QSAR molecular parameters calculated for US EPA ToxCast Phase 1 and 2 chemical compounds tested against embryonic zebrafish

Abstract

Freshwater and marine environments are exposed to small concentrations of many different chemicals produced by industrial, agricultural, pharmaceutical, cosmetic, food, and household applications. Due to concerns regarding potential adverse events from these exposures, regulatory agencies around the world have established aquatic toxicology testing protocols that measure untoward responses in a wide variety of freshwater and marine organisms. Following a literature review of databases on the toxicity of chemicals to fish, the embryonic zebrafish (Danio rerio) database compiled by the Tanguay Laboratory at Oregon State University was determined to be well suited for quantitative structure-activity relationship (QSAR) analysis. This database possesses a number of favorable characteristics including large size (1060 unique US Environmental Protection Agency ToxCast phase 1 and 2 chemical compounds), relatively recent data collected using state-of-the-art methods, 18 simultaneously measured toxicological end points, transparent embryos that develop externally thereby facilitating toxicological evaluation, and the vast majority of the genetic code is expressed and active during early life stages. The molecular parameters calculated for each of the chemicals in the database include the logarithm of the octanol-water partition coefficient, molar volume, and molar refractivity. For each chemical, the availability of these molecular parameter values can facilitate future QSAR studies using any of the 18 different toxicological end points measured as the biological activity of interest.

Improving the ACGIH threshold limit value (TLV) process

“…In 1992, our research group published the first manuscript in what was to become a long-standing collaboration with the late, great Corwin Hansch 71 –78 and following his passing at age 92 in 2011 79 with members of his research group at Pomona College. 80 –82 Dr Hansch was known as the “father of computer-assisted molecule design” for his development of quantitative structure activity relationships. 79 This first manuscript eventually became titled, “Mutagenic activity of a series of synthetic and naturally occurring heterocyclic amines in Salmonella .” One of us (Smith) presented the first draft to Dr Hansch and he asked, “Where are the raw data?” in reference to the raw Ames assay Salmonella bacteria revertant mutation values at each dose level.…”

“…In 1992, our research group published the first manuscript in what was to become a long-standing collaboration with the late, great Corwin Hansch [71][72][73][74][75][76][77][78] and following his passing at age 92 in 2011 79 with members of his research group at Pomona College. [80][81][82] Dr Hansch was known as the "father of computer-assisted molecule design" for his (Fanelli and Ioannidis, 2013) 13 Field of study Estimated magnitude of bias b…”