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New 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives, (4-[4-((4-bromobenzyl)oxy)-phenyl]-1,2,3-thiadiazole (<b>5a</b>), 4-[4-((4-chlorobenzyl)oxy)-phenyl]-1,2,3-thiadiazole (<b>5b</b>)), (4-[4-((4-bromobenzyl)oxy)-phenyl]-1,2,3-selenadiazole (<b>6a</b>), and 4-[4-((4-chlorobenzyl)oxy)-phenyl]-1,2,3-selenadiazole (6b)), were prepared and screened in vitro for their antimicrobial activity against various pathogenic microbes. In addition, two compounds (<b>5a</b> and <b>6a</b>) were examined for their in vivo genotoxicity using rats and an 8-hydroxy-2&#8242;-deoxyguanosine (8-OHdG) assay. Compounds <b>5a</b> and <b>5b</b> were found to be highly active against Gram-positive and Gram-negative bacteria. In addition, a significant inhibition of urinary 8-OHdG level (50.2%) was observed upon treatment of animals with 500 mg/kg body weight (b.w.) of compound <b>6a</b> (<i>p</i> &lt; 0.0001). However, compound <b>5a</b> increased urinary 8-OHdG levels. The lethal dose (LD₅₀) values for compounds <b>5a</b> and <b>6a</b> were determined by an up-and-down procedure (OECD 425; OECD 1998), which showed that these compounds are safe, since the LD₅₀ was &gt;5000 mg/kg b.w. Thus, the tested compounds might have the potential for use as antibiotics, since they have low genotoxicity and strong antimicrobial activity.