In vitro assessment of teratogenic potential of organotin compounds using rat embryo limb bud cell cultures. 1993

J Yonemoto, and H Shiraishi, and Y Soma
Regional and Community Environment Division, National Institute for Environmental Studies, Ibaraki, Japan.

Assessment of the relative teratogenic potential of bis(tri-n-butyltin)oxide (TBTO), tri-n-butyltin chloride (TBT), and its metabolites, i.e., (3-OH)hydroxybutyl dibutyltin chloride ((3-OH-Bu)DBT), di-n-butyltin dichloride (DBT), and butyltin trichloride (MBT) have been conducted using rat embryo limb bud cell cultures (LBC) to gain some knowledge of TBT embryotoxicity and DBT teratogenicity. Triphenyltin chloride (TPT), trimethyltin chloride (TMT), and triethyltin bromide (TET) have also been tested to obtain data for validation of LBC as a teratogen prescreening for organotin compounds. Fifty percent inhibition concentration for cell proliferation (IP50), and for cell differentiation (ID50), and the ratio of the former to the latter (P/D ratio) were obtained. The ID50 values in increasing order were as follows; TPT, DBT < TBT, TBTO < (3-OH-Bu)DBT < TET < TMT << MBT. With the exception of MBT, organotin compounds tested were very strong inhibitors of cell differentiation (ID50; 0.13-1.71 microM) and cell proliferation (IP50; 0.12-2.81 microM). P/D ratios for TBT, (3-OH-Bu)DBT, DBT and MBT were 1.0, 1.43, 1.32 and 1.08, respectively. These results suggest that the proximal toxin of DBT teratogenicity is DBT itself, and TBT is rather embryocidal than teratogenic so that TBT might mask the teratogenic and/or fetotoxic effects of its metabolites.

UI MeSH Term Description Entries
D009947 Organotin Compounds Organic compounds which contain tin in the molecule. Used widely in industry and agriculture. Compounds, Organotin
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005121 Extremities The farthest or outermost projections of the body, such as the HAND and FOOT. Limbs,Extremity,Limb
D005260 Female Females
D000014 Abnormalities, Drug-Induced Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment. Drug-Induced Abnormalities,Abnormalities, Drug Induced,Abnormality, Drug-Induced,Drug Induced Abnormalities,Drug-Induced Abnormality
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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