Journal of Applied Toxicology

Combinations of genotoxic tests provide a better and efficient prediction of human carcinogens. This study summarizes in vivo and in vitro comet assay (CMT) results of group 1 carcinogens selected from the International Agency for Research on Cancer and to discuss the utility of the CMT assay along with other genotoxic assays such as Ames, in vivo micronucleus, and in vivo chromosomal aberration test. In vivo CMT in combination with in vivo chromosomal aberration provided the highest sensitivity (96.7%).

We aimed to elucidate possible mechanisms of maleic acid toxicity by (1) determining the changes of metabolic profile, and (2) investigating the occurrence of oxidative stress. In rats that underwent a 28 day toxicity study via oral gavage, statistical significant body and organ weight changes were observed in the treatment groups, urinary concentrations of 8-hydroxy-2′-deoxyguanosine, 8-nitroguanine and 8-iso-prostaglandin F_2α and levels of several endogenous metabolites, with time- and dose-dependent variations. Findings elucidate the possible mechanisms by which nephro- and hepatotoxicity occur.

In vivo oral toxicity of yttrium oxide nanoparticles (NPs) and microparticles was performed in female rats. There was a clear size-, time- and dose-dependent genotoxicity as well as biodistribution. The majority of yttrium from NP- and microparticle-treated rats was excreted via urine and feces respectively, and the toxic effect of Y₂O₃ particles was probably induced by yttrium ions. Y₂O₃ NP-induced toxicity could be mediated through the modified antioxidant status of the cells.

Although nicotine replacement therapies are considered safer than smoking, recent rodent studies suggest that perinatal nicotine exposure results in cardiac dysfunction; however, the underlying mechanisms are not completely understood. Our study demonstrates that perinatal nicotine exposed male rats at 3 months have a significant decrease in cardiac protein disulfide isomerase, superoxide dismutase 2, tissue inhibitor of metalloproteinase 4 and mitochondrial complex protein expression. This suggests that nicotine may indirectly disrupt cardiac function by decreasing protein disulfide isomerase expression, leading to oxidative damage and mitochondrial damage.

The use of mammalian cell culture models combined with powerful molecular profiling techniques can uncover unknown biochemical bases of toxicity and provide an alternative to toxicity testing in animals. An untargeted metabolomics approach was used to characterize the metabolome of B50 rat neuronal cells, following exposure to two neurotoxic insecticides, permethrin and malathion. Cells were profiled by gas chromatography–mass spectrometry. A number of key intracellular metabolites were identified and important cellular events including energy metabolism were disrupted by chemical exposure.