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This chapter presents the wildlife toxicity assessment for nitroguanidine (NQ), a stable explosive compound used as a propellant in cartridges. This wildlife toxicity assessment addresses only toxicity to mammals, as data for amphibians, reptiles, and birds were lacking. Acute, chronic, and reproductive studies represented three mammalian species (rats, mice, and rabbits) in two orders, and showed limited toxicity of NQ to mammals. Water consumption was the most consistent effect. At high doses (1,000 mg/kg/day) other affects included death, reduced body weight gain, and reduced food consumption, which were attributed to decreased palatability and interference with digestion at 1,000 mg/kg/day. In developmental/reproduction studies, reduced fetal body weight and increased incidence of minor developmental alterations were noted. Thus, in mammals, the no and low observed adverse effect levels (NOAEL and LOAEL) for NQ were estimated to be 316 mg/kg/day and 1,000 mg/kg/day, respectively.

Biomedical, toxicological, and ecological databases were searched for reports and studies about the toxicology of the pesticide aldrin on wildlife (mammals, birds, reptiles, and amphibians). Citations were evaluated for biologically relevant endpoints such as reproduction, development, behavior, growth, and survival. Valid citations were used to develop toxicity reference values. Ingestion toxicity reference values were developed for mammals, birds, and amphibians. A paucity of available studies precluded the creation of ingestion toxicity reference values for reptiles. Inhalation and dermal contact toxicity reference values could not be developed for birds, reptiles, and amphibians due to a paucity of available studies.

This chapter presents the wildlife toxicity assessment (WTA) for chlordane, an organochlorine pesticide that was widely used in the U.S. from 1947 to 1978. Its use was curtailed following an increased concern about its cancer-causing effects, and it was entirely banned for use in 1988. It is highly persistent in the environment, causing a concern for wildlife toxicity. This WTA addresses chlordane’s toxicity to mammals, birds, and reptiles as there were no sufficient data on amphibian toxicity. The studies utilized indicate a moderate toxicity of chlordane, with effects on reproduction in mammals, birds, and reptiles. Based upon the available data in the mammalian studies, a chronic no observed adverse effect level (NOAEL) and low observed adverse effect level (LOAEL) were determined to be 2.1 and 21 milligrams per kilogram per day (mg/kg/day), respectively.

The treatment of chronic myelogenous leukemia (CML) with specific tyrosine kinase inhibitors typically results in clinical success, although therapeutic failure frequently occurs. In order to investigate the biological consequences of treating CML cells with such drugs, we previously reported that the antioxidant selenoprotein glutathione peroxidase-1 (GPx-1) was induced by imatinib in both patient samples and cultured cells. Here, we extend these findings to demonstrate that the treatment of CML cell lines, but not non-CML cells, results in an approximately four-fold increase in the levels of another important antioxidant protein, manganese superoxide dismutase (MnSOD), without altering the steady state levels of the corresponding transcript.

Glutathione peroxidase activity was previously determined to be elevated in lymphocytes obtained from patients treated with the Bcr-Abl kinase inhibitor imatinib mesylate. In order to expand upon this observation, the established chronic myelogenous leukemia cell lines KU812 and MEG-01 were treated with imatinib and the effect on several anti-oxidant proteins was determined. The levels of GPx-1 were significantly increased following treatment with imatinib. This increase was not due to altered steady-state mRNA levels, and appeared to be dependent on the expression of Bcr-Abl, as no increases were observed following imatinib treatment of cells that did not express the fusion protein. The nutrient-sensing signaling protein, mammalian target of rapamycin (mTOR), can be activated by Bcr-Abl and its activity regulates the translation of many different proteins. Treatment of those same cells used in the imatinib studies with rapamycin, an inhibitor of mTOR, resulted in elevated GPx-1 and GPx-4 protein levels independent of Bcr-Abl expression. These proteins all belong to the selenoprotein family of peptides that contain the UGA-encoded amino acid selenocysteine. Collectively, these data provide evidence of a novel means of regulating anti-oxidants of the selenoprotein family via the mTOR pathway.