C ratio TR (Eq. 7), the specificity ratios SRcytotoxicity for neurite-specific effects (Eq. 8), and SRbaseline for neuronal-specific effects (Eq. 9). B Cytotoxicity as a function with the hydrophobicity expressed as liposome ater partition constants (Klip/w). The turquoise circles are the experimental inhibitory concentration for cytotoxicity (IC10; Table two) with recognized baseline toxicants encircled in black. (C) Neurite outgrowth inhibition asa function of Klip/w. Magenta triangles indicate concentration major to ten reduction in neurite length (EC10; Table two) which have been experimentally determined in differentiated SH-SY5Y cells with recognized baseline toxicants encircled in black. Thick gray lines in each plots B and C correspond to predicted baseline toxicity causing ten cytotoxicity (IC10,baseline; Eq. S1) as a function of Klip/w. The gray places indicate when TR or SRbaseline is in between 0.1 andTable two Toxicity values for quantification of enhanced cytotoxicity (TR), neuronal-specific effects (SRbaseline), and neurite-specific effects (SRcytotoxicity) Baseline toxicity logKowa – 1.2 0.six L LL LL four.2.ten L 7.7 five.0.100 1.1.104 eight.7.104 1 L L 42 1370 1 1 1.3 2.four three.7.10 three.three.10 – 1 0.7 1 1.0.ten 1.7.ten 7.7.ten three.9.ten five.six.10 3.six.100 7.7.ten six.0.106 136 two.five.108 1.9.105 logKlip/wa IC10,baseline IC10 (M) (M)bGroup SE or CIcChemical name Mod- EC10 eld (M) SE or CIcCytotoxicity ModeldNeurite outgrowth inhibition TRSRbaseline SRcytotoxicity GroupReclassificatione marksfEndpointspecific controlsNarciclasine CycloheximidePl PlArchives of Toxicology (2022) 96:1039ColchicineBaseline toxicantsRotenone 2-Butoxyethanol 3-Nitroaniline 2-Allylphenol 4-Chloro-3-methylphenol 2-Phenylphenol L L L L L LL LL L L L L LL three.8.10 two.7.10 1.2.ten 6.2.10 1.1.10 L LL LL LL L L L 1.six.ten 4.two.10 5.5.10 2.0.10 1.2.10 6.0.10 four.9.10 two.7.ten 1.1.10 3.3.10 eight.eight.ten six.six.ten 2.6.ten 1.1.ten 3.eight.ten L L L L L L L L L L B B B B B B 7.0.ten L 0.2 84 three.eight 5.1 2.two two.2 35 21 28 1.eight 0.IL-17A Protein Gene ID 6 6.IL-27 Protein Synonyms 2 5.9 0.6 0.three 0.4 0.two 0.4 2283 71 24 11 9.1 271 47 49 4.two 1.9 7.5 five.9 0.5 0.two 0.2 0.two L L L L L LL 81 1.five 0.7 0.2 0.three 0.2 948 two.six two.1 0.3 1.two 0.3 4.two 0.eight 2.four two.1 two three.three 0.six two.five 0.9 1.eight two.5 1.four.10 three.5.10 6.5.10 1.1.10 three.0.10 1.6.10 9.1.ten 1.three.10 four.9.10 1.four.ten four.three two.9.ten 1.7.104.1 0.eight 1.4 two.six three.1 3.4.two 0.six two.two 3.1 3.three three.3.two.ten 1.3.10 five.five.ten 1.4.10 9.four.ten 8.0.104.0.ten eight.7.ten eight.1.ten 7.3.10 three.4.ten 3.eight.103.4.ten 4.9.ten 2.6.ten 4.five.10 8.0.ten 3.two.104-Pentylphenol4.3.10 1.1.10 3.5.ten 4.5.10 1.0.ten [2.eight.10, three.5.10] 6.9.1011.7 1.eight three.1 1.6 4.three 1.two two.four 27 19 four.7 4.7 4.two 7.7 two.three 1.7 two.4 three.1 1.two 1.0 0.eight 0.7 0.six 0.1 3 three three 2 3 3 1 1 1 1 two three 3 three 3 3 3AChE inhibitors3-Hydroxycarbofuran Carbaryl Diazoxon Paraoxon-ethyl Chlorpyrifos-oxonnAChR agonists1.6.10 [6.PMID:22664133 two.10, 9.five.10] [2.two.10, four.7.10] 4.1.ten 5.9.ten 4.five.10 3.6.10 1.0.ten [3.4.ten, 4.1.10] [1.six.10, 1.eight.10] 1.2.10 six.five.10 1.5.ten three.9.ten [1.3.10, 1.four.10]GABA blockers three.two three.8 4.6 two.2.10 three.3 9.four.10Thiamethoxam Imidacloprid Thiacloprid Acetamiprid Clothianidin Fipronil- 0.1 0.six 1.three 1.2 0.7 four.- 0.three 0.7 1.2 1.three two.9 two.1.1.ten 1.0.ten three.four.ten two.6.10 1.eight.10 three.2.103.9.10 2.1.10 7.0.ten 6.2.10 9.3.10 four.3.10Pr Pr Pr Pr PrFipronil sulfone-Endosulfan five.4 6.eight six.9 five.1 six.5 7.1 1.four.10 4.3.10 two.eight.10Sodium channel agonistsDieldrin Bifenthrin four,4′-DDTI (3.1.10) I (four.8.ten) I (1.two.10) 1.five.10 eight.1.ten I (two.eight.10) 5.two.10 [5.1.10, 5.three.10] . 1.six 10 [1.five.10, 1.7.10] 3.5.10 [3.2.ten, 3.8.10] . four.1 ten three.0.10 . 1.1 10 six.five.ten . 1.1 10 9.1.10Table two (continued) Baseline toxicity logKowa 2.five L . . Group logKlip/wa 2.0 L L.

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