Teratogenic phase specificity of butyl benzyl phthalate in rats.

Pregnant rats were given butyl benzyl phthalate (BBP) by gastric intubation at a dose of 0.6, 0.75 or 1.0 g/kg on days 7-9, 10-12 or 13-15 of pregnancy. While treatment with BBP on days 7-9 or 13-15 at doses of 0.75 and 1.0 g/kg was significantly teratogenic, no evidence of teratogenicity was detected when BBP was given on days 10-12. The incidence of malformed fetuses was proportional to the dose of BBP. Treatment on days 7-9 with BBP at doses of 0.75 g/kg and above caused a significant increase in the number of skeletal malformations, such as fusion of the cervical vertebral arches and deformity of the thoracic vertebrae, but neither external nor internal malformations. Treatment on days 13-15 with two higher doses of BBP resulted in a significantly increased incidence of fetuses with external and skeletal malformations such as cleft palate and fusion of the sternebrae. The highest incidence of malformed fetuses occurred after treatment with BBP on days 13-15. It could be concluded that the susceptibility to the teratogenicity of BBP varies with the developmental stage at the time of administration.

[1]  M. Ema,et al.  Evaluation of the embryolethality of butyl benzyl phthalate by conventional and pair‐feeding studies in rats , 1991, Journal of applied toxicology : JAT.

[2]  J. Wilson Methods for administering agents and detecting malformations in experimental animals , 1965 .

[3]  S. Kawamura,et al.  Bone‐Staining Technique for Fetal Rat Specimens without Skinning and Removing Adipose Tissue , 1990 .

[4]  R. Rubin,et al.  Assessment of the mutagenicity of phthalate esters. , 1982, Environmental health perspectives.

[5]  R. Maronpot,et al.  Adverse effects of butyl benzyl phthalate on the reproductive and hematopoietic systems of male rats. , 1985, Toxicology.

[6]  L. Sheldon,et al.  Organic compounds in the Delaware River , 1978 .

[7]  K. Hemminki,et al.  Embryotoxic effects of phtalic acid derivatives, phosphates and aromatic oils used in the manufacturing of rubber on three day chicken embryos. , 1983, Drug and chemical toxicology.

[8]  E K Weisburger,et al.  Test for carcinogenicity of organic contaminants of United States drinking waters by pulmonary tumor response in strain A mice. , 1977, Cancer research.

[9]  M. Ema,et al.  Embryolethality and teratogenicity of butyl benzyl phthalate in rats , 1992, Journal of applied toxicology : JAT.

[10]  Ema Makoto,et al.  Teratogenic evaluation of butyl benzyl phthalate in rats by gastric intubation. , 1992 .

[11]  M. Kasuya Toxicity of butylbenzyl phthalate (BBP) and other phthalate esters to nervous tissue in culture. , 1980, Toxicology Letters.

[12]  M. Ema,et al.  Evaluation of the teratogenic potential of the plasticizer butyl benzyl phthalate in rats , 1990, Journal of applied toxicology : JAT.

[13]  B. Ekwall,et al.  Toxicity of 29 plasticizers to HeLa cells in the MIT-24 system. , 1982, Toxicology.

[14]  E. Zeiger,et al.  Mutagenicity testing of di(2-ethylhexyl)phthalate and related chemicals in Salmonella. , 1985, Environmental mutagenesis.

[15]  J. F. Douglas,et al.  Carcinogenicity testing of phthalate esters and related compounds by the National Toxicology Program and the National Cancer Institute. , 1982, Environmental health perspectives.

[16]  B. Hammond,et al.  A Review of the Subchronic Toxicity of Butyl Benzyl Phthalate , 1987, Toxicology and industrial health.

[17]  L. Sheldon,et al.  Sources and movement of organic chemicals in the Delaware River , 1979 .

[18]  W. Kluwe Carcinogenic potential of phthalic acid esters and related compounds: structure-activity relationships. , 1986, Environmental health perspectives.

[19]  W. E. Gledhill,et al.  An environmental safety assessment of butyl benzyl phthalate. , 1980, Environmental science & technology.

[20]  M. Ema,et al.  Effect of period of exposure on the developmental toxicity of butyl benzyl phthalate in rats , 1992, Journal of applied toxicology : JAT.

[21]  P. Minton,et al.  Terotogenic effects in the chick embryo caused by esters of phthalic acid. , 1970, The Journal of pharmacology and experimental therapeutics.