Acute Toxicity to Rats and Trout with a Focus on Inhalation and Aquatic Exposures

Due to limitations in toxicity data, extrapolations are often performed within and between species. In this context, median lethal concentration (LC50) and dose (LD50) for 231 chemicals, along with physicochemical factors, were log-transformed and compared across several exposure routes in rats (i.e., oral, dermal, intraperitoneal, inhalation, intravenous, subcutaneous) and rainbow trout (i.e., aquatic, oral, dermal, intraperitoneal). Molecular weight (MW), octanol-water partition coefficient (Kow), vapor pressure (VP), and water solubility (S) were intercorrelated (Bonferroni P<0.05). MW (7 of 10 cases) and Kow (3 of 10 cases) were inversely correlated to toxicity endpoints, whereas VP (5 of 10 cases) was positively correlated (Bonferroni P< 0.05). Interspecies correlations were observed in toxicity endpoints over multiple exposure routes (10 of 24 cases), in addition to intraspecies correlations within rat (13 of 15 cases) and within trout (3 of 5 cases) (Bonferroni P<0.05). It was hypothesized that rat inhalation LC50 and trout LC50 would be associated, since air and water exposures correspond to each organismʹs respiratory medium. This hypothesis was supported by their correlation (r=0.68, Bonferroni P<0.05), characterized by a median molar ratio near 1, and further analyzed via regression methods. Comparison of acute toxicity endpoints can, therefore, assist in identifying appropriate extrapolations, likely based on similar toxicokinetics.