Nishimura H, Saito S, Kishida F, Matsuo M
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
Sangyo Igaku. 1994 Nov;36(6):421-7. doi: 10.1539/joh1959.36.6_421.
Acute oral toxicity (LD50-value) of organic chemicals to mice was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. As it was observed in the previous study with rats, parabolic correlations were established between logarithm of LD50-value (mmol/kg body weight, mice) and delta c of all the collected chemicals (n = 85, R = 0.626), alcohols (n = 10, R = 0.683), ketones (n = 7, R = 0.631) and aromatics (n = 62, R = 0.645). Introducing molar volume (Vc) to the above equations did not improve the correlations. Although statistically significant correlations were not found in alcohols and ketones with mice, we successfully assured the theoretical equation regardless of species difference by establishing significant correlations with all the collected chemicals and aromatics. By analysis, we could determine the solubility parameter of 2.27 x 10(4) (J/m3)1/2 for the biological membrane (absorption site) of mice. As the delta c-values which dip the LD50-values are approximately the same for mice and rats, common deleterious effects and mechanism may be working at common target sites. In addition, no species difference in sensitivity (toxicity) was found for the aromatics. For comparison, log P was used to describe LD50 of all the collected chemicals, but no correlation was established (R = 0.004-0.418).
利用有机化学品的热力学参数溶解度参数(δc)分析了有机化学品对小鼠的急性经口毒性(半数致死量值)。正如之前对大鼠的研究所观察到的,在所有收集的化学品(n = 85,R = 0.626)、醇类(n = 10,R = 0.683)、酮类(n = 7,R = 0.631)和芳烃(n = 62,R = 0.645)的半数致死量值(mmol/kg体重,小鼠)的对数与δc之间建立了抛物线相关性。将摩尔体积(Vc)引入上述方程并没有改善相关性。尽管在醇类和酮类与小鼠的实验中未发现具有统计学意义的相关性,但通过与所有收集的化学品和芳烃建立显著相关性,我们成功确定了与物种差异无关的理论方程。通过分析,我们可以确定小鼠生物膜(吸收部位)的溶解度参数为2.27 x 10(4) (J/m3)1/2。由于使半数致死量值降低的δc值在小鼠和大鼠中大致相同,常见的有害作用和机制可能在共同的靶位点起作用。此外,未发现芳烃在敏感性(毒性)方面存在物种差异。为作比较,用log P来描述所有收集化学品的半数致死量,但未建立相关性(R = 0.004 - 0.418)。