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). The investigations of three facilities where highly contaminated animals were raised found pentachlorophenol-treated wood at each site. The congener pattern in the animals' tissues and the lack of elevated PCDD/F levels in other environmental samples, i.e. hay and soil, indicated that the treated wood was the source of contamination. A congener pattern similar to that of pentachlorophenol-exposed animals was seen for the means and medians of the entire data, i.e. OCDD, HpCDD and 1,2,3,6,7,8-HxCDD dominated, the PCDD concentrations equalled or exceeded the furan concentrations, and the concentration of 1,2,3,6,7,8-HxCDD was six times that of the other HxCDD isomers. This suggested that pentachlorophenol-treated wood contributed measurably to many of the animals in this survey. The largest contributors to the median toxic equivalencies were 1,2,3,7,8-PeCDD (40%) and 1,2,3,6,7,8-HxCDD (16%). No clear geographical trends emerged from the data.

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 (0.6 to 2.7 ng/congener per day) for 10 d, followed by 16 d of feed with or without dietary clenbuterol (2 mg/kg feed). Clenbuterol reduced body fat by 28% (P < 0.05), increased muscle mass by 25% (P < 0.02), and decreased liver mass by 7% (P < 0.02). Although the concentrations of most PCDD/F per gram of fat were slightly increased after clenbuterol treatment, the total amount of PCDD/F that remained in fat was reduced by approximately 30%. Muscle PCDD/F concentrations and total burden were decreased by clenbuterol. In contrast, clenbuterol tended to increase concentration, but not total burden of PCDD/F in livers. One congener known to be rapidly metabolized and excreted, 2,3,7,8-TCDF, was the exception to this increase, decreasing 40% with clenbuterol treatment. This was also the congener that showed the greatest reduction in both fat and muscle. Examination of the ratio of PCDD/F in liver and fat revealed that clenbuterol increased the liver's share of the body burden of PCDD/F, from 38 to 75%. In a remediation/disposal context, these findings would be beneficial if clenbuterol lowered the meat and carcass burden of PCDD/F to safe levels, requiring only livers to be disposed of as hazardous waste.

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. These concentrations were closely related to the concentrations of PCP, indicating that analysis for PCP provides an economical method to identify wood with high concentrations of PCDD/Fs. Further evidence for the PCP-treated wood as the source of the beef residues is provided by the similarity of the congener profiles in beef from the sites and those profiles predicted from the profiles in wood.

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; 1.2 mg kg(-1) body weight). Urine and faeces were collected daily for 96 h, while blood was sampled at multiple time points. Tissues were removed for combustion analysis. 2. Each tissue contained < 0.65 of the dose at 96h. Tissues with highest levels of 1278-TCDD, as a percentage of administered dose, were the large and small intestine, rumen, liver and carcass. 3. Urinary excretion accounted for 10.6% of the dose, and faecal excretion accounted for 81.6% of the administered dose. The major urinary and faecal metabolites were isolated and characterized by mass spectrometry and 1H-NMR. 4. Plasma levels of 14C peaked at 24h, and decreased to near background at 96 h. Detectable plasmal levels of 1278-TCDD were observed by 2 h. 5. A hydroxylated metabolite of 1278-TCDD was detected in calf plasma, which has the potential to interfere with thyroid hormone homeostasis.

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; 9.28 microCi] excreted 37.4 +/- 12.1% (mean +/- SD) of the administered radioactivity in bile by 24 h post-dosing. 2. A mono-glucuronide, conjugated at C-10 (the methylpropylamino phenol) of ractopamine, accounted for 76.6% of biliary radioactivity. 3. Urine collected from the colostomized turkey poult (n = 3) orally dosed with synthetic [14C]ractopamine-glucuronides (10.1 mg; 3.6 microCi) contained 11.9 +/- 1.0% (mean +/- SD) of the administered radioactivity 24 h after dosing, indicating that some absorption of radioactivity occurred. Faeces contained 60.6% of the administered radioactivity and carcasses (with gastrointestinal tracts) contained 23.3% of the starting radioactivity. 4. Five colostomized poults were fitted with bile duct cannulas and were dosed intraduodenally with 10.2 mg (3.6 microCi) synthetic [14C]ractopamine-glucuronides. Urine and bile contained 15.5 +/- 2.2 and 16.8 +/- 2.1% respectively of the administered radiocarbon by 24 h post-dosing. Faeces contained 54.3% of the administered radioactivity. Total absorption of the dosed radioactivity averaged 33.4%. 5. Bile and urine collected from the colostomized, bile-duct cannulated bird contained mainly ractopamine glucuronides. Indirect evidence suggests that the dosed ractopamine glucuronides were not absorbed intact.

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. At a later passage, myoblasts failed to exhibit an increase in cell number, protein, or DNA upon exposure to RAC. Both myoblasts and myotubes increased cAMP production in response to 10 microM RAC. The RAC isomers ranked RR >> SR > RS approximately SS in ability to stimulate cAMP production, with essentially no response to SS. The SR produced about 50% of the RR response. Coincubation of propranolol (10 microM) and RAC (10 microM) prevented RAC-stimulated cAMP production in myotubes but not in myoblasts (approximately 35% of cAMP produced by RAC alone). Turkey satellite cells (derived from biceps femoris of 12-wk-old toms) produced essentially no increased cAMP when exposed to 10 microM RAC stereoisomers. Stability of RAC was evaluated under laboratory storage and culture conditions. The RAC was stable for more than 4 mo when stored in deuterated DMSO (>98% purity) at room temperature or in aqueous solutions at -80 degrees C, as determined from sequential nuclear magnetic resonance studies. Radiolabeled RAC was incubated for 72 h in the presence of serum-containing medium, with or without C2C12 cells. Ninety-eight percent of the parent compound found in the medium at time zero was present in the medium as parent at the end of 72 h. The cellular cAMP response to RAC through beta-adrenergic receptors seems to be stereospecific. If the state of myoblasts and myotubes in vitro reflects the in vivo state, then the ractopamine effect in vivo on cellular processes (including cell division and protein and DNA accumulation) may be independent of beta-adrenergic receptors in muscle.

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. Conversion of the predioxin ranged from 0.5% to 153% and depended on the amount of predioxin and OCDD present in the diet. The analytical procedures used for sample preparation did not appear to cause conversion of the predioxin to OCDD. The mechanism for biological conversion may be enzymatic or spontaneous.

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. Although these same congeners were bioconcentrated in adipose tissue (BCF approximately 10), consumer products such as ribeye showed concentrations less than what were found in the animal feed (BCF approximately 0.1). Distribution of the dioxins and furans into various lipid compartments appeared to be rather uniform in back fat, perirenal fat, and ribeye for tetra to hexa congeners. Ribeye, serum, and liver lipids had higher concentrations of the higher chlorinated congeners, due in part to not reaching a steady state. An unexpected source of dioxin and furan contamination was discovered during the experiment, resulting in the control animals having concentrations of some congeners that were equal to or in some cases greater than those of the dosed animals. Pentachlorophenol-treated wood components in the pole barn where the feeding experiment was conducted were found to have contributed to the animals' exposure.

Metabolism of N-isopropylacetanilide in rat.

1. Radioactivity from oral doses of N-isopropyl[1-14C]acetanilide was excreted in urine (53.5%), faeces (8.1%) and expired air (17.0%) of rat. 2. Enterohepatic circulation occurred during formation of approximately 34% of the metabolites. N-isopropylacetanilide was metabolized by oxidation in all moieties of the molecule with subsequent conjugation with glucuronic and sulphuric acids. 3. The sulphate ester of 4'-hydroxyacetanilide (acetaminophen) was the major metabolite (28 % of the dose).

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. Ractopamine and stereoisomers were delivered via i.p. implanted osmotic pumps for 14 d, and rats were then slaughtered. Control rats were fitted with osmotic pumps containing saline. Ractopamine increased (P < .05) feed intake (d 1 to 6); body weight; carcass CP; and intake, apparent absorption, retention, and retained:intake ratio of CP on d 1 to 6 of the study. Ractopamine decreased (P < .05) carcass lipid and visceral lipid. Rats dosed with the RR stereoisomer responded similarly to rats dosed with RAC, except for carcass lipid. Carcass lipid was decreased (P < .01) by RAC relative to controls, but it was not different from controls in rats treated with the RR isomer. Compared with controls, BW, carcass CP, and CP retention were increased by the RR stereoisomer, and visceral lipid was decreased. The RS isomer also decreased visceral lipid (P < .10), but variables measured in rats dosed with the RS, SR, and SS isomers generally did not differ from controls. Results of this study indicate that the RR isomer of RAC is responsible for a majority of the leanness-enhancing effects of RAC in rats.

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. Metabolites were identified from the feces, bile, and urine by GC-MS or negative ion FAB MS and 1H NMR. The two major fecal metabolites were hydroxylated tetra- and triCDDs. Glucuronide and sulfate conjugates of these hydroxyl metabolites were found in the urine and bile. Minor metabolites included dichlorocatechol, dihydroxylated tetra- and triCDDs, and conjugates of these compounds.

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. The dominance of the NIH-shift products in the metabolism of tetrachlorodibenzo-p-dioxins indicates that the same isomers may be produced from differently substituted chlorinated dioxins.

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 concentration of total 14C-labelled residues (14C-SDM equivalents) in tissues other than the gastrointestinal tract ranged from 99-1 ppm (plasma) to 13.8 ppm (adipose tissue) 12 h after dosing. Seventy-two hours after dosing tissue concentrations ranged from 5.4 ppm (plasma) to 0.5 ppm (skeletal muscle). The concentration in the large intestine was substantially higher (10.4 ppm) than in the stomach (2.8 ppm) and small intestine (1.4 ppm) 72 h after dosing. 2. Of the 14C, 77% was excreted in the urine from 0 to 72 h after dosing with 14C-SDM, mostly in the 0-24-h collection. Fifteen percent was excreted in the faeces from 0 to 72 h after dosing, with most of this occurring 36-72 h post-dosing. 3. 14C-SDM accounted for 24% (liver) to 66% (adipose tissue) and the N4-acetyl derivative of SDM (N4-Ac-SDM) accounted for 10% (skeletal muscle) to 35% (kidney) of the total 14C in the tissues 12 h after dosing. The N4-glucose conjugate of SDM (G-SDM) was a major 14C-labelled compound in skeletal muscle (21% of total) and liver (28%) but it was not detected in adipose tissue or kidney. The N4-glucuronic acid conjugate of SDM (GA-SDM) was a minor metabolite in kidney, but was not detected in other tissues collected 12 h after dosing. Desamino SDM was a minor metabolite in the kidney. A minor metabolite in plasma was identified as the sulphate ester of 3-hydroxysulphadimethoxine. 4. 14C-labelled fractions isolated from 0 to 6-h urine included N4-Ac-SDM (82%), SDM (3%) and GA-SDM (6%).

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. 2. 14C-Labelled residues (ppm 14C-levamisole equivalents) in blood were highest at 3 h (2.2 ppm, oral dose) or 6 h (2.1 ppm, subcutaneous dose) and then declined to less than 0.5 ppm 48 h after dosing. 3. 14C-Labelled residues in milk were highest in samples collected from 0-12 h after dosing (1.55 ppm and 1.86 ppm of levamisole equivalents from oral and subcutaneously dosed animals, respectively) and declined to 0.06 ppm in milk collected from 36-48 h after dosing. Milk collected from 0-48 h after dosing accounted for 0.2% (oral dose) and 0.6% (subcutaneous dose) of the total 14C-activity administered as 14C-levamisole. The parent compound, 14C-levamisole, accounted for 12% or less (declined with time after dosing) of the total 14C-activity in the milk. Three 14C-labelled metabolites (formed by oxidation of imidazoline ring and/or opening of thiazolidine ring) in the milk were isolated and identified. 4. Urinary excretion accounted for 83% and 84% and faecal excretion accounted for 11% and 9% of the total 14C-activity given orally and subcutaneously, respectively, as 14C-levamisole. No 14C-levamisole was detected in the urine; the major urinary metabolite (formed by opening of thiazolidine ring) was isolated and identified. 5. The 14C-activity remaining in the animals 48 h after dosing was widely distributed in body tissues; however, the concentration in the liver was substantially higher than in all other tissues examined. Less than 5% of the 14C-activity in the liver was present as 14C-levamisole.

Identification of ractopamine hydrochloride metabolites excreted in rat bile.

1. Rats dosed orally with 2.85 +/- 0.30 mg [14C]ractopamine HC1 [(1R*, 3R*), (1R*, 3S*)-4-hydroxy-alpha-[[[3-(4-hydroxyphenyl)- 1-methylpropyl]-amino]-methyl]([U-14C]benzenemethanol)hydrochloride] containing 1.44 +/- 0.15 microCi radioactivity excreted 58 +/- 7% of the administered radioactivity in the bile within 24 h. Absorption and excretion of radioactivity was rapid as 55% of the administered radiocarbon was excreted into the bile during the first 8-h collection period. 2. Radioactivity excreted in rat bile was partitioned by XAD-2 column chromatography and reverse-phase hplc into at least seven different crude metabolite fractions; metabolites representing approximately 76% of the biliary radioactivity were isolated and identified from four of the crude metabolite fractions. 3. Approximately 46% of the biliary radioactivity was identified as a sulphate-ester, glucuronic acid diconjugate of ractopamine. Identification was based on 1H-nmr and negative-ion FAB-ms spectroscopy. Enzymatic and chemical hydrolysis of the sulphate-ester followed by co-chromatography of the hydrolysis products with synthetic ractopamine mono-glucuronides, established the site of sulphation at the C-10' phenol (phenol attached to carbinol) and glucuronidation at the C-10 phenol (phenol attached to methylpropyl amine) of ractopamine. 4. A metabolite representing approximately 6% of the biliary radioactivity was identified as a ractopamine mono-sulphate conjugate by using mass spectral and 1H-nmr techniques. Sulphate was conjugated at the C-10' phenol of ractopamine and was not stereospecific. 5. Approximately 25% of the biliary radioactivity was identified as ractopamine mono-glucuronides. The major site of glucuronidation was at the C-10 phenol, but ractopamine glucuronidated at the C'-10 phenol was also present.

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. 2. Rat gavaged with propachlor and methoxypropachlor eliminated 14C mostly in urine, whereas rat gavaged with alachlor, butachlor and metolachlor eliminated 14C about equally divided between urine and faeces. When bile ducts were cannulated, the gavaged rat eliminated most of the 14C in bile for all compounds. The amount of 14C in bile from the propachlor-gavaged rat was less than that for the other acetanilides, with the difference being in the urine. 3. The mercapturic acid metabolites 2-methylsulphinyl-N-(1-methylhydroxyethyl)-N-phenylacetam ide and 2-methylsulphinyl-N-(1-methylmethoxyethyl)-N-phenylacetam ide were isolated from the urine and bile of the methoxypropachlor-gavaged rat. 4. Bile was the major route for 14C elimination when MAP metabolites of alachlor, butachlor and metolachlor were perfused into a renal artery. Urine was the major route for 14C elimination when MAP metabolites of propachlor and methoxypropachlor were perfused. Mercapturic acid conjugates were major metabolites in bile and urine when MAP metabolites were perfused. 5. We conclude that alkyl groups on the phenyl portion of the acetanilide causes biliary elimination to be favoured over urinary elimination.

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. The ratios of intensities of selected mass spectral ions containing 12C6 and the corresponding ions containing 13C6 were used for residue quantitation. Sulmet, which was always the most abundant residue in the blood, decreased to less than 100 ppb 4 days after the last doses were given and to less than 10 ppb 7 days after the last doses. The concentrations of sulmet in milk were approximately one fifth the concentrations of sulmet in blood. The concentrations of lac-sulmet and Ac-sulmet in milk were lower than the concentrations of sulmet in milk.

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. As indicated by urinary excretion, absorption of neomycin was greater in 3-d-old calves (11.1 +/- 1.8% of the dose) than in 54- to 64-d-old nonruminating calves (1.5 +/- .58% of the dose) dosed similarly. Absorption of neomycin was similar in nonruminating (1.5 +/- .58%) and ruminating (2.13 +/- .62%) calves when the doses were administered in solution via a nippled bottle. In ruminating calves, absorption was somewhat less when the dose was administered on feed via a gelatin capsule (.5 +/- .06% of the dose) than when given in solution via a nippled bottle (2.13 +/- .62% of the dose). In calves dosed at 3 d of age, 14C concentration in the kidneys represented 55 +/- 4.9 ppm of neomycin equivalents. The next highest concentration occurred in the livers, which contained less than 5% of the level in kidneys. Tissue concentrations of 14C were related to absorption (as indicated by urinary excretion). Isolation and characterization (positive-ion fast atom bombardment mass spectroscopy and nuclear magnetic resonance spectroscopy) of 14C compounds in kidneys of calves dosed at 3 d of age indicated that at least 90% of the 14C was present as neomycin. Neomycin was also the major 14C compound in feces of all calves (70 to 80% of the 14C present).(ABSTRACT TRUNCATED AT 250 WORDS)

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. Three methylthio-turnover processes are proposed in the intermediary metabolism of pentachlorothioanisole.