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EC number: 204-661-8 | CAS number: 123-91-1
Toxicological information
Developmental toxicity / teratogenicity
Currently viewing:
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:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Teratogenesis study of dioxane in rats
- Author:
- Giavini, E. , Vismara C and Broccia ML
- Year:
- 1 985
- Bibliographic source:
- Toxicol. Letters 26, 85-88
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 1,4-dioxane
- EC Number:
- 204-661-8
- EC Name:
- 1,4-dioxane
- Cas Number:
- 123-91-1
- Molecular formula:
- C4H8O2
- IUPAC Name:
- 1,4-dioxane
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Calco Italy
- Weight at study initiation: 178-182 gram
- Housing: females caged overnight with males.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 60
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- daily administration by gavage at a constant volume (3 mL/kg)
- Details on mating procedure:
- Females were caged overnight with males. The day on which sperm was found in the vaginal smear was considered day 1 of gestation.
- Duration of treatment / exposure:
- gestation day 6-15
- Frequency of treatment:
- daily
- Duration of test:
- the animals were killed on day 21 of pregnancy
Doses / concentrationsopen allclose all
- Dose / conc.:
- 258 mg/kg bw/day (actual dose received)
- Remarks:
- corresponding to 0.25 mL/kg bw/d
- Dose / conc.:
- 517 mg/kg bw/day (actual dose received)
- Remarks:
- corresponding to 0.5 mL/kg bw/d
- Dose / conc.:
- 1 034 mg/kg bw/day (actual dose received)
- Remarks:
- corresponding to 1.0 mL/kg bw/d
- No. of animals per sex per dose:
- 0 mL/kg bw/day (control): 18 (17 pregnant)
0.25 mL/kg bw/day: 18 (17 pregnant)
0.5 mL/kg bw/day: 19 (19 pregnant)
1.0 mL/kg bw/day: 20 (20 pregnant) - Control animals:
- yes
Examinations
- Maternal examinations:
- Food consumption: daily
Weight determination: every three days - Ovaries and uterine content:
- corpora lutea, implantations, resorptions, live fetuses
- Fetal examinations:
- Examination of the viscera and skelatal obervations
- Statistics:
- The data were analysed using Student's f-test or analysis of variance, except for pre- and postimplantation loss and frequency of malformations, which were analysed using 2 x 2 contingency tables.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The females treated with 1 mL/kg bw/d showed a slightly smaller weight gain during treatment, which continued during the second stage of gestation.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption in the females treated with 1mL/kg bw/d was decreased during treatment, especially evident in the first 2 days of treatment.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Number of implantations was slightly decreased at 1 mL/kg bw and preimplantation loss was slightly increased at this dose level.
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- no effects observed
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 517 mg/kg bw/day
- Basis for effect level:
- body weight and weight gain
- food efficiency
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The average weight of live foetuses from dams treated with 1 mL/kg bw was significantly less than controls.
- Reduction in number of live offspring:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Number of foetuses alive was slightly decreased at 1 mL/kg bw/d.
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the dose level of 1mL/kg bw/d a delay of ossification was found in the area of the sternum. There was no indication for teratogenicity.
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 517 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: slightly decreased number of implantations and number of foetuses alive, slightly increased preimplantation loss, delay of ossification in the area of the sternum
- Remarks on result:
- other: effects seen only at dose levels inducing maternal toxicity, too
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Applicant's summary and conclusion
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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