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At least 19 recordsLinked to original sources

Pharmacokinetic modeling in aquatic animals. 1. Models and concepts

While clinical and toxicological applications of pharmacokinetics have continued to evolve both conceptually and experimentally, pharmacokinetics modeling in aquatic animals has not progressed accordingly. In this paper we present methods and concepts of pharmacokinetic modeling in aquatic animals using multicompartmental, clearance-based, non-compartmental and physiologically-based pharmacokinetic models. These models should be considered as alternatives to traditional approaches, which assume that the animal acts as a single homogeneous compartment based on apparent monoexponential elimination.

Aquatic Toxicology

Antioxidant effects of selenium on lung injury in paraquat intoxicated rats

CONTEXT: Paraquat (PQ) causes lethal intoxication by inducing oxidant injury to the lung. Selenium is a cofactor for glutathione peroxidase (GPx), which is one of the major endogenous antioxidant enzymes. OBJECTIVE: To determine whether selenium post-treatment activates GPx, decreases lung injury, and improves survival in PQ intoxicated rats. MATERIALS AND METHODS: Male Spraque-Dawley rats were categorized into three groups: sham (n = 6), PQ (n = 12), and PQ + Se (n = 12). In the PQ and PQ + Se groups, 50 mg/kg of PQ was administered intraperitoneally. After 10 minutes, 60 μg/kg of Se (PQ + Se) or saline (PQ) was administered via the tail vein. Six rats per group were euthanized 6 hours or 24 hours later. Lung tissues were harvested for the measurement of GPx activity, reduced glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) and for histological analysis. Using separated set of rats, survival of PQ (n = 10) and PQ + Se (n = 10) were observed for 72 hours. RESULTS: GPx activity in the PQ group at the 6-hour and 24-hour time points was lower than in the sham group (p < 0.006). GPx activity in the PQ + Se group at the 6-hour and 24-hour time points was higher than in the PQ group at the same time (p < 0.006). GPx activity in the PQ + Se group at 24 hours was higher than at 6-hour time point and also higher than in the sham group (p < 0.006). The GSH/GSSG ratio in the PQ + Se group at 24 hours was lower than that in the sham group (p < 0.006). MDA levels in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). MDA levels at 24 hours in the PQ + Se group was lower than in the PQ group (p < 0.006). Acute lung injury (ALI) scores in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). ALI scores at 24 hours in the PQ + Se group were lower than in the PQ group. Survival rates did not differ between PQ and PQ + Se (p = 0.869). CONCLUSION: Single dose of selenium post-treatment activates GPx and attenuates lipid peroxidation and lung injury early after paraquat intoxication, but does not improve 72 hours of survival.

Clinical Toxicology

Development of a novel flow cytometric approach to evaluate fish sperm chromatin using fixed samples

The integrity of the paternal DNA is essential for the accurate transmission of genetic information, yet fertilization is not inhibited by chromatin breakage. Some methods are available for the sensitive detection of DNA damage and can be applied in studies of environmental toxicology, carcinogenesis, aging, and assisted reproduction techniques in both clinical and experimental settings. Because semen samples obtained from remote locations undergo chromatin damage prior to laboratory assessment, the present study was undertaken to evaluate treatments for effective chromatin staining in the development of a DNA fragmentation assay using fixed milt from yellow perch (Perca flavescens). Similar to the sperm chromatin structure assay (SCSA), susceptibility of nuclear DNA to acid-induced denaturation was measured by flow cytometry (FCM). Use of 10% buffered formalin for milt fixation allowed easier peak discrimination than 4% paraformaldehyde. The effects of time and temperature of incubation in 0.08 N HCl were evaluated in order to determine the ideal conditions for promoting DNA decondensation and making strand breaks more available for staining and detection by FCM. The best results were obtained with incubation at 37°C for 1 minute, followed by cold propidium iodide staining for 30 minutes.

Conference Paper

Toxicokinetics of PAHs in Hexagenia

The accumulation kinetics of two waterborne polycyclic aromatic hydrocarbons (PAHs), benzo[a]pyrene (BAP) and phenanthrene (PHE), were studied in the mayfly nymph ( Hexagenia limbata ). The uptake clearance decreased while the bioconcentration of BAP increased with an increase in weight of the H. limbata nymph. The relationship between uptake clearance and bioconcentration for PHE was variable, and bioconcentration was greater for the heavier animals. Two kinetic models were used to evaluate the effect of nymph weight on disposition of PAHs: (a) the amount-uptake clearance model, similar to models most frequently used in environmental toxicology; and (b) a clearance-volume model, similar to models used in clinical pharmacology. The two models gave similar predictive results but were different in a few cases. These differences in common parameter estimation probably resulted from methodologies used and high data variability rather than the models themselves, since they are mathematically equal. Some of the parameters are unique to each of the models and are defined and described. The clearance of oxygen from water is inversely and linearly related to the weight of the mayfly nymphs, but oxygen clearances were always much less than the uptake clearances of the PAHs. The high PAH uptake clearance compared to oxygen clearance implies a greater surface area or efficiency for PAH accumulation from water.

Environmental Toxicology and Chemistry

Avian toxicologic diagnosis

This chapter describes the sources and pathophysiology of some potential poisons that affect birds and summarizes useful laboratory tests. The diagnosis of poisoning in birds, as in mammals, requires a complete and accurate history, careful observation of clinical signs, and a thorough necropsy evaluation. Appropriate sample handling and analysis, based on consultation with the diagnostic toxicologist, are critical (Table 19--1). Veterinary toxicology laboratories are becoming increasingly specialized, with only certain laboratories capable of analyzing for drug residues or anticoagulants, for example. Although a local laboratory may not be able to fulfill a specific test request, they may recommend an alternative laboratory or may be willing to forward the sample. As a general rule in suspect poisoning cases, large tissue samples of liver, kidney, brain, and subcutaneous fat and of crop, proventriculus, and ventriculus contents should be collected at necropsy and frozen. Appropriate samples should be submitted frozen, with the remainder held in the freezer for possible later testing. A second set of tissues should be placed in 10% formalin for histopathologic examination.

Book chapter

Seasonal variation in diagnostic enzymes and biochemical constituents of captive northern bobwhites and passerines

1. A variety of biochemical measurements were taken periodically in captive northern bobwhite ( Colinus virginianus L.), European starlings ( Sturnus vulgaris L.), red-winged blackbirds ( Agelaius phoeniceus L.) and common grackles ( Quiscalus quiscula L.) to determine whether baseline values remain sufficiently stable throughout the year for general clinical use in the absence of concurrent control specimens. 2. Variables included whole blood hemotacrit and hemoglobin, plasma lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, aspartate aminotransferase, alinine aminotransferase, creatine kinase, butyrylcholinesterase, alkaline phosphatase, glucose, albumin, total protein, creatinine, urea nitrogen, uric acid, cholesterol, and triglycerides, and brain acetylcholinesterase. Butyrl- and acetylcholinesterase were included because of their specific uses in toxicology. 3. Significant seasonal differences were detected for each of the variables except brain acetylcholinesterase in at least one of the species. Significant species differences were detected during at least one season for all of the variables measured. 4. All species were maintained outdoors, but only northern bobwhites came into reproductive condition and showed sex-differences in the clinical variables during their normal breeding season. 5. It was concluded that reference values for the 18 clinical variables measured could be calculated from our data for adult specimens of the species studied, and that results for one species cannot be extrapolated with certainty to any other species. 6. Estimated normal bounds for each of the 18 variables measured by commonly used clinical procedures are presented for reproductively quiescent northern bobwhites, European starlings, red-winged blackbirds, and common grackles.

Comparative Biochemistry and Physiology, Part B: C

Developmental toxicity in white leghorn chickens following in ovo exposure to perfluorooctane sulfonate (PFOS)

Studies show that perfluorinated compounds cause various toxicological effects; nevertheless, effects on immune function and developmental endpoints have not been addressed at length. This study examined the effects of perfluorooctane sulfonate (PFOS) in white leghorn hatchlings on various developmental, immunological, and clinical health parameters. In addition, serum PFOS concentrations were determined by LC/MS/MS. Embryonic day (ED) 0 eggs were injected with either safflower oil/10% DMSO (control, 0 mg/kg egg wt) or PFOS in safflower oil/10% DMSO at 1, 2.5, or 5 mg/kg egg wt, and the chicks were grown to post-hatch day (PHD) 14. Treatment with PFOS did not affect hatch rate. Following in ovo exposure chicks exhibited increases in spleen mass at all treatment levels, in liver mass at 2.5 and 5 mg/kg egg wt, and in body length (crown-rump length) at the 5 mg/kg treatment. Right wings were shorter in all treatments compared to control. Increases in the frequency of brain asymmetry were evident in all treatment groups. SRBC-specific immunoglobulin (IgM and IgY combined) titers were decreased significantly at all treatment levels, while plasma lysozyme activity was increased at all treatment levels. The PHA skin test response decreased in relation to increasing PFOS dose. Serum concentrations where significant immunological, morphological, and neurological effects were observed at the lowest dose (1 mg/kg egg wt) averaged 154 ng PFOS/g serum. These concentrations fall within environmental ranges reported in blood samples from wild caught avian species; thereby, verifying that the environmental egg concentrations used for the injections do indeed relate to serum levels in hatchlings that are also environmentally relevant. These data indicate that immune alterations and brain asymmetry can occur in birds following in ovo exposure to environmentally relevant concentrations of PFOS and demonstrates the need for further research on the developmental effects of perfluorinated compounds in various species. ?? 2009 Elsevier Inc.

Reproductive Toxicology

Determination of the median toxic dose of type C botulism in lactating dairy cows

Because of the difficulty in identifying botulinum toxin in cattle, it is hypothesized that cattle are sensitive to levels of toxin below the detection limits of current diagnostic techniques (the mouse protection bioassay and the immunostick enzyme-linked immunosorbent assay [ELISA] for type C botulinum toxin). Using an up-down method for toxicologic testing, the median toxic dose (MTD50) for cattle was determined. Four lactating Holstein cows were dosed at 0.125 or 0.25 ng/kg with Clostridium botulinum type C toxin and failed to develop clinical signs of botulism during the 7-day observation period. Three cows given 0.50 ng/kg of toxin developed clinical signs of botulism. From these results, the MTD50 was calculated at 0.388 ng/kg (3.88 mouse lethal doses/kg) using the trim-logit method. These results suggest that cattle are 12.88 times more sensitive to type C botulinum toxin than a mouse on a per kilogram weight basis. The mouse protection bioassay and the immunostick ELISA for type C botulinum toxin failed to identify the presence of the toxin in the serum, blood, and milk samples taken from all 7 animals.

Journal of Veterinary Diagnostic Investigation

Exposure of predatory and scavenging birds to anticoagulant rodenticides in France: Exploration of data from French surveillance programs

Wild raptors are widely used to assess exposure to different environmental contaminants, including anticoagulant rodenticides (ARs). ARs are used on a global scale for rodent control, and act by disruption of the vitamin K cycle that results in haemorrhage usually accompanied by death within days. Some ARs are highly persistent and bioaccumulative, which can cause significant exposure of non-target species. We characterized AR exposure in a heterogeneous sample of dead raptors collected over 12 years (2008–2019) in south-eastern France. Residue analysis of 156 liver samples through LC-MS/MS revealed that 50% (78/156) were positive for ARs, with 13.5% (21/156) having summed second-generation AR (SGAR) concentrations >100 ng/g ww. While SGARs were commonly detected (97.4% of positive samples), first-generation ARs were rarely found (7.7% of positive samples). ARs were more frequently detected and at greater concentration in predators (prevalence: 82.5%) than in scavengers (38.8%). Exposure to multiple ARs was common (64.1% of positive samples). While chlorophacinone exposure decreased over time, an increasing exposure trend was observed for the SGAR brodifacoum, suggesting that public policies may not be efficient at mitigating risk of exposure for non-target species. Haemorrhage was observed in 88 birds, but AR toxicosis was suspected in only 2 of these individuals, and no difference in frequency of haemorrhage was apparent in birds displaying summed SGAR levels above or below 100 ng/g ww. As for other contaminants, 17.2% of liver samples (11/64) exhibited Pb levels compatible with sub-clinical poisoning (>6 μg/g dw), with 6.3% (4/64) above the threshold for severe/lethal poisoning (>30 μg/g dw). Nine individuals with Pb levels >6 μg/g dw also had AR residues, demonstrating exposure to multiple contaminants. Broad toxicological screening for other contaminants was positive for 18 of 126 individuals, with carbofuran and mevinphos exposure being the suspected cause of death of 17 birds. Our findings demonstrate lower but still substantial AR exposure of scavenging birds compared to predatory birds, and also illustrate the complexity of diagnosing AR toxicosis through forensic investigations.

Science of the Total Environment

Diagnostic histological findings in Yosemite toads (Bufo canorus) from die-off in the 1970s

Twelve adult and 25 larval Yosemite toad ( Bufo canorus ) specimens from the eastern Sierra Nevada of California were examined histologically for evidence of infectious, toxicological, and degenerative diseases. The preserved toads were selected from 21 that had been salvaged or collected during a die-off in 1976-1979 that immediately preceded a population decline. Causes of death of four toads were determined histologically; clinical signs and field observations suggested causes of death of three more. Four toads died of infectious diseases, including chytridiomycosis of the skin ( N = 1), bacillary septicemia ( N = 2), and combined chytridiomycosis and bacterial septicemia ( N = 1). Infections by a funguslike organism ( Dermosporidium penneri ), renal myxozoa ( Leptotheca ohlmacheri ), larval Rhabdias, various gastrointestinal nematodes, urinary bladder flukes, and lung flukes were detected in five specimens. No evidence of degenerative diseases, virus infections, or intoxications was found. The variety of lethal diseases and our inability to determine the causes of death of five specimens suggests that one or more histologically undetectable diseases or intoxications may have also contributed to the deaths and population decline.

California

Oral and intramuscular toxicity of inorganic and organic mercury chloride to growing quail

The lethal toxicity of inorganic (HgCl 2 ) and organic (CH 3 HgCl) mercury chloride was compared for Coturnix (Japanese quail, Coturnix japonica) of different ages from hatch through adulthood by single‐dose acute oral and intramuscular injections and by a 5‐d dietary trial. Sublethal mercury toxicity was studied by evaluation of plasma and brain cholinesterase activity. CH 3 HgCl was more toxic than HgCl 2 in all tests at each age tested. LD50s consistently increased over the first 4 wk for both acute methods and both mercurials and then stabilized. The striking difference between single‐dose acute and 5‐d dietary tests was that CH 3 HgCl averaged about twice as toxic as HgCl 2 by both acute methods, compared to 100 times as toxic by the dietary method. For example, at 2 wk of age, the oral LD50s for CH 3 HgCl and HgCl 2 were 18 and 42 mg/kg and the dietary LC50s were 47 and 5086 ppm. When birds were fed HgCl 2 and developed clinical signs of intoxication, they could recover once treatment was withdrawn; however, on CH 3 HgCl, clinical signs often commenced after treatment was withdrawn, and then actually intensified for several days and culminated in death.

Journal of Toxicology and Environmental Health

Effects of dietary ABATE® on reproductive success, duckling survival, behavior, and clinical pathology in game-farm mallards

Forty-four pairs of game-farm mallards ( Anas platyrhynchos ) were fed ABATE ® 4E (temephos) to yield 0, 1, or 10 ppm ABATE ® beginning before the initiation of lay, and terminating when ducklings were 21 days of age. The mean interval between eggs laid was greater for hens fed 10 ppm ABATE ® than for controls. Clutch size, fertility, hatchability, nest attentiveness of incubating hens, and avoidance behavior of ducklings were not significantly affected by ABATE ® ingestion. The percentage survival of ducklings to 21 days of age was significantly lower in both treated groups than in controls, but brain acetylcholinesterase (AChE) activity was not inhibited in young which died before termination of the study. In 21-day-old ducklings, aspartate aminotransferase (AST) activity increased and plasma nonspecific cholinesterase (ChE) activity was inhibited by about 20% in both treatment groups, but there were no significant differences in brain AChE or plasma alanine aminotransferase (ALT) activities, or plasma uric acid concentration. Clinical chemistry values of adults were not affected. No ABATE ® , ABATE ® sulfoxide, or ABATE ® sulfone residues were found in eggs or tissue samples.

Archives of Environmental Contamination and Toxico

Toxicity of trimethyltin and triethyltin to mallard ducklings

Trimethyltin chloride (TMTC) and triethyltin chloride (TETC) were fed to mallard ( Anas platyrhynchos ) ducklings for 73 to 75 d, beginning when ducklings were 3 to 4 d old. Diets were mixed to contain 0, 0.5, 5 or 50 ppm Sn as either TMTC or TETC. Mortality occurred only in the 5 ppm (2/5 ducklings) and 50 ppm (5/5 ducklings, all dying within 5 d) TMTC groups. Death was preceded by cephalic tremors, lethargy and ataxia; these clinical signs also were observed in surviving ducklings from the 5 ppm TMTC group, but not the 0.5 ppm TMTC group. Ducklings fed 5 and 50 ppm Sn as TMTC exhibited degeneration of the large neurons of the pons, medulla oblongata, gray matter of the spinal cord and pyramidal cells of the cerebral cortex. TETC-fed ducklings showed few signs of clinical toxicosis. Ducklings fed 50 ppm Sn as TETC exhibited mild to severe vacuolization of the white matter of the brain and spinal cord; these lesions were not present in ducklings fed 5 ppm Sn as TETC. Liver, spleen, kidney, thymus, bursa of Fabricius and skeletal muscle presented no abnormal histopathology for either organotin compound. Hematocrit, hemoglobin and plasma aspartate aminotransferase; alanine aminotransferase; lactate dehydrogenase; alkaline phosphatase; and cholinesterase values were determined for the 5- and 50- ppm TMTC and TETC groups, and were not different from those of controls ( p < 0.05). Lesions and clinical signs of toxicosis in ducklings were consistent with those described for mammals exposed to TMTC and TETC. The effect threshold for TMTC in ducklings appears to exceed current environmental concentrations. Environmental concentrations of TETC have not been reported.

Environmental Toxicology and Chemistry

Safety of florfenicol administered in feed to tilapia (Oreochromis sp.)

The safety of Aquaflor&reg; (50% w/w florfenicol [FFC]) incorporated in feed then administered to tilapia for 20 days (2x the recommended duration) at 0, 15, 45, or 75 mg/kg body weight/day (0, 1, 3, or 5x the recommended dose of 15 mg FFC/kg BW/d) was investigated. Mortality, behavioral change, feed consumption, body size, and gross and microscopic lesions were determined. Estimated delivered doses were >96.9% of target. Three unscheduled mortalities occurred but were considered incidental since FFC-related findings were not identified. Feed consumption was only affected during the last 10 dosing days when the 45 and 75 mg/kg groups consumed only 62.5% and 55.3% of the feed offered, respectively. There were significant, dose-dependent reductions in body size in the FFC-dose groups relative to the controls. Treatment-related histopathological findings included increased severity of lamellar epithelial hyperplasia, increased incidence of lamellar adhesions, decreased incidence of lamellar telangiectasis in the gills, increased glycogen-type and lipid-type hepatocellular vacuolation in the liver, decreased lymphocytes, increased blast cells, and increased individual cell necrosis in the anterior kidney, and tubular epithelial degeneration and mineralization in the posterior kidney. These changes are likely to be of minimal clinical relevance, given the lack of mortality or morbidity observed. This study has shown that FFC, when administered in feed to tilapia at the recommended dose (15 mg FFC/kg BW/day) for 10 days would be well tolerated.

Toxicologic Pathology

Field evaluation of lead effects on Canada geese and mallards in the Coeur d'Alene River Basin, Idaho

Hatch year (HY) mallards ( Anas platyrhynchos ) in the Coeur d'Alene (CDA) River Basin had higher concentrations of lead in their blood than HY Western Canada geese ( Branta canadensis moffitti ) (geometric means 0.98 versus 0.28 μg/g, wet weight). The pattern for adults of both species was similar, although geometric means (1.77 versus 0.41 μg/g) were higher than in HY birds. HY mallards captured in the CDA River Basin in 1987 contained significantly lower lead concentrations in their blood than in 1994–95 (0.36 versus 0.98 μg/g); however, some very young mallards were sampled in 1987, and concentrations in adults were not significantly different in 1987, 1994, or 1995 (1.52, 2.07, 1.55 μg/g, respectively). Both species in the CDA River Basin in 1994–95 showed significantly reduced red blood cell delta-aminolevulinic acid dehydratase (ALAD) activity compared to the reference areas: Canada geese (HY −65.4 to −86.0%, adults −82.3%), and mallards (HY −90.7 to −95.5%, adults −94.1%). Canada goose goslings were divided into size classes, and the two smaller classes from the CDA River Basin had significantly elevated free erythrocyte protoporphyrin (protoporphyrin) levels compared to the reference area (15.2× and 6.9×). HY and adult mallards both had significantly elevated protoporphyrin (5.9× and 7.5×). Recognizing that interspecific differences exist in response and sensitivity to lead, it appears (at least for hemoglobin and hematocrit) that Canada geese were more sensitive to lead than mallards, i.e ., adverse hematologic effects occur at lower blood lead concentrations. Only Canada geese from the CDA River Basin, in spite of lower blood lead concentrations, had significantly reduced mean hemoglobin and hematocrit values. No euthanized Canada geese (all HYs) from CDA River Basin were classified as clinically lead poisoned, but 38 Canada geese found dead in the CDA River Basin during a concurrent study succumbed to lead poisoning between 1992 and 1997. Only 6 (15.8%) of these 38 contained ingested lead shot, which contrasts greatly with the 75–94% incidence of ingested lead shot when mortality was due to lead shot ingestion. Lead from other contaminated sources ( i.e ., sediments and vegetation) in the CDA River Basin was strongly implicated in most Canada goose deaths. Based on the 31 live mallards and Canada geese collected in the CDA River Basin, which were representative of the live populations blood sampled only, the prevalence of subclinical and clinical lead poisoning (as determined by liver lead concentrations, excluding birds with ingested lead shot) was higher in mallards: subclinical (4 of 8, 50% HYs and 6 of 11, 55% adults); clinical (0% HYs and 4 of 11, 36% adults), with less data available for Canada geese (only 1 of 9, 11% HYs marginally subclinical). The clinically lead-poisoned mallards had extremely high concentrations of lead in blood (2.69–8.82 μg/g) and liver (6.39–17.89 μg/g). Eight mallards found dead in the CDA River Basin during a concurrent study were diagnosed as lead poisoned, and only one (12.5%) contained ingested lead shot, which again strongly implicates other lead sources. The finding of dead lead poisoned Canada geese together with the high percentage of live mallards classified as subclinically or clinically lead poisoned, in combination with the low incidence of ingested lead shot causes us concern for both of these species, which live in association with lead-contaminated sediment in the CDA River Basin.

Idaho

Acid precipitation and food quality: Effects of dietary Al, Ca and P on bone and liver characteristics in American black ducks and mallards

American black ducks ( Anas rubripes ) and mallards ( A. platyrhynchos ) were fed diets varying in concentrations of aluminum (Al), calcium (Ca), and phosphorus (P) for 10 weeks to identify toxic effects of Al under conditions representative of areas with acid precipitation. Femur and liver tissues were analyzed for Al, Ca, and P concentrations and structural characteristics. At two weeks of age, both species demonstrated pronounced differences in femur Al and P concentrations and femur mass from dietary Al and interaction between Ca:P regimen and Al; Low Ca:Low P enhanced Al storage and decreased P and mass in femurs. Femur Ca was lowest in the Low Ca:Low P regimen but was not affected by dietary Al. At 10 weeks, femur and liver Al continued to vary with dietary Al. Elevated Al and reduced Ca lowered modulus of elasticity. Femur P increased with elevated dietary P in black ducks. Elevated dietary P negated some of the effects of dietary Al on femur mass in black ducks. Reduced Ca concentrations weakened bones of both species and lowered both Ca and P. An array of clinical signs including lameness, discoloration of the upper mandible, complete and greenstick fractures, and death were responses to elevated Al and Ca:P regimen. Black ducks seemed to display these signs over a wider range of diets than mallards. Diets of 1,000 mg/kg Al had toxic effects on both species, particularly when combined with diets low in Ca and P.

Archives of Environmental Contamination and Toxico

Safety of Aquaflor (florfenicol, 50% Type A Medicated Article), administered in feed to channel catfish, Ictalurus punctatus

Aquaflor, a feed premix containing the broad spectrum antibacterial agent florfenicol (50% w/w), is being developed for use to control enteric septicemia (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative enterobacterium Edwardsiella ictaluri . The recommended dose of Aquaflor to control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was to determine the safety of Aquaflor administered in feed to channel catfish at doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days. Parameters evaluated included daily mortality, behavioral (appetite, distribution, flight/fright response), and water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Medicated feed consumption was 67—86% of target with group mean doses of 8.5 mg/kg BW/day, 24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically observable changes noted at any of the dose levels tested. Aquaflor-related changes were limited to the food consumption and histopathology data. Although Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg BW/day groups, there were no differences in fish growth among the treatment groups. Aquaflor-related histopathology findings were limited to a histomorphologically evident dose-dependent decrease in hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys, and spleens of channel catfish.

Toxicologic Pathology