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At least 19 recordsLinked to original sources
PubMed1982

Effect of carbadox and various dietary copper levels for weanling swine.

Two experiments were conducted to evaluate the responses to carbadox and Cu additions in the postweaning diet of swine. The first trial contained 470 pigs in five replicates in a 2 X 5 factorial arrangement in a randomized complete block design. Weanling pigs 4-wk of age were fed diets containing 0 or 55 ppm carbadox and 0, 125, 375 or 500 ppm Cu for a 5-wk period. Copper levels of 125 and 250 ppm resulted in improved pig gains and feed intakes, but at 500 ppm, gains and feed intake declined. Carbadox resulted in enhanced gain and feed performance throughout the trial, but most notably during the initial 2-wk period. Copper improved performance measurements only during the latter 3-wk and for the overall period. There was an additive performance response when carbadox and Cu (125 ppm) were provided in combination. When carbadox was not provided, growth responses increased to the 250 ppm dietary Cu level. Liver, kidney cortex, heart and plasma Cu concentrations increased quadratically as dietary Cu levels increased, with the greatest change occurring between 250 and 500 ppm dietary Cu levels. A N and Cu balance trial in group feeding conditions involving 65 pigs was conducted in two replicates of a 2 X 2 X 5 factorial arrangement of a split-block design. Pigs were ad libitum fed diets with or without 250 ppm Cu and carbadox at 0 or 55 ppm for a 5-wk period. A fifth treatment group fed the 250 ppm Cu plus carbadox diet was pair-fed to the pigs fed the basal treatment. Growth rate and N retention increased when carbadox, but not when Cu was provided. When carbadox and Cu were provided in combination, either ad libitum or pair-fed, N retention was greater than when the basal diet was fed. This response was attributed to the carbadox addition. The carbadox addition reduced Cu retention and liver Cu concentrations.

Animals↗
PubMed1991

Optimization and ruggedness testing of the determination of residues of carbadox and metabolites in products of animal origin. Stability studies in animal tissues.

A method developed for the determination of residues of carbadox and its metabolites in swine tissues using high-performance liquid chromatography with on-line precolumn enrichment and postcolumn derivatization with UV-VIS detection was optimized and the applicability of the method was extended to plasma and eggs. With the optimized method, more than twenty samples per person per day can be analysed. In the matrices investigated, the observed limit of determination for carbadox is 0.5-1 micrograms/kg and for desoxy-carbadox 0.5-2 micrograms/kg. The mean recovery for desoxy-carbadox in kidney, muscle and liver as established by two laboratories over a 2-month period is 95% (relative standard deviation = 14%, N = 37, 10 micrograms/kg). In other matrices the recoveries are between 83 and 91%. The recovery for carbadox is 70-80% in muscle, plasma and eggs. The method has been used routinely in pharmacokinetic and surveillance studies. Stability studies of kidney and liver samples spiked with carbadox showed that carbadox is rapidly decomposed (in vitro metabolism). After storage for about 1 h at 4 degrees C, more than 50% of the added amount is converted by reduction to desoxy-carbadox. In contrast, carbadox is stable in eggs and muscle under spiking conditions and during storage at -20 degrees C. Desoxy-carbadox is stable during spiking and storage at -20 degrees C in eggs and muscle. In kidney and liver, its stability was good under spiking conditions but could not be proved unequivocally during storage.

Animals↗
PubMed1988

Some pharmacokinetic observations of carbadox medication in pigs.

Concentrations of carbadox and a first metabolite, desoxycarbadox, were measured in contents of the porcine gastrointestinal tract after in-feed administration of carbadox in therapeutic dosages (100-150 ppm). The levels of carbadox in the relevant parts of the gastrointestinal tract were found to be lower than the MIC-values reported for enteropathogenic microorganisms at their sites of action. The presented observations do not provide a pharmacological rationale for the therapeutic use of carbadox in the treatment of dysentery and diarrhoea in swine. The carbadox levels encountered in the proximal part of the gut (stomach, duodenum) however, seem to indicate that in-feed administration of 50 ppm carbadox can provide an effective prophylaxis against Treponema hyodysenteriae, a causative agent in swine dysentery. The timecourse of the blood levels of carbadox and desoxycarbadox after in-feed administration of carbadox (50 ppm) and the concentration profiles in the gastrointestinal tract are discussed with regard to the disposition of this drug in pigs.

Animal Feed↗
PubMed1989

Clinical signs and performance of pigs during the administration of different levels of carbadox and after withdrawal.

An experiment was designed to study the clinical effects of carbadox in pigs. Five different carbadox levels were tested namely 25, 50, 100, 150, and 200 ppm. They were compared with a control group fed on a diet without medication. After 10 weeks all pigs received a diet without carbadox till the end of the experiment, 21 weeks after the start. After two weeks of carbadox treatment the first clinical signs were observed in the 200 ppm group. The most obvious effects seen were production of dry faeces and drinking of urine from the floor or from pen-mates. Other signs were a decreased abdominal volume, a pale skin with long withered hair, perverted eating and a restless behaviour. The haematocrit values in pigs receiving 100 ppm and upwards were increased. There was a negative correlation between the dose of carbadox and the time after which the response occurred. Weight gain was significantly lowered and feed conversion essentially poorer in the 200 ppm, 150 ppm and 100 ppm groups during the treatment as compared to the controls. No growth promoting effect was seen in the 25 and 50 ppm groups. After withdrawal of carbadox, clinical signs persisted in the 150 and 200 ppm groups. The 100 ppm group produced normal faeces 5 weeks after withdrawal, whereas drinking of urine persisted. From this study it appears that only an oral dosage of 25 ppm or lower can be given to pigs without risks of toxic effects. The widely claimed growth promoting effect of carbadox could not be confirmed in this study. This might be due to the small number of animals per group.

Animals↗
PubMed1990

Clinical signs and performance of pigs treated with different doses of carbadox, cyadox and olaquindox.

An experiment was designed to study the clinical effects of different levels of carbadox, cyadox and olaquindox in the ration on health, weekly weight gain and feed conversion in pigs. Four different carbadox and olaquindox (25, 50, 100 and 200 ppm) levels and five different cyadox (25, 50, 100, 200 and 400 ppm) levels were tested in groups of 6 pigs during 6 weeks. The 13 groups were compared with a control group fed on the same diet with only vehicle. After one week the first clinical sign, a high faecal dry matter (FDM) content, was observed in the 200 ppm carbadox group, followed by the 100 and 50 ppm carbadox, the 400 and 100 ppm cyadox, and the 200 and 100 ppm olaquindox groups two weeks later. A second clinical sign, urine drinking from the floor or from pen-mates, was observed in the same pens, occurring in the same sequence. The third important clinical sign, a decreased abdominal volume, was also observed in almost the same sequence, however, in the 50 ppm olaquindox and cyadox groups this clinical sign was not observed. Average weekly weight gain was significantly decreased in the higher carbadox and olaquindox groups. Weight gain was significantly increased in the 200 ppm cyadox group. Hematocrit values were significantly increased in the 200 and 100 ppm carbadox groups only. From this study one may conclude that, within the dosages used, carbadox is more harmful than olaquindox for pigs, and it seems that cyadox is harmless for pigs in dosages up to 400 ppm.

Animals↗
PubMedDate not supplied

Liquid chromatographic monitoring of the depletion of carbadox and its metabolite desoxycarbadox in swine tissues.

A liquid chromatographic method was used to monitor a depletion study of carbadox (and its most important metabolite, desoxycarbadox) in young pigs fed carbadox-treated rations for 1 week. Carbadox was found in blood (20 ppb), blood serum (26 ppb), and muscle tissue 24 h after withdrawal from treated ration; residues were reduced to a trace (less than 2 ppb) in 48 h, and eliminated by 72 h. Desoxycarbadox, although not detected in blood, was found in muscle (17 ppb) 24 h after withdrawal; it was reduced to 9 ppb at 48 h and to a trace by 72 h. Although no carbadox was detected in liver 24 h after withdrawal, appreciable desoxycarbadox (125 ppb) was found in liver 24 h after withdrawal; it was reduced to 17 ppb at 48 h and to a trace by 72 h. Whereas only a trace of carbadox was found in kidney 24 h after withdrawal, 186 ppb desoxycarbadox was found in kidney at 24 h, 34 ppb at 48 h, and a trace at 72 h. No metabolite of carbadox other than desoxycarbadox was found in extracts of swine tissues during this medicated feed trial, and no metabolite was found in blood extracts by using the established methodology. The effect of tissue storage (aging) at -20 degrees C on levels of the drug and its metabolite was a modest alteration of residue levels. The inadvertent use of feed adulterated with furazolidone and initially medicated with chlortetracycline, sulfamethazine, and penicillin G, did not affect the uptake of carbadox in this depletion study or interfere with the analytical methodology.

Animal Feed↗
PubMed1979

Modified method for carbadox in feeds: collaborative study.

The official first action method for carbadox in swine feed, 42.C01-42.C04, was modified in 2 respects. First, the samples were leached overnight at room temperature instead of boiled for 1 hr. This change avoided problems with overheating and excessive evaporation. Second, the dilution scheme for samples spiked with carbadox standard solution was changed to give absorbance values that were within the optimum working range of all types of spectrophotometers. The modified procedure was collaboratively studied by 21 laboratories. The repeatability standard deviation (sigma0) and reproducibility standard deviation (sigmax) were sigma0 = 0.00029% and sigmax = 0.00056% (8.9% of grand mean) for feeds containing 0.00617% carbadox; and sigma = 0.0012% and sigmax = 0.0019% (9.3% of grand mean) for feeds containing 0.0198% carbadox. The between-laboratory variance ratio was significant for feeds containing 0.0198% carbadox. The mean per cent of intent values for feeds containing 0.00617% carbadox and 0.0198% carbadox were 102% and 104%, respectively. In general, the statistical results were comparable to those previously obtained for the official first action method. Consequently, the modified procedure is not recommended as a replacement for the official first action method.

Animal Feed↗
PubMed1985

Effect of carbadox on growth, fasting metabolism, thyroid function and gastrointestinal tract in young pigs.

Five experiments were done with 34 weanling and 24 growing crossbred gilts. Individually penned pigs were fed ad libitum (expt 1) or pair-fed (expt 2 through expt 5) for either 2 (expt 1 through expt 4) or 3 (expt 5) wk. Mean body weight gain and gain/feed values were significantly (P less than 0.05) greater in pigs fed carbadox (a synthetic antimicrobial). Fasting O2 consumption and CO2 production of pigs were measured during the 32- to 48-h (expt 1, 4 and 5) or during the 24- to 40-h (expt 2 and 3) postprandial periods with indirect open circuit calorimeters. Carbadox reduced O2 consumption significantly (P less than 0.05) in expt 2, but had no significant effect on CO2 production in any of the five experiments. The weight of thyroid gland and the plasma concentrations of L-3,3',5-triiodothyronine (T3) and thyroxine (T4) of pigs were not altered by carbadox. The mean weight, but not the length, of small intestine tended to be less in pigs fed carbadox. It is suggested that the growth-promoting effect of carbadox on young pigs may be associated with the weight of small intestine and its physiological processes such as metabolic rate. However, no definite effects of carbadox on whole-animal fasting metabolic rate and thyroid function could be demonstrated by the methods used in the present study.

Animals↗
PubMedDate not supplied

Liquid chromatographic determination of carbadox in complete feeds, premixes, and concentrates: interlaboratory study.

A liquid chromatographic (LC) method previously published for the determination of carbadox in finished feeds and premixes was slightly modified and tested in an interlaboratory study. The feed samples are extracted with methanol-acetonitrile (50 + 50) after wetting with water. The extracts are purified over a short alumina column. An aliquot of the eluate is analyzed with reverse phase liquid chromatography with ultraviolet detection. Before the actual interlaboratory study, a prestudy with 2 familiarization feed samples was performed. For the interlaboratory study, 2 series of meal and pelleted samples were prepared with carbadox from different suppliers. Eight collaborating laboratories received 6 feed samples previously milled and ground and 4 pelleted samples which had to be ground by the collaborator's in-house method. Collaborators also received 3 carbadox concentrates (about 10% w/w) and 4 premix samples derived from the concentrates (about 1% w/w). Coefficients of variation under reproducibility conditions were 8.3% for meal samples and 4.9% for pellets. A minor but significant effect was noted for the influence of pelleting temperature on the carbadox content. A minor and insignificant effect was observed for the influence of the milling and grinding procedure on the carbadox content. Alumina cleanup of 1% premixes was not essential, although the resulting chromatograms were cleaner. A slight difference in reproducibility was observed with concentrates (10%) when 0.2 or 0.5 g sample size was used, although the average carbadox concentration found was the same. For premixes and concentrates, coefficients of variation under reproducibility conditions were low, ranging from 2.9 to 7.5%.

Animal Feed↗
PubMed1981

Mutagenicities of carbadox and olaquindox--growth promoters for pigs.

Carbadox and olaquindox were examined for mutagenicities in the repair tests with Bacillus subtilis (rec assay) and Salmonella typhimurium (uvr assay) and in the reverse mutation test (TA100 and TA98 of S. typhimurium). Both compounds were positive in the rec and uvr assays, and were highly mutagenic for strains TA100 and TA98. Carbadox was about 6 times move mutagenic than olaquindox in the absence of S9 mix. When incubated in S9 mix or bacterial cytosol (BC) mix for various times at 37 degree C, carbadox was found to lose its mutagenic activities easier than olaquindox. The mutagenicity of carbadox was almost inactivated at 10 min after incubation with S9 mix, but olaquindox still retained its activities even at 20 min. While carbadox required 20 min to be inactivated in BC mix, olaquindox was not completely inactivated even if incubated for 60 min.

Bacillus subtilis↗
PubMed1986

[Protein supply and the use of carbadox in growing swine].

In a growth experiment with 144 pigs of the landrace breed in the body weight range of 20 to 100 kg the effect of Carbadox at constant and decreasing levels in the feed until 60 kg body weight on the growth performance and the digestibility of the nutrients in rations with a varying protein supply was studied. The following results were obtained: The supplementation of Carbadox to protein rich diets caused only a small increase in daily body weight gain and feed conversion ratio. The increase of growth performance as a consequence of the addition of Carbadox was more pronounced with the low protein diets. From this result a protein sparing effect of Carbadox can be derived. The effect of Carbadox on growth performance could be observed from 20 to 60 kg body weight and over the whole experimental period from 20 to 90 kg. The increase of growth performance could be largely explained by a better digestibility of the nutrients.

Animal Feed↗
PubMed1981

R plasmid with carbadox resistance from Escherichia coli of porcine origin.

Escherichia coli isolates of porcine fecal origin from a farm where the antibacterial agent carbadox was used were examined for resistance to carbadox (Cdxr). Of 72 strains examined, 24 showed resistance to this drug. All 24 Cdxr strains, except one, were also resistant to tetracycline (Tcr), streptomycin (Smr), spectinomycin (Spcr), sulfadimethoxine (Sur), kanamycin (Kmr), ampicillin (Apcr), or a combination of tetracycline, streptomycin, spectinomycin, sulfadimethoxine, and ampicillin. The Cdxr character was invariably transmissible by conjugation to E. coli K-12 jointly with other drug resistance, with the resistance patterns present in transconjugants being Cdxr Smr Spcr Apcr or Cdxr Smr Spcr Sur Apcr. About 25% of these transconjugants simultaneously lost the resistance to carbadox, streptomycin, spectinomycin, and ampicillin or carbadox, streptomycin, spectinomycin, sulfadimethoxine, and ampicillin or carbadox, streptomycin, spectinomycin, sulfadimethoxine, and ampicillin in the presence of acriflavine. Agarose gel electrophoretic analysis of deoxyribonucleic acid from a transconjugant showed a single plasmid deoxyribonucleic acid molecule with a molecular weight of about 28 x 10(6), which was capable of transforming E. coli C to Cdxr Smr Spcr Apcr. This resistance was transmissible by conjugation as a unit to other K-12 strains. These results confirmed the presence of an R plasmid specifying the Cdxr character in the host strain.

Animals↗
PubMed1984

Responses of weanling pigs to dietary supplementation with vitamin C or carbadox.

A 2 X 2 factorial arrangement with two levels (0, 660 ppm) of vitamin C and two levels (0, 55 ppm) of carbadox supplementation was used in two experiments with 112 crossbred pigs weaned between 4 and 5 wk of age. An 18% protein corn-soybean meal-oats-dried whey starter diet was used as the basal diet. Each diet was fed ad libitum for a 4-wk period to three replicates of four pigs in Exp. 1 and to four replicates of four pigs in Exp. 2. Vitamin C supplementation produced a significantly higher plasma vitamin C concentration in weanling pigs, but, contrary to results of our previous study, failed to improve average daily gain of the pigs. Daily gain was, however, improved significantly by carbadox supplementation. Carbadox also produced a significantly higher plasma vitamin C concentration in pigs after a 7-d lag period. Plasma Fe concentration of pigs was not affected by supplemental vitamin C, but was significantly higher in those fed carbadox-supplemented diets. Plasma ceruloplasmin concentration increased significantly in all treatment groups from the initial sampling period (d 0) to subsequent periods. No interactions between supplemental vitamin C and carbadox were observed in daily gain, feed efficiency and the measured plasma constituents.

Animals↗
PubMed1989

Changes in plasma renin activity and renal immunohistochemically demonstrated renin in carbadox treated pigs.

Carbadox is known to induce toxic effects on the adrenal cortex, resulting in hypoaldosteronism. To study the involvement of carbadox on the renin-angiotensin system, weaned piglets of five weeks old received feed supplemented with 0 (control group), 50, 100, 150 or 200 ppm carbadox. After four weeks the 100 and 150 ppm groups had significantly higher plasma renin activity levels than the control group and after nine weeks plasma renin activity levels of all treated groups were significantly higher than the control group. Five and 10 weeks after carbadox administration, three and two pigs, respectively, of all groups were necropsied and the kidneys were screened for immunohistochemically demonstrated renin. All dosed pigs demonstrated an increase of immunoreactive renin, which was dose- and time-related. From these results it is concluded that carbadox induces activation of the renin-angiotensin system, secondary to the suppressing effect on mineralocorticoid secretion and that these changes may be responsible for part of the clinical picture.

Administration, Oral↗
PubMed1989

Comparative study of the effect of the effect of carbadox, olaquindox and cyadox on aldosterone, sodium and potassium plasma levels in weaned pigs.

To study the effects of olaquindox and cyadox on aldosterone, sodium and potassium in the blood in comparison with the effects of carbadox, weaned pigs were fed these compounds in different doses. Pigs treated with 100 and 200 ppm carbadox showed a significant decline of aldosterone after five and three weeks, respectively, compared with control values. In the 200 ppm group treatment was interrupted at week 4. With olaquindox a continuous, significant decline was found from 50 ppm and above after five weeks, and from 25 ppm and above (but excluding the 100 ppm group), after six weeks. In the cyadox groups a significant decline was measured after six weeks in the 50, 200 and 400 ppm groups. Only the 200 ppm group had an earlier response at three and five weeks. A decrease of sodium to hyponatraemic levels in the carbadox groups was seen after three weeks in the 200, and after five weeks in the 100 ppm group. In the olaquindox groups only the 200 ppm dosage showed a consistent decrease to hyponatraemic levels from four weeks treatment. In the cyadox groups the 200 ppm dosage reached a hyponatraemic level after six weeks. An increase of potassium to hyperkalaemic levels occurred at 100 and 200 ppm carbadox dosage after four and three weeks, respectively, and at 200 ppm olaquindox dosage after four weeks. No hyperkalaemic levels were seen in the cyadox groups. It is concluded that the toxic effect of olaquindox, despite minor differences, is comparable with that of carbadox but that cyadox is less toxic.

Aldosterone↗
PubMedDate not supplied

Liquid chromatographic determination of carbadox and desoxycarbadox in medicated feeds and in porcine gastrointestinal tract.

A liquid chromatographic method for the assay of carbadox and desoxycarbadox in medicated feeds and porcine stomach and intestinal contents is described. Samples were extracted with dimethylformamide-water and cleaned up on an alumina column. The eluate was chromatographed using either gradient elution for simultaneous assay of both compounds or isocratic elution for carbadox only. Detection of carbadox by its native fluorescence yielded a sensitive and specific assay without interferences by metabolites or matrix components. The optimal UV absorption of desoxycarbadox was at 280 nm. Mean recoveries of carbadox in spiked feed and stomach contents were 104 and 97%, respectively; mean recovery of desoxycarbadox in stomach contents was 106%. The day-to-day reproducibility for carbadox in different feed samples and stomach contents samples had a coefficient of variation of 6-13%.

Animal Feed↗
PubMed1975

[Toxicity by relay. II. A method for the asessment of safety to human consumers of carbadox, a growth-promoting additive to the feed of slaughter pigs].

A toxicity by relay. II. A method for the assessment of safety to human consumers of carbadox, a growth-promoting additive to the feed of slaughter pigs. A new methodology called "toxicity by relay" has been used to assess the potential hazard to humans of incorporating an additive into animal feeds. This methodology considers a farm-reared animal as a "relay" between the food additive and the human consumer, and employs laboratory animals as "pseudo-consumers". These laboratory animals are fed throughout their entire lives with the meat or organs of the "relay" animals which have been reared on feeds supplemented with various levels of the additive. In the present study, the toxicity of carbadox was assessed in this way. In pigs, where it is used as a growth promoter, carbadox is metabolised into serveal different products, and so an assessment of its safety using traditional methods of studying the toxicity of a substance and tis known metabolites, would perhaps be subject to error. A safety factor for man, in relation to the safety factors for rats and dogs, was calculated using (a) the comparative consumption of the laboratory animals and man; (b) an assessment of the highest dosage likely to be consumed in normal circumstances compared to the laboratory dosage, and (c) the consideration that in the laboratory there is no period of withdrawal from feeding before sacrifice as is the case with animals for slaughter. Pigs were used as "relays" in the present study by supplementing their feed with carbadox. The meat and/or livers of these animals were then fed daily to (a) rats for a period of 3 generations; (b) rats for 24-25 months, and (c) dogs for 60 months. No abnormalities were observed at the termination of the experiments. We may therefore conclude that there is no hazard for the human consumer from the use of carbadox as a pig-feed additive.

Animal Feed↗
PubMed1986

Hypoaldosteronism in piglets induced by carbadox.

An exploratory study was made of the mechanisms underlying the toxic action of carbadox in young pigs: dehydration, loss of appetite and at autopsy seemingly specific and selective structural alterations of the glomerular zone of the adrenal cortex. Administration of carbadox in the feed, in dosages of 150 ppm (approximately 6 mg X kg-1 b. wt X day-1) caused a rapid decline in the plasma aldosterone levels (to 10% of control) followed by significant changes in the sodium and potassium levels in blood. Characteristic for the toxic action of carbadox are the rapid and seemingly selective and specific alterations in the aldosterone-releasing zona glomerulosa of the adrenals. Our results indicate that with carbadox a functional and possibly reversible extirpation of the adrenal zona glomerulosa can be achieved in pigs.

Adrenal Cortex↗