[Analysis of acute toxicity (LD50-value) of organic chemicals to mammals by solubility parameter (delta). (1) Acute oral toxicity to rats].
Acute oral toxicity (LD50-value) of organic chemicals to rats was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. Certain parabolic correlations were established between logarithm of LD50-value (mmol/kg body weight, rats) and delta c of all the collected chemicals (n = 144, R = 0.578), alcohols (n = 29, R = 0.587), ketones (n = 7, R = 0.962), aldehydes (n = 9, R = 0.621), ethers (n = 5, R = 0.890), acetates (n = 7, R = 0.670) and aromatics (n = 84, R = 0.736). Introducing molar volume (Vc) to the above equations could not improve the correlation. In the study, we assumed that as for acute toxicity, chemicals taken into the mammals through biological membrane first disturb the homeostasis, which causes certain biological reactions (i.e. death) and that amounts of the chemicals intaken are regulated by their solubility in the membrane. Based on the assumption, we drew a theoretical equation, which describes LD50 by a parabolic function of delta c. A regression analysis using the equation gave significant correlations as stated above, which incarnates the assumption. A solubility parameter of 2.30 x 10(4) (J/m3)1/2 was also determined for the biological membrane (absorption site) of rats. For comparison, log P was used to describe LD50 of all the chemicals, but no correlation was established (R = 0.164-0.443).
Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd.
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Nishimura
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Saito
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Kishida
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Matsuo
D000085:Acetates / Q000633:toxicity; D000284:Administration, Oral; D000438:Alcohols / Q000633:toxicity; D000447:Aldehydes / Q000633:toxicity; D000818:Animals; D004987:Ethers / Q000633:toxicity; D007659:Ketones / Q000633:toxicity; D007928:Lethal Dose 50; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D014116:Toxicology
D000085:Acetates; D000438:Alcohols; D000447:Aldehydes; D004987:Ethers; D007659:Ketones