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EC number: 235-922-4 | CAS number: 13048-34-5
- 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
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- 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

Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
- Report date:
- 1983
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- ; only a single dose was tested.
- Principles of method if other than guideline:
- The aim of the study was to evaluate the embryo/fetal toxicity and teratogenic effects of the test substance when administered by gavage to pregnant rats from day 6 to day 15 of gestation. The test material was administered to a group of 22 female rats at a single dose level of 750 mg/kg bw. Another group served as a common control and received only corn oil.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Hexamethylene diacrylate
- EC Number:
- 235-921-9
- EC Name:
- Hexamethylene diacrylate
- Cas Number:
- 13048-33-4
- Molecular formula:
- C12H18O4
- IUPAC Name:
- hexane-1,6-diyl bisacrylate
- Details on test material:
- - Name of test material (as cited in study report): 1,6-Hexanediol diacrylate; coded as C-255
- Analytical purity: no data given
- Impurities (identity and concentrations): no data given
- Lot/batch No.: 3-81
- Physical state: light amber liquid
- Storage condition of test material: room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. Kingston, New York
- Age at study initiation: ca. 5 weeks
- Weight at study initiation:
- Fasting period before study:
- Housing: individual in elevated wire-mesh cages; during mating two females were housed with one male
- Diet: Purina Rodent Laboratory Chow, ad libitum
- Water: ad libitum
- Acclimation period: ca. 9 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24-25 °C
- Humidity (%): 57 +- 4.8 %
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The amount of compound required for each group was weighed, filled to volume with the vehicle and stirred on a magnetic stirrer. The prepared dilutions were transferred to amber bottles and labelled. Before use, the prepared dilutions were well shaken and the animals were dosed while the solutions were mixed on a magnetic stirrer. Fresh solutions were prepared weekly.
VEHICLE:
- Duke´s Corn Oil, a yellow liquid was received from the C.F. Sauer Co. Richmond, Virginia and used as vehicle.
- Lot/batch no.: 80235 - Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- Following a health status examination by a staff veterinarian, the males and females (1 male per 2 females) were placed in breeding cages for a maximum of 3 weeks. Females were rotated after the tenth day of mating. Mating was confirmed by the presence of a vaginal plug or by daily examination of vaginal smears for the presence of sperm. The day that mating was confirmed was designated as day 0 of gestation for each female placed on study.
- Duration of treatment / exposure:
- day 6 to day 15 of gestation
- Frequency of treatment:
- daily
- Duration of test:
- until day 20 of gestation
Doses / concentrations
- Dose / conc.:
- 750 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 22 mated females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on a range-finding study.
Test compound (HDDA) was evaluated for tolerance in pregnant rats to determine dose levels for a subsequent teratology screening study. Test substance was administered by gavage at 100, 500 and 1000 mg/kg/day (6 inseminated females per dose) from Days 6-15 of gestation. At the dose of 1000 mg/kg/day, clinical signs, decrease of bodyweight were observed. As the dose of 100 and 500 mg/kg/day were well tolerated by females, the dose of 750 mg/kg/d was selected to evaluate the embryo/fetal toxicity and teratogenic effects of HDDA.
Examinations
- Maternal examinations:
- DETAILED CLINICAL OBSERVATIONS: mortality, moribundity and clinical signs
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: on day 0, 6, 9, 12, 15 and 20 of gestation
WATER CONSUMPTION AND COMPOUND INTAKE:
- Time schedule for examinations: on day 6-8, 9-11, 12-14, 15-17 and 18-20 of gestation
POST-MORTEM EXAMINATIONS:
- Sacrifice on gestation day 20:
On day 20 of gestation, females were sacrificed by carbon dioxide asphyxiation and the fetuses were taken by cesarean section. Following gross examination of each dam, the number of corpora lutea per ovary and the number and placement of implantation sites, early and late resorptions, and live and dead fetuses in each uterine horn were recorded. Fetuses were removed from the placenta, individually identified, examined externally, weighed, sexed, and measured from the frontal-parietal suture to the base of the tail (crown-rump distance). Gravid and nongravid uterine weights (with ovaries attached) were recorded.
- Organ Weights:
Following careful dissection and trimming to remove fat and other contiguous tissue in a uniform manner, the gravid and nongravid uterine weights (with ovaries attached) of each female were taken for organ weighing.
- Tissue Preservation:
The uterus and ovaries of each dam, in addition to unusual lesions, were preserved in 10 % neutral buffered formalin. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - Visceral Examination of Fetuses:
Approximately one-third of the fetuses from each litter were fixed in Bouin's solution, sectioned, and examined by Wilson's freehand razor technique (Wilson and Warkany, 1965), and sealed in plastic. The prepared sections were re-examined against a light box with the aid of magnification.
- Skeletal Examination of Fetuses:
After undergoing external examinations, approximately two-thirds of all fetuses from each litter were opened by longitudinal incision and the viscera examined grossly. The fetuses were then placed in M5 ethyl alcohol and the skeletons were stained in a potassium hydroxide - Alizarin red S solution (modified Staples and Schnell, 1964). Each skeleton was examined with the aid of magnification on a light box for bone alignment, degree of ossification, and anomalies. The number of sternebrae, ribs, caudal vertebrae, and bones of the extremities were noted and recorded. The fetuses examined by Wilson's technique were preserved In Bouin's solution and sealed in plastic after sectioning. The fetuses stained for skeletal examination were preserved in plastic in a glycerin ethanol (1:1) solution with several crystals of thymol to retard bacterial growth. - Statistics:
- Survival was statistically analyzed by the National Cancer Institute Package (Thomas, Breslow, & Gart, 1977).
The mean maternal body weight changes (Days 0-6, 6-15, 15-20, and 0-20), mean maternal food and water consumptions (Days 6-9, 9-12, 12-15, 15-18, 18-20, and 6-20), percent males per litter, mean fetal body weights and lengths, fetal viability, percent resorptions, implantation efficiency, gravid and nongravid uterine weights, and the incidence of visceral and skeletal anomalies and variants were analyzed by Box's test for homogeneity of variances (Box, 1949). This test was followed by a one-way classification analysis of variance (ANOVA), if the variances proved to be homogenous. If the variances proved to be heterogenous, a rank transformation of data was performed, which was followed by Box´s test and ANOVA. If ANOVA of untransformed or transformed data was significant, Dunnet´s T-test was used for control vs. treatment group mean comparisons.
Pregnancy rates were analyzed by a test of multiple proportions using one degree of freedom Chi-square test with Yates´continuity correction. All pairwise comparisons were evaluated at the 5.0 % probability (one-tailed) level. - Indices:
- no
- Historical control data:
- no
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- An increased incidence of clinical symptoms was noted (wheezing, dyspnea, urine stains, wasted feed, rough haircoat, hunched pasture, bloody crust on the eyes, nase, snouth, and frontpaws, salivation and alopecia).
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality occured during treatment.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Mean body weight changes lower than the control, but not statistically significant were observed in the treated group during the treatment phase.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- In the treated group a statistically significant increase in water consumption was noted on days 18 and 20 and in total water consumption, compared to control.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The most distinct alterations attributed to treatment were noted in the stomachs of the treated animals. The findings consisted of discoloured material or fluid in the stomach; gas distending the stomach; discoloured, ulcerated or raised areas in the glandular or nonglandular portion of the stomach. glandular mucosa smooth; walls thick or thin/smooth; and nonglandular mucosa thin and pale, or thick and rough. Other gross pathology findings were considered to be incidental in nature and showed no relation to treatment.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- Results were comparable between treated and controls animals.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- Results were comparable between treated and controls animals.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- Results were comparable between treated and controls animals.
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- Results were comparable between treated and controls animals.
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- Results were comparable between treated and controls animals.
- Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- Results were comparable between treated and controls animals.
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.DescriptionIncidenceAndSeverityEffectsOnPregnancyDuration): Results were comparable between treated and controls animals. - Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- Results were comparable between treated and controls animals.
- Other effects:
- no effects observed
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- LOAEL
- Remarks:
- (maternal systemic toxicity)
- Effect level:
- 750 mg/kg bw/day (nominal)
- Basis for effect level:
- other: maternal toxicity
Maternal abnormalities
- Abnormalities:
- effects observed, treatment-related
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Skeletal examinations included incidences of cleft palate in 1 pup. A high incidence of dilated ureters was noted in both treated and control groups.
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- A higher than control mean incidence of visceral variants was noted (but not statistically significant). Statistically significant increased mean incidence of skeletal variants was observed. The majority of the findings were due to delayed ossification of the various bone structures examined. The authors suggested that this response was resulting from the maternal toxicity noted.
- Visceral malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- A higher than control mean incidence of visceral variants was noted (but not statistically significant).
- Other effects:
- not examined
Effect levels (fetuses)
- Key result
- Dose descriptor:
- LOAEL
- Remarks:
- (developmental toxicity)
- Effect level:
- 750 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- effects observed, treatment-related
Overall developmental toxicity
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Maternal toxicity and foetoxicity on rats were observed in this developmental study at the dose of 750 mg/kg/d. The embryotoxic effects resulted probably from maternal toxicity.
- Executive summary:
Test compound (HDDA) was evaluated for tolerance in pregnant rats to determine dose levels for a subsequent teratology screening study. Test substance was administered by gavage at 100, 500 and 1000 mg/kg/day (6 inseminated females per dose) from Days 6-15 of gestation. At the dose of 1000 mg/kg/day, clinical signs, decrease of bodyweight were observed. As the dose of 100 and 500 mg/kg/day were well tolerated by females, the dose of 750 mg/kg/d was selected to evaluate the embryo/fetal toxicity and teratogenic effects of HDDA.
In the main study, the test substance was administered by gavage from Days 6-15 of gestation to 22 females at the dose of 750 mg/kg/d.
Compound-related maternal toxicity was observed: increased incidence of clinical signs, slight decrease of body weight gains and an increased incidence of gross pathology findings (stomach).
Pregnancy rates, corpora lutea and implantations, and mean implantation efficiency (number of implantations per number of corpora lutea) were generally comparable for treated animals and controls.
A higher than control number of fetuses exhibiting skeletal variants was observed in the HDDA group. The incidence was found to be significant both skeletal and lagging ossification. Taken together, maternal toxic effects as well as embryotoxic effects were observed. According to the authors, the embryotoxic effects resulted from maternal toxicity.
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