Using membrane–water partition coefficients in a critical membrane burden approach to aid the identification of neutral and ionizable chemicals that induce acute toxicity below narcosis levels

Abstract

The risk assessment of thousands of chemicals used in our society benefits from adequate grouping of chemicals based on the mode and mechanism of toxic action (MoA).

Partitioning into phosphatidylcholine–cholesterol membranes: liposome measurements, coarse-grained simulations, and implications for bioaccumulation

“…The membrane–water coefficients overcome many of the challenges associated with octanol–water partitioning, are more biologically relevant, and have been demonstrated to be an accurate alternative for estimating bioaccumulation and baseline toxicity. 12–15…”

“…The membrane-water coefficients overcome many of the challenges associated with octanol-water partitioning, are more biologically relevant, and have been demonstrated to be an accurate alternative for estimating bioaccumulation and baseline toxicity. [12][13][14][15] The most common experimental methods for determining K MW and D MW include (1) liposomes, [16][17][18] (2) solid-supported lipid membranes (SSLM) 19 and (3) retention on a chromatographic column coated with immobilized articial membrane phospholipids (IAM-HPLC). [20][21][22] Each has its strengths and weaknesses.…”

“…26 This method is efficient, and has been used to estimate lipophilicity in several ecotoxological studies. 15,27 However, the environment in an HPLC column does not perfectly represent the structure of a real lipid membrane. In particular, the interactions of charged species with the silica surface can affect the results, and conversion of retention factors to partition or distribution coefficients requires empirical correction factors.…”