The relative toxicity of brodifacoum enantiomers

Abstract

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 50 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.

Persistent Coagulopathy After Synthetic Cannabinoid Use

“…It acts as a vitamin K antagonist inhibiting vitamin K 2,3-epoxide reductase, preventing activation of vitamin K1. Therefore, reducing the activation of clotting factors II, VII, IX, and X and proteins C and S. In contrast to warfarin, BDF has an exceptionally long-acting biological half-life of 90 days due to minimal metabolism and limited clearance [7]. Although no longer available for residential consumers, products containing BDF are still being used for commercial pest control and structural pest control markets [8].…”

Sugar, Spice, and Bleeding

“…It exists as cis-and trans-enantiomers of 4hydroxycoumarin. BDF-cis is significantly more toxic than BDF-trans, and racemic BDF has intermediate potency [2]. In the past, patients with BDF poisoning presented due to accidental exposure to rodenticides, psychosis leading to rodenticide ingestion, and deliberate rodenticide ingestion during suicide attempts [3][4][5].…”