bw, respectively. Clinical observations for the above groups included lethargy, paralysis, and piloerection. The LD50 was calculated by probit analysis to be approximately 471 mg/kg bw. 377 mg/kg bw was estimated to be 80% of the LD50 and was selected as the high dose for the micronucleus test.
RESULTS OF DEFINITIVE STUDY
At the highest dose level, mortality (15/38 animals), clinical signs and bone marrow toxicity (reduced ratio PCE/Total E) were observed. These effects were also apparent in some animals in the mid-dose group. No increase in the number of micronucleated polychromatic erythrocytes was detected at any of the sampling times. Experimental conditions as well as the criteria for the determination of test responses are well defined and appropriate. Positive controls gave the expected response.
Summarized results can be found in Attachment 1 in the attached background material.
Applicant's summary and conclusion
- Conclusions:
- The study was conducted similar to OECD guideline 474 and under GLP conditions.
Under the conditions of the test, the test substance did not increase the incidence of micronucleated polychromatic erythrocytes in bone marrow and was concluded to be negative in the micronucleus test using male and female CD-1 mice.
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