Nishimura H, Saito S, Kishida F, Matsuo M
Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd.
Sangyo Igaku. 1994 Nov;36(6):428-34. doi: 10.1539/joh1959.36.6_428.
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)
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家兔的急性皮肤毒性(LD50值)。正如之前对大鼠和小鼠的研究所观察到的那样,在所有收集的化学品(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)中,LD50值(mmol/kg体重,家兔)的对数与δc之间也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。在该研究中,我们假设哺乳动物经皮肤吸收的化学物质对体内稳态的干扰与有机化学品对大鼠和小鼠的急性口服毒性类似。通过与所有收集的化学品、醇类和芳烃类建立具有统计学意义的相关性,我们成功证实了该理论方程,而与物种和给药途径无关。通过分析,我们可以确定家兔生物膜(吸收部位)的溶解度参数为2.24×10⁴(J/m³)¹/²。由于使家兔LD50值降低的皮肤δc值与大鼠和小鼠急性口服毒性中的大致相同,共同的有害作用和机制可能在共同的靶位点起作用。然而,家兔LD50值的回归曲线略高于大鼠和小鼠的,这可能反映了身体吸收的化学物质数量的差异。(摘要截于250字)