[用溶解度参数(δ)分析有机化学品对哺乳动物的急性毒性(ld50值)(3).对家兔的急性皮肤毒性]。

H Nishimura, S Saito, F Kishida, M Matsuo
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引用次数: 18

摘要

用化学物质的热力学参数溶解度参数(δ c)分析了有机化学物质对家兔的急性皮肤毒性(ld50值)。与之前对大鼠和小鼠的研究一样,所收集到的所有化学物质(n = 56, R = 0.498)、醇类(n = 19, R = 0.857)、酮类(n = 7, R = 0.711)、醛类(n = 7, R = 0.633)和芳烃类(n = 20, R = 0.613)的ld50值(mmol/kg体重,兔子)的对数与δ c之间也存在抛物线相关关系。在上述方程中引入摩尔体积(Vc)并没有改善相关性。在这项研究中,我们假设哺乳动物皮肤吸收的化学物质也会扰乱体内平衡,就像大鼠和小鼠口服有机化学物质的急性毒性一样。通过建立与所有收集到的化学物质、醇类和芳烃的统计显著相关性,我们成功地证实了理论方程,无论物种和给药途径如何。通过分析,我们确定了兔生物膜(吸收部位)的溶解度参数为2.24 × 10(4) (J/m3)1/2。由于家兔的皮肤δ c值与大鼠和小鼠的急性口服毒性大致相同,因此共同的有害作用和机制可能在共同的靶点起作用。而家兔的ld50值的回归曲线略高于大鼠和小鼠,这可能反映了人体吸收化学物质量的差异。(摘要删节250字)
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[Analysis of acute toxicity (LD50-value) of organic chemicals to mammals by solubility parameter (delta) (3). Acute dermal toxicity to rabbits].

Acute dermal toxicity (LD50-value) of organic chemicals to rabbits was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. As it was observed in the previous studies with rats and mice, parabolic correlations were also established between logarithm of LD50-value (mmol/kg body weight, rabbits) and delta c of all the collected chemicals (n = 56, R = 0.498), alcohols (n = 19, R = 0.857), ketones (n = 7, R = 0.711), aldehydes (n = 7, R = 0.633) and aromatics (n = 20, R = 0.613). Introduction of molar volume (Vc) to the above equations did not improve the correlations. In the study, we assumed that chemicals absorbed dermally by the mammals similarly disturb the homeostasis, as in acute oral toxicities of organic chemicals to rats and mice. We successfully confirmed the theoretical equation regardless of species and routes of administration by establishing statistically significant correlations with all the collected chemicals, alcohols and aromatics. By analysis, we could determine the solubility parameter of 2.24 x 10(4) (J/m3)1/2 for the biological membrane (absorption site) of rabbits. As the dermal delta c-values which dip the LD50-values for rabbits are approximately the same as in acute oral toxicities with rats and mice, common deleterious effects and mechanism may be working at the common target sites. The regression curves of LD50-values of rabbits, however, are slightly higher than those of rats and mice, which may reflect the difference in amounts of the chemicals absorbed by the body.(ABSTRACT TRUNCATED AT 250 WORDS)

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