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Phase specificity of developmental toxicity after oral administration of mono-n-butyl phthalate in rats
M Ema1, R Kurosaka, A Harazono
1National Institute of Health Sciences, Osaka Branch, 1-1-43, Hoenzaka, Chuo-ku, Osaka 540, Japan.
Abstract:
The objective of this study was to further characterize the developmental toxicity of mono-n-butyl phthalate (MBuP), which is one of the major metabolites of n-butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP). Pregnant rats were given MBuP by gastric intubation at a dose of 500, 625 or 750 mg/kg on days 7-9, days 10-12, or days 13-15 of pregnancy. A significantly increased incidence of postimplantation loss was noted in pregnant rats given MBuP on days 7-9 and days 10-12 at doses of 625 mg/kg and above and on days 13-15 at doses of 500 mg/kg and above. No evidence of teratogenicity was found when MBuP was given on days 10-12 of pregnancy. A significantly increased incidence of fetuses with external malformations was found after treatment with MBuP on days 7-9 and days 13-15 at doses of 625 and 750 mg/kg. A significantly increased incidence of fetuses with skeletal malformations was observed after treatment with MBuP on days 7-9 at doses of 500 mg/kg and above and on days 13-15 at doses of 625 mg/kg and above. Deformity of the cervical vertebrae was predominantly observed following treatment with MBuP on days 7-9. Cleft palate and fusion of the sternebrae were exclusively found following treatment with MBuP on days 13-15. It could be concluded that the manifestation of deviant development induced by MBuP varies with the developmental stage at the time of administration.
Insights
Mono-n-butyl phthalate (MBuP) causes developmental toxicity in rats, including malformations and postimplantation loss. The specific effects of MBuP depend on the timing of exposure during pregnancy.
Area of Science:
- Toxicology
- Developmental Biology
- Reproductive Science
Background:
- Mono-n-butyl phthalate (MBuP) is a major metabolite of common phthalates like n-butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP).
- Understanding the developmental toxicity of MBuP is crucial due to its prevalence as a metabolite.
Purpose of the Study:
- To characterize the developmental toxicity of mono-n-butyl phthalate (MBuP) in pregnant rats.
- To investigate the impact of MBuP exposure at different gestational stages on fetal development.
Main Methods:
- Pregnant rats were administered MBuP via gastric intubation at doses of 500, 625, or 750 mg/kg.
- Exposure occurred during specific critical periods: days 7-9, 10-12, or 13-15 of gestation.
- Fetal development was assessed for postimplantation loss, teratogenicity, external malformations, and skeletal malformations.
Main Results:
- Increased postimplantation loss was observed with MBuP doses of 625 mg/kg and above on days 7-9 and 10-12, and 500 mg/kg and above on days 13-15.
- External malformations (e.g., cervical vertebrae deformity) occurred after MBuP exposure on days 7-9 and 13-15.
- Skeletal malformations, including cleft palate and fused sternebrae, were noted following MBuP administration on days 13-15.
- No teratogenicity was detected when MBuP was administered on days 10-12.
Conclusions:
- The developmental toxicity of MBuP is dose-dependent and stage-specific.
- MBuP exposure can lead to significant postimplantation loss and malformations in rat fetuses.
- The timing of MBuP exposure during gestation critically influences the type and incidence of developmental abnormalities observed.
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