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EC number: 202-860-4 | CAS number: 100-52-7
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: test to investigate the inhibition of aldehydedehydrogenase on the metabolism of the test substance, non-GLP
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 984
- Report date:
- 1984
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The in vitro oxidation of the test substance was studied in liver samples from disulfiram-treated and control rats. Disulfiram is used in the treatment of alcoholism to inhibit aldehydedehydrogenase
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Benzaldehyde
- EC Number:
- 202-860-4
- EC Name:
- Benzaldehyde
- Cas Number:
- 100-52-7
- Molecular formula:
- C7H6O
- IUPAC Name:
- benzaldehyde
- Details on test material:
- Batch No.: not specified
Purity: reagent grade
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Wistar rat lvier
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Male and female Wistar rats, weighing 250-350 g, were obtained from the breeding facilities of the Biochemistry Department at Purdue University.The rats were killed by cervical dislocation and the livers were quickly removed and placed in an ice-cold sucrose medium (pH 7.2) containing 0.25 M sucrose, 0.5 mM EDTA and 5 mM Tris-HC1. The subcellular fractions were isolated from a 10% (w/v) liver homogenate in this sucrose medium by differential centrifugation.
Administration / exposure
- Route of administration:
- infusion
- Vehicle:
- other: acetonitrile
- Details on exposure:
- Livers were quickly removed and placed in ice-cold 0.25M sucrose medium, pH 7.2. Liver slices, obtained by the use of a Stadie-Riggs tissue slicer, weighed 35-70 mg and were approximately 0.3 mm thick. The slices were placed in 5-ml glass vials containing 1 mL of Krebs improved Ringer II medium, pH 7.5, saturated with 95:50 O2/CO2 and fitted with Teflon-coated septurn caps. The vials were placed in a 25 ° shaking water bath, and the test substance was injected into vials with a Hamilton syringe through the septum.
- Duration and frequency of treatment / exposure:
- 10 min
Doses / concentrations
- Remarks:
- Doses / Concentrations:
The final concentrations of the test substance were 25 or 250 µM.
- No. of animals per sex per dose / concentration:
- None stated
- Control animals:
- yes
- Positive control reference chemical:
- None stated
- Details on study design:
- None stated
- Details on dosing and sampling:
- Liver slice incubations.
The reaction was terminated after 10 min by placing the vials on ice, and shortly afterwards a 0.8-mL aliquot of the solution was transferred to a new glass vial and 0.1 mL of 0.6 M ZnSO4 and 0.1mL of 0.7 M NaOH were added. The precipitate was removed by centrifugation at 1000 g for 10 min at 4 °. The concentrations of the test substance in the supernatant fractions were determined fluorometrically with the use of potassium-activated ALDH from yeast, or with purified beef liver ALDH obtained from this laboratory. The assay mixture contained 100 mM sodium pyrophosphate buffer (pH 9.0), 0.5 mM NAD and 100 mM KCl when yeast ALDH was used. The recovery of the substance from tissue blanks treated immediately with ZnSO4 and NaOH was approximately 90%, and nearly 100% in samples without added slices. ALDH activity in the slice was calculated as the rate of aldehyde disappearance during the first 10 min. The rate of aldehyde disappearance was linear with time for at least 30 min. The rate of disappearance was measured in three slices from each rat liver, and the calculated mean value was taken as one observation. The difference in activity between slices from controls and disulfiram-treated rats was the same whether the rate of disappearance per mg protein or per mg of slice was used.
Experiments with intact mitochondria.
To verify the integrity of the isolated mitochondria, the following tests were made: (1) the coupling of electron transport to oxidative phosphorylation, and the impermeability of the inner mitochondrial membrane to NADH. Both tests were performed with the use of a Yellow Springs Instrument Clark oxygen electrode. Mitochondria (2-3 mg protein) was added to an incubation medium containing 5 mM MgSO4, 10 mM KCl, 0.25 M sucrose, 1 mM EDTA and 10 mM potassium phosphate buffer (pH 7.4). First, the oxygen consumption was recorded after addition of 5 mM pyruvate and malate, and then again after addition of 1 mM ADP. The marked increase in oxygen utilization in the presence of ADP demonstrated good coupling of the electron transport system to oxidative phosphorylation. The second test was performed by first recording oxygen consumption in the presence of ADP and then after addition of 0.1 mM NADH. Finding no increase in oxygen consumption after adding NADH demonstrated that there was no damage to the mitochondrial inner membrane during isolation of mitochondria. These two tests were performed with each preparation of isolated mitochondria before the incubation experiments were initiated. The incubation mixture was prepared in 5-mL glass vials with Teflon-coated septum caps and contained mitochondria (2-3 mg protein), 1 mM ADP and incubation medium (saturated with 95:5 O2/CO2) in a total volume of 1.1mL. The test substance was added with a Hamilton syringe to a final concentration of 200 µM, and the vials were placed in a 25 ° shaking water bath. The corresponding volume of acetonitrile was added to incubations employing acetaldehyde as the substrate. After a 10-min incubation the reaction was terminated by adding 0.1 mL of 0.6 M ZnSO4 and 0.7 M NaOH. The precipitate was removed by centrifugation at 1000g for 10min at 4 °. The concentrations of the test substance in the supernatant fraction, as well as the rate of aldehyde disappearance was determined as described in experiments with rat liver slices. To assay ALDH located in mitochondrial intermembrane space, 5 µM rotenone and 0.5 mM NAD were added to the incubation mixture. - Statistics:
- None stated
Results and discussion
Main ADME results
- Type:
- metabolism
- Results:
- With subcellular fractions, from livers of disulfiram-treated and control rats, the inhibition of ALDH was obtained when the test substance was a substrate in cytosol and mitochondria.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- With 25 µM substrate, both cytosol and mitochondria appeared to make a nearly equal contribution to the oxidation of the test substance. When the Km values for the test substance with aldehyde dehydrogenase (ALDH) were determined, two Km values (3 and 120 µM) were obtained with mitochondria, but only a single Km value (25 µM) was obtained with the cytosolic fraction. The relatively high Km (2.9 mM) found with microsomes makes it unlikely that microsomes are important in the oxidation of the test substance. In intact mitochondria, with 200 µM the test substance, the matrix space enzyme accounted for 62%, of the total ALDH activity. With subcellular fractions, from livers of disulfiram-treated and control rats, the inhibition of ALDH was obtained when the test substance was a substrate in cytosol and mitochondria. Microsomal ALDH was not inhibited by disulfiram. In liver slices from rats given disulfiram, a statistically significant inhibition was found when a significant inhibition (24%) was observed only with the lower substrate concentration. Finding that both mitochondrial fractions and slices were less inhibited at the higher substrate concentration implies that the high Km enzyme is not inhibited.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
It can be concluded that, in rat, disulfiram inhibiting liver ALDH affects oxidation of the test substance as well. Aldehydedehydrogenase is an essential enzyme for the metabolism of the test substance. - Executive summary:
The in vitro oxidation of the test substance was studied in liver samples from disulfiram-treated and control rats. Disufiram is an inhibitor of aldehydedehydrogenase (ALDH) and used as treatment for alcoholics.
It can be concluded that, in rat, disulfiram inhibiting liver ALDH also affects oxidation of the test substance.
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