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

Abstract

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 (IP 50), and for cell differentiation (ID 50), and the ratio of the former to the latter (P/D ratio) were obtained. The ID 50 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 (ID 50; 0.13–1.71 μM) and cell proliferation (IP 50; 0.12–2.81μM). 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.