The Hard-Soft Acid and Base hypothesis can be used to predict the potential bio-reactivity (electrophilicity) of a chemical with intracellular proteins, resulting in neurotoxicity. Twelve chemicals predicted to be neurotoxic were evaluated in vitro in rat dorsal root ganglia (DRG) for effects on cytotoxicity (%LDH), neuronal structure (total neurite length/neuron, NLPN), and neurophysiology (mean firing rate, MFR). DRGs were treated acutely on days in vitro (DIV) 7 (1–100 μM) with test chemical; %LDH and NLPN were measured after 48 h. 4-cyclohexylhexanone (4-C) increased %LDH release at 50 (29%) and 100 μM (56%), citronellal (Cit) and 1-bromopropane increased %LDH at 100 μM (22% and 26%). 4-C, Cit, 2,5 Hexanedione (2,5Hex), phenylacetylaldehyde (PAA) and 2-ethylhexanal decreased mean NLPN at 48 h; 50 and 100 μM for 4-C (28% and 60%), 100 μM Cit (52%), 100 μM 2,5- Hex (37%) 100 μM PAA (41%) and 100 μM for 2-ethylhexanal (23%). Separate DRG cultures were treated on DIV 14 and changes in MFR measured. Four compounds decreased MFR at 50 or 100 μM: Acrylamide (−83%), 3,4-dichloro-1-butene (−93%), 4-C (−89%) and hexane (−79%, 50 μM). Changes in MFR and NLPN occurred in absence of cytotoxicity. While the current study showed little cytotoxicity, it gave insight to initial changes in MFR. Results provide insight for future chronic exposure experiments to evaluate neurotoxicity.

硬软酸碱假设可用于预测化学物质与细胞内蛋白质的潜在生物反应性（亲电性），从而导致神经毒性。在大鼠背根神经节 (DRG)中体外评估了12 种预测具有神经毒性的化学物质对细胞毒性 (%LDH)、神经元结构（总神经突长度/神经元，NLPN）和神经生理学（平均放电率，MFR）的影响。在体外数天对DRGs 进行急性治疗(DIV) 7 (1–100 μM) 与测试化学品；48 小时后测量 %LDH 和 NLPN。4-环己基己酮 (4-C) 在 50 (29%) 和 100 μM (56%) 时增加了 %LDH 释放，香茅醛 (Cit) 和 1-溴丙烷在 100 μM 时增加了 %LDH（22% 和 26%）。4-C、Cit、2,5 己二酮 (2,5Hex)、苯乙酰醛 (PAA) 和 2-乙基己醛在 48 小时时降低了平均 NLPN；50 和 100 μM 用于 4-C（28% 和 60%）、100 μM C​​it (52%)、100 μM 2,5- Hex (37%) 100 μM PAA (41%) 和 100 μM 用于 2-乙基己醛（ 23%）。在 DIV 14 上处理单独的 DRG 培养物并测量 MFR 的变化。四种化合物在 50 或 100 μM 时降低了 MFR：丙烯酰胺 (-83%)、3,4-二氯-1-丁烯 (-93%)、4-C (-89%) 和己烷（-79%、50 μM） . MFR 和 NLPN 的变化发生在没有细胞毒性的情况下。虽然目前的研究显示出很少的细胞毒性，但它提供了 MFR 的初始变化的见解。