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Developmental effects of plasticizer butyl benzyl phthalate after a single administration in rats
M Ema1, E Miyawaki, K Kawashima
1National Institute of Health Sciences, Osaka Branch, Japan. ema@nihs.go.jp
Insights
Butyl benzyl phthalate (BBP) causes developmental toxicity in rats, with specific days during organogenesis showing increased susceptibility. The timing of BBP exposure significantly influences the type of teratogenic effects observed in developing embryos.
Area of Science:
- Toxicology
- Developmental Biology
- Reproductive Science
Background:
- Butyl benzyl phthalate (BBP) is an environmental chemical.
- Phthalates are known endocrine disruptors with potential developmental toxicity.
- Understanding critical windows of susceptibility is crucial for risk assessment.
Purpose of the Study:
- To identify specific days during organogenesis when exposure to BBP induces developmental toxicity.
- To characterize the dose-dependent and day-specific teratogenic effects of BBP.
- To elucidate the varying responses of embryos to BBP based on developmental stage.
Main Methods:
- Pregnant rats were administered single doses of BBP via gastric intubation during specific days of organogenesis (days 6-16).
- Doses administered were 1000 mg/kg (days 13-15) and 1500 mg/kg (days 6-16).
- Embryolethality and teratogenicity, including specific malformations, were evaluated.
Main Results:
- Post-implantation embryolethality occurred following BBP exposure on days 6-16, with the exception of day 7.
- Teratogenic effects were observed after BBP administration on days 6, 7, 9, 10, 12, 14, and 15.
- Specific malformations included cervical vertebrae deformities (day 7), cleft palate, and sternebrae fusion (day 15).
Conclusions:
- The developmental toxicity of BBP is critically dependent on the timing of exposure during organogenesis.
- BBP induces distinct teratogenic responses during early and late stages of organogenesis.
- These findings highlight the importance of developmental stage in mediating BBP's teratogenic potential.
Abstract:
The objective of this study was to determine the susceptible day for the developmental toxicity of butyl benzyl phthalate (BBP) by a single administration on one of the days during organogenesis. Pregnant rats were given a single dose of BBP by gastric intubation at a dose of 1000 mg kg(-1) on one of days 13-15 of pregnancy and at 1500 mg kg(-1) on one of days 6-16 of pregnancy. Post-implantation embryolethality was found in pregnant rats given on one of days 6-16, except for day 7. Teratogenicity was noted after a single dosing of BBP on one of days 6, 7, 9, 10, 12, 14 and 15. Deformity of the cervical vertebrae frequently was observed after administration of BBP on day 7. Cleft palate and fusion of the sternebrae were found exclusively, after administration of BBP on day 15. It can be concluded that the manifestation of deviant development induced by BBP varies with the developmental stage at the time of administration and that BBP induces two discrete responses from embryos to teratogenicity during early and late organogenesis.