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EC number: 202-987-5 | CAS number: 101-90-6
- 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

Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- in vivo and in vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Objective of study:
- metabolism
- toxicokinetics
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Enzyme kinetics: Alkylating activity was estimated according to the procedure of Friedman and Boger; the test solution was reacted at 100°C with 0.4 mL of a 5% acetone solution of 4-(4'-nitrobenzyl)pyridine (NBP) in 3 mL acetate buffer (pH 4.6) for 20 min. After cooling 5 mL ethylacetate and 1 mL 2 N sodium hydroxide was added, the mixture was shaken vigorously, centrifuged and the light absorbance of the upper organic phase was measured immediately at 540 nm.
Liver homogenate postmitochondrial supernatant (S-9) was prepared from either uninduced mice or from induced rats; enzyme induction in the latter case was by the combination treatment of beta-naphthoflavone and phenobarbital. For the experiments, the S-9 was diluted to the desired concentration with phosphate buffered saline (PBS). The determination of the protein content was performed by Lowry analysis. The measurements of enzyme kinetics were conducted in the following way: 50 µL of a DMSO-solution of the various test compounds was incubated with 1 ml S-9 for 10 min at 37°C, yielding final concentrations of 5-100 µg/mL for RDGE and 20-100 µg/mL for the two diol-epoxides. At the end of the incubation period the enzymatic reaction was stopped by the addition of a threefold excess of ice-cold acetone. After centrifugation the supernatant was assayed for alkylating activity by the NBP-procedure. The difference between the absorbance values before and after incubation was then used in the calculation of the kinetic parameters. Time-course experiments were performed in the same way with the reaction stopped at various times after the addition of S-9; the metabolites produced by S-9 were also isolated in this manner, namely by acetone precipitation of proteins, centrifugation and subsequent concentration of the supernatant. Judging from the absorbance values obtained with these compounds either in the presence or in the absence of S-9, the recoveries of parent compounds and metabolites, respectively, obtained with this procedure were between 90% and 100%.
Metabolism kinetics: Male and female ICR-mice were given the test compound by gavage. The animals were kept in metabolic cages, where they had access to water only during the experiment. Urine and faeces were collected for 1-4 h. Urinary metabolites were then extracted either by ethylacetate at pH 7 and pH 2, or by XAD-2 adsorption. Analysis of urinary and S-9 metabolites was by thin-layer chromatography on silica gel plates in acetone/hexane (1:1) as the most suitable solvent system. - GLP compliance:
- no
- Specific details on test material used for the study:
- Resorcinol diglycidyl ether (RDGE) was obtained by reacting an about 4-fold excess of epichlorohydrin with the aromatic compound, resorcinol. After a few hours of stirring at an elevated temperature an exact equivalent of sodium hydroxide was added slowly to this solution. Purification was then by vacuum distillation. In the same manner the 14C-labelled compound used in this study, namely [14C] resorcinol diglycidyl ether (R*DGE), resorcinol di-[14C]glycidyl ether (RDG*E), were synthesized from the appropriately 14C-labelled precursor substances, which were obtained from Amersham (Amersham, U.K.). The presumed bis-diol and diol-epoxide metabolites were also synthesized in an analogous manner by the reaction of resorcinol with glycidylglycerine alone, or in combination with epichlorohydrin, in this case followed by the sodium hydroxide addition.
- Radiolabelling:
- yes
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Institute of Animal Husbandry (University of Zurich)
- Housing: metabolic cages
- Water: access only during the experiment
- Route of administration:
- oral: gavage
- Vehicle:
- DMSO
- Remarks:
- 10% aqueous DMSO
- Duration and frequency of treatment / exposure:
- once
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Control animals:
- no
- Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: urine, faeces
- Time and frequency of sampling: 60, 120 and 240 min
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: tissues (liver homogenate postmitochondrial supernatant S-9)
- From how many animals: from uninduced mice or from induced rats
- Method type(s) for identification: TLC combined with light absorbance at 540 nm
- Limits of detection and quantification: NA - Type:
- metabolism
- Results:
- RDGE seems to become fully detoxified during its passage through the organism
- Details on excretion:
- 4 hours after RGDE gavage at 1000 mg/kg, 46.8% of applied dose was recovered from urine.
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: 6 min
- Remarks:
- apparent half-life of RDGE metabolism
- Metabolites identified:
- yes
- Details on metabolites:
- Urinary metabolites (% of amount applied to thin-layer plate): bis-diol (64%), unidentified polar conjugates (21%) and phenol-diol (4%)
- Conclusions:
- The degradation of the reactive epoxide groups in RDGE to the bis-diol occurs as a continuous process. The compound binds to the enzyme and both glycidyl residues are converted sequentially to the bis-diol.
Reference
Various concentrations of RDGE, as well as of this respective diol-epoxide derivatives were incubated for ten minutes and the respective maximal reaction velocities and the Michaelis-Menten constants of these compounds were estimated by means of Lineweaver-Burk plots.
Kinetic paremeters for the enzymatic inacivation of RDGE
Metabolite |
Km(apparent) |
Vmax(apparent) E540/min/mg protein |
|
µg substrate/mL |
nM/mL |
||
RDGE Bis-epoxide Diol-epoxide |
140 42 |
630 175 |
90 55 |
Description of key information
No experimental toxico-kinetic data are available for assessing adsorption, distribution and excretion of the substance. Based on effects seen in the human health toxicity studies and physico-chemical parameters The substance is expected to be readily absorbed via the oral and inhalation route and somewhat lower via the dermal route. Using the precautionary principle for route to route extrapolation the final absorption percentages derived are: 50% oral absorption, 50% dermal absorption and 100% inhalation absorption.
The metabolism is described in the robust study summary of Basic toxicokinetics.
Key value for chemical safety assessment
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 50
- Absorption rate - inhalation (%):
- 100
Additional information
Present the text of the toxico-kinetic assessment here and add the file to this endpoint summary
No bioaccumulation is < 500, Low is < 2000 and high is > 2000
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