Journal of Applied Toxicology

Dioxins are ubiquitous environmental challenges to humans, with a pervasiveness that arises from 200 years of rapid industrialization. Despite their penetrance of the human biota, these compounds are poorly understood in terms of their true physiological potential for harm, and the mechanisms by which they impact cellular and organ level function are only recently becoming clear. Here, we summarize dioxin exposure paradigms and the resulting physiological effects that have been documented in animals and humans.

A review of the Chinese literature was conducted to summarize the occurrence of poisonous plant species on temperate grasslands in China. We focus on locoweeds (Astragalus and Oxytropis spp.), drunken horse grass (Achnatherum inebrians [Hance] Keng ex Tzvelev), and langdu (Stellera chamaejasme L.) for information on their toxins, distribution and ecology, control methods and alternate uses. Of the almost 1300 poisonous species found on grasslands in China, these species are responsible for an estimated 80% of all livestock losses.

K027 is a promising new acetylcholinesterase reactivator with low acute toxicity and broad spectrum efficacy. The main aim was to compare the pharmacokinetics of K027 and trimedoxime (single i.m. application, equimolar doses). Near identical plasma profiles were obtained for both compounds. No differences were found in the C_max mean ± SD values and AUC_0-180min. However, the percent coefficient of variation of the first-order rate constant of absorption (k_a) was 3-fold higher (p<0.01) providing evidence for more erratic absorption of trimedoxime.

Olanzapine is an atypical antipsychotic drug that has been increasingly used in acute treatment and therapeutic support for schizophrenia. Olanzapine treatment induced a reduction in plasma testosterone levels, and testicular, epididymal and prostatic weights. Histopathologic and histomorphometric analysis of spermatogenesis indicated testicular degeneration. Olanzapine treatment in rats promoted endocrinological changes and lesions in the testis, leading to a disturbance in spermatogenesis.

We examined the effects of SP600125 on zebrafish development. It was observed that SP600125 at concentrations equivalent to or lower than its effective dosage as a JNK inhibitor caused severe developmental defects during zebrafish organogenesis. The first noticeable deformities were swim bladder deflation and pericardium edema. Phenotypes of major developmental abnormalities resembled those caused by TCDD, a persistent and dangerous environmental toxin. Our study indicates that SP600125 is unsuitable for zebrafish developmental studies as a JNK inhibitor.

Environmental estrogens can influence the reproductive system and have been shown to disrupt gametogenesis in males. We cloned all three carp Cyprinus carpio, estrogen receptors [ER; ERa, ERb1 and ERb2] and applied a transient transfection ERE-luciferase reporter assay system using mammalian cells. cERb2 showed a higher sensitivity to the natural steroid oestrogen, 17b-estradiol, than cERa. This is a powerful assay for toxicology, and provides a tool for future studies examining the receptor-environmental chemical interactions and estrogen disrupting mechanisms in carp.

Cytochrome c oxidase activity in brains excised from mice treated with cyanide and various prophylactic treatments suggests that a recently proposed sulfur donor, thiotaurine, is not as effective as thiosulfate. Further, thiotaurine appeared to inhibit cytochrome c oxidase activity slightly, independent of cyanide treatment. The EC₇₅ for cytochrome c inhibition by cyanide in the different treatment regimens correlated very well with the LD₅₀ determined from mortality data, supporting cytochrome c oxidase inhibition as a major mechanism for cyanide toxicity.

The present study evaluated the cytogenotoxic potential of antimalarial drug atovaquone towards human lymphocytes. Two different clinically relevant concentrations of atovaquone obtained from the plasma concentrations used for prophylactic treatment and the treatment of malaria were used with and without S9 metabolic activation. Atovaquone was not cytogenotoxic in the given concentrations, regardless of metabolic activation. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity.

Heterocyclic amines (HCAs) are naturally produced during cooking processes for meats and fish. Among HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as ‘reasonably anticipated to be a human carcinogen’. The present study investigated the correlation between human exposure levels of PhIP and the role of genetic polymorphisms of enzymes on PhIP metabolism. The SNPs of CYP1A1/T6235C (MSP I) and CYP1A2/-2467delT showed significant differences in PhIP excretion (P< 0.05). These results could improve understanding of populations subject to PhIP-derived health risk.

Phosgene can induce fatal pulmonary edema. Oxidative stress and inflammatory responses are believed to be involved in this process. In the present study, we aim to investigate the therapeutic effects of ethyl pyruvate (EP) on phosgene-induced pulmonary edema and the underlying mechanisms. We found that EP had a protective role against phosgene-induced pulmonary edema, which was mediated in part by inhibiting MAPK activation and subsequently down-regulating COX-2 and iNOS expression as well as decreasing the production of NO and PGE₂.