Toxic Element Contamination of Natural Health Products and Pharmaceutical Preparations

Background

Concern has recently emerged regarding the safety of natural health products (NHPs)–therapies that are increasingly recommended by various health providers, including conventional physicians. Recognizing that most individuals in the Western world now consume vitamins and many take herbal agents, this study endeavored to determine levels of toxic element contamination within a range of NHPs.

Methods

Toxic element testing was performed on 121 NHPs (including Ayurvedic, traditional Chinese, and various marine-source products) as well as 49 routinely prescribed pharmaceutical preparations. Testing was also performed on several batches of one prenatal supplement, with multiple samples tested within each batch. Results were compared to existing toxicant regulatory limits.

Results

Toxic element contamination was found in many supplements and pharmaceuticals; levels exceeding established limits were only found in a small percentage of the NHPs tested and none of the drugs tested. Some NHPs demonstrated contamination levels above preferred daily endpoints for mercury, cadmium, lead, arsenic or aluminum. NHPs manufactured in China generally had higher levels of mercury and aluminum.

Conclusions

Exposure to toxic elements is occurring regularly as a result of some contaminated NHPs. Best practices for quality control–developed and implemented by the NHP industry with government oversight–is recommended to guard the safety of unsuspecting consumers.     

Comparative Assessment of Essential and Toxic Metals in the Blood of Rheumatoid Arthritis Patients and Healthy Subjects

The present study deals with the comparative evaluation of essential and toxic metals in rheumatoid arthritis and healthy donors. Blood samples collected from rheumatoid arthritis patients and healthy subjects were analysed for selected essential and toxic metals (Ca, Mg, Fe, Zn, Cu, Co, Mn, Cr, Cd and Pb). The samples were digested in nitric acid and perchloric acid mixture, followed by quantification of the metals using atomic absorption spectrometry. Mean levels of Ca, Mg, Fe and Zn were significantly higher in the blood of healthy donors; however, elevated levels of Cd, Co, Cr, Cu and Pb were observed in blood of the patients. The correlation coefficients among the selected metals in the blood of arthritis patients were significantly different compared with the healthy counterparts. Multivariate cluster analysis revealed mutual apportionment of the essential and toxic metals in blood of the patients, whereas, in controls, the essential and toxic metals revealed diverse apportionment. Variations in the metal levels with gender, residence and smoking habits were also evaluated in both donor groups. Relative distribution, correlation and apportionment of the essential and toxic metals in the blood of the patients were significantly different than of controls.     

Methyl Ethyl Ketone Safety Characterization for Infants and Children: Assessment in the USEPA Voluntary Children's Chemical Evaluation Program

A safety characterization specific to children was performed for methyl ethyl ketone (MEK) according to the guidelines of the Voluntary Children's Chemical Evaluation Program (VCCEP). The characterization indicates that MEK exposures are not expected to pose an acute or chronic risk to children. Hazard information, summarized as per the VCCEP Tier structure, indicated no need for additional studies. All exposure pathways potentially relevant to children were considered, including child contact with environmental media, food, drinking water, parental transfer to child (human milk or dermal contact), direct consumer product use, and presence during product use. The assessment found that exposures from anthropogenic sources that children may encounter on a daily basis are very low, and in particular well below the chronic inhalation and oral health benchmarks (RfC and RfD) derived by the U.S. Environmental Protection Agency (USEPA). Indoor uses of consumer products can result in higher acute exposures, but these are short-lived and also fall below chronic benchmarks adjusted to an acute timeframe. In addition, MEK is rapidly metabolized and excreted, thus acute exposures do not lead to an increase in body burden over time. The USEPA concluded the VCCEP submission sufficiently characterized potential risks to children, and that no additional toxicity tests were needed for MEK.     

Assessment of Efficacy and Quality of Two Albendazole Brands Commonly Used against Soil-Transmitted Helminth Infections in School Children in Jimma Town,Ethiopia

BackgroundThere is a worldwide upscale in mass drug administration (MDA) programs to control the morbidity caused by soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura and hookworm. Although anthelminthic drugs which are used for MDA are supplied by two pharmaceutical companies through donation, there is a wide range of brands available on local markets for which the efficacy against STHs and quality remain poorly explored. In the present study, we evaluated the drug efficacy and quality of two albendazole brands (Bendex and Ovis) available on the local market in Ethiopia.Conclusion/SignificanceThe study revealed that differences in efficacy between the two brands of albendazole (ABZ) tablets against hookworm are linked to the differences in the in-vitro drug release profile. Differences in uptake and metabolism of this benzimidazole drug among different helminth species may explain that this efficacy difference was only observed in hookworms and not in the two other species. The results of the present study underscore the importance of assessing the chemical and physicochemical quality of drugs before conducting efficacy assessment in any clinical trials to ensure appropriate therapeutic efficacy and to exclude poor drug quality as a factor of reduced drug efficacy other than anthelminthic resistance. Overall, this paper demonstrates that “all medicines are not created equal”.     

Evaluation of Extractables in Processed and Unprocessed Polymer Materials Used for Pharmaceutical Applications

Polymeric materials are often used in pharmaceutical packaging, delivery systems, and manufacturing components. There is continued concern that chemical entities from polymeric components may leach into various dosage forms, particularly those that are comprised of liquids such as parenterals, injectables, ophthalmics, and inhalation products. In some cases, polymeric components are subjected to routine extractables testing as a control measure. To reduce the risk of discovering leachables during stability studies late in the development process, or components that may fail extractables release criteria, it is proposed that extractables testing on polymer resins may be useful as a screening tool. Two studies have been performed to evaluate whether the extractables profile generated from a polymer resin is representative of the extractables profile of components made from that same resin. The ELSIE Consortium pilot program examined polyvinyl chloride and polyethylene, and another study evaluated polypropylene and a copolymer of polycarbonate and acrylonitrile butadiene styrene. The test materials were comprised of polymer resin and processed resin or molded components. Volatile, semi-volatile, and nonvolatile chemical profiles were evaluated after headspace sampling and extraction with solvents of varying polarity and pH. The findings from these studies indicate that there may or may not be differences between extractables profiles obtained from resins and processed forms of the resin depending on the type of material, the compounds of interest, and extraction conditions used. Extractables testing of polymer resins is useful for material screening and in certain situations may replace routine component testing.KEY WORDS: extractables, PC/ABS, polyethylene, polypropylene, polyvinylchloride     

Prospects of Inducing Resistance in Fodder Species against Toxic Ions and Metals

ABSTRACT

Experiments were carried out with various salts and their combinations to ascertain the impact of these salts on seedling traits of fodder species and to identify tolerant species. Length-based traits showed a repressed effect, whereas weight-based traits were increased under salt stress. Furthermore, accumulation of Na⁺, Ca²⁺, and Cl^? ions and metals (Cu²⁺, Fe²⁺, and Al³⁺) increased in various organs of seedlings due to various salt treatments. Contrastingly, K⁺, K⁺/Na⁺, and Ca²⁺/Cl^? decreased, showing priority for specific salts. Seedling traits, such as shoot length sensitivity and shoot biomass, provide an effective mean of selection for tolerant or susceptible genotypes. Diverse types of tolerance mechanisms were present in cultivars to detoxify the effect of ions and metals. Cultivars that showed low susceptibility index, high shoot biomass, and high metal concentration were salt includers and could be utilized for bioremediation of the affected areas, whereas tolerant cultivars that showed low susceptibility index, metals concentration, and comparable shoot biomass to that of the control were salt excluders and could be utilized for fodder purposes.     

Toxic Metals in Breast Milk Samples from Ankara, Turkey: Assessment of Lead, Cadmium, Nickel, and Arsenic Levels

Toxic metals are one of the significant groups of chemical contaminants that humans are exposed to by oral, inhalation, and dermal routes. Exposure to these chemicals begins with intrauterine life and continues during lactation period at the first years of life. Breastfeeding has a much more special place than other nutrition options for infants. However, when possibility of contaminant transfer by breast milk is considered, its safety and quality is essential. Regarding infant and mother health and limited number of information on this field in Turkey, measuring contamination levels in breast milk is important. Therefore, in the present study, lead (Pb), cadmium (Cd), nickel (Ni), and arsenic (As) levels were measured by atomic absorption spectrometry in 64 breast milk samples obtained from mothers from Ankara, Turkey. Pb and Ni levels in breast milk samples were found to be 391.45?±?269.01?μg/l and 43.94?±?33.82?μg/l (mean ± SD), respectively. Cd was found only in one of 64 samples, and the level was 4.62?μg/l. As level was below the limit of quantification (LOQ, 7.6?μg/l) in all samples. These findings will accurately direct strategies and solutions of protection against contaminants in order to reduce their levels in biological fluids.     

Status of Toxic Metals in Biological Samples of Diabetic Mothers and Their Neonates

The mechanism of transport of trace elements from the mother to the newborn is still not well known. The aim of present study was to compare the status of trace toxic elements, arsenic (As), cadmium (Cd), and lead (Pb) in biological samples (whole blood, urine and scalp hair) of insulin-dependent diabetic mothers (age ranged 30-40) and their newly born infants (n = 76). An age and socioeconomics matched 68 nondiabetic mothers and their infants, residing in the same locality, who were selected as referents. The elemental concentrations in all three biological samples were determined by an electrothermal atomic absorption spectrometer, prior to microwave-assisted acid digestion. The mean values of As, Cd, and Pb in all biological samples of diabetic mothers and their infants were significantly higher as compared to the referent mother-infant pair samples (p < 0.01). The high levels of As, Cd, and Pb in biological samples of diabetic women may play a role in the pathogenesis of diabetes mellitus and impacts on their neonates.     

A Study of Safety Factors for Risk Assessment of Drugs Used for Treatment of Attention Deficiency Hyperactivity Disorder in Sensitive Populations

The aim of this study was to search the literature through the library and Internet resources from pharmaceutical companies and associations to obtain pharmacoki-netic and pharmacodynamic data for six of the most used drugs for treatment of Attention Deficiency Hyperactivity Disorder (ADHD). The drugs included meth-ylphenidate, pemoline, haloperidol, bupropion, imipramine, and desipramine. The data collected allowed the evaluation of the 10X uncertainty factor, which was related to healthy adults and sensitive populations (children, elderly and health affected). Once the extensive database review was completed, the data were used to calculate a composite factor (kinetics x dynamics) for each drug. Ten of the 12 data-derived composite factors were less than 10. Therefore, incorporation of human kinetic and dynamic data into risk assessment can help to reduce the uncertainties associated with sensitive subgroups.     

Endothelial Function and Serum Concentration of Toxic Metals in Frequent Consumers of Fish

Background

Endothelial dysfunction is involved in the pathogenesis of atherosclerosis. Consumption of fish is associated with reduced cardiovascular risk, but there is paucity of data concerning its effect on endothelial function. Furthermore, investigation of the effects of fish consumption on health must take into account the ingestion of contaminants, including transition metals and some metalloids, which may have unfavorable effects on health, including those on the cardiovascular system. We investigated the association between fish consumption, endothelial function (flow mediated dilation of the brachial artery), and serum concentration of some toxic metals in apparently healthy people.

Methods

Twenty-nine high fish consumers (at least 3 portions a week) were compared with 25 low fish consumers (less than 1 portion a week). All participants were free of diabetes, cardiovascular or other systemic diseases. Serum metal (antimonium, arsenic, mercury, lead, cobalt, copper, zinc, selenium, strontium) concentrations were measured in subgroups of 24 high fish consumers and 19 low fish consumers.

Results

Both groups exhibited similar habitual dietary patterns, age and anthropometric characteristics. The high fish consumers had higher flow mediated dilation (9.7±1.8 vs. 7.3±1.9%; P<0.001), but also higher serum concentrations of mercury (5.87±2.69 vs. 1.65±1.10 mcg/L; P<0.001) and arsenic (6.04±3.25 vs. 2.30±1.58 mcg/L; P<0.001). The fasting plasma glucose concentrations were significantly correlated with both mercury (r = 0.39; P = 0.01) and arsenic concentrations (r = 0.55; P<0.001).

Conclusions

Habitual consumption of high amounts of fish is associated with better endothelial function despite higher serum concentrations of mercury and arsenic.     

Health Risk Assessment of Consumption of Heavy Metals in Market Food Crops from Sialkot and Gujranwala Districts,Pakistan

This study was performed to investigate the potential health risk of heavy metals (HMs) through consumption of market food crops (MFCs) in the Sialkot and Gujranwala districts, Pakistan. Both study areas are located in industrialized regions of the country, where atmospheric pollution is a problem and irrigation of food crops is mostly practiced on the use of wastewater/contaminated water. For the purpose of this study, MFCs samples were collected and assessed for HMs (Cr, Ni, Cd, Pb, Mn, Cu, Zn, and Fe) by using flame atomic absorption spectrophotometry. Concentration of HMs such as Pb and Cd exceeded the Food and Agriculture/World Health Organization's recommended limits in all MFCs, while Cr in most of the vegetables of the Sialkot and Gujranwala districts also exceeded that limit. The health risk index was >1 in Triticum aestivum for Pb and Cd intake in the Sialkot district and only Pb in the Gujranwala district. Therefore, this study suggests pretreatment of wastewater and its utilization for lawns and green belts irrigation, rather than for food crops. This study also suggests a regular monitoring of HMs in the irrigation water, subsequent soil, air, and MFCs in order to prevent or reduce health hazards.     

蒲公英护肤品的安全性评价

蒲公英具有无毒、温和、安全性高的特点 ,这已经为我国民间长期应用实践和有关药理及临床方面的研究所验证。以蒲公英提取物为功能性成分的蒲公英护肤品其使用安全性究竟如何 ?根据ＧＢ7919— 87《化妆品安全性评价程序和方法》对南京野生植物综合利用研究院研制的蒲公英护肤品进行了安全性评价试验。1　材料和方法1.1　小鼠经口急性毒性试验材料和方法实验动物 :昆明种健康小鼠 4 0只 ,体重 18～2 2ｇ ,雌雄各半。实验方法 :霍恩氏法。动物禁食 16ｈ后分性别按体重随机分入 1.0 0、2 .0 5、4 .6 6和 10 .0 0ｇ/ｋｇｂ .ｗｔ各 4个剂量组 ,…     

四种护脾养胃类中药水提物抗氧化能力测定

以罗丹明B为显色剂,采用分光光度法测定了护脾养胃类方剂中常见的当归、五味子、黄芩、红枣等四种中药水提物对·OH的清除能力.实验表明:这些中药永提取物对·OH都具有较强的清除作用,呈现明显的量效关系,其中红枣的清除能力最强.据此评价了这四种中药水提取物抗氧化能力大小顺序为:红枣＞当归＞黄芩＞五味子.     

Performance and Safety of Praziquantel for Treatment of Intestinal Schistosomiasis in Infants and Preschool Children

Background

In 2012 the WHO formally recognised that infants and preschool children are at significant risk of schistosomiasis and qualify for treatment with praziquantel (PZQ). Targeted surveys determining both the performance and safety of this drug are now needed in endemic areas. We have formally assessed parasitological cure and putative side-effects in a prospective cohort of Schistosoma mansoni-infected children (aged 5 months–7 years old) in lakeshore settings of Uganda.

Methodology/Principal Findings

From a total of 369 children found to be egg-patent for intestinal schistosomiasis, 305 were followed-up three to four weeks after PZQ treatment and infection status re-assessed. Separately, a previously tested side-effect questionnaire was employed before and 24 hours after PZQ treatment to assess incidence and amelioration of symptoms in young children and their mothers. While the overall observed parasitological cure was 56.4%, a significant difference was found between a sub-set of children who had a history of multiple PZQ treatments (between one and four in an 18 month period), where cure rate was 41.7%, and those who had never received treatment (cure rate was 77·6%). PZQ proved to be safe, with only mild reported side effects which cleared within a month after treatment. Prevalence of reported symptoms was significantly lower in children than in mothers, and fewer side-effects were reported upon subsequent rounds of PZQ treatment.

Conclusion/Significance

Our findings show that PZQ treatment of young children resulted in satisfactory cure rates, and marked reduction in egg-output, with only mild and transient reported side-effects. However, the cure rate is clearly lower in younger children and those with history of previous treatment. Cure rate, but not egg reduction rate, was also lower in children with heavier pre-intervention infection intensity. With chemotherapy now recommended as a long-term strategy for disease control in young children, research into optimising the periodicity of targeted treatment strategies is now crucial.     

复合性状转基因植物的应用现状与安全评价

复合性状转基因植物能够同时表达两个或多个外源基因,可以满足种植者多元化需求和带来多重效益,成为目前转基因植物研发及应用的一个重要趋势。世界各国由于监管理念不同,对育种复合后代的遗传稳定性和基因互作的看法不同,对复合性状转基因植物的安全评价采取了不同的模式。综述了目前复合性状转基因植物的应用现状、不同国家的评价模式,并提出了我国对复合性状转基因植物安全评价的建议。