The effect of warfarin on plasma clotting time in wild house mice (Mus musculus L.).
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Animals↗
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Field trials of calciferol combined with warfarin against wild house-mice (Mus musclus L.).
A combination of calciferol (vitamin D(2)) and warfarin, each at 0.025% in medium oatmeal bait, failed to control six of seven house-mouse (Mus musculus L.) populations infesting urban and farm buildings. In three further treatments with both calciferol and warfarin at 0.05% in dehusked canary seed bait plus 5% corn oil, mortality, estimated from the consumption of pre- and post-treatment census bait, ranged between 94.2 and 97.4%. Finally, among sixteen treatments done with calciferol at 0.1% and warfarin at 0.025% in various cereal baits, the best results (97.0-100%) were obtained in six treatments where the bait-base was whole canary seed; this was so whether the poison bait was applied directly or after a 3-day pre-baiting period. It is concluded that calciferol at 0.1% plus warfarin at 0.025% is an effective combination against house-mice, especially when used with whole canary seed. The role played by warfarin in the poison mixture needs to be investigated further.
Animals↗
An analysis of the susceptibilities of several populations of Rattus norvegicus to warfarin.
An analysis was made of the dose-response of several populations of Rattus norvegicus fed upon baits containing 0.005% warfarin for various numbers of days. Warfarin-susceptible populations fell within a narrow range, with LFP 50s and LFP 98s (lethal feeding periods in days to obtain 50% and 98% mortalities respectively) of up to 3.0 and 5.0 days respectively. The probability of an individual rat from these populations surviving a six-day feeding period was estimated at 0.003 or less. Populations with responses falling beyond these limits were regarded as warfarin-resistant.Six of nine populations of R. norvegicus, from England, Germany and the United States, were determined to be warfarin-susceptible within the narrow limits given above. In all six cases, no animals survived the six-day WHO feeding test for anticoagulant susceptibility. In three populations from the United States, where rats survived six days feeding, their population responses clearly fell outside the measures given above. It is suggested, tentatively, that anticoagulant-resistant Norway rat populations be defined as those whose LFP 50 and LFP 98 exceeds 3.0 and 5.0 days respectively, and in which the probability of an individual animal surviving a six-day feeding upon 0.005% warfarin is 0.01 or more.
Animals↗
Toxicity tests on suspected warfarin resistant house mice (Mus musculus L.).
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Animals↗
Field trials of difenacoum against warfarin-resistant infestations of Rattus norvegicus.
The anticoagulant difenacoum was tested at two concentrations, 0-005 and 0-01%, in bait against warfarin-resistant rat infestations in farm buildings. Twelve out of the 14 treatments in which the lower concentration of the anticoagulant was used resulted in complete control. One of the remaining two treatments was probably also completely successful, but in the other a few rats, that were not eating the poisoned baits, were still active after 30 days of baiting. All six treatments done using the stronger concentration of poison were completely effective. Since it took as long to control infestations with 0.01% as with 0.005% difenacoum in treatments carried out under similar conditions, the lower concentration is recommended for use against warfarin-resistant rats.
4-Hydroxycoumarins↗
Efficacy of alpha-chlorhydrin in sewer rat control.
A single application of the male chemosterilant, alpha-chlorhydrin, to a problem sewer rat infestation resulted in reductions of rat numbers and distribution which was comparable to effects of warfarin baiting methods. Rat numbers were reduced by more than 85% by both methods. More rapid mortality and recruitment were evident for warfarin effects; the alpha-chlorhydrin treated population had a longer lag phase of growth so that reinfestation of sewer habitat to pre-treatment numbers, and distribution over a 40 square block area, required approximately 1.5-2 times longer after alpha-chlorhydrin treatment when compared with warfarin treatment. Comparisons of changes in rat densities in infested sewers following the two treatments indicate that recovery of warfarin treated populations is achieved by reproductive recruitment followed by dispersal while alpha-chlorhydrin treated populations recover by slower immigration and later reproductive recruitment. Alpha-chlorohydrin should be a useful addition to a limited arsenal of rat control agents because of its specificity for the Norway rat, its single dose effectiveness as a toxicant-chemosterilant, and its short environmental half-life.
Animals↗
Evaluation of coumatetralyl against two predominant murid species.
Coumatetralyl was evaluated in the laboratory against Bandicota bengalensis and Rattus rattus. Feeding tests with 0.0375% coumatetralyl baits produced 100% mortality after a single day feeding period in B. bengalensis and after a 10-day period in R. rattus. The anticoagulant bait is less palatable in comparison to plain bait. In the case of R. rattus, LFP50 and LFP98 and their 95% confidence limits were 3.89 (2.62-5.77) days and 11.22 (6.1-20.65) days respectively. Median period of survival and its 95% confidence limits of B. bengalensis and R. rattus were 4.7 (3.85-5.7) days and 11.2 (9.33-13.44) days respectively.
4-Hydroxycoumarins↗
Laboratory evaluation of anticoagulant-treated baits for control of the northern palm squirrel, Funambulus pennanti Wroughton.
Individually caged northern palm squirrels, Funambulus pennanti, were fed with bait containing 0.025% warfarin or fumarin, 0.0075% chlorophacinone or 0.005% brodifacoum for a fixed number of days varying from 1 to 14. Brodifacoum (WBA 8119) was found most toxic since 66% and 70% of the animals died after one and two days' feeding respectively. Chlorophacinone killed 70% of the squirrels after three days' feeding. Squirrels were relatively tolerant to warfarin and fumarin since the mortality after a period of 14 days' feeding was only 58% and 75% respectively.
Animals↗
Field trials of bromadiolone against infestations of warfarin-resistant Rattus norvegicus.
Baiting with 0.005% bromadiolone in medium oatmeal or soaked wheat completely controlled infestations of warfarin-resistant rats on farms when surplus amounts of the poisoned baits were maintained until rats ceased to feed on them. The speed with which control was achieved was the same as with other anticoagulants that have been tested in this way.Poison baiting with 0.005% bromadiolone for only 1, 4 or 7 days achieved respectively about 49, 77 and 81% control of similar farm rat infestations.
4-Hydroxycoumarins↗
Evaluation of brodifacoum against T. indica, M. hurrianae and R. rattus.
Brodifacoum was evaluated in the laboratory against the two gerbils, Tatera indica and Meriones hurrianae and the house rat, Rattus rattus. The acute oral LD50 for these rodents was found to be 0.10 mg/kg, 0.083 mg/kg and 0.77 mg/kg respectively. Feeding tests with 0.002% and 0.005% brodifacoum produced a 100% mortality after a 3-day feeding period in the gerbils and after a 4-day period in R. rattus. The anticoagulant is toxic at both the concentrations to all three species but is less palatable in comparison to plain baits. Results of this laboratory evaluation indicates that 0.002% brodifacoum-treated bait can be effectively used against T. indica, M. hurrianae and R. rattus.
4-Hydroxycoumarins↗
The fate of the cyclic nitramine explosive RDX in natural soil.
The sorption-desorption behavior and long-term fate of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) was examined in sterilized and nonsterilized topsoil. Results of this study indicate that although RDX is not extensively sorbed by the topsoil (Ks(d) of 0.83 L/kg), sorption is nearly irreversible. Furthermore, there was no difference in the sorption behavior for sterile and nonsterile topsoil. However, over the longterm, RDX completely disappeared within 5 weeks in nonsterile topsoil, and 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) metabolites formed in the aqueous phase. Over the same period, recovery of RDX from sterile topsoil was high (55-99%), and the nitroso metabolites were not detected. Only traces of RDX were mineralized to CO2 and N2O by the indigenous microorganisms in nonsterile topsoil. Of the RDX that was mineralized to N2O, one N originated from the ring and the other from the nitro group substituent, as determined using N15 ring-labeled RDX. However, N2O from RDX represented only 3% of the total N2O that formed from the process of nitrification/denitrification.
Adsorption↗
Insights into the formation and degradation mechanisms of methylenedinitramine during the incubation of RDX with anaerobic sludge.
In an earlier study, we reported that hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) biodegraded with domestic anaerobic sludge to produce a key RDX ring cleavage intermediate that was tentatively identified as methylenedinitramine (O2NNHCH2NHNO2) using LC/MS with negative electrospray ionization (ES-). Recently, we obtained a standard material of methylenedinitramine and thus were able to confirm its formation as the key initial RDX intermediate. In water alone or in the presence of sludge, methylenedinitramine decomposed to N20 and HCHO. Only in the presence of sludge HCHO converted further to carbon dioxide. To test our hypothesis that water was involved in the formation of methylenedinitramine during incubation of RDX with sludge, we allowed the energetic compound to biodegrade in several D2O/H2O solutions (90, 50, and 0% v/v). We observed three distinctive deprotonated or dedeuterated mass ions at 135, 136, and 137 Da that were attributed to the formation of nondeuterated (H-methylenedinitramine), monodeuterated (D1-methylenedinitramine), and dideuterated methylenedinitramine (D2-methylenedinitramine), respectively. Two controls were prepared in D2O both in the absence of sludge; the first contained methylenedinitramine, and the second contained RDX. Neither control produced any deuterated methylenedinitramine, thus excluding the occurrence of any abiotic D/H exchange between D2O and either methylenedinitramine or RDX. The results supported the occurrence of an initial enzymatic reaction on RDX, yet they did not provide compelling evidence on whether methylenedinitramine was an initial RDX enzymatic hydrolysis product or simply formed via the spontaneous hydrolysis of an anonymous initial RDX enzymatic product.
Bacteria, Anaerobic↗
Biotransformation of hexahydro-1,3,5-trinitro-1,3,5-tiazine catalyzed by a NAD(P)H: nitrate oxidoreductase from Aspergillus niger.
Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) can be efficiently mineralized with anaerobic domestic sludge, but the initial enzymatic processes involved in its transformation are unknown. To test the hypothesis that the initial reaction involves reduction of nitro group(s), we designed experiments to test the ability of a nitrate reductase (EC 1.6.6.2) to catalyze the initial reaction leading to ring cleavage and subsequent decomposition. A nitrate reductase from Aspergillus niger catalyzed the biotransformation of RDX most effectively at pH 7.0 and 30 degrees C under anaerobic conditions using NADPH as electron donor. LC/MS (ES-) chromatograms showed the formation of hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and methylenedinitramine as key initial products of RDX, but neither the dinitroso neither (DNX) nor trinitroso (TNX) derivatives were observed. None of the above detected products persisted, and their disappearance was accompanied by the accumulation of nitrous oxide (N20), formaldehyde (HCHO), and ammonium ion (NH4+). Stoichiometric studies showed that three NADPH molecules were consumed, and one molecule of methylenedinitramine was produced per RDX molecule. The carbon and nitrogen mass balances were 96.14% and 82.10%, respectively. The stoichiometries and mass balance measurements supported a mechanism involving initial transformation of RDX to MNX via a two-electron reduction mechanism. Subsequent reduction of MNX followed by rapid ring cleavage gave methylenedinitramine which in turn decomposed in water to produce quantitatively N2O and HCHO. The results clearly indicate that an initial reduction of a nitro group by nitrate reductase is sufficient for the decomposition of RDX.
Aspergillus niger↗
Use of liquid chromatography/tandem mass spectrometry to detect distinctive indicators of in situ RDX transformation in contaminated groundwater.
An important element of monitored natural attenuation is the detection in groundwater of distinctive products of pollutant degradation or transformation. In this study, three distinctive products of the explosive RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) were detected in contaminated groundwater from the Iowa Army Ammunition Plant; the products were MNX (hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine), DNX (hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine), and TNX (hexahydro-1,3,5-trinitroso-1,3,5-triazine). These compounds are powerful indicators of RDX transformation for several reasons: (a) they have unique chemical features that reveal their origin as RDX daughter products, (b) they have no known commercial, industrial, or natural sources, and (c) they are well documented as anaerobic RDX metabolites in laboratory studies. The products were analyzed by LC/MS/MS (liquid chromatography/mass spectrometry/mass spectrometry) with selected reaction monitoring and internal standard quantification using [ring-U-15N]RDX. Validation tests showed the novel LC/MS/MS method to be of favorable sensitivity (detection limits ca. 0.1 microg/L), accuracy, and precision. The products, which were detected in all groundwater samples with RDX concentrations of > ca. 1 microg/L (25 out of 55 samples analyzed), were present at concentrations ranging from near the detection limit to 430 microg/L. MNX was the typically the most abundant of the three nitroso-substituted products; concentrations of the products seldom exceeded 4 mol % of the RDX concentration, although they ranged as high as 26 mol % (TNX). Geographic and temporal distributions of RDX, MNX, DNX, and TNX were assessed. A degradation product resulting from RDX ring cleavage, methylenedinitramine, was not detected by LC/MS/MS in any sample (detection limit ca. 0.6-4 microg/L). This extensive field characterization of MNX, DNX, and TNX distributions in groundwater by a highly selective analytical method (LC/MS/MS) is significant because very little is known about the occurrence of intrinsic RDX transformation in contaminated aquifers.
Biotransformation↗
Risk assessment of an acetaminophen baiting program for chemical control of brown tree snakes on Guam: evaluation of baits, snake residues, and potential primary and secondary hazards.
The brown tree snake (Boiga irregularis) is a significant ecological, agricultural, and economic pest on Guam. Acetaminophen has recently been identified as a promising snake toxicant. Subsequent experimentation has shown that acetaminophen-mouse baits are readily consumed by and acutely toxic to browntree snakes. Before implementing an island-wide acetaminophen-mouse baiting program for the reducton of brown tree snake populations,the potential risks to nontarget wildlife must be evaluated. Quantification of nontarget hazards by comparing potential exposure levels to toxicity values suggested a significant level of concern for rodents, cats, pigs, and birds. For these species, subsequent calculations and field and laboratory experiments, which quantified acetaminophen consumption under field conditions, indicated that acetaminophen consumption was minimal. These results indicate that the advantages of using acetaminophen to reduce brown tree snake populations on Guam outweigh the minimal risks to nontarget feral and wildlife species.
Acetaminophen↗
Photodegradation of RDX in aqueous solution: a mechanistic probe for biodegradation with Rhodococcus sp.
Recently we demonstrated that Rhodococcus sp. strain DN22 degraded hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) (1) aerobically via initial denitration followed by ring cleavage. Using UL 14C-[RDX] and ring labeled 15N-[RDX] approximately 30% of the energetic chemical mineralized (one C atom) and 64% converted to a dead end product that was tentatively identified as 4-nitro-2,4-diaza-butanal (OHCHNCH2NHNO2). To have further insight into the role of initial denitration on RDX decomposition, we photolyzed the energetic chemical at 350 nm and pH 5.5 and monitored the reaction using a combination of analytical techniques. GC/ MS-PCI showed a product with a [M+H] at 176 Da matching a molecular formula of C3H5N5O4 that was tentatively identified as the initially denitrated RDX product pentahydro-3,5-dinitro-1,3,5-triazacyclohex-1-ene (II). LC/MS (ES-) showed that the removal of RDX was accompanied by the formation of two other key products, each showing the same [M-H] at 192 Da matching a molecular formula of C3H7N5O5. The two products were tentatively identified as the carbinol (III) of the enamine (II) and its ring cleavage product O2NNHCH2NNO2CH2NHCHO (IV). Interestingly, the removal of III and IV was accompanied by the formation and accumulation of OHCHNCH2NHNO2 that we detected with strain DN22. At the end of the experiment, which lasted 16 h, we detected the following products HCHO, HCOOH, NH2CHO, N2O, NO2-, and NO3-. Most were also detected during RDX incubation with strain DN22. Finally, we were unable to detect any of RDX nitroso products during both photolysis and incubation with the aerobic bacteria, emphasizing that initial denitration in both cases was responsible for ring cleavage and subsequent decomposition in water.
Biodegradation, Environmental↗
Electrochemical reduction of hexahydro-1,3,5-trinitro-1,3,5-triazine in aqueous solutions.
Electrochemical reduction of RDX, hexahydro-1,3,5-trinitro-1,3,5-triazine, a commercial and military explosive, was examined as a possible remediation technology for treating RDX-contaminated groundwater. A cascade of divided flow-through cells was used, with reticulated vitreous carbon cathodes and IrO2/Ti dimensionally stable anodes, initially using acetonitrile/water solutions to increase the solubility of RDX. The major degradation pathway involved reduction of RDX to the corresponding mononitroso compound, followed by ring cleavage to yield formaldehyde and methylenedinitramine. The reaction intermediates underwent further reduction and/or hydrolysis, the net result being the complete transformation of RDX to small molecules. The rate of degradation increased with current density, but the current efficiency was highest at low current densities. The technique was extended successfully both to 100% aqueous solutions of RDX and to an undivided electrochemical cell.
Electrochemistry↗
Abiotic transformation of hexahydro-1,3,5-trinitro-1,3,5-triazine by Fe(II) bound to magnetite.
RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine), a nitramine explosive, is often found as a subsurface contaminant at military installations. Though biological transformations of RDX are often reported, abiotic studies in a defined medium are uncommon. The work reported here was initiated to investigate the transformation of RDX by ferrous iron (Fe(II)) associated with a mineral surface. RDX is transformed by Fe(II) in aqueous suspensions of magnetite (Fe3O4). Negligible transformation of RDX occurred when it was exposed to Fe(II) or magnetite alone. The sequential nitroso reduction products (MNX, DNX, and TNX) were observed as intermediates. NH4+, N2O, and HCHO were stable products of the transformation. Experiments with radiolabeled RDX indicate that 90% of the carbon end products remained in solution and that negligible mineralization occurred. Rates of RDX transformation measured for a range of initial Fe(II) concentrations and solution pH values indicate that greater amounts of adsorbed Fe(II) result in faster transformation rates. As pH increases, more Fe(II) adsorbs and k(obs) increases. The degradation of RDX by Fe(II)-magnetite suspensions indicates a possible remedial option that could be employed in natural and engineered environments where iron oxides are abundant and ferrous iron is present.
Adsorption↗