Plasma pharmacokinetics of the mycotoxin deoxynivalenol following oral and intravenous administration to sheep

The pharmacokinetics of deoxynivalenol (DON) were studied in sheep after administrating intravenous and oral doses (0.5 and 5.0 mg/kg, respectively). The plasma concentrations were measured using an electron-capture gas chromatographic method. After iv administration DON plasma levels were found to decrease biexponentially, showing a rapid distribution phase (t 1/2 alpha = 12-23 min), followed by a slower elimination phase (t 1/2 beta = 57-78 min). Only trace levels of DON could be detected in plasma 7 hr post-dosing. Further pharmacokinetic data suggest that DON was confined mainly to extracellular fluid, and did not appear to undergo any significant binding or uptake by tissue. After oral dosing, DON was quickly absorbed (t-max 4.0-5.3 hr), but had a systemic bioavailability of only 7.5%; due in part to its rapid and efficient metabolism by rumen microorganisms. Half-life of elimination (t 1/2 beta) was 100-125 min following oral administration, and depending on the animal, required 20-30 hr to be cleared from the system. The metabolic formation of the glucuronide conjugate after iv and oral administration of DON appeared to occur quite efficiently (iv, 21%; oral, 75%), and its elimination half-lives (iv, 150-200 min; oral 6.1-7.1 hr) were considerably longer than that of the parent toxin. Detection in plasma of the de-epoxide metabolite, DOM-1, accounted for only a minor portion of the dose after either dosing regimen (iv, less than 2.0%; oral, less than 0.3%), occurring predominantly as the glucuronide conjugate.     

Broad range analysis of endocrine disruptors and pharmaceuticals using gas chromatography and liquid chromatography tandem mass spectrometry

Endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs) have been globally detected in impacted natural waters. The detection of trace quantities of EDCs and PPCPs in the environment is of great concern since some of these compounds have known physiological responses at low concentrations. EDCs can have a wide range of polarities, acidic and basic moieties, and exist in trace quantities, which often requires numerous complex extractions, large sample collection volumes, and multiple instrumental analyses. A comprehensive method has been developed allowing for the analysis of 58 potential EDCs in various water matrices using a single solid-phase extraction (SPE) of a 1 L sample with subsequent analyses using both gas chromatography and liquid chromatography, each coupled with tandem mass spectrometry (GC–MS/MS and LC–MS/MS). Instrument detection limits ranged between 0.12–7.5 pg with corresponding method reporting limits of 1–10 ng l⁻¹ in water. Recoveries for most compounds were between 50% and 112% with good reproducibility (RSD 6–22%).     

Nontransmission of deoxynivalenol (vomitoxin) to milk following oral administration to dairy cows

The absorption of deoxynivalenol (DON; vomitoxin), a trichothecene mycotoxin produced by Fusarium species, was studied in the dairy cow. Serum and milk DON levels were quantitated following a single oral dose of 920 mg DON to each of two lactating cows of similar weight. Maximum blood levels for the two animals following DON administration were 200 and 90 ng/ml serum, occurring at times 4.7 and 3.5 hr, respectively. By 24 hr after dosing only trace levels (less than 2 ng/ml) were still detectable. DON in its conjugated form accounted for 24-46% of the total levels present in serum. Free and conjugated DON were also present in cow's milk, but only extremely low amounts (less than 4 ng/ml) were detected. Detection of DON was carried out utilizing Sep-Pak C18 extraction cartridges for isolation, with additional purification of the sample achieved by passing the extract through a short charcoal/alumina column. The extract was then reacted with N-heptafluorobutyrylimidazole prior to quantitation of the resulting DON-tris-heptafluorobutyrate derivative by combined gas chromatography-quadrupole mass spectrometry, using multiple selected ion monitoring. Detection limits were as low as 1 ng/ml (1 ppb).     

Hazardous waste incineration emissions in perspective

There has been increasing concern over the stack emissions of toxic substances from hazardous waste incinerators, and with improved sampling and analytical technology, measurements are being made at lower and lower levels to support risk assessment and various types of decision-making. However, it is generally difficult to visualize these levels of emissions, which span many orders of magnitude. Data on stack emissions were compiled from various research and compliance testing programs, and representative examples of various types of emissions were plotted on a series of graphs that spans the entire range of concentrations that may be encountered. The result is an illustrative tool for communication as to what emissions from hazardous waste incinerators are actually like.     

Deltamethrin residues in milk and tissues of lactating dairy cows.

Lactating dairy cows were fed deltamethrin (2 or 10 mg kg-1 feed) for 28 consecutive days and deltamethrin residues measured in milk and tissues. Deltamethrin residues were higher relative to dose administered. The order of relative concentrations of deltamethrin in tissues, measured 1, 4, and 9 days after the last dose was: renal fat greater than subcutaneous fat greater than forequarter muscle greater than hindquarter muscle greater than liver greater than kidney. Depletion of deltamethrin residues in milk was very rapid indicating the half-life of the insectide of about 1 day. Trace amounts of deltamethrin metabolites 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (less than 0.0235 ppm) and 3-phenoxybenzoic acid (less than 0.034 ppm) were also detected in milk and tissues of treated cows.     

Minimal transmission of zearalenone to milk of dairy cows

Milk and plasma levels of zearalenone (ZEN), alpha-zearalenol (alpha-ZEL), beta-zearalenol (beta-ZEL) and conjugated metabolites were determined after feeding lactating cows with ZEN. In those instances where ZEN and alpha- and beta-ZEL were detected in milk or plasma, they occurred only as conjugates hydrolysable by treatment with a mixture of beta-glucuronidase and aryl sulfatase. With studies where 50 or 165 mg was fed daily to three cows for 21 day periods, neither dosage showed the presence of ZEN or metabolites in either milk or plasma (detection limits: milk, 0.5 ng/ml, ZEN, alpha-ZEL; 1.5 ng/ml, beta-ZEL; plasma, 2-3 times higher). A dose of 544.5 mg zearalenone per day given to a single cow for 21 days yielded maximum concentrations of only 2.5 ng ZEN/ml and 3.0 ng alpha-ZEL/ml in the milk. In plasma, up to 3 ng ZEN/ml could be detected during the initial 4 days of treatment. At a dose of 1.8 g of zearalenone given over a one day feeding period, maximum milk levels of 4.0 ng ZEN/ml, 1.5 ng alpha-ZEL/ml, and 4.1 ng beta-ZEL/ml were observed during the initial 2 days; corresponding maximum levels after a one day dose of 6.0 g zearalenone were 6.1, 4.0 and 6.6 ng/ml milk on days 2-3. In plasma, peak ZEN concentrations (9 and 13 ng/ml at the lower and higher one-day doses, respectively) occurred 12 hr after initial dosing, and declined to negligible levels by days 5-7. Neither alpha- nor beta-ZEL were detected in plasma. Since measurable levels required very high oral doses of ZEN, milk would not normally pose a human health hazard as a result of feeding rations containing ZEN to lactating dairy cows.     

The effect of acute administration of the mycotoxin zearalenone to female pigs

Crystalline zearalenone was administered to young female pigs at dose levels of 0, 3.5, 7.5 and 11.5 mg zearalenone/kg body weight. All animals receiving the mycotoxin exhibited vulva vaginitis and had enlarged reproductive tracts, 1 week after dosing. Free zearalenone was found in the blood, feces and urine of dosed animals. The highest zearalenone level detected was 2.61 ng/ml from a pig that received the 7.5 mg/kg dose. After 24 hours, feces collected contained on average upto 308 ng zearalenone per g of dried feces. Zearalenone levels of up to 59 ng/ml, and alpha-zearalenol levels of up to 155 ng/ml urine were found. beta-zearalenol was also detected in the urine.     

Distribution of deoxynivalenol in cerebral spinal fluid following administration to swine and sheep 1

Abstract

Deoxynivalenol (DON) is one of the major mycotoxins produced by Fusarium fungi. In evaluating DON as a potent CNS (emetic, anorexic) agent, its cerebral spinal fluid (CSF) and plasma pharmacokinetics were studied in pigs, a species very sensitive to the effects of DON, and sheep, a more tolerant animal. After intravenous administration, DON was detected very rapidly (<2.5 min) in the CSF of both species, but whereas peak levels (t‐max) occurred at 5–10 min in sheep, in swine it was 30–60 min. It would appear that the very rapid and extensive tissue distribution of DON in swine (Vdγ = 1.13 1 kg^‐1) may be slowing the rate of diffusion of the toxin into the CSF compared to sheep (Vd_β = 0.19 1 kg^‐1) where the toxin is confined essentially to the extracellular compartment. Area under curve calculations indicate approximately 2 1/2 times the amount of toxin eventually reaches the pig CSF compared to sheep CSF.

A good relationship between blood‐CSF DON levels was apparent in both species, although limitations in detection methods made it impossible to resolve a slow terminal phase (γ) in swine CSF which was evident in the plasma profile after iv administration.

Following oral administration of DON to pigs, a close correlation between plasma and CSF DON levels was observed. The toxin could be detected in CSF for up to 20 hr post‐dosing.     

Determination of fumonisins in milk

Abstract

Fumonisin B₁ (FB₁) and fumonisin B₂ (FB₂) were determined in milk by liquid chromatography (LC) following immunoaffinity column cleanup. Recoveries from milk spiked with 5–50 ng each fumonisin/ml averaged 79–109%. The aminopentol hydrolysis product of FB₁ (AP₁) was determined by LC after cleanup on a C₁₈solid phase phase extraction column; mean recoveries were 69–83% at spiking levels of 50–100 ng AP₁/ml milk. Detection limits were of the order 3–7 ng/ml for FB₁ and FB₂, and 20–25 ng/ml for AP₁. A stability study showed no losses of FB₁ and FB₂ in milk under conditions of freezing, refrigeration and boiling. A transmission study using four cows dosed with pure FB₁, either orally (1.0 and 5.0 mg FB₁/kg b.w.) or by i.v. injection (0.05 and 0.20 mg FB₁/kg b.w.) showed no detectable residues of FB, or AP₁ in the milk, with or without hydroiytic treatment with β‐glucuronidase/sulfatase to liberate any conjugates.