Safety considerations for dietary supplement manufacturers in the United States.

Due to significant dietary supplement use in the US, product manufacturers must understand the importance of implementing a robust approach to establishing safety for all ingredients, including dietary ingredients, components, and finished dietary supplement products. Different regulatory pathways exist by which the safety of dietary ingredients can be established, and thus allowed to be marketed in a dietary supplement. For individual dietary ingredients, safety information may come from a variety of sources including history of safe use, presence of the ingredient in foods, and/or non-clinical and clinical data.

Human and Aquatic Toxicity Potential of Petroleum Biodegradation Metabolite Mixtures in Groundwater from Fuel Release Sites.

The potential toxicity to human and aquatic receptors of petroleum fuel biodegradation metabolites (oxygen-containing organic compounds [OCOCs]) in groundwater has been investigated as part of a multi-year research program. Whole mixtures collected from locations upgradient and downgradient of multiple fuel release sites were tested using: 1) in vitro screening assays for human genotoxicity (the gamma-H2AX assay) and estrogenic effects (estrogen receptor transcriptional activation assay), and 2) chronic aquatic toxicity tests in 3 species (Ceriodaphnia dubia, Raphidocelis subcapitata, and Pimephales promelas). In vitro screening assay results demonstrated that the mixtures did not cause genotoxic or estrogenic effects.

Life cycle of petroleum biodegradation metabolite plumes, and implications for risk management at fuel release sites.

This paper summarizes the results of a 5-y research study of the nature and toxicity of petroleum biodegradation metabolites in groundwater at fuel release sites that are quantified as diesel-range "Total Petroleum Hydrocarbons" (TPH; also known as TPHd, diesel-range organics (DRO), etc.), unless a silica gel cleanup (SGC) step is used on the sample extract prior to the TPH analysis. This issue is important for site risk management in regulatory jurisdictions that use TPH as a metric; the presence of these metabolites may preclude site closure even if all other factors can be considered "low-risk.

Comparative oral dose toxicokinetics of sodium selenite and selenomethionine.

Selenium (Se) poisoning by different forms of Se occurs in the United States. However, the toxicokinetics of different selenocompounds after oral ingestion is not well documented. In this study the toxicokinetics of Se absorption, distribution and elimination were determined in serum and whole blood of lambs that were orally dosed with increasing doses of Se as sodium selenite (inorganic Se) or selenomethionine (SeMet, organic Se).

Dietary toxicity of soluble and insoluble molybdenum to northern bobwhite quail (Colinus virginianus).

Limited data are available on the effects of molybdenum (Mo) on avian wildlife, which impairs evaluation of ecological exposure and risk. While Mo is an essential trace nutrient in birds, little is known of its toxicity to birds exposed to molybdenum disulfide (MoS2), the predominant form found in molybdenite ore. The chemical form and bioavailability of Mo is important in determining its toxicity.

Identification of ester metabolites from petroleum hydrocarbon biodegradation in groundwater using GC×GC-TOFMS.

In an effort to understand the nature and toxicity of petroleum hydrocarbon degradation metabolites, 2-dimensional gas chromatography linked to a time-of-flight mass spectrometer (GC×GC-TOFMS) was used to conduct nontargeted analysis of the extracts of 61 groundwater samples collected from 10 fuel release sites. An unexpected result was the tentative identification of 197 unique esters. Although esters are known to be part of specific hydrocarbon degradative pathways, they are not commonly considered or evaluated in field studies of petroleum biodegradation.

Developmental toxicity study of sodium molybdate dihydrate administered in the diet to Sprague Dawley rats.

Molybdenum is an essential nutrient for humans and animals and is a constituent of several important oxidase enzymes. It is normally absorbed from the diet and to a lesser extent from drinking water and the typical human intake is around 2μg/kg bodyweight per day. No developmental toxicity studies to contemporary standards have been published and regulatory decisions have been based primarily on older studies where the nature of the test material, or the actual dose levels consumed is uncertain.

90-Day subchronic toxicity study of sodium molybdate dihydrate in rats.

This study investigated the subchronic toxicity of molybdenum (Mo) in Sprague-Dawley rats given sodium molybdate dihydrate in the diet for 90days at dose levels of 0, 5, 17 or 60mgMo/kgbw/day. The study complied with OECD Test Guideline (TG) 408, with additional examination of estrus cycles and sperm count, motility, and morphology from OECD TG 416. The overall no-observed-adverse-effect level was 17mgMo/kgbw/day, based on effects on body weight, body weight gain, food conversion efficiency and renal histopathology (females only) at 60mgMo/kgbw/day.

Non-targeted analysis of petroleum metabolites in groundwater using GC×GC-TOFMS.

Groundwater at fuel release sites often contains nonpolar hydrocarbons that originate from both the fuel release and other environmental sources, as well as polar metabolites of petroleum biodegradation. These compounds, along with other polar artifacts, can be quantified as "total petroleum hydrocarbons" using USEPA Methods 3510/8015B, unless a silica gel cleanup step is used to separate nonpolar hydrocarbons from polar compounds prior to analysis. Only a limited number of these metabolites have been identified by traditional GC-MS methods, because they are difficult to resolve using single-column configurations.

Coordinated regulation of murine cardiomyocyte contractility by nanomolar (-)-epigallocatechin-3-gallate, the major green tea catechin.

Green tea polyphenolic catechins exhibit biological activity in a wide variety of cell types. Although reports in the lay and scientific literature suggest therapeutic potential for improving cardiovascular health, the underlying molecular mechanisms of action remain unclear. Previous studies have implicated a wide range of molecular targets in cardiac muscle for the major green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), but effects were observed only at micromolar concentrations of unclear clinical relevance.

Moxidectin toxicity in senescence-accelerated prone and resistant mice.

Moxidectin has been used safely as an antiparasitic in many animal species, including for the eradication of the mouse fur mite, Mycoptes musculinus. Although no side effects of moxidectin have previously been reported to occur in mice, 2 strains of the senescence-accelerated mouse (SAMP8 and SAMR1) sustained considerable mortality after routine prophylactic treatment. To investigate the mechanism underlying this effect, moxidectin toxicosis in these mice was evaluated in a controlled study.

Using roquefortine C as a biomarker for penitrem A intoxication.

Penitrem A is a well-recognized tremorgenic mycotoxin produced by several Penicillium spp. However, most natural cases of penitrem A intoxication have been associated with Penicillium crustosum. Another Penicillium sp.

In vitro study of the effectiveness of three commercial adsorbents for binding oleander toxins.

Introduction: Oleander (Nerium oleander) poisoning is a common problem found in many parts of the world. The oleander toxicity is due to oleandrin and its aglycone metabolite oleandrigenin. Activated charcoal is a useful gastrointestinal decontamination agent that limits the absorption of ingested toxins.

Case report: potential arsenic toxicosis secondary to herbal kelp supplement.

Context: Medicinal use of dietary herbal supplements can cause inadvertent arsenic toxicosis.

Case Presentation: A 54-year-old woman was referred to the University of California, Davis, Occupational Medicine Clinic with a 2-year history of worsening alopecia and memory loss. She also reported having a rash, increasing fatigue, nausea, and vomiting, disabling her to the point where she could no longer work full-time.

Determination of alpha-amanitin in serum and liver by multistage linear ion trap mass spectrometry.

This paper describes a rapid LC-MS/MS/MS method for the analysis of alpha-amanitin in serum and liver. Serum was initially prepared by precipitation of proteins with acetonitrile and subsequent removal of acetonitrile with methylene chloride. Liver was prepared by homogenization with aqueous acetonitrile and subsequent removal of acetonitrile using methylene chloride.

LC-MS/MS screen for penitrem A and roquefortine C in serum and urine samples.

A rapid LC-MS/MS method, using a triple quadrupole/linear ion trap mass spectrometer, was developed for determination of penitrem A and roquefortine C in serum and urine samples. Penitrem A and roquefortine C were extracted from samples with methylene chloride. The extracts were injected onto a liquid chromatograph coupled with a hybrid triple quadrupole/linear ion trap mass spectrometer.

Comparative toxicosis of sodium selenite and selenomethionine in lambs.

Excess consumption of selenium (Se) accumulator plants can result in selenium intoxication. The objective of the study reported here was to compare the acute toxicosis caused by organic selenium (selenomethionine) found in plants with that caused by the supplemental, inorganic form of selenium (sodium selenite). Lambs were orally administered a single dose of selenium as either sodium selenite or selenomethionine and were monitored for 7 days, after which they were euthanized and necropsied.

Evaluation of the respiratory elimination kinetics of selenium after oral administration in sheep.

Objective: To evaluate the respiratory excretion and elimination kinetics of organic and inorganic selenium after oral administration in sheep.

Animals: 38 crossbred sheep.

Procedures: Selenium was administered PO to sheep as a single dose of 0, 1, 2, 3, or 4 mg/kg as sodium selenite or selenomethionine.

Diagnosis of zinc phosphide poisoning in chickens using a new analytical approach.

Approximately 200 chickens were found dead after the flooring of a slat-and-litter house was breached. No clinical signs of illness were observed in the surviving birds. During necropsy, rolled oats were found in the chickens' crops and gizzards, and the contents had a petroleum-like odor.

Acute depigmentation of fertile brown eggs in a commercial layer operation.

Rapid depigmentation of brown eggs is an infrequent but startling event in the commercial egg industry that can result in significant economic losses. Loss of shell pigment in brown-shelled eggs is caused by various factors. In many cases, the exact cause of flock-wide pigment loss remains undetermined.

Diagnosis of Taxus (yew) poisoning in a horse.

A 2-year-old bay Thoroughbred colt was found dead overnight in its stall without a known history of any illness, existing disease, or toxicant exposure. No information on the clinical signs before this animal's death was reported. A full necropsy was performed the next morning and revealed a mild to moderate degree of endocardial hemorrhages in both ventricles.