Synergistic toxicity between arsenic and methylated selenium compounds

Arsenite has been known for half a century to have a protective effect against selenium poisoning. Paradoxically, arsenite inhibits the conversion of inorganic selenium salts to methylated excretory products, although methylation has long been regarded as a detoxification mechanism for selenium. Moreover, there is evidence for a pronounced synergistic toxicity between arsenite and methylated selenium metabolites. We investigated the effect of arsenite on the acute toxicity of a variety of methylated or nonmethylated selenium compounds, as well as methylated forms of sulfur and tellurium. Adult male rats were injected with sodium arsenite (4 mg As/kg bw, s.c.) 10 min prior to injection of the test compounds; at the doses employed, none of the test compounds caused mortality, nor did arsenite, when given alone. When given with arsenite, the following methylated compounds produced toxic signs and high morality at the indicated dosages (mg Se/kg): Methylseleninic acid (2), dimethylselenoxide (2), trimethylselenonium chloride (3), selenobetaine (2), selenobetaine methylester (2, also 1 and 0.5), and Se-methylselenocysteine (2). Toxic signs but not mortality occurred when arsenite was given with selenomethionine (2 mg Se/kg). No enhancement of toxic signs or mortality occurred when arsenite was given with sulfobetaine (0.8 mg S/kg), dimethylsulfide (320 mg S/kg), or the following (nonmethylated) forms of selenium: sodium selenite (2), selenocystine (2), and phenylselenol (2). Arsenite also increased the toxicity of trimethyltelluronium chloride (4.8 mg Te/kg). Like arsenite, periodate-oxidized adenosine (100 mumoles/kg), which is known to inhibit the formation of dimethylselenide and trimethylselenonium ion in vivo, caused increased 24 h mortality when given with various methylated selenium compounds.(ABSTRACT TRUNCATED AT 250 WORDS)