Browsing by Subject "RDX (chemical)"
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Item Acute and chronic toxicity of hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) in deer mice (Peromyscus maniculatus)(Texas Tech University, 2007-08) Smith, Jordan Ned; Cobb, George P.; Cox, Stephen B.; Smith, Ernest E.; Stormberg, Angelica I.; Theodorakis, Christopher W.Contamination of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been identified at areas of explosive manufacturing, processing, storage, and usage in a variety of environmental media. Conversion of RDX to anaerobic N-nitroso metabolites (hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX)) has been demonstrated in the environment and in vivo, in the gastrointestinal tract of mammals. Thus, potential exists for human and wildlife exposure to these N-nitroso compounds. Few papers report acute or chronic toxicity of these N-nitroso metabolites, thus my research is to assess acute and chronic toxicity of these compounds. Acute toxicity was assessed using acute oral median lethal dose (LD50). This was determined in deer mice (Peromyscus maniculatus) of three age classifications (21 d, 50 d, and 200 d) for RDX, MNX, and TNX using the U.S. EPA Up-and-Down Procedure (UDP). Hexahydro-1,3,5-trinitro-1,3,5-triazine and N-nitroso metabolites caused similar overt signs of toxicity. Median lethal dose for 21 d deer mice were 136, 181, and 338 mg/kg for RDX, MNX, and TNX respectively. Median lethal dose for 50 d deer mice were 319, 575, and 999 mg/kg for RDX, MNX, and TNX respectively. Median lethal dose for 200 d deer mice were 158, 542, and 338 mg/kg for RDX, MNX, and TNX respectively. These data suggest that RDX is the most potent compound tested, and age dependent toxicity may exist for all compounds. Chronic toxicity was evaluated with a reproductive study and a multigenerational study. Following exposure, reproductive toxicity of TNX was evaluated in three consecutive cohorts (F1A-C) of deer mice. TNX was administered ad libitum via drinking water at four exposure levels-control (0 µg/L), 1µg/L, 10 µg/L, and 100 µg/L. Endpoints investigated include: reproductive success, offspring survival, offspring weight gain, offspring organ weights, and liver TNX residues. Data from this study indicate that TNX bioaccumulates in the liver and is associated with postpartum mortality, dose dependent decrease in body weight from birth to weaning, and decrease in kidney weight in deer mice offspring. While exposed to TNX via drinking water ad libitum, deer mice were bred in a multigenerational fashion (parents produced offspring, which bred to produce more offspring) to produce three generations F1A-D, F2A-B, and F3A. TNX was administered at four exposure levels-control (0 µg/L), 10 µg/L, 100 µg/L, and 1 mg/L. Endpoints investigated include: reproductive success, offspring survival, offspring weight gain, and offspring organ weights. Data from this study indicate that TNX is associated with decreased litter size and increased postpartum mortality of offspring. Brain weights demonstrated a generational increase in dosed mice euthanized near the time of puberty. No teratogenic effects were linked with exposure to TNX. With tissue samples from both the reproductive and multigenerational studies, 12 microsatellite DNA loci were amplified and analyzed using both change in original parent allele frequencies and the parent/offspring approach of direct mutation rate calculation to assess genotoxicty of TNX in vivo. Findings demonstrate no dose dependent differences in deviation from parent microsatellite DNA allele frequencies or direct microsatellite mutation rate using the parent/offspring approach.Item Reproductive and developmental toxicity of highly energetic compounds in zebrafish (Danio rerio)(2006-08) Mukhi, Sandeep; Patino, Reynaldo; Anderson, Todd A.; Carr, James A.; Lee, Vaughan H.; Smith, Ernest E.There has been growing concern in recent years about a variety of toxicants, some of which are highly energetic in nature, that can affect human and ecosystem health. Highly energetic compounds such as perchlorate and hexahydro-1,3,5-trinitro-1,3,5-triazine (known as RDX) have been reported in various environments worldwide. The ecotoxicological impacts of these chemicals are relatively not fully understood. The overall objective of this study was to access the toxicological effects of these two chemicals on reproduction, development and other activities in a model aquatic organism, the zebrafish (Danio rerio). Perchlorate is a known thyroid-disrupting chemical. Exposure to environmental relevant concentrations of perchlorate caused several pathological alterations in thyroid follicles of zebrafish, which were used to establish novel and sensitive biomarkers of perchlorate exposure (Chapter 1). Namely, angiogenesis and ¡®colloidal T4 ring¡¯ intensity were far more sensitive indicators of thyroid disruption than previous available biomarkers. The developmental toxicity of perchlorate was studied in larval zebrafish (Chapter 2). Exposure to perchlorate at concentrations that inhibited thyroid function affected growth (length) and the sex ratio of exposed populations. Treatment with perchlorate skewed the sex ratio towards females, whereas co-treatment with thyroxine (T4) skewed the sex ratio towards males. This is the first report for teleost fishes indicating that thyroid hormone is involved in the process of gonadal sex determination and differentiation. An effect of perchlorate on the reproductive performance of zebrafish was also observed in a long-term exposure study (Chapter 3). After 16 weeks of exposure to perchlorate, a decline was observed in the level of T4, but not triiodothyronine, in whole-body homogenates of mothers and their embryos. Perchlorate also impaired fecundity (packed-egg volume), although egg diameters were increased and fertilization and hatching rates were unaffected. Analyses of the embryos also indicated impaired growth of jaw-forming cartilages (Meckel¡¯s and ceratohyal). Relatively little information is available concerning the lethal and sublethal effects of RDX in teleosts. The acute toxicity of RDX was determined for larval zebrafish (Chapter 4). The median lethal concentration of RDX was estimated (96-h LC50, 23-26 ppm), and effects on the surviving fish such as vertebral column deformities and behavioral abnormalities were also documented. The chronic toxicity and bioconcentration potential of RDX were subsequently determined in adult zebrafish (Chapter 5). Long-term exposure to RDX caused severe mortality at a concentration of 9.6 ppm. The bioconcentration factor for RDX was low but slightly increased with time of exposure, from ¡Ü1 at 4 and 8 weeks of exposure to >2 at 12 weeks. The RDX metabolite, MNX, was also found in whole-body extracts. Both RDX and MNX were undetectable in whole-body extracts 2 weeks after the fish were transferred to clean water. Lastly, the effects of RDX at sublethal concentrations on reproduction and egg quality were determined (Chapter 6). Exposure to RDX at the relatively low concentration of 0.5 ppm caused a short-lived increase in fecundity within 2 weeks of the onset of exposures; whereas no effects were noted at the higher concentration tested, 3.2 ppm. Egg fertilization rates and embryo hatching rates were unaffected by parental exposures to RDX. It is concluded that exposure to environmental perchlorate and RDX can potentially impact the health of teleosts, an important component of the aquatic biota.Item Uptake, distribution, and fate of RDX and MNX in dark green bulrush plants(2009-05) Sanka, Sameera; Jackson, Andrew W.Constructed wetlands are emerging as a promising technology for remediation of water contaminated with low RDX concentrations. A study on the ability of dark green bulrush (Scirpus atrovirens), a wetland plant, to uptake RDX will help to find its utility in constructed wetlands. In this study RDX uptake in actively growing bulrush was evaluated over a sixteen week period at different RDX exposure levels (0.5, 1, 3 mg/l). Plant samples along with influent water, effluent water, and final soil samples were analyzed for RDX, MNX, TNX and DNX. After 16 weeks of exposure and sacrificing 7 of the 9 sets of plants, exposure to RDX was discontinued. The remaining two sets of plants were sacrificed at weeks 19 and 22. RDX concentration in plants substantially decreased during the period of no exposure. About 97% of the RDX concentration in the top third and 75% in bottom and middle thirds of the leaf was lost during the six weeks of cessation to RDX exposure. RDX uptake in mature bulrush was also evaluated over a six week period at 1 mg/l exposure concentration. RDX was detected at higher concentrations in the top third of the leaf when compared to middle and bottom thirds in actively growing as well as in mature bulrush. MNX was detected in 99% of plant and soil samples. DNX and TNX were detected in few bottom thirds of the leaf and root portions of the bulrush in very low concentrations (0.003 to 0.03 mg/kg), but were very rarely detected in other samples. MNX uptake in mature bulrush was also evaluated over a five week period at 0.5 mg/l exposure concentration. Unaccounted MNX in the treatment systems of bulrush exposed to 0.5 mg/l MNX was around 59% compared to unaccounted RDX of 19, 23 and 38% respectively for 0.5, 1, 3 mg/l RDX exposure treatment systems. No bleaching or necrosis was observed during the course of the experiment in any of the plants. The results are suggesting that RDX exposure up to 3.0 mg/l does not have any adverse effects on bulrush. RDX accumulation in actively growing bulrush increased with time but in mature bulrush RDX accumulation remained more or less constant.