Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in cattle raised at agricultural research facilities across the USA and the influence of pentachlorophenol-treated wood.

Adipose tissue samples from 158 cattle raised locally at experiment stations across the USA were analysed for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F). While 80% of the samples had PCDD/F concentrations that fell within the range of a previous US survey of beef animals (not detected -4.1 ppt toxic equivalency), several animals had exceptionally high concentrations (8-54 ppt toxic equivalency).

Effects of clenbuterol on body stores of polychlorinated dibenzofurans (PCDF) and dibenzo-p-dioxins (PCDD) in rats.

Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF), persistent pollutants that accumulate in the food chain, pose a risk to humans through consumption of tainted livestock. Clenbuterol, a leanness-enhancing agent, was tested for usefulness in PCDD/F body store reduction through body fat reduction (the predominant site of accumulation). To mimic the situation of contaminated animals, rats were given feed with or without a mixture of PCDD/F (0.

Treated wood in livestock facilities: relationships among residues of pentachlorophenol, dioxins, and furans in wood and beef.

Wood and other environmental samples were collected from sites that produced beef with higher than average residues of dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF). Analyses of these samples for PCDD/Fs and pentachlorophenol (PCP) indicated that the high beef residues were associated with PCP-treated wood in the animal facilities. Concentrations of PCDD/Fs in wood as toxic equivalents ranged from 10 to 320,000 pg/g.

Metabolism of [14C]1,2,7,8-tetrachlorodibenzo-p-dioxin in a ruminating Holstein calf.

1. [UL-7,8-ring 14C]-1,2,7,8-tetrachlorodibenzo-p-dioxin (1278-TCDD) was administered orally to a ruminating Holstein bull calf (43.6 kg; 1.

Metabolism of N-isopropylacetanilide in rat.

1. Radioactivity from oral doses of N-isopropyl[1-14C]acetanilide was excreted in urine (53.5%), faeces (8.

Tissue distribution, excretion, and metabolism of 1,2,7,8-tetrachlorodibenzo-p-dioxin in the rat.

A tissue distribution, excretion, and metabolism study was conducted using a relatively non-toxic dioxin congener, i.e., 1,2,7,8-tetrachlorodibenzo-p-dioxin (1278-TCDD), to gain a better understanding of mammalian metabolism of dioxins.

Chlorinated dibenzo-p-dioxin and dibenzofuran concentrations in beef animals from a feeding study.

Four calves were fed polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans for 120 days at levels somewhat higher than what may be found in forage near some waste incinerators and manufacturing plants. Four calves were fed identical diets but without the chemicals. Using bioelectrical impedance measurements of total body fat, 30-50% of the dosed 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, and 2,3,4,7,8-PeCDF was estimated to be retained by the animals.

Identification of turkey biliary metabolites of ractopamine hydrochloride and the metabolism and distribution of synthetic [14C]ractopamine glucuronides in the turkey.

1. The bile duct cannulated turkey poult (n = 3) dosed orally with [14C]ractopamine HCl [(1R*,3R*),(1R*,3S*)-4-hydroxy-alpha-[[[3-(4-hydroxy[14C]phenyl)-1-methy lpropyl]amino]methyl]-benzenemethanol hydrochloride; 19.9 mg; 9.

Response of C2C12 mouse and turkey skeletal muscle cells to the beta-adrenergic agonist ractopamine.

The effects of ractopamine (RAC) and ractopamine stereoisomers (RR, RS, SR, and SS) on cyclic AMP (cAMP) production, total protein, and DNA concentrations in mouse skeletal muscle cells (C2C12) were evaluated. The RAC (10 microM) caused an approximately 30% increase in cell number, protein, and DNA concentrations in myoblasts after 48 h; no differences were found in myotubes. The RAC-stimulated increase of these variables in myoblasts was blocked by the presence of equimolar concentrations of propranolol.

An investigation of the in vivo formation of octachlorodibenzo-p-dioxin.

The in vivo formation of dioxins from chemical precursors was investigated in rats. Sprague-Dawley rats were fed pentachlorophenol or a predioxin in peanut oil for 14 days. Mass balance calculations indicated that pentachlorophenol was not converted to dioxins; however, the predioxin, nonachloro-2-phenoxyphenol, was converted to OCDD.

Effects of ractopamine HCl stereoisomers on growth, nitrogen retention, and carcass composition in rats.

The objectives of this study were to determine the effects of ractopamine HCl (RAC) stereoisomers (RR, RS, SR, and SS) on performance, carcass composition, and nitrogen retention in growing female rats. Forty-eight rats (eight rats/treatment) were treated with 0 or 320 microg/d of RAC or with 80 microg/d of the RR, RS, SR, or SS stereoisomers of ractopamine. Rats had free access to feed and water before and during the experiment.

Metabolism and disposition of 1,4,7,8-tetrachlorodibenzo-p-dioxin in rats.

Metabolism studies of 1,4,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a relatively nontoxic dioxin congener, were undertaken to gain a better understanding of mammalian metabolism of dioxins without the problems associated with the use of the most toxic congener, 2,3,7,8-TCDD. 14C-1,4,7,8-TCDD was dosed to conventional and bile-cannulated rats at a level of 8 mg/kg. The 14C was excreted almost entirely in 72 hours with the major routes of excretion feces and bile.

The USDA perspective on dioxin concentrations in dairy and beef.

The major dioxin-related research activities in the United States Department of Agriculture are 1) a survey of dioxin levels in beef samples collected at 13 experiment stations throughout the United States, 2) a feeding study of eight dioxins, four furans, and three PCB at levels equal to or above levels expected at highly industrialized locations, and 3) metabolism studies of 14C-labeled dioxin congeners. Preliminary results indicate that geographical location may influence dioxin concentrations in beef and that bulls may have concentrations higher than those in other slaughter animals. Metabolism of nontoxic congeners seems to be rather complex, involving the arene oxide pathway, NIH type shifting of chlorine, and conjugation with sulfuric acid and glucuronic acids.

Identification of NIH-shifted metabolites of 1,3,7,8-tetrachlorodibenzo-p-dioxin in the rat by NMR comparison with synthesized isomers.

In the rat, 1,3,7,8-tetrachlorodibenzo-p-dioxin was oxidatively metabolized to the NIH-shifted products 2-hydroxy-1,4,7,8-tetrachlorodibenzo-p-dioxin and 3-hydroxy-1, 2,7,8-tetrachlorodibenzo-p-dioxin. The chlorine substitution patterns were determined by comparison with 1H NMR spectra of six synthesized isomers in CDCl3, CD3OD, and acetone-d6. Glucuronide and glucuronide-sulfate conjugates of the monohydroxy dioxins were identified in the bile by FAB-MS.

Metabolism of 14C-sulphadimethoxane in swine.

1. 14C-sulphadimethoxine (4-amino-N-(2,6-dimethoxy-4-pyrimidinyl)benzene-[U-14C]-sulphonamide; 14C-SDM) was given orally (60 mg/kg body weight) to eight swine (weight 27-32 kg). Urine and faeces were collected from 0 to 72 h after dosing and tissue samples were collected from animals exsanguinated at 12, 24, 48 and 72 h after dosing.

The disposition of 14C-levamisole in the lactating cow.

1. 14C-Levamisole 1(-)-2,3,5,6-tetrahydro-6-phenyl[U-14C]imidazo[2,1-b]-thiazole was administered orally and subcutaneously to lactating cows (8 mg/kg body weight). Urine, faeces, milk and blood samples were collected from 0-48 h after dosing and tissues were collected 48 h after dosing.

Identification of ractopamine hydrochloride metabolites excreted in rat bile.

1. Rats dosed orally with 2.85 +/- 0.

Comparative metabolism and elimination of acetanilide compounds by rat.

1. 14C-labelled propachlor, alachlor, butachlor, metolachlor, methoxypropachlor and some of their mercapturic acid pathway metabolites (MAP) were given to rat either by gavage or by perfusion into a renal artery. MAP metabolites were isolated from bile and urine.

Depletion of residues from milk and blood of cows dosed orally and intravenously with sulfamethazine.

Cows were dosed orally (n = 4) or intravenously (n = 4) with sulfamethazine [sulmet; 4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzenesulfonamide] for 5 consecutive days (220 mg/kg of body weight on day 1 and 110 mg/kg on days 2-5). The concentrations of sulmet, N4-acetylsulfamethazine (Ac-sulmet), and the N4-lactose conjugate of sulfamethazine (lac-sulmet) were measured in milk and blood collected at 24 h intervals after the last doses of sulmet were given. The method of analysis included (1) spiking of samples with known amounts of 13C6-labeled reference compounds, (2) resolution of the 3 compounds by reversed-phase chromatography, (3) hydrolysis of lacsulmet, (4) treatment with diazomethane to yield N1-methyl derivatives, and (5) gas chromatography/mass spectrometry.

Neomycin metabolism in calves.

Disposition of oral neomycin in calves was determined using 14C-labeled neomycin. The influences of age, diet, and method of administration were observed. All calves were killed 96 h after a single oral dose of [14C]neomycin (approximately 30 mg/kg) and the distribution of 14C in excreta and tissues was determined.

Glutathione-mediated methylthio-turnover and sex differences in the metabolism of pentachlorothioanisole by rat.

1. Sex differences observed in the metabolism of pentachlorothioanisole in rat were due to: (1) greater excretion in urine by females, and greater biliary excretion by males; (2) formation of pentachlorophenyl mercapturic acid pathway metabolites by females; and (3) redox-cycling between methylthio and methylsulphoxyl oxidation congeners in intermediary metabolites by females. 2.

Metabolism and disposition of ractopamine hydrochloride by turkey poults.

Ractopamine HCl, ((1R*,3R*),(1R*,3S*)-4-hydroxy-alpha-[[[3-(4- hydroxyphenyl)-1-methylpropyl]-amino]methyl]benzenemethanol hydrochloride), is a beta-adrenergic agonist that is under evaluation as a nutrient repartitioning agent in livestock. Because ractopamine metabolism has not been evaluated in turkeys, the objectives of this study were to synthesize and identify products of ractopamine metabolism and to determine the stereoselective metabolism and tissue distribution of [14C]ractopamine HCl in orally dosed turkey poults. Glucuronides of diastereoisomeric [14C]ractopamine, and the (1R,3R) and (1R,3S) stereoisomers of ractopamine were synthesized by use of microsomal proteins immobilized on Sepharose beads.

Lactose conjugation of sulphonamide drugs in the lactating dairy cow.

1. 14C-Sulphamethazine (4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene-[U-14C]-sulphonamide; 220 mg/kg of body weight) was given orally or i.v.

Toxicity of 2,6-dichlorothiobenzamide (chlorthiamid) and 2,6-dichlorobenzamide in the olfactory nasal mucosa of mice.

The toxic effects of the herbicide chlorthiamid (2,6-dichlorothiobenzamide) and its major environmental metabolite 2,6-dichlorobenzamide (DCBA) were examined in the nasal passages of C57Bl mice following single ip injections. Chlorthiamid (12.25, and 50 mg/kg) induced an extensive destruction of the olfactory region, similar to that previously observed with the analogue dichlobenil (2,6-dichlorobenzonitrile).

Glutathione-S-transferase-mediated methylthio displacement and turnover in the metabolism of pentachlorothioanisole by rats.

1. The metabolism of pentachlorothioanisole to bis-(methylthio)tetrachlorobenzene was shown to involve turnover of about 50% of the original methylthio group. 2.