TitleThe relative toxicity of brodifacoum enantiomers.
Publication TypeJournal Article
Year of Publication2019
AuthorsFeinstein DL, Gierzal K, Iqbal A, Kalinin S, Ripper R, Lindeblad M, Zahkarov A, Lyubimov A, van Breemen R, Weinberg G, Rubinstein I
JournalToxicol Lett
Date Published2019 May 15
Keywords4-Hydroxycoumarins, Animals, Anticoagulants, Cell Line, Tumor, Half-Life, Humans, Lethal Dose 50, Male, Mitochondria, Neurons, Rabbits, Rats, Rats, Sprague-Dawley, Rodenticides, Stereoisomerism

Brodifacoum (BDF) is a potent, long-acting anticoagulant rodenticide that can cause fatal poisoning in humans. The chemical structure of BDF includes 2 chiral carbons, resulting in 2 pairs of diastereomers, BDF-cis (R/S and S/R) and BDF-trans (R/R and S/S). However, the relative potency of these molecules is not known. The purpose of this study was to compare the in vitro and in vivo toxic effects of the 2 BDF diastereomer pairs. In adult Sprague-Dawley rats BDF-cis was significantly more toxic than BDF-trans (LD values of 219 versus 316 μg/kg, respectively) while racemic BDF had intermediate potency (266 μg/kg). In adult New Zealand white rabbits, BDF-cis had a longer half-life than BDF-trans which could contribute to its observed increased toxicity. Lastly, BDF-cis (10 μM), but not BDF-trans, damaged cultured SH-SY5Y human neuroblastoma cells by attenuating mitochondrial reductive capacity. Taken together, these data suggest that different toxic manifestations of BDF poisoning in mammals could be attributed, in part, to differences in relative enantiomer concentrations present in racemic formulations of this commercially-available toxicant.

Alternate JournalToxicol. Lett.
PubMed ID30779948
PubMed Central IDPMC6408973
Grant ListU01 NS083457 / NS / NINDS NIH HHS / United States