Lactic Acid Salts of Nicotine Potentiate the Transfer of Toxic Metals into Electronic Cigarette Aerosols.

The designs and liquid formulations of Electronic Nicotine Delivery System (ENDS) devices continue to rapidly evolve. Thus, it is important to monitor and characterize ENDS aerosols for changes in toxic constituents. Many ENDS liquid formulations now include the addition of organic acids in a 1 to 1 molar ratio with nicotine. Metal concentrations in aerosols produced by ENDS devices with different nicotine salt formulations were analyzed. Aerosols from devices containing lactic acid had higher nickel, zinc, copper, and chromium concentrations than aerosols produced by devices containing benzoic acid or levulinic acid. Our scanning electron microscope with energy dispersive X-ray analytical findings showed that the metals determined in the inductively coupled plasma-mass spectrometry analytical results were consistent with the metal compositions of the ENDS device components that were exposed to the liquids and that nickel is a major constituent in many ENDS internal components. As a result of the exposure of the nickel-containing components to the ENDS liquids, resulting aerosol nickel concentrations per puff were higher from devices that contained lactic acid in comparison to devices with benzoic or levulinic acid. The aerosol nickel concentrations in 10 puffs from ENDS-containing lactic acid were, in some cases, hundreds of times higher than cigarette mainstream smoke nickel deliveries. Thus, the design of an ENDS device in terms of both physical construction components and the liquid chemical formulations could directly impact potential exposures to toxic constituents such as metals.

Toxic Metals in Liquid and Aerosol from Pod-Type Electronic Cigarettes.

High-quality, accurate data on liquid contents and aerosol emissions from electronic nicotine delivery systems (ENDS, e.g., e-cigarettes) are crucial to address potential health concerns as these devices evolve and mature. Metals are an important class of ENDS constituents that merit attention as they have various health implications. Proper sampling, handling and aerosol trapping materials are essential to generate accurate quantitative metal data and to reduce the likelihood of inaccurate results originating from inappropriate collection vessels and materials that contribute to high background levels. Published methods that meet these criteria were applied to the analyses of chromium, nickel, copper, zinc, cadmium, tin and lead in liquid and aerosol from mint/menthol and tobacco flavors of currently popular pod-based devices from three manufacturers. Metal concentrations from pods that had not been used for generating aerosol ranged from below our lowest reportable level to 0.164 µg/g for Cr, 61.3 µg/g for Ni, 927 µg/g for Cu, 14.9 µg/g for Zn, 58.2 µg/g for Sn and 2.56 µg/g for Pb. Cadmium was included in our analyte panel and was not present above detection limits in liquid or aerosol. Aerosol metal concentrations (using a 55-mL puff) ranged from below our lowest reportable level to 29.9 ng/10 puffs for Cr, 373 ng/10 puffs for Ni, 209 ng/10 puffs for Cu, 4,580 ng/10 puffs for Zn, 127 ng/10 puffs for Sn and 463 ng/10 puffs for Pb. Our results showed some metal delivery from all the products examined and highly variable metal levels between manufacturer, brand and package.

Analysis of Toxic Metals in Aerosols from Devices Associated with Electronic Cigarette, or Vaping, Product Use Associated Lung Injury.

Research gaps exist in toxic metals characterization in e-cigarette, or vaping, products (EVPs) as these analytes typically have low concentrations and most standard aerosol trapping techniques have high metals background. An additional complication arises from differences in the EVP liquid formulations with nicotine products having polar properties and non-nicotine products often being non-polar. Differences in polar and non-polar matrices and the subsequent aerosol chemistries from various EVPs required modifications of our previously reported nicotine-based EVP aerosol method. Validation and application of the expanded method, suitable for both hydrophobic and hydrophilic aerosols, are reported here. The metals analyzed for this study were Al, Cr, Fe, Co, Ni, Cu, Cd, Sn, Ba, and Pb. The method limits of detection for the modified method ranged from 0.120 ng/10 puffs for Cd to 29.3 ng/10 puffs for Al and were higher than reported for the previous method. Results of the analyses for metals in aerosols obtained from 50 EVP products are reported. Cannabinoid based EVP aerosols were below reportable levels, except for one sample with 16.08 ng/10 puffs for Cu. Nicotine-based EVP results ranged from 6.72 ng/10 puffs for Pb to 203 ng/10 puffs for Sn. Results of the analyses for these metals showed that aerosols from only 5 of the 50 devices tested had detectable metal concentrations. Concentrations of toxic elements in the aerosols for nicotine-based EVP aerosol metal concentration ranges were consistent with previously published results of aerosol analyses from this class of devices.

A review of data for quantifying human exposures to micro and nanoplastics and potential health risks.

Plastic debris have been shown to degenerate to particle sizes that can be transported in air, water, and food. Small particles are documented to enter and exit our bodies and translocate to and from some internal organs. Health effects on respiratory, hepatic, immune, and gastrointestinal systems have been reported in humans and other mammals in response to elevated particle or fiber exposures. These health effects differed by plastic type and size, and there was evidence of dose response for a few health endpoints. We conducted a systematic word search and reviewed published literature to identify microplastic and nanoplastic studies that quantified exposure via the ingestion, inhalation, and subcutaneous absorption (not dermal) exposure pathways; identified translocation, internal dose, and associations with health effects and markers related to exposures to specific sizes and types of plastics. We identified the data gaps in relating exposure data to health effects and biomarkers, most notably the lack of characterization of plastic particles and fibers smaller than 10 µm in most media.

Toxic Metal-Containing Particles in Aerosols from Pod-Type Electronic Cigarettes.

The popularity of electronic cigarettes (electronic nicotine delivery systems or ENDS) has grown rapidly over the past decade. With the continued evolution of ENDS, and the arrival of newer replaceable pod devices on the market, it is prudent to examine their emissions to help determine potential health risks to the user. Metal-containing particles were examined in aerosol from several pod-based devices from three manufacturers that offer flavored liquids in their respective products. Previous ENDS metal emissions studies focused on the total toxic metal concentrations in aerosols and have suggested that the principal sources are oxidized internal metal components that are in contact with the liquid. Most metal oxides have limited solubility, and it is likely that some metal content in ENDS aerosol may present as particles rather than dissolved forms. Examining the composition and number of particles in the ENDS aerosols is important because inhaled metal oxide particles cause pulmonary inflammation. Chronic inhalation of ENDS aerosol may lead to inflammatory cell activation in the lungs. Therefore, this study was designed to measure metal oxide particle concentrations and sizes in ENDS aerosols from select pod-based systems. Aerosol samples were generated with pod liquids (tobacco, mint or menthol) from devices produced by three manufacturers using CORESTA Recommended Method 81 parameters with a high-purity fluoropolymer aerosol trap. Particle sizes for chromium, iron, nickel, copper, zinc, tin and lead oxides were measured in triplicate using single particle inductively coupled plasma-mass spectrometry and dynamic light scattering. A novel aspect of these measurements included using dual element particle analysis to infer particle source component material. Particle concentrations in aerosols from the devices were variable between devices and from pod to pod, ranging from no detectable chromium- and zinc-containing particles in aerosol from some pods to 222,000 lead containing particles per 10 puffs from individual pods.

Analysis of Toxic Metals in Electronic Cigarette Aerosols Using a Novel Trap Design.

Since 2006 the domestic popularity and sales of electronic cigarettes (i.e., electronic nicotine delivery systems or ENDS) have grown rapidly. Although the constituents of the aerosol produced by ENDS have been previously investigated, differences in puff regimens and aerosol trapping schema in published literature often complicate result comparisons and data interpretation. As the ENDS product designs continue to evolve, there is a critical need to develop and validate robust methodologies for laboratory testing, appropriate aerosol generation and trapping media required for accurate determinations of ENDS aerosol metals deliveries. A simple, high metals purity, fluoropolymer trap was developed and validated that meets standard machine puffing regimen (CORESTA Recommended Method 81) specifications and exhibits negligible acid extractable metal backgrounds. Using a standard machine puffing regimen in combination with a fluoropolymer condensation trap, aerosol was generated and collected from select ENDS devices for analysis of chromium, nickel, copper, zinc, cadmium, tin, and lead with triple quadrupole inductively coupled plasma mass spectrometry. Devices tested spanned a range of commercial products, including flavored variants of JUUL pods, refillable tank systems, rechargeable cartridges, and single-use ENDs devices. Results showed that for aerosols generated under a fixed puffing regimen (50 puffs/collection), metal concentrations ranged from below the detection limits (LOD) to 614 ng copper and 339 ng zinc per 10 puffs. Cadmium concentrations were below LOD for all devices tested. Device specific aerosol levels of Sn and Pb ranged from below LOD to low nanogram levels. Cr and Ni were transported in aerosols at levels equivalent to, or slightly higher than in mainstream cigarette smoke using a standard smoking regimen. The generally lower levels of specific metals, Cd and Pb, transmitted in ENDS aerosols compared to mainstream cigarette smoke reflect possible reduction of harm for smokers who substitute the use of ENDS as cessation devices in place of smoking cigarettes.

Analysis of Toxic Metals in Liquid from Electronic Cigarettes.

As the technology of electronic nicotine delivery systems (ENDS), including e-cigarettes, evolves, assessing metal concentrations in liquids among brands over time becomes challenging. A method for quantification of chromium, nickel, copper, zinc, cadmium, tin, and lead in ENDS liquids using triple quadrupole inductively coupled plasma mass spectrometry was developed. The method's limits of detection (LODs) were 0.031, 0.032, 3.15, 1.27, 0.108, 0.099, 0.066 µg/g for Cr, Ni, Cu, Zn, Cd, Sn, and Pb respectively. Liquids analyzed were from different brands and flavors of refill bottles or single-use, rechargeable, and pod devices from different years. Scanning electron microscopy with energy dispersive spectroscopy further evaluated the device components' compositions. Refill liquids before contacting a device were below lowest reportable levels (LRL) for all metals. Copper and zinc were elevated in liquids from devices containing brass. Cadmium was

Aluminum in Tobacco Products Available in the United States.

A quantitative method for the analysis of aluminum in tobacco products was developed, validated and applied to select samples. Samples were prepared using standard microwave digestion of tobacco from various products. Detection and quantification utilized sector field inductively coupled plasma-mass spectrometry. Method applicability to analyze aluminum in a range of tobacco products was demonstrated with quantitative analyses of smokeless tobacco products, cigarette tobacco, little cigar tobacco and roll-your-own/pipe tobacco. Though these products represent a convenience sampling, we observed that smokeless tobacco products, as a category, had the lowest average aluminum concentrations. Roll-your-own or pipe tobacco and little cigar tobacco had higher median and ranges of aluminum concentrations than cigarette and smokeless tobacco samples.

Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities.

Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs.

Biomarkers of exposure to new and emerging tobacco delivery products.

Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products. Here, we review current methods for measuring exposure to new and emerging tobacco products, such as electronic cigarettes, little cigars, water pipes, and cigarillos. Rigorously validated biomarkers specific to these new products have not yet been identified. Here, we discuss the strengths and limitations of current approaches, including whether they provide reliable exposure estimates for new and emerging products. We provide specific guidance for choosing practical and economical biomarkers for different study designs and experimental conditions. Our goal is to help both new and experienced investigators measure exposure to tobacco products accurately and avoid common experimental errors. With the identification of the capacity gaps in biomarker research on new and emerging tobacco products, we hope to provide researchers, policymakers, and funding agencies with a clear action plan for conducting and promoting research on the patterns of use and health effects of these products.

Electrothermal Vaporization-QQQ-ICP-MS for Determination of Chromium in Mainstream Cigarette Smoke Particulate.

Chromium is transported in mainstream tobacco smoke at very low concentrations. However, when chromium is deposited too deeply in the lungs for mucociliary clearance, or is in a particle that is too large to pass directly through tissues, it bioaccumulates in the lungs of smokers. It is important to determine the concentrations of chromium that are transported in mainstream smoke. Several reliable studies have resulted in reports of chromium concentrations in smoke particulate that were below limits of detection (LODs) for the instruments and methods employed. In this study, electrothermal vaporization-triple quad-inductively coupled plasma-mass spectrometry (ETV-QQQ-ICP-MS) was chosen for determination of chromium concentrations in mainstream smoke because of the high sensitivity of ETV combined with QQQ-ICP-MS. The smoke from five reference, quality control, and commercial cigarettes was analyzed using ETV-QQQ-ICP-MS with isotope dilution for quantitative determination of chromium. The method LOD was sufficiently low that chromium concentrations in mainstream smoke could indeed be determined. The chromium concentrations in the smoke particulate were between 0.60 and 1.03 ng/cigarette. The range of chromium concentrations was at or below previously reported LODs. Determination of the oxidation state of the chromium transported in mainstream smoke would also be important, in consideration of the fact that both chromium(III) and chromium(VI) oxidation states cause inhalation toxicity, but chromium(VI) is also a carcinogen. It was possible to separate the oxidation states using ETV-QQQ-ICP-MS. However, determination of individual species at the levels found in mainstream smoke particulate matter was not possible with the present method.

Electron Microscopic Analysis of Silicate and Calcium Particles in Cigarette Smoke Tar.

Scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM-EDS) supplies information that is complementary to those data traditionally obtained using inductively coupled plasma-mass spectrometry for analysis of inorganic tobacco and tobacco smoke constituents. The SEM-EDS approach was used to identify select inorganic constituents of mainstream cigarette smoke "tar." The nature of SEM-EDS instrumentation makes it an ideal choice for microstructural analyses as it provides information relevant to inorganic constituents that could result from exposure to combusted tobacco products. Our analyses show that aluminum silicates, silica, and calcium compounds were common constituents of cigarette mainstream smoke "tar." Identifying inorganic tobacco smoke constituents is important because inhalation of fine inorganic particles could lead to inflammatory responses in the lung and systemic inflammatory responses. As cigarette smoking causes chronic inflammation in the respiratory tract, information on inorganic particulate in mainstream smoke informs efforts to determine causative agents associated with increased morbidity and mortality from tobacco use.

Triple Quad-ICP-MS Measurement of Toxic Metals in Mainstream Cigarette Smoke from Spectrum Research Cigarettes.

We previously reported toxic metal concentrations in the mainstream smoke from 50 varieties of commercial cigarettes available in the USA using quadrupole inductively coupled plasma-mass spectrometry (ICP-MS). However, efforts to continue producing high quality data on select mainstream cigarette smoke constituents demand continued improvements in instrumentation and methodology and application of the methodology to cigarettes that differ in design or construction. Here we report a new application of 'triple quad'-ICP-MS instrumentation to analyze seven toxic metals in mainstream cigarette smoke from the Spectrum variable nicotine research cigarettes. The Spectrum cigarettes are available for research purposes in different configurations of low or conventional levels of nicotine, mentholated or nonmentholated, and tar delivery ranges described as 'low tar' or 'high tar'. Detailed characterizations of specific harmful or potentially harmful constituents delivered by these research cigarettes will help inform researchers using these cigarettes in exposure studies, cessation studies and studies related to nicotine addiction or compensation.

Electron Microscopic Analysis of Surface Inorganic Substances on Oral and Combustible Tobacco Products.

Although quantitative trace toxic metal analyses have been performed on tobacco products, little has been published on inorganic particulate constituents on and inside the products. We analyzed these constituents using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS). The nature of SEM-EDS instrumentation makes it an ideal choice for inorganic particulate analyses and yields relevant information to potential exposures during consumption of oral tobacco products, and possibly as a consequence of smoking. Aluminum silicates, silica and calcium compounds were common inorganic particulate constituents of tobacco products. Aluminum silicates and silica from soil were found on external leaf surfaces. Phytolithic silica, found in the lumen of the plant leaf, is of biogenic origin. Calcium oxalate was also apparently of biogenic origin. Small mineral deposits on tobacco could have health implications. Minerals found on the surfaces of smokeless tobacco products could possibly abrade the oral mucosa and contribute to the oral inflammatory responses observed with smokeless tobacco product use. If micron and sub-micron size calcium particles on cigarette filler were transported in mainstream smoke, they could potentially induce a pulmonary irritant inflammation when inhaled. The transport of aluminum silicate and silica in smoke could potentially also contribute to chronic inflammatory disease.

High-Throughput Determination of Mercury in Tobacco and Mainstream Smoke from Little Cigars.

A method was developed that utilizes a platinum trap for mercury from mainstream tobacco smoke, which represents an improvement over traditional approaches that require impingers and long sample preparation procedures. In this approach, the trapped mercury is directly released for analysis by heating the trap in a direct mercury analyzer. The method was applied to the analysis of mercury in the mainstream smoke of little cigars. The mercury levels in little cigar smoke obtained under Health Canada Intense smoking machine conditions ranged from 7.1 × 10(-3) to 1.2 × 10(-2) mg/m(3). These air mercury levels exceed the chronic inhalation minimal risk level corrected for intermittent exposure to metallic mercury (e.g., 1 or 2 h per day, 5 days per week) determined by the Agency for Toxic Substances and Disease Registry. Multivariate statistical analysis was used to assess associations between mercury levels and little cigar physical design properties. Filter ventilation was identified as the principal physical parameter influencing mercury concentrations in mainstream little cigar smoke generated under ISO machine smoking conditions. With filter ventilation blocked under Health Canada Intense smoking conditions, mercury concentrations in tobacco and puff number (smoke volume) were the primary physical parameters that influenced mainstream smoke mercury concentrations.

Determination of Toxic Metals in Little Cigar Tobacco with 'Triple Quad' ICP-MS.

Smoking remains the leading cause of preventable death in the USA. Much of the focus on harmful and potentially harmful constituents (HPHCs) in tobacco products has been on cigarettes. Little cigars gained popularity over the last decade until tobacco taxes made cigarettes more expensive in the USA. Many little cigar brands are similar in size with cigarettes and may be smoked in a similar manner. Scant data are available on HPHC concentrations in little cigars, therefore we developed and applied a new analytical method to determine concentrations of 10 toxic metals in little cigar tobacco. The method utilizes 'triple quadrupole' ICP-MS. By optimizing octapole bias, energy discrimination and cell gas flow settings, we were able to accurately quantify a range of elements including those for which the cell gas reactions were endothermic. All standard modes (Single Quad No Gas, MS-MS NH3/He and MS-MS O2) were utilized for the quantitation of 10 toxic metals in little cigar tobacco, including uranium, which was added as an analyte in the new method. Because of the elimination of interfering ions at 'shifted analyte masses', detection limits were lower compared with a previous method. Tobacco selenium concentrations were below the limit of detection in the previous method, but the new technology made it possible to report all selenium concentrations.

Cigarette smoke cadmium breakthrough from traditional filters: implications for exposure.

Cadmium, a carcinogenic metal, is highly toxic to renal, skeletal, nervous, respiratory and cardiovascular systems. Accurate and precise quantification of mainstream smoke cadmium levels in cigarette smoke is important because of exposure concerns. The two most common trapping techniques for collecting mainstream tobacco smoke particulate for analysis are glass fiber filters and electrostatic precipitators. We observed that a significant portion of total cadmium passed through standard glass fiber filters that are used to trap particulate matter. We therefore developed platinum traps to collect the cadmium that passed through the filters and tested a variety of cigarettes with different physical parameters for quantities of cadmium that passed though the filters. We found <1% cadmium passed through electrostatic precipitators. In contrast, cadmium that passed through 92 mm glass fiber filters on a rotary smoking machine was significantly higher, ranging from 3.5 to 22.9% of total smoke cadmium deliveries. Cadmium passed through 44 mm filters typically used on linear smoking machines to an even greater degree, ranging from 13.6 to 30.4% of the total smoke cadmium deliveries. Differences in the cadmium that passed through from the glass fiber filters and electrostatic precipitator could be explained in part if cadmium resides in the smaller mainstream smoke aerosol particle sizes. Differences in particle size distribution could have toxicological implications and could help explain the pulmonary and cardiovascular cadmium uptake in smokers.

Toxic metal concentrations in mainstream smoke from cigarettes available in the USA.

Public health officials and leaders of 168 nations have signaled their concern regarding the health and economic impacts of smoking by becoming signatory parties to the World Health Organization Framework Convention on Tobacco Control (FCTC). One of FCTC's purposes is to help achieve meaningful regulation for tobacco products in order to decrease the exposure to harmful and potentially harmful constituents (HPHCs) delivered to users and those who are exposed to secondhand smoke. Determining baseline delivery ranges for HPHCs in modern commercial tobacco products is crucial information regulators could use to make informed decisions. Establishing mainstream smoke delivery concentration ranges for toxic metals was conducted through analyses of total particulate matter (TPM) collected with smoking machines using standard smoking regimens. We developed a rapid analytical method with microwave digestion of TPM samples obtained with smoking machines using electrostatic precipitation under the ISO and Intense smoking regimens. Digested samples are analyzed for chromium, manganese, cobalt, nickel, arsenic, cadmium and lead using inductively coupled plasma-mass spectrometry. This method provides data obtained using the ISO smoking regimen for comparability with previous studies as well as an Intense smoking regimen that represents deliveries that fall within the range of human exposure levels to toxic metals.

Establishment of toxic metal reference range in tobacco from US cigarettes.

Smoking remains the leading cause of preventable death in the United States. There are numerous harmful substances in tobacco and tobacco smoke. Among the more than 4,000 identified compounds in smoke, many metals contribute to the health risks associated with tobacco use. Specific metals found in tobacco and tobacco smoke have been classified as carcinogens by the International Agency for Research on Cancer. Exposure to toxic metals can cause outcomes including inflammation, sensitization and carcinogenesis. Metals in tobacco are transported in tobacco smoke proportionally with their concentrations in tobacco filler for a given cigarette design. To quantitatively examine the metal content in numerous tobacco products, high throughput methods are desired. This study developed a simple, rapid tobacco digestion method coupled with a sensitive analytical method using inductively coupled plasma-mass spectrometry. Because of known memory effects and volatility of mercury, quantitative determinations of mercury were made with a direct combustion analyzer. The methods were utilized to examine arsenic, beryllium, cadmium, chromium, cobalt, lead, manganese, mercury and nickel contents in cigarette tobacco and to establish a reference range for the metals in 50 varieties of cigarettes available in the US. These results are comparable to the limited data sets reported by others and with available standard reference material values.

Sample Preparation Problem Solving for Inductively Coupled Plasma-Mass Spectrometry with Liquid Introduction Systems I. Solubility, Chelation, and Memory Effects.

This tutorial was adapted from the first half of a course presented at the 7th International Conference on Sector Field Inductively Coupled Plasma Mass Spectrometry in 2008 and the 2012 Winter Conference on Plasma Spectrochemistry on sample preparation for liquid introduction systems. Liquid introduction in general and flow injection specifically are the most widely used sample introduction methods for inductively coupled plasma-mass spectrometry. Nevertheless, problems persist in determination of analytes that are commonly investigated, as well as in specialty applications for those seldom considered by most analysts. Understanding the chemistry that is common to different groups of analytes permits the development of successful approaches to rinse-out and elimination of memory effects. This understanding also equips the analyst for development of successful elemental analytical approaches in the face of a broad spectrum of matrices and other analytical challenges, whether the sample is solid or liquid.