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EC number: 203-920-2 | CAS number: 111-91-1
- 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
Specific investigations: other studies
Administrative data
- Endpoint:
- mechanistic studies
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was performed by the NTP in support of an earlier 90 day study to further investigate the mechanism of action of cardiotoxicity. No specific guideline was followed. There is no data on GLP. The publication describeds the findings in detail.
Data source
Reference
- Reference Type:
- publication
- Title:
- Critical Pathways in Heart Function: Bis(2-chloroethoxy)methane-Induced Heart Gene Transcript Change in F344 Rats
- Author:
- Dunnick, J., Blackshear, P., Kissling, G., Cunningham, M., Parker, J., Nyska, A.
- Year:
- 2 006
- Bibliographic source:
- Toxicologic Pathology, 34:348–356, 2006
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- GLP compliance:
- not specified
- Type of method:
- in vivo
- Endpoint addressed:
- not applicable
Test material
- Reference substance name:
- Bis(2-chloroethoxy)methane
- EC Number:
- 203-920-2
- EC Name:
- Bis(2-chloroethoxy)methane
- Cas Number:
- 111-91-1
- Molecular formula:
- C5H10Cl2O2
- IUPAC Name:
- 1-chloro-2-[(2-chloroethoxy)methoxy]ethane
- Details on test material:
- Chemical name: Bis(2-chloroethoxy)methane
Batch No.: lot B007269977
Supplier: Karl Industries, Aurora, Ohio,
Purity: 98.5% pure (National Toxicology Program, 2000).
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
Administration / exposure
- Route of administration:
- dermal
- Vehicle:
- ethanol
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 16 days
- Frequency of treatment:
- Solutions of CEM were prepared in 95% ethanol for dosing by dermal administration daily, excluding weekends, for two weeks plus two consecutive dosages before the last sacrifice on study-day 16, at which animals had received a total of 12 doses.
- Post exposure period:
- None
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 200, 400, 600 mg/kg bw
Basis:
nominal conc.
- No. of animals per sex per dose:
- 12 (RNA was extracted from hearts of 6 control rats, and from 6 rats from each treatment group (200, 400, or 600 mg/kg) at day 2 and day 5 just 1 hour after dosing.)
- Control animals:
- yes, concurrent vehicle
Results and discussion
- Details on results:
- The down-regulation of ATP subunit transcripts (Atp5j, ATP5k), which reside in the mitochondrial membranes, indicated a decrease in energy supply at day 2 and day 5. This was accompanied by down-regulation of transcripts involved in high-energy consumption processes such as membrane transport and ion channel transcripts (e.g., abc1a, kcnj12). The up-regulation of transcripts encoding for temperature regulation and calcium binding proteins (ucp1 and calb3) only at the 2 low exposure levels, suggest that these adaptive processes cannot occur in association with severe cardiotoxicity as seen in hearts at the high exposure level. Transcript expression changes occurred within 2 days of CEM exposure, and were dose- and time-dependent.
Applicant's summary and conclusion
- Conclusions:
- Gene transcript changes after exposure to the heart toxin, bis(2-chloroethoxy)methane (CEM), were analyzed to elucidate mechanisms in cardiotoxicity and recovery. The heart transcript changes suggest that CEM cardiotoxicity activates protective processes associated energy conservation and maintenance of heart function.
- Executive summary:
Gene transcript changes after exposure to the heart toxin, bis(2-chloroethoxy)methane (CEM), were analyzed to elucidate mechanisms in cardiotoxicity
and recovery. CEM was administered to 5-week-old male F344/N rats at 0, 200, 400, or 600 mg/kg by dermal exposure, 5 days per week, for a total of 12 doses by study day 16. Heart toxicity occurred after 2 days of dosing in all 3 regions of the heart (atrium, ventricle, interventricular septum) and was characterized by myofiber vacuolation, necrosis, mononuclear-cell infiltration, and atrial thrombosis. Ultrastructural analysis revealed that the primary site of damage was the mitochondrion. By day 5, even though dosing was continued, the toxic lesions in the heart began to resolve, and by study day 16, the heart appeared histologically normal. RNA was extracted from whole hearts after 2 or 5 days of CEM dosing. After a screen for transcript change by microarray analysis, dose-response trends for selected transcripts were analyzed by qRT-PCR. The selected transcripts code for proteins involved in energy production, control of calcium levels, and maintenance of heart function. The down-regulation of ATP subunit transcripts (Atp5j, ATP5k), which reside in the mitochondrial membranes, indicated a decrease in energy supply at day 2 and day 5. This was accompanied by down-regulation of transcripts involved in high-energy consumption processes such as membrane transport and ion channel transcripts (e.g., abc1a, kcnj12). The up-regulation of transcripts encoding for temperature regulation and calcium binding proteins (ucp1 and calb3) only at the 2 low exposure levels, suggest that these adaptive processes cannot occur in association with severe cardiotoxicity as seen in hearts at the high exposure level. Transcript expression changes occurred within 2 days of CEM exposure, and were dose- and time-dependent. The heart transcript changes suggest that CEM cardiotoxicity activates protective processes associated energy conservation and maintenance of heart function.
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