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Pulmonary toxicity of stable and radioactive lanthanides.

The pulmonary toxicity of inhaled lanthanides has been the subject of debate. In question have been the relative contributions of radioactive vs. stable elements in the development of lanthanide-associated progressive pulmonary interstitial fibrosis. The central question of this debate is: Are lanthanide dusts that are devoid of radioactive contaminants capable of producing progressive pulmonary disease, or are lanthanide-induced lesions more appropriately termed "benign pneumoconioses"? This paper examines the epidemiologic and experimental record in order to answer the above question. It is clear from the available data that significant pathogenic potential of inhaled lanthanides exists and is related to the type and physicochemical form of the material inhaled and to the dose and duration of exposure. Contamination of the dust with radioactive materials may accelerate and enhance the pathologic response, depending on the form and dose of radioactivity encountered. Nevertheless, there is little evidence to suggest that the level of radioactive contamination of occupationally encountered lanthanide dusts is sufficient to be included as a risk factor for pulmonary disease. Thus, the pulmonary syndrome induced by stable rare earths includes progressive pulmonary fibrosis and should not be referred to as "benign pneumoconiosis."

Administration, Inhalation↗

Reevaluation of the committed dose equivalent from 232Th and its radioactive progeny.

Multicompartmental models were used in ICRP Publication 30 to describe the metabolism of radioactive elements and their retention in specific organs and tissues. Despite their use of more complicated and sophisticated metabolic models than those used in its earlier ICRP Publication 2 in 1959, the ICRP assumed that the radioactive progeny of 232Th that are produced in the body metabolize like their parents in its Publication 30. This assumption was made for mathematical simplicity and out of necessity when organs and tissues named for the parent are not included in the model of the progeny. This simplifying assumption can lead to overestimates of doses to tissues, especially the critical cells on bone surfaces. More realistic metabolic models and parameter values for 232Th and its radioactive progeny have been developed to estimate the total committed dose equivalent from 232Th and all of its radioactive progeny per unit intake of 232Th only. It is believed that this research has led to (1) more realistic estimates of doses from 232Th and its radioactive progeny over any applicable period of time after an intake, (2) more appropriate derived limits, and (3) metabolic models that can be used in the design of bioassay programs.

Biophysical Phenomena↗

Security of radioactive material at academic institutions.

In recent years, regulatory emphasis on the prevention of loss, theft and intentional misuse of radioactive materials at academic institutions has forced radiation safety personnel to devote increasing amounts of time and effort to address security issues. NRC regulations require that radioactive materials used or stored in controlled or unrestricted areas be secure from unauthorized removal or be under constant surveillance when in use. This leaves open to interpretation what types of security are required for radioactive materials in restricted areas. Adhering to the goal of keeping exposures As Low As Reasonable Achievable (ALARA), a risk-based system for radioactive materials security in a university setting is proposed based on Annual Limits of Intake (ALI). This system establishes levels of security based on physical form, activity and concentration. Using this system, radiation safety personnel can more effectively establish reasonable security measures for radioactive material consistent with minimizing the realistic potential of serious harm or injury.

Drug Storage↗

A new, peroral non-radioactive vitamin B12 absorption test compared with the Schilling test.

The results of a non-radioactive, peroral absorption test have been compared with the results of the traditional Schilling test in 31 cobalamin-deficient patients. The non-radioactive test is simple to perform, is less costly than the Schilling test and seems to give reliable results. The non-radioactive test should be performed after cobalamin treatment, but not until the plasma cobalamin value has declined to below 450 pmol/l. Normal Schilling test was noted in one-third of the patients, while normal non-radioactive test was noted in only one-fifth of the patients. The results reveal some discrepancies between the two tests regarding the response to intrinsic factor. In the non-radioactive test without intrinsic factor, the great variation in values may reflect varying secretion of intrinsic factor, possibly secondary to infestation with Helicobacter pylori. "False normal" Schilling test seems to be more common than previously believed.

Administration, Oral↗

Incorporation of radioactive seleno-(75Se)-methionine into mumps virus.

Mumps virus was grown in embryonated chicken eggs in the presence of radioactive seleno-((75)Se)-methionine. Virus in the allantoic and amniotic fluids was concentrated in a sucrose density gradient, and a peak of viral material coincided with a significant peak of (75)Se-radioactivity. The radioactivity was acid-insoluble and remained associated with the virus after purification by erythrocyte adsorption and elution and centrifugation on a second sucrose density gradient. After amino-acid hydrolysis of the radioactive virus, only (75)Se-methionine was recovered by chromatographic analysis. These results demonstrate that the radioactive (75)Se-methionine was incorporated into protein of infectious mumps virus.

Adsorption↗

Biliary excretion of radioactivity after intravenous administration of 3H-1,25-dihydroxyvitamin D3 in man.

Biliary radioactivity excretion was studied in 10 patients with postcholecystectomy T-tube drainage after intravenous administration of 3H-1,25-dihydroxyvitamin D3. The mean +/- SD radioactivity excreted in T-tube bile expressed as a percentage of the administered dose was 18.9 +/- 10.7% per 24 hours. After correction for incomplete bile collection the value obtained was 28.8 +/- 12.8%. The mean chloroform solubility of the biliary radioactivity increased from 17.0 +/- 8.4% to 69.4 +/- 15.1% after incubation with beta-glucuronidase. High performance liquid chromatography of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than 1,25(OH)2D3. The percentage radioactivity eluting as 3H-1,25(OH)2D3 increased from approximately 2.4 +/- 1.9 to 16.2 +/- 8.0 after incubation with beta-glucuronidase. We conclude that significant amounts of intravenously administered 3H-1,25(OH)2D3 are excreted in bile, mostly as more polar metabolites. The increase in free 3H-1,25(OH)2D3 after incubation with beta-glucuronidase indicates that glucuronides of 1,25(OH)2D3 are present in bile.

Adult↗

Distribution of 14 high risk HPV types in cervical intraepithelial neoplasia detected by a non-radioactive general primer PCR mediated enzyme immunoassay.

AIM: To evaluate the presence of high risk human papillomaviruses (HPV) in cervical smears showing intraepithelial neoplasia (CIN). METHODS: The presence of 14 high risk HPV was evaluated in 114 cervical smears with CIN of different degrees, by comparing a non-radioactive polymerase chain reaction (PCR) enzyme immunoassay (EIA) with conventional PCR followed by radioactive Southern blot hybridisation. General primer PCR amplicons detecting low risk and high risk HPV were typed for 14 different high risk HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) by a non-radioactive PCR-EIA. Virus load of HPV 16 positive CIN was assessed using the semiquantitative PCR-EIA. RESULTS: Histological evaluation confirmed CIN I in 49 cases (mean age 29.0 years, range 17 to 52), CIN II in 31 cases (mean age 30.8 years, 18 to 54), and CIN III in 34 cases (mean age 31.1 years, 16 to 57). The non-radioactive PCR-EIA showed an overall agreement rate of 90% (kappa value 0.75) when compared with conventional general primer PCR followed by radioactive Southern blot hybridisation. High risk HPVs were detected in 47% of CIN I, 77% of CIN II, and 97% of CIN III (p < or = 0.02). HPV types 39, 51, 56, and 58 were found in CIN I exclusively (between 2% and 8%). HPV 16 and HPV 31 were detected in 12% and 2% of CIN I, 35% and 21% of CIN II, and 74% and 13% of CIN III, respectively (p < or = 0.03 and p < or = 0.04). The virus load estimated by the semiquantitative PCR-EIA of HPV 16 was similar in CIN I, CIN II, and CIN III. CONCLUSIONS: The PCR-EIA has high clinical sensitivity for detecting CIN II/III (90%). There was a significantly higher prevalence rate of HPV 16 and 31 in CIN III than in CIN I and II.

Adolescent↗

A radio-gas chromatographic method for determining the specific radioactivity of glycolic acid in -14C-labeled leaf tissue.

A method for the extraction and quantitative determination of both the mass and radioactivity of glycolic acid from -14C-labeled leaf tissue is described. The recoveries of both mass and radioactivity from standard [1-14C]glycolic acid solutions averaged 98 percent, and recovery of radioactivity added to plant samples as [1-14C]glycolic acid was over 90 percent after the complete procedure. The method was reliable with total samples containing as little as 130 nmol of glycolic acid. The mass of glycolic acid recovered from sunflower leaf tissue was proportional to the amount of tissue extracted. In experiments with different plant material, the amount of glycolic acid varied between 530 and 1120 nmol/dm-2 of leaf tissue. The specific radioactivity of the glycolic acid in sunflower leaf tissue during photosynthesis in -14CO(2) was never more than 20 percent of the specific radioactivity of the -14CO(2) supplied.

Carbon Dioxide↗

Radioiodination of rhenium cyclized alpha-melanocyte-stimulating hormone resulting in enhanced radioactivity localization and retention in melanoma.

Radiohalogenated alpha-melanocyte-stimulating hormone (alpha-MSH) analogs were proposed for melanoma imaging and potential radiotherapy because alpha-MSH receptors are overexpressed on both mouse and human melanoma cell lines. However, biodistribution studies in tumor-bearing mice with radiohalogenated alpha-MSH peptides showed very rapid tumor radioactivity wash out due to lysosomal degradation of the radiohalogenated complex after internalization, which decreased the therapeutic efficacy significantly (R. Stein et al., Cancer Res., 55: 3132-3139, 1995; P. K. Garg et al., Bioconjugate Chem., 6: 493-501, 1995.). The melanoma-targeting metallopeptide ReO[Cys(3,4,10),D-Phe(7)]alpha-MSH(3-13) (ReCCMSH) was shown to possess high tumor uptake and retention properties (J. Chen et al., Cancer Res., 60: 5649-5658, 2000). Therefore, three peptides, Ac-Lys-ReCCMSH(Arg(11)), Ac-D-Lys-ReCCMSH(Arg(11)), and [Nle(4),D-Phe(7)]alpha-MSH (NDP) (for comparison), labeled with N-succinimidyl 4-[(125)I]iodobenzoate ((125)I-PIB), were prepared and evaluated in vitro and in vivo to develop radiohalogenated alpha-MSH peptide analogs with high tumor uptake, retention, and favorable biodistribution characteristics. In vitro cell binding and internalization data showed that approximately 90% of radioiodinated peptides were internalized at 2 h in cultured B16/F1 melanoma cells. Cellular retention studies showed that the receptor-bound radioiodinated linear alpha-MSH analog NDP was released from the cells into the medium very quickly, whereas significant amounts of cell-associated radioactivity remained in the cells for Ac-Lys((125)I-3- or 4-iodobenzoate (IBA))-ReCCMSH(Arg(11)) and Ac-D-Lys((125)I-IBA)-ReCCMSH(Arg(11)). The in vitro data clearly demonstrate that rhenium cyclization significantly enhanced peptide trapping in the cells, as did D-amino acid incorporation. The combination of these two effects resulted in a 2.9-fold increase in the retention of radioactivity for Ac-D-Lys((125)I-IBA)-ReCCMSH(Arg(11)) relative to (125)I-IBA-NDP at 4 h. In vivo studies also showed that Ac-D-Lys((125)I-IBA)-ReCCMSH(Arg(11)) exhibited extremely high radioactivity accumulation and prolonged retention in the tumor. Ac-D-Lys((125)I-IBA)-ReCCMSH(Arg(11)) and Ac-Lys((125)I-IBA)-ReCCMSH(Arg(11)) exhibited much higher tumor uptake at 24 h after injection compared with (125)I-IBA-NDP [7.18% injected dose/gram (ID/g), 4.92% ID/g, and 0.26% ID/g, respectively]. Ac-D-Lys((125)I-IBA)-ReCCMSH(Arg(11)) also showed very fast whole body clearance and low nonspecific radioactivity accumulation in normal tissues compared with (125)I-IBA-NDP and Ac-Lys((125)I-IBA)-ReCCMSH(Arg(11)). A tumor:blood ratio of 34.3 was observed for Ac-D-Lys((125)I-IBA)-ReCCMSH(Arg(11)) at 24 h postinjection, whereas values of 4.3 and 2.0 were observed for Ac-Lys((125)I-IBA)-ReCCMSH(Arg(11)) and (125)I-IBA-NDP, respectively. The biodistribution data clearly demonstrate that both rhenium cyclization and D-Lys incorporation enhanced the tumor localization and retention of the radiolabel. Therefore Ac-D-Lys-ReCCMSH(Arg(11)) is an excellent candidate for additional therapeutic studies.

Animals↗

beta-Particle-emitting radioactive stent implantation. A safety and feasibility study.

BACKGROUND: This study represents the Heart Center Rotterdam's contribution to the Isostents for Restenosis Intervention Study, a nonrandomized multicenter trial evaluating the safety and feasibility of the radioactive Isostent in patients with single coronary artery disease. Restenosis after stent implantation is primarily caused by neointimal hyperplasia. In animal studies, beta-particle-emitting radioactive stents decrease neointimal hyperplasia by inhibiting smooth muscle cell proliferation. METHODS AND RESULTS: The radioisotope (32)P, a beta-particle emitter with a half-life of 14.3 days, was directly embedded into the Isostent. The calculated range of radioactivity was 0.75 to 1.5 microCi. Quantitative coronary angiography measurements were performed before and after the procedure and at 6-month follow-up. A total of 31 radioactive stents were used in 26 patients; 30 (97%) were successfully implanted, and 1 was embolized. Treated lesions were in the left anterior descending coronary artery (n=12), the right coronary artery (n=8), or the left circumflex coronary artery (n=6). Five patients received additional, nonradioactive stents. Treated lesion lengths were 13+/-4 mm, with a reference diameter of 2.93+/-0. 47 mm. Minimum lumen diameter increased from 0.87+/-0.28 mm preprocedure to 2.84+/-0.35 mm postprocedure. No in-hospital adverse cardiac events occurred. All patients received aspirin indefinitely and ticlopidine for 4 weeks. Twenty-three patients (88%) returned for 6-month angiographic follow-up; 17% of them had in-stent restenosis, and 13% had repeat revascularization. No restenosis was observed at the stent edges. Minimum lumen diameter at follow-up averaged 1.85+/-0.69 mm, which resulted in a late loss of 0.99+/-0. 59 mm and a late loss index of 0.53+/-0.35. No other major cardiac events occurred during the 6-month follow-up. CONCLUSIONS: The use of radioactive stents with an activity of 0.75 to 1.5 microCi is safe and feasible.

Adult↗

Edge restenosis after implantation of high activity (32)P radioactive beta-emitting stents.

BACKGROUND: A high restenosis rate has been reported at the edges ("edge restenosis") of (32)P radioactive stents with an initial activity level of 3 to 12 microCi. This edge effect might be due to balloon injury and to a low dose of radiation at the stent margins. The aim of this study was to evaluate whether the implantation of (32)P radioactive stents with a higher activity level (12 to 21 microCi) combined with a nonaggressive stent implantation strategy could solve the problem of edge restenosis. METHODS AND RESULTS: We compared the results of lesions treated with single radioactive BX stents with an activity of 12 to 21 microCi (group 2, n = 54 lesions) with the results of lesions treated by single radioactive BX stents with an initial activity level of 3 to 12 microCi (group 1, n = 42 lesions). There were no procedural events. At the 6-month follow-up, no myocardial infarctions, deaths, or stent thromboses had occurred. Intrastent binary restenosis was 0% in group 1 versus 4% in group 2 (n = 2, both at the ostium of the right coronary artery, P = NS). Intrastent neointimal hyperplasia was significantly lower in group 2 than in group 1. The intralesion (intrastent plus peri-stent) restenosis rate was 38% in group 1 versus 30% in group 2 (P = NS). Conclusions-Single (32)P radioactive stents with an initial activity level of 12 to 21 microCi reduced intrastent neointimal hyperplasia compared with stents of 3 to 12 microCi, but they did not solve the problem of edge restenosis, even if a nonaggressive stent implantation strategy was used.

Angioplasty, Balloon, Coronary↗

Angiographical follow-up after radioactive "Cold Ends" stent implantation: a multicenter trial.

BACKGROUND: Radioactive stents with an activity of 0.75 to 12 microCi have shown >40% edge restenosis due to neointimal hyperplasia and negative remodeling. This trial evaluated whether radioactive Cold Ends stents might resolve edge restenosis by preventing remodeling at the injured extremities. METHODS AND RESULTS: The 25-mm long (15-mm radioactive center and 5-mm nonradioactive ends) Cold Ends stents had an activity of 3 to 12 microCi at implantation. Forty-three stents were implanted in 43 patients with de novo native coronary artery disease. Two procedural, 1 subacute, and 1 late stent thrombosis occurred. A restenosis rate of 22% was observed with a shift of the restenosis, usually occurring at the stent edges of radioactive stents, into the Cold Ends stents. The most severe restenosis occurred at the transition zone from radioactive to nonradioactive segments, a region located in dose fall-off. CONCLUSION: Cold Ends stents did not resolve edge restenosis.

Adult↗

A comparison of the metabolism of radioactive 17-isoaldosterone and aldosterone administered intravenously and orally to normal human subjects.

After intravenous and oral administration of radioactive aldosterone to normal subjects, 7.3 +/- 0.4 (SE) and 5.4 +/- 0.5 (SE)%, respectively, of the dose was recovered from a 48-hour collection of urine as aldosterone released by mild acid hydrolysis (from aldosterone 18-glucuronide), and 35 +/- 5 (SE) and 39 +/- 4 (SE)%, respectively, was recovered as tetrahydroaldosterone after incubation with beta-glucuronidase.After intravenous and oral administration of 17-isoaldosterone-4-(14)C to a similar group of subjects, 35 +/- 3 (SE) and 53 +/- 4 (SE)%, respectively, of the dose was recovered as 17-isoaldosterone released by acid and less than 5% as total metabolites after incubation with beta-glucuronidase. No detectable radioactivity (< 0.5%) could be recovered as tetrahydroaldosterone or as a compound with the expected chromatographic properties of tetrahydro-17-isoaldosterone. The total radioactivity in the neutral extracts was also relatively small (< 2%) after administration of either labeled aldosterone or 17-isoaldosterone. The radioactivity as aldosterone in the neutral extract was much lower after oral [0.017 +/- 0.003 (SE)%] than after intravenous [0.21 +/- 0.04 (SE)%] administration of labeled aldosterone. The radioactivity as 17-isoaldosterone in the neutral extract was similar after intravenous [0.20 +/- 0.02 (SE)%] and after oral [0.38 +/- 0.18 (SE)%] administration of 17-isoaldosterone. These results indicated that, due to lack of A-ring reduction of the molecule and the consequent slowing of hepatic clearance, 17-isoaldosterone is converted to an acid-labile conjugate (presumably 17-isoaldosterone 18-glucuronide) as the major metabolite. 17-Isoaldosterone was not secreted or converted to aldosterone to any significant extent in the normal subjects investigated.

Aldosterone↗

Absorption, distribution and excretion of 14C-chloroquine after single oral administration in albino and pigmented rats: binding characteristics of chloroquine-related radioactivity to melanin in-vivo.

Chloroquine is an antimalarial agent that has been reported to have distinct affinity to melanin. After single oral administration of 14C-chloroquine at a dose of 20mg kg-1 under non-fasting conditions, the absorption, distribution and excretion of 14C-chloroquine-related radioactivity were studied in albino and pigmented rats. The objectives of the study were to investigate differences in the disposition of chloroquine between albino and pigmented rats and to define its in-vivo binding characteristics to melanin-containing ocular tissues. Extensive uptake of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there was no quantitative differences in the distribution of radioactivity found between albino and pigmented rats except for melanin-containing tissues, such as the uveal tract of the eye and perhaps hair follicles. There was selective and strong binding of drug-related compounds to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value of 158.42 +/- 7.86 micrograms equiv g-1 (mean+/-s.e.) at 1 week and decreased very slowly with a terminal half life of 4476 h (187 day). The uveal tract concentrations at 24 weeks were still high (67.75 +/- 6.19 micrograms equiv g-1). The AUC for uveal tract was 842.3 mg.h g-1. A relatively high concentration was still determined in the uveal tract even at 48 weeks after single oral dosing by whole-body autoradiography. The uveal tracts separated from one eye of each rat were extracted with 0.067 M phosphate buffer (pH 7.4) and 1 M HCl-EtOH (30:70) successively. In pigmented rats, almost all radioactivity was released from the tissue with 1 M HCl-EtOH (30:70), indicating that the strong binding by melanin was reversible, and that hydrophobic or electrostatic interaction would play a critical role in the binding of chloroquine and its metabolites with the melanin-containing ocular tissues. Approximately 70% of the radioactivity given was recovered in urine and faeces up to 144 h after dosing both in pigmented and albino rats. The excretion pattern in pigmented rats was similar to that seen in albino rats.

Administration, Oral↗

A simple and non-radioactive technique to study the effect of monophosphoesters on matrix vesicle-mediated calcification.

A simple and non-radioactive technique based on O-cresolpthalein complexone assay was developed to study in vitro non-radioactive calcium ((40)Ca) deposition by isolated matrix vesicles. Using this technique, the effect of various phosphoester substrates including ATP, AMP and beta-GP on in vitro MV-calcification was studied. O-cresolpthalein complexone assay with non-radioactive calcium demonstrated that AMP or beta-GP were more effective in promoting calcium deposition by isolated MVs than ATP. The application of this non-radioactive technique, which is highly sensitive and simple, would offer a useful alternative approach to the routinely used radiometric biomineralization assay which employs radioactive (45)Ca.

Journal Article↗

Incorporation of radioactivity from [14C]lactate into the glycogen of cultured mouse astroglial cells. Evidence for gluconeogenesis in brain cells.

A pure population of astroglial cells was selected from heterogeneous astroglia-rich primary cultures in a medium containing sorbitol instead of glucose. It was shown that astroglial cells synthesize glycogen when they are returned to a glucose-containing medium, and that when [14C]lactate is also present the synthesized glycogen is radioactively labelled. Compared with the degree of incorporation of radioactivity in the presence of tritiated glucose, the incorporation of radioactivity from lactate was small but significant. After incubation of astroglial cells with radioactively labelled lactate, the glycogen was isolated and enzymatically hydrolysed to glucose, which was found to be radioactively labelled. Astrocytes are therefore able to convert lactate to glucosyl residues, a metabolic pathway known as gluconeogenesis. It is proposed that astrocytic gluconeogenesis may consume lactic acid formed in neighboring cells such as neurons, during anaerobic glycolysis at times of high energy demand.

Animals↗

Distribution of radioactivity in the organs of the rat and mouse after injection of L-(3H)prolyl-L-leucyl-glycinamide.

The distribution of radioactivity after intrajugular injection of L-(3H)-prolyl-L-leucyl-glycinamide has been studied by whole-body autoradiography in the mouse and by direct measurement of radioactivity in individual organs of the rat. There is good agreement between results obtained with the two techniques and animal species. High levels of radioactivity were found in the pineal gland, anterior pituitary, posterior (including intermediate) lobe of the pituitary, and epididymal and brown fat. Lower uptake of radioactivity occurred in the submaxillary gland, kidney, and adrenal gland. The preferential uptake of radioactivity by the pineal gland after injection of the labelled tripeptide suggests a role for this hypothalamic hormone in the control of pineal activity.

Adipose Tissue↗

Total radioactive residues and clenbuterol residues in swine after dietary administration of [14C]clenbuterol for seven days and preslaughter withdrawal periods of zero, three, or seven days.

Nine barrows (23.8 +/- 0.9 kg) and 9 gilts (23.1 +/- 0.9 kg) were used to determine the disposition of radiocarbon after oral [14C]clenbuterol (4-amino-alpha-[t-butylaminomethyl]-3,5-dichlorobenzyl [7-(14)C]alcohol hydrochloride) administration and to determine total and parent residues in edible tissues. Three barrows and three gilts, housed in metabolism crates, were fed 1 ppm [14C]clenbuterol HCl for seven consecutive days in three separate trials; a single barrow and gilt from each trial was slaughtered after 0-, 3-, or 7-d preslaughter withdrawal periods. Urine and feces were collected during the dosing and the withdrawal period; edible and inedible tissues were collected at slaughter. Total recovery of radiocarbon was 94.2 +/- 6.5%. Total clenbuterol absorption was greater than 75% for barrows and 60% for gilts. Total radioactive residues in tissues were not different (P > 0.05) between barrows and gilts. Concentrations of parent clenbuterol in liver, kidney, skeletal muscle, adipose tissue, and lung did not differ between barrows and gilts (P > 0.05). Total radioactive and parent residues declined in tissues as withdrawal period increased. After the 0-d withdrawal period, total liver residues (286 ppb) were approximately equal to lung residues, twice those of the kidney, and about 15 times those of adipose tissue and skeletal muscle. After a 7-d withdrawal period, total radioactive residues in liver (15 ppb) were roughly three times greater than lung, kidney, and adipose tissue total residues and about 13 times those of skeletal muscle total residues. Parent clenbuterol represented 79, 63, 42, 67, and 100% of the total radioactive residue in adipose tissue, kidney, liver, lung, and skeletal muscle, respectively, in hogs slaughtered with a 0-d withdrawal period. With increasing withdrawal period, the percentage of total radioactive residue present as parent clenbuterol within edible tissues (including lung) decreased, so that after a 7-d withdrawal period, 7, 16, and 29% of the total residue was composed of parent clenbuterol in kidney, liver, and lung, respectively. After a 7-d withdrawal period, parent clenbuterol exceeded the European maximum residue limit (0.5 ppb) 4.6-fold in liver and 2.4-fold in lung. In muscle, clenbuterol was approximately 40 times the limit after a 0-d withdrawal period but had dropped below 0.5 ppb after a 3-d withdrawal period. Results from this study indicate that clenbuterol HCl is well absorbed in swine and that the use of clenbuterol in this species in an off-label manner is inconsistent with human food safety standards used in developed countries.

Animals↗