Total Radioactive Residues Research Articles

Behavior and fate of a novel neonicotinoid cycloxaprid in water–sediment systems through position-specific C-14 labeling

Neonicotinoid insecticides are ubiquitous worldwide, are problematic for pollinators and other nontarget creatures and affect the stability of the environment. These negative impacts prompt the ongoing development of alternatives. Cycloxaprid, a novel cis-nitromethylene neonicotinoid, exhibits high efficacy against imidacloprid-resistant pests and is viewed as a promising alternative candidate. However, information about the fate of cycloxaprid in water–sediment systems is limited. To bridge this knowledge gap, radioactive isotope-labeled 14C-cycloxaprid was employed to determine the formation of residues, transformation products, and degradation pathways. First, the mass balance analysis of residue was investigated. The extractable residue of cycloxaprid accounted for 100–40% of the total radioactive residue; cycloxaprid could transform into bound residue (0–54%) and mineralization (0–0.015%). It was partitioned from the water phase to sediments with dissipation half-lives of 6.62 d in the Dianshan Lake sample and 4.61 d in the Jinhui Port sample. Three degradation products were then detected and identified by liquid chromatography coupled to mass spectrometry. Its main metabolite, 2-chloro-5-[(2-(nitromethylene)-1-imidazolidinyl)methyl]pyridine, was more toxic than the parent compound and should be given priority in monitoring. Ring opening, carboxylation, and reduction of nitro groups were confirmed as the primary degradation pathways. The present study assessed the fate of cycloxaprid in two different water–sediment systems for the first time, and this information could provide insight into the potential ecological impacts of cycloxaprid and more precisely into evaluating its environmental risks in the future.

Metabolism of esfenvalerate in tomato plants (Solanum lycopersicum).

The metabolic fate of esfenvalerate (1), 14C-labeled at the chlorophenyl or phenoxyphenyl ring, in tomato plants was investigated by spraying it three times at 15 g/ha. The overall metabolic trend of 1 was similar in foliage and fruit. The applied 1 gradually penetrated into the foliage/fruit, and approximately 30% of the total radioactive residue (TRR) distributed within the plant. The applied radioactivity remained mostly intact on the plant surface, while its degradation proceeded via ester cleavage to produce two corresponding acids derived from the chlorophenyl and phenoxyphenyl moieties, followed by saccharide conjugation at the inner tissues (each <5%TRR). While 1 retained its optical configuration (2S,αS) on the plant surface and in the fruit, a very slight isomerization at the α-cyanobenzyl carbon occurred to form a (2S,αR) isomer in the foliage (≤1%TRR). The isomerization at another asymmetric carbon C2 in the isovaleric acid moiety did not proceed on/in the plant for 1 or its metabolite.

Distribution and Chemical Fate of [36Cl]Chlorine Dioxide Gas on Avocados, Eggs, Onions, and Sweet Potatoes.

Fate and distribution studies were conducted with [36Cl]-chlorine dioxide in avocados, eggs, onions, and sweet potatoes. Experiments utilized sealed, darkened chambers, 5 mg of 36ClO2 (g), and two-hour exposure periods. Total radioactive residues were quantitated in gas purges, tank rinses, reaction chambers, and on fractions specific to each food. Deposition of the radioactive residue was mostly a surface phenomenon; transfer of radioactivity into albumen occurred in egg, but radioactivity did not penetrate the onion tunic and only small amounts of activity were present in avocado flesh. Potato skin contained essentially all the potato radiochlorine. Regardless of the food product, nearly all radioactive residue was present in edible tissues as chloride ions; the chlorite ion was present only in egg-rinse water. Small amounts (10% or less) of radioactivity were present as chlorate ions, which would be a useful marker compound for chlorine dioxide sanitation.

Metabolism of the Strobilurin Fungicide Mandestrobin in Wheat.

The metabolic fate of a new fungicide, mandestrobin, labeled with 14C at the phenoxy or benzyl ring was examined in wheat after a single spray application at 300 g/ha. Mandestrobin penetrated into foliage over time, with both radiolabels showing similar 14C distribution in wheat, and 2.8-3.3% of the total radioactive residue remained on the surface of straw at the final harvest. In foliage, mandestrobin primarily underwent mono-oxidation at the phenoxy ring to produce 4-hydroxy or 2-/5-hydroxymethyl derivatives, followed by their subsequent formation of malonylglucose conjugates. In grain, the cleavage of its benzyl phenyl ether bond was the major metabolic reaction, releasing the corresponding alcohol derivative, while the counterpart 2,5-dimethylphenol was not detected. The constant RS enantiomeric ratio of mandestrobin showed its enantioselective metabolism to be unlikely on/in wheat.

14C]Butachlor의 벼에 대한 흡수 및 대사

Abstract In the present study, the metabolism of [ 14 C]butachlor was investigated in rice plant according tothe OECD test guideline No. 501. [ 14 C]Butachlor was treated as granule to paddy water by application of1.5 kg ingredient (a.i.)/ha at the 3~4 leave stage of rice plant. At 85 days after treatment (DAT), samples ofpanicle, foliage, and roots were taken for radioactivity analysis. Upon harvest at 126 DAT, rice plants wereseparated into brown rice, husk, straw, and root parts. Amounts of total radioactivity absorbed by rice plantranged from 8.6 to 9.8% of applied radioactivity (AR). Total radioactive residues (TRRs) of rice plant at 126DAT was the highest as 4.0421 mg/kg (7.3% AR) in the straw followed by 1.4595 mg/kg (2.4% AR) in theroot, 0.7257 mg/kg (0.1% AR) in the husk. The lowest level recording 0.1020 mg/kg (0.1% AR) was foundin brown rice. Each part was extracted with various solvents and solvent/water mixtures. Greater than 70% ofTRRs was readily extractable from foliage, panicle, husk and straw. Only 34.0% of the brown rice and 43%of root based on TRRs were extractable showing that the residues were completely assimilated in the planttissue. The level of non-extractable radioactivity was ranged from 26.2 to 66.0% of TRRs. From this study,five tentative major metabolites (M1, M2, M3, M4 and M5) were observed in rice extracts. Among themetabolites, 2,6-diethylaniline assigned as M4 was identified in rice plant by comparing to retention time ofreference standard. Un-metabolized butachlor was not detected in any fractions. In soil extracts, N-(butoxymethyl)-N-(2,6-diethyl phenyl)acetamide, 2,6-diethylaniline, M2, M3 and M5 were observed. And theconcentration of butachlor was low level (ca. 0.03 mg/kg). Key words Environmental fate, Plant metabolism, Total radioactive residues, OECD TG 501, Butachlor

Pharmacokinetics and Excretion of 14C-Labeled Polyethylene Glycol (60 kDa) in Rats

Introduction: Although there is no evidence for PEG-related safety issues with PEGylated proteins in the clinic, questions relating to the pharmacokinetics including disposition and excretion of PEG are being raised more frequently by health authorities nowadays, particularly for PEGylated proteins used chronically and/or in the pediatric population (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/11/WC500135123.pdf).BAY 94-9027, a B-domain–deleted recombinant FVIII with a 60-kDa branched PEG molecule attached via a maleimide linker to an amino acid using site-specific PEGylation, is in clinical development for acute and prophylactic intravenous treatment of hemophilia A. The objective of this study was to investigate the pharmacokinetics and excretion of radioactivity (unchanged compound and radioactive metabolites) after single intravenous administration of 14C-labeled BAY 1025662 (cysteine linker-[60-kDa] PEG part of BAY 94-9027 with the 14C label covalently integrated in the linker) in male Wistar rats.Methods: The administered dose was 11 mg/kg body weight related to BAY 1025662 (approximated human lifetime dose of PEG 60 kDa resulting from treatment with BAY 94-9027). The concentrations and amounts of radioactivity in urine, feces, blood, plasma, and selected organs and tissues were investigated in order to determine the excretion via urine and feces, and the pharmacokinetics of total radioactivity and radioactive residues in the animal body.Results: After single intravenous administration of 14C-BAY 1025662 to rats, a fast initial elimination of 14C radioactivity was observed; 63.2% of administered radioactivity was excreted within the first 24 hours (51.4% in urine, 11.8% in feces). Up to day 7, 75.6% of administered radioactivity was excreted predominantly via urine. The balance/recovery of radioactivity on day 7 amounted to 99.0% in relation to the administered radioactive dose. The radioactive residue in the animals amounted to 23.4% of administered dose. The majority of the residual radioactivity was recovered in the carcass and skin, followed by liver and kidneys. The excretion of radioactivity continued at steadily decreasing levels until the end of the study. The daily radioactivity excretion decreased from 2.1% at 72 hours to 0.013% of dose at 6 months after administration of 14C-BAY 1025662. The cumulative excretion of radioactivity via urine and feces was calculated (partly interpolated) to 92.2% of the administered radioactive dose by the end of the experiment on day 168 (74.5% via urine, 17.4% via feces, and 0.294% recovered in the cage wash). The radioactivity was continuously albeit slowly eliminated from the investigated organs and tissues. The elimination half-life of radioactivity was 26 and 23 days in blood and plasma, respectively. The corresponding elimination half-lives of radioactivity were 35, 41, and 31 days in the liver, carcass, and skin, respectively. Radioactivity elimination from kidneys was biphasic with a terminal half-life of 92 days. The radioactive residues in the animals excluding the gastrointestinal tract decreased during the study from 22.5% on day 7 to 1.79% of dose at the end of the study on day 168. There was no indication for any retention or irreversible binding of radioactivity in the animal body. The total recovery of radioactivity (cumulative excretion plus residues in the animals) was 94% in relation to the administered dose at the end of the experiment on day 168.Conclusions: In this study, nearly complete excretion of the 60-kDa PEG molecule (measured as total radioactivity) could be observed, with a fast initial elimination in the first few days and a subsequent considerably slower process until the end of the observation period (6 months). These results are in agreement with recently proposed fast and slow processes for the renal excretion of large PEG and PEG proteins (Baumann, A. et al. Drug Discov Today. 2014:[Epub ahead of print, http://dx.doi.org/10.1016/j.drudis.2014.06.002]). DisclosuresBaumann:Bayer Pharma AG: Employment. Schwarz:Bayer Pharma AG: Employment. Seidel:Bayer Pharma AG: Employment. Hucke:Bayer Pharma AG: Employment. Steinke:Bayer Pharma AG: Employment. Buehner:Bayer Pharma AG: Employment.

Fate of 17β-Estradiol in Anaerobic Lagoon Digesters

The fate of [C]17β-estradiol ([C]E2) was monitored for 42 d in triplicate 10-L anaerobic digesters. Total radioactive residues decreased rapidly in the liquid layer of the digesters and reached a steady-state value of 22 to 26% of the initial dose after 5 d. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analyses of the liquid layer of the anaerobic digesters indicated a rapid degradation of E2 to estrone (E1), which readily adsorbed to the sludge layer subsequent to its formation. Estrone was the predominant steroid identified under anaerobic digestion in the liquid layer or sorbed to sludge at 42 d. Methane formation represented 11.1 ± 5.7% of the initial E2 fortification with 0.3 to 0.5% of the starting E2 mineralized to carbon dioxide. Maximum [C]methane production appeared between Days 4 and 7. An estimate of estrogenicity of the final product based on reported estrogen equivalents for E1 and E2 was 2% of the original in active digesters. Anaerobic digestion of swine waste has several management benefits; moreover, this study demonstrated that it reduces the potential of environmental release of estrogens, which are known endocrine disruptors.

Marker Residue Determination of Tritium-Labeled Ivermectin in the Muscle of Aquacultured Largemouth Bass, Hybrid Striped Bass, and Yellow Perch following Oral Treatment

The residue depletion profiles of tritium-labeled ivermectin and its metabolites in the muscle of aquacultured largemouth bass (LMB), hybrid striped bass (HSB), and yellow perch (YP) following oral treatment are reported. Fish were administered ³H-ivermectin at the dose level of 0.1 mg/kg body weight (7-9 μCi) in a gel capsule via stomach tube. At each postdose withdrawal time, six fish of each species were sedated with buffered MS-222 and blood samples taken. Fish were then euthanized, and fillets with adhering skin (scales removed) and bile samples were collected. The muscle fillets were homogenized in dry ice to a fine powder. Aliquots of tissue, plasma, and bile were assayed for total radioactive residue (TRR). The homogenized muscle was extracted in acetonitrile or methanol followed by high-performance liquid chromatographic (HPLC) analysis to determine the presence of parent ivermectin and its potential metabolites. The highest TRR concentrations (ivermectin equivalents) of 53, 45, and 44 ng/g (ppb) were obtained on postdose day 1 for HSB, LMB, and YP, respectively. The TRR depleted most slowly in HSB to 25 ppb at day 91, followed by YP to 19 ppb at day 42 and then by LMB to 22 ppb at day 35. The total residue of ivermectin and its metabolites by HPLC analysis followed the same depletion pattern in the three species. Additionally, the depletion rate of TRR of ³H-ivermectin in the three species followed the pattern bile > plasma > muscle. The results further indicate that one of the polar metabolites of ivermectin could serve as a potential marker residue as an indication of use, rather than the parent ivermectin.

Dissipation of 17β‐Estradiol in Composted Poultry Litter

The excreted estrogen rate of all livestock in the United States is estimated at 134 kg d. The influence of manure treatment on the fate of estrogens is critical in deciding the recycling of over 300 million dry tons of livestock produced annually. The effects of two common manure management practices, heated composting and ambient temperature decomposition, on the fate of 17β-estradiol in poultry litter were determined. A mixture of poultry litter, wood chips, and straw was amended with [C]17β-estradiol and allowed to undergo decomposition with a laboratory-scale heated composter (HC) or room temperature incubation (RTI) for 24 d. Radiolabel in the finished products was fractionated into water-extractable, acetone-extractable, nonextractable, and mineralized fractions. Total 17β-estradiol radioactive residues in the HC and RTI ( = 2) treatments were not different ( > 0.05), except that statistically less 17β-estradiol was mineralized to CO during HC than RTI (1.1 vs. 10.0% for HC and RTI, respectively). Estrone was the major degradation product in extracts of HC and RTI treatments as determined by liquid chromatography/mass spectrometry analyses. The nonextractable residues indicated no quantitative differences among the humins between the treatments. An estimated 3% of the fortified estrogenicity remained after HC treatment, and 15% of the fortified estrogenicity remained after RTI treatment. If reduction of water-removable, biologically active 17β-estradiol is the treatment goal, then HC treatment would be slightly preferred over ambient temperature degradation. However, unmanaged, ambient temperature litter piles are less costly and time consuming for food animal producers and result in greater mineralization and similar immobilization of estradiol.

Metabolism of a New Herbicide, [14C]Pyribenzoxim, in Rice

The in vivo metabolism of a new herbicide pyribenzoxim (benzophenone Ο-[2,6-bis(4,6-dimethoxypyrimidin-2-yloxy)benzoyl]oxime) in rice was carried out using container trials. Two radiolabeled forms of [carbonyl-(14)C]pyribenzoxim (P1) and [ring-(14)C(U)]pyribenzoxim (P2) were treated separately as formulations for foliar treatment by single applications of 50 g of active ingredient (ai)/ha at the 4-6 leaves stage. At 0, 7, 30, and 60 days after treatment (DAT), samples of panicle, foliage/rest of plant, and roots were taken for analysis. Upon harvest (120 DAT), rice plants were separated into grain, husk, straw, and root parts. Total radioactive residues (TRRs) at each sampling date were determined to show that the final radioactive residues at harvest were low in grain, husk, straw, and roots, accounting for <17 ppb. The concentration of final residues in the rice plant decreased rapidly, and less than 0.1% of initial TRRs remained at harvest. At 7 DAT, metabolite 1 [M1, 2,6-bis(4,6-dimethoxypyrimidin-2-yloxy)benzoic acid] and two unknown compounds (other-1 and other-2) were detected in foliage extract, accounting for 3.5% TRRs (21.0 ppb), 3.1% TRRs (19.0 ppb), and 9.0% TRRs (54.3 ppb), respectively, while 26.1% of M1 was observed in solvent wash. Any other metabolites were not detected in the plant, including expected metabolite M3 (benzophenone oxime). On the basis of the results obtained, a metabolic pathway of pyribenzoxim in a rice plant was proposed.

Bioconcentration of Pirimiphos-methyl in Killifish (Oryzias latipes)

Killifish (Oryzias latipes) were exposed to an organophosphate pesticide, pirimiphos-methyl, in a flow-through system to determine the bioconcentration factor (BCF) following GLP (Good Laboratory Practice). This study was conducted at two different concentrations (1 and 10 μg/L) of 14 C-labeled pirimiphos-methyl for 28 days uptake and 14 days depuration according to the OECD 305 test guideline. The BCFss for total radioactive residues in whole fish were 1,251 and 1,277 for low and high concentrations, respectively. The BCFk based on the uptake and depuration rate constants were 1,200 for both low and high concentrations. During the depuration phase, the accumulated test substance was rapidly depurated from fish. Greater than 95% of the residue at steady-state was depurated after 2 days. Although the measured BCF values were high, pirimiphos-methyl could be evaluated as a low risk from bioaccumulation by aquatic organisms due to the short depuration period and low amount of bound residue (1.5%). We suggest that in evaluating bioaccumulation, not only the BCF should be considered, but also depuration time and bound residue in aquatic organisms give an indication of the potential environmental risks.

Absorption, Tissue Distribution, And Elimination of Residues after 2,4,6-Trinitro[14C]toluene Administration to Sheep

The compound 2,4,6-trinitrotoluene (TNT) is a persistent contaminant of some industrial and military sites. Biological bioremediation techniques typically rely on the immobilization of TNT reduction products rather than on TNT mineralization. We hypothesized that sheep ruminal microbes would be suitable for TNT destruction after phytoremediation of TNT-contaminated soils by cool-season grasses. Therefore we investigated the fate of [14C]TNT in ruminating sheep to determine the utility of ruminant animals as a portion of the bioremediation process. Three wether sheep were dosed with 35.5 mg each of dietary unlabeled TNT for 21 consecutive days. On day 22 sheep (41.9 +/- 3.0 kg) were orally dosed with 35.5 mg of [14C]TNT (129 microCi; 99.1% radiochemical purity). Blood, urine, and feces were collected at regular intervals for 72 h. At slaughter, tissues were quantitatively collected. Tissues and blood were analyzed for total radioactive residues (TRR); excreta were analyzed for TRR, bound residues, and TNT metabolites. Plasma radioactivity peaked within 1 h of dosing and was essentially depleted within 18 h. Approximately 76% of the radiocarbon was excreted in feces, 17% in urine, with 5% being retained in the gastrointestinal tract and 1% retained in tissues. Parent TNT, dinitroamino metabolites, and diaminonitro metabolites were not detected in excreta. Ruminal and fecal radioactivity was essentially nonextractable using ethyl acetate, acetone, and methanol; covalent binding of fecal radioactive residues was evenly distributed among extractable organic molecules (i.e., soluble organic matter, soluble carbohydrate, protein, lipid, and nucleic acid fractions) and undigested fibers (cellulose, hemicellulose, and lignin). This study demonstrated that TNT reduction within the ruminant gastrointestinal tract leads to substantial immobilization of residues to organic matter, a fate similar to TNT in other strongly reducing environments.

Residue depletion of tritium-labeled ivermectin in rainbow trout following oral administration

The residue depletion and metabolism of tritium-labeled ivermectin were studied in the muscle tissue of rainbow trout following oral treatment. Fish were administered 3H-ivermectin at the dose level of 0.1 mg/kg of body weight (9.25 μCi) in a gel-capsule via stomach tube. At each of the following withdrawal times 6 fish were sedated with MS-222, euthanatized, bled, scaled and fillets with adhering skin and bile collected: 1, 3, 7, 14, 28, 35 and 42 days. The muscle tissues were homogenized in dry ice and analyzed for total radioactive residues (TRR) by sample oxidation. The homogenized tissue was further extracted with acetonitrile for residue characterization by high pressure liquid chromatography (LC).Maximum TRR of 71 ng/g and 3857 ng/mL (ivermectin equivalent concentration) were detected in muscle and bile, respectively, by sample oxidation on post-dose day 3. LC analysis of the muscle extract revealed that the maximum TRR of 55 ng/g (representing ivermectin and metabolites) was also detected on post-dose day 3. By post-dose day 35, about 65% of the TRR in the muscle tissue was an unknown metabolite. Preliminary mass spectrometry results indicated that the unknown metabolite may be 3″-O-demethyl-ivermectin B1a. This metabolite could serve as a potential marker residue for ivermectin in rainbow trout, in contrast to cattle, swine and sheep where the parent ivermectin is known to be the marker residue.

Total Radioactive Residues and Residues of [36Cl]Chlorate in Market Size Broilers

The oral administration of chlorate salts reduces the numbers of Gram-negative pathogens in gastrointestinal tracts of live food animals. Although the efficacy of chlorate salts has been demonstrated repeatedly, the technology cannot be introduced into commercial settings without first demonstrating that chlorate residues, and metabolites of chlorate remaining in edible tissues, represent a negligible risk to consumers. Typically, a first step in this risk assessment is to quantify the parent compound and to identify metabolites remaining in edible tissues of animals treated with the experimental compound. The objectives of this study were to determine the pathway(s) of chlorate metabolism in market broilers and to determine the magnitude of chlorate residues remaining in edible tissues. To this end, 12 broilers (6 weeks; 2.70+/-0.34 kg) were randomly assigned to three treatments of 7.4, 15.0, and 22.5 mM sodium [36Cl]chlorate dissolved in drinking water (n=4 broilers per treatment). Exposure to chlorate, dissolved in drinking water, occurred at 0 and 24 h (250 mL per exposure), feed was withdrawn at hour 38, water was removed at hour 48, and birds were slaughtered at hour 54 (16 h after feed removal and 8 h after water removal). The radioactivity was rapidly eliminated in excreta with 69-78% of the total administered radioactivity being excreted by slaughter. Total radioactive residues were proportional to dose in all edible tissues with chloride ion comprising greater than 98.5% of the radioactive residue for the tissue (9.4-97.8 ppm chlorate equivalents). Chlorate residues were typically greatest in the skin (0.33-0.82 ppm), gizzard (0.1-0.137 ppm), and dark muscle (0.05-0.14 ppm). Adipose, liver, and white muscle tissue contained chlorate concentrations from 0.03 to 0.13 ppm. In contrast, chlorate concentrations in excreta eliminated during the 6 h period prior to slaughter ranged from 53 to 71 ppm. Collectively, these data indicate that broilers rapidly convert chlorate residues to an innocuous metabolite, chloride ion, and that chlorate residues in excreta remain fairly high during the time around slaughter. Because the target tissue of chlorate is the lower gastrointestinal tract, the relatively high distribution of parent chlorate to inedible gastrointestinal tissues and low distribution to edible tissues is favorable for the biological activity and for food safety considerations. These data, when used in conjunction with a toxicological assessment of chlorate, can be used to determine a likely risk/benefit ratio for chlorate.

Pharmacokinetics of ruminally dosed sodium [36Cl]chlorate in beef cattle

The recently recognized potential of sodium chlorate as a possible preharvest food safety tool for pathogen reduction in meat animals has spurred interest in the pharmacokinetics of intraruminally dosed chlorate. Six Loala cattle were assigned (one heifer and one steer per treatment) to one of three intraruminal doses of radiolabeled sodium [36Cl]chlorate (21, 42, or 63 mg/kg body weight) administered in four equal aliquots over a 24-h period. Blood and serum were collected (29 samples in 48 h). Total radioactive residues were measured and the radioactive moieties were speciated. Chlorate appeared rapidly in blood and serum after dosing. For animals administered a dose of 42 or 63 mg/kg, the half-life of absorption was estimated at 0.6-0.9 h. Serum chlorate concentrations progressively increased with aliquot administration until peaking at 6-21 parts per million at 26 h. Between aliquot administrations, serum chlorate levels typically peaked in 3.5 h or less. The half-life of chlorate elimination ranged between 6.9 and 11 h, depending on the dose. Ultimately, absorption of chlorate removes it from its desired site of action, the lower gastrointestinal tract, thereby reducing its efficacy. Further research is needed to develop a chlorate formulation that will allow passage to the lower gastrointestinal tract.

Tissue Distribution, Elimination, and Metabolism of Sodium [36Cl]Perchlorate in Lactating Goats

Perchlorate has contaminated water sources throughout the United States but particularly in the arid Southwest, an area containing large numbers of people and few water sources. Recent studies have demonstrated that perchlorate is present in alfalfa and that perchlorate is secreted into the milk of cows. Studies in lactating cows have indicated that only a small portion of a perchlorate dose could be accounted for by elimination in milk, feces, or urine. It was hypothesized that the remainder of the perchlorate dose was excreted as chloride ion. The purpose of this study was to determine the fate and disposition of (36)Cl-perchlorate in lactating dairy goats. Two goats (60 kg) were each orally administered 3.5 mg (16.5 muCi) of (36)Cl-perchlorate, a dose selected to approximate environmental perchlorate exposure but that would allow for adequate detection of radioactive residues after a 72 h withdrawal period. Blood, milk, urine, and feces were collected incrementally until slaughter at 72 h. Total radioactive residue (TRR) and perchlorate concentrations were measured using radiochemical techniques and liquid chromatography mass spectrometry (LC-MS-MS). Peak blood levels of TRR occurred at 12 h ( approximately 195 ppb) postdose; peak levels of parent perchlorate, however, occurred after only 2 h, suggesting that perchlorate metabolism occurred rapidly in the rumen. The serum half-life of perchlorate was estimated to be 2.3 h. After 24 h, perchlorate was not detectable in blood serum but TRR remained elevated (160 ppb) through 72 h. Milk perchlorate levels peaked at 12 h (155 ppb) and were no longer detectable by 36 h, even though TRRs were readily detected through 72 h. Perchlorate was not detectable in skeletal muscle or liver at slaughter (72 h). Chlorite and chlorate were not detected in any matrix. The only radioactive residues observed were perchlorate and chloride ion. Bioavailability of perchlorate was poor in lactating goats, but the perchlorate that was absorbed intact was rapidly eliminated in milk and urine.

Effect of Sodium [36Cl]Chlorate Dose on Total Radioactive Residues and Residues of Parent Chlorate in Growing Swine

An experimental chlorate-based product has been shown to be efficacious in eliminating economically important, Gram-negative human pathogens in the gastrointestinal tracts of food animals. Prior to the commercial marketing of such a product, the magnitude and chemical nature of residues remaining in edible tissues must be determined. Thus, the objective of this study was to determine the tissue distribution and elimination of sodium [36Cl]chlorate in orally dosed swine. Three sets of pigs, each consisting of a barrow and a gilt, were orally dosed with a total of 20, 40, or 60 mg of sodium [36Cl]chlorate per kg body weight via the drinking water. Urine and feces were collected throughout the 30 h study. Twenty-four hours after the last exposure to [36Cl]chlorate, each pig was harvested and both edible and inedible tissues were collected. Urine and tissue samples were analyzed for total radioactive residues and for chlorate metabolites. Elimination of radioactivity in urine averaged 81.6, 83.7, and 83.9% of the total dose for the low, medium, and high doses, respectively. Fecal elimination of radioactivity averaged 1.1% of the dosed radiochlorine across all doses. Parent chlorate always represented greater than 97.4% of the urinary radiochlorine with the remaining radiochlorine being excreted as chloride ion. Chlorate represented 39-77% of fecal radioactivity, depending upon dose. Chlorate concentrations in edible tissues ranged from 0.01 to 0.49 ppm, with residues in liver and skeletal muscle generally lower than those in kidney and adipose tissue. Chlorate residues were concentrated in thyroid tissues (7.7-25.4 ppm) relative to edible tissues. No evidence for the presence of chlorite was observed in excreta or in tissues. Results of this study suggest that further development of chlorate as a preharvest food safety tool in swine merits consideration.

Toxicokinetics of 14C-Atrazine and Its Metabolites in Stage-66 Xenopus laevis

Several recent studies have focused on the toxicodynamic implications of amphibian exposure to the commonly used herbicide atrazine (2-chloro-4-ethylamine-6-isopropylamino-s-triazine). These studies are an important part of the risk assessment process; however, the underlying mechanisms of atrazine toxicodynamics are lacking. In an attempt to more fully describe atrazine exposure, the toxicokinetics of atrazine were studied in stage-66 Xenopus laevis larvae. The absorption, distribution, and excretion capacity of these larvae were found to be comparable to those observed in fish. The calculated bioconcentration factor (BCF) was 1.5-1.6 mLwater/glarvae, and by use of whole-body autoradiography, the radiolabel was found to be concentrated in the gall bladder and gastrointestinal tract. Elimination of atrazine was rapid with a half-life of 48 min. The high metabolic capacity of stage-66 X. laevis larvae was demonstrated where, following 8 h of exposure to 14C-atrazine, the percentages of atrazine and its metabolites deethyldeisopropylatrazine (DACT), deisopropylatrazine (DIA), and deethylatrazine (DEA) in larvae, determined by thin-layer chromatography, were 49.8% +/- 3.3%, 9.8% +/- 2.1%, 16.1% +/- 2.5%, and 15.6% +/- 2.0%, respectively. An unknown metabolite(s) was also produced and accounted for the remaining proportion of the total body radioactive residues. This metabolite(s) is hypothesized to be a conjugate of either atrazine or one of its metabolites. These metabolites, namely, DIA, were responsible for the long elimination half-life (72 h) of the total body radioactive residues. These toxicokinetics data would provide better insights in the interpretation of toxicodynamic data.

Effect of Sodium [36Cl]Chlorate Dose on Total Radioactive Residues and Residues of Parent Chlorate in Beef Cattle

The objectives of this study were to determine total radioactive residues and chlorate residues in edible tissues of cattle administered at three levels of sodium [36Cl]chlorate over a 24-h period and slaughtered after a 24-h withdrawal period. Three sets of cattle, each consisting of a heifer and a steer, were intraruminally dosed with a total of 21, 42, or 63 mg of sodium [36Cl]chlorate/kg of body weight. To simulate a 24-h exposure, equal aliquots of the respective doses were administered to each animal at 0, 8, 16, and 24 h. Urine and feces were collected in 12-h increments for the duration of the 48-h study. At 24 h after the last chlorate exposure, cattle were slaughtered and edible tissues were collected. Urine and tissue samples were analyzed for total radioactive residues and for metabolites. Elimination of radioactivity in urine and feces equaled 20, 33, and 48% of the total dose for the low, medium, and high doses, respectively. Chlorate and chloride were the only radioactive chlorine species present in urine; the fraction of chlorate present as a percentage of the total urine radioactivity decreased with time regardless of the dose. Chloride was the major radioactive residue present in edible tissues, comprising over 98% of the tissue radioactivity for all animals. Chlorate concentrations in edible tissues ranged from nondetectable to an average of 0.41 ppm in skeletal muscle of the high-dosed animals. No evidence for the presence of chlorite was observed in any tissue. Results of this study suggest that further development of chlorate as a preharvest food safety tool merits consideration.

Tissue Distribution, Elimination, and Metabolism of Dietary Sodium [36Cl]Chlorate in Beef Cattle

Two steers (approximately 195 kg) were each dosed with 62.5 or 130.6 mg/kg body weight sodium [36Cl]chlorate for three consecutive days. All excreta were collected during the dosing and 8 h withdrawal periods. The apparent radiochlorine absorption was 62-68% of the total dose with the major excretory route being urine. Parent chlorate was 65-100% of the urinary radiochlorine; chloride was the only other radiochlorine species present. Similarly, residues in edible tissues were composed of chloride and chlorate with chloride being the major radiolabeled species present. Chlorate represented 28-57% of the total radioactive residues in skeletal muscle; in liver, kidney, and adipose tissues, chlorate ion represented a smaller percentage of the total residues. Chlorate residues in the low dose steer were 26 ppm in kidney, 14 ppm in skeletal muscle, 2.0 ppm in adipose tissue, and 0.7 ppm in liver. These data indicate that sodium chlorate may be a viable preharvest food safety tool for use by the cattle industry.