溶解パラメータ(δ)による化学物質の哺乳動物に対する急性毒性(LD_<50>)の解析 : (3)ウサギの急性経皮毒性

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Acute dermal toxicity (LD_<50>-value) of organic chemicals to rabbits was analyzed by using solubility parameter (δc), 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 LD_<50>-value (mmol/kg body weight, rabbits) and δc 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 2.24×10^4(J/m^3)^<1/2> for the biological membrane (absorption site) of rabbits. As the dermal δc-values which dip the LD_<50>-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 LD_<50>-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. For comparison, log P was used to describe LD_<50> of all the collected chemicals, and significant correlations were observed in parabolic and bilinear equation (n=56, R=0.522, 0.584), but no relationships were established for aromatics.
社団法人日本産業衛生学会の論文
1994-11-20

溶解パラメータ(δ)による化学物質の哺乳動物に対する急性毒性(LD_<50>)の解析 : (3)ウサギの急性経皮毒性

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