[Analysis of acute toxicity (LD50-value) or organic chemicals to mammals by solubility parameter (delta) (2). Acute oral toxicity to mice].
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).
Nishimura
H
H
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
Saito
S
S
Kishida
F
F
Matsuo
M
M
D000085:Acetates / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000438:Alcohols / Q000008:administration & dosage / Q000633:toxicity*; D000447:Aldehydes / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D007659:Ketones / Q000008:administration & dosage / Q000633:toxicity*; D007928:Lethal Dose 50; D051379:Mice; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D012995:Solubility; D013329:Structure-Activity Relationship
D000085:Acetates; D000438:Alcohols; D000447:Aldehydes; D007659:Ketones; D011083:Polycyclic Compounds