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EC number: 216-823-5 | CAS number: 1675-54-3
- 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 vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- not specified
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 981
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 978
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 979
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
Materials and methods
- Objective of study:
- other: Distribution/elimination and metabolism following a single oral or dermal dose.
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Absorption, metabolism and elimination study of BADGE in mice
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane
- EC Number:
- 500-033-5
- EC Name:
- 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane
- Cas Number:
- 25068-38-6
- Molecular formula:
- (C15 H16 O2 . C3 H5 Cl O)x
- IUPAC Name:
- 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane
- Reference substance name:
- 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane
- EC Number:
- 216-823-5
- EC Name:
- 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane
- Cas Number:
- 1675-54-3
- Molecular formula:
- C21H24O4
- IUPAC Name:
- 2,2'-[propane-2,2-diylbis(4,1-phenyleneoxymethylene)]dioxirane
- Details on test material:
- Test substance- 1675-54-3
Radiolabeled 14C-BADGE (2,2 Bis-[4-(2,3-epoxypropoxy)phenyl][2-14C]propane was synthesized with a specific radioactivity of 6.33 uCi/mg, and shown to have a radiochemical purity of >99% when analyzed. The radiochemical was diluted with non-radiolabeled material as required.
Constituent 1
Constituent 2
- Radiolabelling:
- yes
- Remarks:
- radiolabeled in 2,2- Bis-[4-(2,3-epoxypropoxy)phenyl][2-14C]propane
Test animals
- Species:
- mouse
- Strain:
- CF-1
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Mice were approximately 28 g in weight when used.
Administration / exposure
- Route of administration:
- other: dermal and oral gavage
- Vehicle:
- other: oral-dimethyl sulphoxide:water (3:1), dermal- acetone
- Details on exposure:
- Dermal Application
Six male mice were dosed with BADGE in acetone, the dose equivalent of 56 mg/kg.
Oral Dose
Six male mice were dosed with BADGE in dimethyl sulphoxide and water (3:1), the dose equivalent of 55 mg/kg . - Duration and frequency of treatment / exposure:
- single oral or dermal dose
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Single oral dose of 56 mg/kg or 56 mg/kg dermally of BADGE.
- No. of animals per sex per dose / concentration:
- 6 male mice/dose group
- Control animals:
- no
- Positive control reference chemical:
- not applicable
- Details on study design:
- Dermal Application
Six male mice were dosed with BADGE in acetone, the dose equivalent of 56 mg/kg and offered water and food ad libitum. Urine and feces were collected daily. After sacrifice, tissue samples, blood, urine, and feces were analyzed for radioactivity.
Oral Dose
Six male mice were dosed with BADGE in dimethyl sulphoxide and water (3:1), the dose equivalent of 55 mg/kg and offered water and food ad libitum. Urine and feces were collected daily. After sacrifice, tissue samples, blood, urine, and feces were analyzed for radioactivity.
Radioactivity Determination
Tissues were homogenated and body fluids were extracted. Radioactivity was determined by counting twice in a liquid scintillation counter. - Details on dosing and sampling:
Dermal Application
Urine and feces were collected daily. After sacrifice, tissue samples, blood, urine, and feces were analyzed for radioactivity.
Oral Dose
Urine and feces were collected daily. After sacrifice, tissue samples, blood, urine, and feces were analyzed for radioactivity.- Statistics:
- not applicable
Results and discussion
- Preliminary studies:
- not applicable
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Dermal absorption. When 14C-DGEBPA was applied to the shaved dorsal area of mice (56 mg/kg body wt), daily elimination of radioactivity in the urine rose to a maximum of only 1.3% dose two days after treatment. During the remaining six days of the experiment the daily excretion of radioactivity slowly fell to 0.3% of dose. A similar pattern of elimination was observed for feces. Daily excretion of radioactivity rose to a broad maximum of approximately 8% two and three days after the dermal application, falling to 2.3% of the dose after eight days. A relatively large proportion of the administered dose could be extracted from the skins of the mice one (67%), three (41%) and eight (11%) days after treatment. Additionally, a mean figure of 26% of the administered dose could be recovered by washing the foil, covering the application area, with methanol. The radioactivity recovered in this manner, remained approximately constant throughout the experiment.
The methanol-acetone extract of the skin was analyzed by TLC. One day after treatment 97% of the extractable radioactivity on the skin was DGEBPA; 3% was unidentified polar material. After eight days the corresponding figures were 81% and 19% of the extractable activity respectively. After methanol-aceone extraction, the skin was further extracted with methanol-water to yield 0.1% dose and finally with 3M HCl to give 0.2% dose. Samples of the extracted skin were combusted and the results showed that the amount of 14C chemically bound to the skin increased from 0.3% dose after one day, to 0.5% after three days and to 1.8% dose after eight days.
The toal recovery of radioactivity including cage washings was 95%.
Oral dosing. When 14C-DGEBPA was dosed orally to mice (~55 mg/kg), radioactivity was eliminated mostly in the feces (~80%) and to a lesser extent in the urine (~11%) over the first three days of the experiment. Excretion was very rapid, being over 88% of the administered dose within two days. The tissue radioactivity rapidly depleted from all the tissues studied during the course of the eight day experiment. The total recovery of radioactivity, including cage washings, was 93%. - Details on distribution in tissues:
- The level of radioactivity remaining in the animals eight days after treatment was 0.74% of the administered dose excluding the figure for the skin. Most of this activity was located in the intestines of the animals (0.55% of dose, mean figure from the two animals).
- Details on excretion:
- Dermally-applied BADGE (56 mg/kg) to mice was slowly eliminated in the feces (20% of dose) and urine (3%) as a mixture of metabolites, over three days. Another 20 % was excreted in the feces and 2% in the urine between days 3 and 8 after application of test material to the skin. Most of the applied radioactivity (66%) was extracted from the application area and its covering foil.
When BADGE was given orally to mice, it was rapidly excreted; 80% in the feces and 11% in the urine 0-3 days following a single oral dose. Over 88% of the administered dose was eliminated within 2 days. The tissue radioactivity rapidly depleted from all the tissues studies during the course of the eight day experiment. The total recovery of radioactivity, including cage washings, was 93%.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The urinary and fecal metabolite profiles derived from dermal application and oral dosing were essentially similar. The major metabolic transformation is by hydrolytic ring-opening of the two epoxide rings to form diols. This metabolite (the bis-diol of BADGE) is excreted in both free and conjugated forms and is further metabolized to various carboxylic acids, including two containing a methylsulphonyl moiety in amounts representing about 5% of the dose. The high activity of epoxide hydratase towards BADGE suggests that glyceraldehyde and not glycidaldehyde is formed in vivo.
Any other information on results incl. tables
Percutaneous absorption of DGEBPA is slow; 90% of the applied radiochemical can be recovered from the skin and foil covering the application area 24 h after application. This figure falls to about 40% after eight days. As a result of this slow absorption, a low, approximately constant, dose of DGEBPA was being absorbed by the mice each day. The amount of radiochemical bound to the skin after eight days of continuous contact was 1.8% of the applied dose. There was some evidence to suggest that the rate of chemical binding was higher during the first half of the experiment than during the second half. This effect probably a result of 'saturation' of the reactive sites in the skin (e.g. thiol and amino groups) by interaction with DGEBPA. No signs of irritation were observed during the experimental period.
The 14C-DGEBPA was applied to the skin in acetone (50 ul), and although percutaneous absorption of the chemical was slow, the solvent could have facilitated the initial absorption of the compound. A limited study in which two mice were exposed to 14C-DGEBPA in the absence of solvent, to test this hypothesis, indicated that the initial absorption was indeed facilitated by the solvent, but the daily excretion of 14C from day four onwards was aprroximately the same.
The results from the oral dosing experiement show that 14C-DGEBPA is rapidly eliminated from the body. After eight days only approximately 0.1% of the dose remained from the body. After eight days only approximately 0.1% of the dose remained in the animals. There was considerable inter-animal variation in this experiment. Mice 2 and 5 (oral dosage) excreted considerably less feces in the first 24 h after dosing, and as a result, the tissue 14C of mouse 2 was higher than that of mouse 1 (both killed after one day). In addition, mouse 5 excreted considerably more 14C in the feces after two and three days compared with that for the other animals.
The urinary and fecal metabolic profiles from the dermal and oral studies are similar despite the very different elimination data in the two experiments and therefore were not dependent on the route of administration of the compound. The major metabolic pathway is hydrolytic opening of the two epoxide groups to form the bis-diol of DGEBPA. This compound is eliminated to a small extent in both free and conjugated forms; however, the majority undergoes further metabolic transformations to carboxylic acids. The methyl ester of bis-diol of DGEBPA is the major metabolite excreted by mice (24%of dose in three days). The phenol diol of DGEBPA, is excreted in amounts totaling 5% of the administered dose within 3 days in the urine and feces. It is most likely formed by oxidative dealkylation of DGEBPA or of the bis-diol. The three-carbon unit is lost either as glyceraldehyde; an endogenous chemical, or as glycidaldehyde, a known bacterial mutagenic and mammalian skin carcinogen (van Duuren, Orris and Nelson, 1965).
Hepatic epoxide hydratases are present in largest amounts in the rabbit, then mouse, one membrane-bound and the other soluble in the liver cytosol. The enzyme was found in low amounts in the rat.
van Duuren, B. L., Orris, L. and Nelson, J. (1965). J National Cancer Institute 35:707
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
Dermally applied BADGE to mice was only slowly eliminated in the feces (20% of dose) and urine (3%) as a mixture of metabolites, over three days. When BADGE was given orally to mice, it was rapidly excreted; 80% in the feces and 11% in the urine 0-3 days following a single oral dose. The urinary and fecal metabolite profiles derived from dermal application and oral dosing were essentially similar. The major metabolic transformation is by hydrolytic ring-opening of the two epoxide rings to form diols. This metabolite (the bis-diol of BADGE) is excreted in both free and conjugated forms and is further metabolized to various carboxylic acids, including two containing a methylsulphonyl moiety in amounts representing about 5% of the dose. The high activity of epoxide hydratase towards BADGE suggests that glyceraldehyde and not glycidaldehyde is formed in vivo. No bisphenol A was formed following treatment of mice with BADGE. - Executive summary:
14C-DGEBPA dermally applied to mice was only slowly eliminated in the feces (20% dose) and urine (3%), as a mixture of metabolites, over three days. Most of the applied radioactivity (66% dose) was extracted from the application area and its covering foil. When 14C-DGEBPA was given orally to mice it was rapidly excreted; 80% of the administered 14C was eliminated in the feces and 11% in the urine 0 -3 days after a single oral dose. The urinary and fecal metabolite profiles derived from dermal application and oral dosing were essentially similar. The major metaoblic transformation of orally ingested 14C-DGEBPA is by hydrolysing ring-opening of the two epoxide rings to form diols. This metabolite (the bis-diol of DGEBPA) is excreted in both free and conjugated forms and is further metabolized to various carboxylic acids, including two containings a methylsulphonyl moiety. The product of oxidative dealkylation either of DGEBPA (with concomitant formation of glycidaldehyde) or of the bis-diol of DGEBPA (with concomitant formation of glyceraldehyde) is excreted in both free and conjugated forms in amounts representing 5% of the dose. The high activity of epoxide hydratase towards DGEBPA suggests that glyceraldehyde and not glycidaldehyde is formed in vivo. Hepatic epoxide hydratase activity towards DGEBPA measured in vitro decreased in the order rabbit>mouse>rat. Two discrete epoxide hydratases are present in large amounts in the mouse. One is membrane-bound in the liver microsomal fraction and the other is a 'soluble' enzyme located in the liver cytosol. This cytosolic enzyme was present in only very small amounts in the rat. No bisphenol A was formed following treatment of mice with BADGE.
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