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Developmental effects of di-n-butyl phthalate after a single administration in rats
M Ema1, A Harazono, E Miyawaki
1National Institute of Health Sciences, Osaka Branch, Japan.
Insights
Di-n-butyl phthalate (DBP) exposure during pregnancy causes developmental toxicity in rats. The specific malformations observed depend on the day of exposure, indicating critical windows for DBP teratogenicity.
Area of Science:
- Toxicology
- Developmental Biology
- Reproductive Science
Background:
- Di-n-butyl phthalate (DBP) is a common environmental chemical.
- Phthalates are known endocrine disruptors with potential developmental toxicity.
- Understanding the timing of DBP's effects is crucial for risk assessment.
Purpose of the Study:
- To identify the susceptible developmental periods for di-n-butyl phthalate (DBP)-induced toxicity in pregnant rats.
- To characterize the specific teratogenic effects of DBP at different gestational stages.
Main Methods:
- Pregnant rats received a single oral dose of DBP (1500 mg/kg) on gestational days 6-16.
- Evaluated postimplantation loss, external, skeletal, and internal malformations in fetuses.
- Correlated DBP exposure timing with specific teratogenic outcomes.
Main Results:
- DBP exposure on days 6-16 increased postimplantation loss, except on days 7 and 11.
- Specific malformations varied by exposure day: skeletal (day 8), skeletal/internal (day 9), and external/skeletal (day 15).
- Cervical vertebrae deformity (day 8), renal pelvis dilatation (day 9), and cleft palate (day 15) were notable findings.
Conclusions:
- DBP-induced developmental toxicity is highly dependent on the timing of exposure during gestation.
- DBP exhibits distinct teratogenic effects on embryonic development during specific critical windows (days 8-9 and day 15).
- These findings highlight the importance of gestational timing in DBP risk assessment.
Abstract:
The objective of this study was to determine the susceptible day for the developmental toxicity of di-n-butyl phthalate (DBP). Pregnant rats were given a single dose of DBP by gastric intubation at 1500 mg kg(-1) on one of days 6-16 of pregnancy. A significant increase in the incidence of postimplantation loss was found in pregnant rats given DBP on one of days 6-16, except for days 7 and 11. Significant increases in the incidences of fetuses with skeletal malformations, of fetuses with skeletal and internal malformations and of fetuses with external and skeletal malformations were noted after a single dosing of DBP on day 8, on day 9 and on day 15, respectively. Deformity of the cervical vertebrae was frequently observed after administration of DBP on day 8. Deformity of the cervical and thoracic vertebrae and ribs and dilatation of the renal pelvis were predominantly found in fetuses of dams treated with DBP on day 9. Cleft palate and fusion of the sternebrae were exclusively detected after administration of DBP on day 15. It could be concluded that the manifestation of deviant development induced by DBP varies with the developmental stage at the time of administration and that DBP induces two discrete responses from embryos to teratogenicity on days 8 and 9 and on day 15 of pregnancy.