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Diss Factsheets
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EC number: 907-437-4 | CAS number: -
- 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
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Toxicity to reproduction: other studies
Administrative data
- Endpoint:
- toxicity to reproduction: other studies
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Not reported
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented study conducted to GLP and although no International Test guideline available
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 997
- Report date:
- 1997
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Adult ovariectomised rats (8 per group) were treated orally for 7 days (4 test groups + 1 vehicle control + 3 groups for positive control Diethylstilbestrol)
All rats were subjected to vaginal lavage daily during the 7 day dosing period in order to detect vaginal cornification.
All surviving rats were euthanized 24 hours after the final dose when final bodyweights and uterine weights were recorded. - GLP compliance:
- yes
- Type of method:
- in vivo
Test material
- Reference substance name:
- Benzoflex 2-45
- IUPAC Name:
- Benzoflex 2-45
- Reference substance name:
- Oxydiethylene dibenzoate
- EC Number:
- 204-407-6
- EC Name:
- Oxydiethylene dibenzoate
- Cas Number:
- 120-55-8
- Molecular formula:
- C18H18O5
- IUPAC Name:
- 2-[2-(benzoyloxy)ethoxy]ethyl benzoate
- Details on test material:
- - Name of test material (as cited in study report): Benzoflex 2-45 (Diethylene glycol dibenzoate DEGDB)
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Kingston, NY, USA.
- Age at study initiation: (P) x 9 wks
- Weight at study initiation: (P) Females: 170 -200 g
- Fasting period before study: Not applicable
- Housing: Individually in stainless steel hanging wire cages.
- Diet: Purina rodent chow (#5001), ad libitum
- Water: Mains (Montgomery County) tap water, ad libitum
- Acclimation period: 3 days prior to ovariectomy. Following a 6-7 days post surgery recovery period, evaluation of cell types was conducted daily for one week prior to initiation of treatment.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Ranged 61°F to 76°F
- Humidity (%): Ranged 41% - 69%
- Photoperiod (hrs dark / hrs light): 10 hours dark/14 hours light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
No details are available on the method of preparation of the dose solutions
VEHICLE
- Justification for use and choice of vehicle (if other than water): Test substance is poorly soluble in water
- Amount of vehicle (if gavage): 5 mL/kg/day
- Lot/batch no. (if required): Mazola corn oil purchased from a local supermarket.
- Purity: Not stated but food grade - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Dosed once per day
- Frequency of treatment:
- Daily
- Duration of test:
- 7 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 500 mg/kg bw/day (nominal)
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 8 females per group
- Control animals:
- yes, concurrent vehicle
- other: Positive control: ethylstilbestrol (DES) at 2.5, 5 & 10 µg/kg/day
- Details on study design:
- Eight ovariectomised rats per group (4 test groups + 1 vehicle control + 3 groups positive control diethylstilbestrol) were orally dosed for 7 days. All rats were observed daily for clinical signs and subjected to vaginal lavage daily during the 7 day dosing period in order to detect vaginal cornification. All surviving rats were euthanized 24 hours after the final dose when final bodyweights and uterine weights were recorded.
- Statistics:
- The occurrence of vaginal cornification was expressed as the number of rats showing vaginal cornification (for one or more days) over the number of rats treated. A z-test of proportions was used to compare the test groups to the control animals. The group means ± SE were calculated for body weights on day 0 and day 7 and a parametric one way analysis of variance (ANOVA) was performed. For a significant F value (p< 0.05), a Student-Newman-Keuls multiple range test was performed to determine differences among groups. Group means ± SE were also calculated for the uterine weights and uterine weight/final body weight ratios. These data were compared using a non parametric one way ANOVA on ranks followed by Dunn's comparison to the designated control group.
Results and discussion
Effect levels
open allclose all
- Dose descriptor:
- other: estrogenic activity
- Effect level:
- > 2 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Based on induction of vaginal cornification compared to vehicle & positive controls
- Dose descriptor:
- other: estrogenic activity
- Effect level:
- > 2 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Based on increase in uterine weight to final bodyweight
Observed effects
These observations included aggressiveness, rapid shallow breathing, red or brown discharge on the muzzle, piloerection, tremors, kyphosis, lethargy, scruffy coat, convulsions, hypothermia, vocalization and discharge around the eyes. Of the five affected animals, two rats were found dead, two moribund animals were euthanized and one rat survived to day 7. At necropsy the four animals found dead or euthanized prior to day 7 had considerable weight loss and exhibited abnormalities in the gastrointestinal tract. In most cases, the stomach was distended with a solid sticky material resembling food and the duodenum contained little or no food (primarily gas and some liquid). The feces within the lower gastrointestinal tract tended to be either hardened tacky/sticky. All four rats appeared to be in or a dehydrated condition (decreased peritoneal fluid hardened feces in colon). The 4 surviving rats treated with 2000 mg/kg/day had no gross abnormalities at necropsy on day 7. The rats treated with 500, 1000 and 1500 mg/kg/day appeared normal during the study and at necropsy on day 7.
Any other information on results incl. tables
With respect to estrogenic activity, DES (the positive control) stimulated a dose dependent induction of vaginal cornification. The 2.5 µg DES/kg/day dose was a threshold dose for this endpoint, in that the onset for the cornification response was of longer duration and more variable than in the 5.0 and 10.0 µg/kg/day groups. In addition, unlike the mid and high dose DES groups, not all rats in the low dose DES group gave a vaginal cornification response. Further, in the low dose DES group the number of rats cornified per number treated was significantly increased (p<0.05) only on days 4, 6 and 7 of the study, whereas for the mid and high dose DES groups this endpoint was significantly increased (p<0.05) from study days 3 through 7 and days 2 through 7, respectively.
In contrast DEGDB did not induce vaginal cornification at doses of 500, 1000, 1500 or 2000 mg/kg/day x 7 days. Hence by this endpoint DEGDB did not sjhow estrogenic activity.
DES tended to suppress body weight gain in a dose-dependent manner over the 7 day dosing period. Suppression of body weight gain or loss is a well known biological effect of potent estrogens. Only the high dose of DEGDB tended to decrease bodyweight gain but this effect was not significantly different for animals surviving 7 days of dosing.
DES induced a dose-dependent increase in uterine weight and uterine weight to final body weight ratio. Both parameters were increased significantly (p<0.05) at all dose levels of DES as compared to the vehicle control group. In contrast DEGDB did not stimulate an uterine weight increase or an increase in the uterine weight to final body weight ratio at doses of 500, 1000, 1500 and 2000 mg/ kg/day x 7 days.
Collectively, these data demonstrate that DEGDB did not possess estrogenic activity up to and including the maximally tolerated dose.
Applicant's summary and conclusion
- Conclusions:
- Diethylylene glycol dibenzoate did not possess estrogenic activity up to and including the maximally tolerated dose.
- Executive summary:
A study was performed to investigate whether the test substance, diethylylene glycol dibenzoate, had the potential for estrogenic activity when evaluated in a seven day rat vaginal cornification/uterine weight bioassay. The study was conducted to GLP but no formal international test guidelines were applicable.
Eight ovariectomised rats per group (4 test groups + 1 vehicle control + 3 groups positive control Diethylstilbestrol (DES)) were orally dosed for 7 days. All rats were subjected to vaginal lavage daily during the 7 day dosing period in order to detect vaginal cornification. All surviving rats were euthanized 24 hours after the final dose when final bodyweights and uterine weights were recorded.
DES, the positive control, resulted in a dose dependent induction of vaginal cornification. In contrast DEGDB did not induce vaginal cornification at doses of 500, 1000, 1500 and 2000 mg/kg/day x 7 days. Hence by this endpoint the test compound showed no estrogenic activity.
DES also induced a dose dependent increase in uterine weight and uterine weight to final body weight ratio. Conversely, DEGDB did not stimulate a uterine weight increase or an increase in the uterine weight to final body weight ratio at doses of 500, 1000, 1500 and 2000 mg/ kg/day x 7 days.
Collectively, these data demonstrate that DEGDB did not possess estrogenic activity up to and including the maximally tolerated dose.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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