Keith E. Levine

Mercury in first-cut baby hair of children with autism versus typically-developing children

Children with autism were examined to determine amounts of mercury (Hg) in their baby hair and the factors that might affect Hg body burden. US children with autism (n = 78) and matched controls (n = 31) born between 1988 and 1999 were studied. Hg in first-cut baby hair was determined using cold vapor atomic fluorescence spectrometry (CVAFS). Twenty samples were split and also measured with Neutron Activation Analysis (NAA). Logistic regression analysis showed that compared to children with higher levels of mercury (above 0.55 mcg g−1), children with lower levels of mercury in their hair (below 0.55 mcg g−1) were 2.5-fold more likely to manifest with autism. Children with autism had similar mercury exposure as controls from maternal seafood and maternal dental amalgams. Children with autism also had 2.5-fold higher incidence of oral antibiotic use during their first 18 months of life. Their mothers were possibly more likely to use oral antibiotics during pregnancy or nursing. The amount of Hg in the baby hair of children with autism showed a significant correlation with the number of maternal dental amalgams. The lower level of Hg in the baby hair of children with autism indicates an altered metabolism of Hg, and may be due to a decreased ability to excrete Hg. This is consistent with usage of higher amounts of oral antibiotics, which are known to inhibit Hg excretion in rats due to alteration of gut flora, and may exert a similar effect in humans. Higher usage of oral antibiotics in infancy may also partially explain the high incidence of chronic gastrointestinal problems seen in individuals with autism.

Exposure to Hexavalent Chromium Resulted in Significantly Higher Tissue Chromium Burden Compared With Trivalent Chromium Following Similar Oral Doses to Male F344/N Rats and Female B6C3F1 Mice

In National Toxicology Program 2-year studies, hexavalent chromium [Cr(VI)] administered in drinking water was clearly carcinogenic in male and female rats and mice, resulting in small intestine epithelial neoplasms in mice at a dose equivalent to or within an order of magnitude of human doses that could result from consumption of chromium-contaminated drinking water, assuming that dose scales by body weight(3/4) (body weight raised to the 3/4 power). In contrast, exposure to trivalent chromium [Cr(III)] at much higher concentrations may have been carcinogenic in male rats but was not carcinogenic in mice or female rats. As part of these studies, total chromium was measured in tissues and excreta of additional groups of male rats and female mice. These data were used to infer the uptake and distribution of Cr(VI) because Cr(VI) is reduced to Cr(III) in vivo, and no methods are available to speciate tissue chromium. Comparable external doses resulted in much higher tissue chromium concentrations following exposure to Cr(VI) compared with Cr(III), indicating that a portion of the Cr(VI) escaped gastric reduction and was distributed systemically. Linear or supralinear dose responses of total chromium in tissues were observed following exposure to Cr(VI), indicating that these exposures did not saturate gastric reduction capacity. When Cr(VI) exposure was normalized to ingested dose, chromium concentrations in the liver and glandular stomach were higher in mice, whereas kidney concentrations were higher in rats. In vitro studies demonstrated that Cr(VI), but not Cr(III), is a substrate of the sodium/sulfate cotransporter, providing a partial explanation for the greater absorption of Cr(VI).

Mercury levels and fish consumption practices in women of child-bearing age in the Florida Panhandle

The southeastern United States, and in particular the coastal areas along the Gulf of Mexico (Gulf Coast) in Florida, experience some of the highest levels of mercury deposition in the country. Although the State of Floridas coastal border is among the longest in the United States, and the State has issued fish consumption advisories due to mercury on multiple fish species, few data have been systematically collected to assess mercury levels in the human population of the state or to assess the efficacy of the consumption advisories. Because of the generally high rate of seafood consumption among coastal populations, the human population in the Florida Panhandle, near Pensacola, FL is potentially exposed to elevated levels of mercury. In the present study, we analyzed hair mercury levels in women of child-bearing age (16-49 years) who had resided near Pensacola, FL for at least 1 year. We also surveyed the fish consumption practices of the cohort and evaluated awareness of the Florida Fish Consumption Advisory. Hair mercury levels were significantly higher in women who consumed fish within the 30 days prior to sampling (p<0.05) and in those women who were unaware of the consumption advisory (p<0.05). Only 31% of the women reported knowledge of the consumption advisory and pregnant women exhibited lower awareness of the advisory than non-pregnant women. The data suggest that public health interventions such as education and fish advisories have not reached the majority of women in the counties surrounding Pensacola who are most at risk from consumption of fish with high levels of mercury.

Low-Cost, Modular Electrothermal Vaporization System for Inductively Coupled Plasma Atomic Emission Spectrometry

In this investigation, commercially available tungsten filaments were employed to electrothermally vaporize liquid samples prior to their introduction into an inductively coupled plasma (ICP). These filaments were extracted from standard 150 W slide projector bulbs. The temperature of the tungsten coil was controlled by supplying a desired current at 120 V ac. A small sample volume, typically 20 μL, was manually pipetted onto the coil and dried at a 2.3 A current. At the conclusion of this dry step, a 7.4 A atomization current was applied, and sample atoms were sputtered off the coil and rapidly introduced into the plasma as a dense plug by a flow of Ar/H2 gas. A charge-coupled device (CCD) array detector allowed for multielement determinations. Simultaneously collected data are presented for Ag, Ba, Be, Cd, Cu, Fe, Mn, Pb, Sr, and Zn. Many of these test elements are of biological importance either as cumulative poisons or as essential nutrients. Each also possesses one or more strong ICP emission lines in the spectral range of the CCD detector. The utility of this inexpensive electrothermal vaporization (ETV)-ICP method is evaluated for botanical and biological samples through the use of standard reference materials (NIST SRM 1547 “Peach Leaves” and NIST SRM 1566a “Oyster Tissue”).

Arsenic Exposure and Incidence of Type 2 Diabetes in Southwestern American Indians

Association of urinary arsenic concentration with incident diabetes was examined in American Indians from Arizona who have a high prevalence of type 2 diabetes and were screened for diabetes between 1982 and 2007. The population resides where drinking water contains arsenic at concentrations above federally recommended limits. A total of 150 nondiabetic subjects aged ≥25 years who subsequently developed type 2 diabetes were matched by year of examination and sex to 150 controls who remained nondiabetic for ≥10 years. Total urinary arsenic concentration, adjusted for urinary creatinine level, ranged from 6.6 µg/L to 123.1 µg/L, and inorganic arsenic concentration ranged from 0.1 µg/L to 36.0 µg/L. In logistic regression models adjusted for age, sex, body mass index, and urinary creatinine level, the odds ratios for incident diabetes were 1.11 (95% confidence interval (CI): 0.79, 1.57) and 1.16 (95% CI: 0.89, 1.53) for a 2-fold increase in total arsenic and inorganic arsenic, respectively. Categorical analyses suggested a positive relationship between quartiles of inorganic arsenic and incident diabetes (P = 0.056); post-hoc comparison of quartiles 2-4 with quartile 1 revealed 2-fold higher odds of diabetes in the upper quartiles (OR = 2.14, 95% CI: 1.19, 3.85). Modestly elevated exposure to inorganic arsenic may predict type 2 diabetes in American Indians. Larger studies that include measures of speciated arsenic are required for confirmation.

Additional perspectives on chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka – lessons learned from the WHO CKDu population prevalence study

The recent emergence of an apparently new form of chronic kidney disease of unknown aetiology (CKDu) has become a serious public health crisis in Sri Lanka. CKDu is slowly progressive, irreversible, and asymptomatic until late stages, and is not attributable to hypertension, diabetes, or other known aetiologies. In response to the scope and severity of the emerging CKDu health crisis, the Sri Lanka Ministry of Health and the World Health Organization initiated a collaborative research project from 2009 through 2012 to investigate CKDu prevalence and aetiology. The objective of this paper is to discuss the recently published findings of this investigation and present additional considerations and recommendations that may enhance subsequent investigations designed to identify and understand CKDu risk factors in Sri Lanka or other countries.

Evaluation of a high pressure, high temperature microwave digestion system:

A high-pressure, high-temperature focused microwave digestion system was evaluated and compared with a conventional, closed-vessel digestion system. A suite of 18 test elements was determined in six Standard Reference Materials (Peach Leaves, Orchard Leaves, Oyster Tissue, Bovine Liver, Bituminous Coal, and River Sediment) by inductively coupled plasma atomic emission spectrometry and electrothermal atomic absorption spectrometry. Observation of the graphite furnace background absorbance for the digestates, and their high-performance liquid chromatograms, demonstrate that the high-pressure, high-temperature system results in a more complete destruction of the sample matrix. The high-temperature system also shows higher accuracy for the test metals in the reference materials (average error 7.1%) than the conventional system (11.8%). Finally, the high-temperature system has a per-sample analysis time (7.5 min) that is 10 min faster than the conventional system. On the negative side, the high-temperature system is not capable of monitoring temperature during a digestion program. As a result, vessel rupture is common during method development. This results in complete destruction of the vessel, and the emission of potentially dangerous exhaust fumes into the laboratory environment.

A simple, low cost, multielement atomic absorption spectrometer with a tungsten coil atomizer

An inexpensive, multielement atomic absorption spectrometer utilizing a tungsten coil atomizer has been developed. The novel optical arrangement employs three 60° beam combiners to blend the spectral output from four light sources such as electrodeless discharge lamps, or hollow cathode lamps, and then direct that output over an atomizer. This instrument uses an inexpensive tungsten coil atomizer that is extracted from a standard 150 W projector bulb. The temperature of the coil is computer-controlled by changing the voltage across the coil. A low voltage is first used to dry the sample then a higher voltage is used to atomize the sample. Simultaneous detection of the analyte absorption signals is accomplished using a charge-coupled device. The elements of interest in this study were Cd, Pb, and Cu. Near-line background correction was used to correct for nonspecific analyte absorption.

Redesigning the DNA‐Targeted Chromophore in Platinum–Acridine Anticancer Agents: A Structure–Activity Relationship Study

Platinum-acridine hybrid agents show low-nanomolar potency in chemoresistant non-small cell lung cancer (NSCLC), but high systemic toxicity in vivo. To reduce the promiscuous genotoxicity of these agents and improve their pharmacological properties, a modular build-click-screen approach was used to evaluate a small library of twenty hybrid agents containing truncated and extended chromophores of varying basicities. Selected derivatives were resynthesized and tested in five NSCLC cell lines representing large cell, squamous cell, and adenocarcinomas. 7-Aminobenz[c]acridine was identified as a promising scaffold in a hybrid agent (P1-B1) that maintained submicromolar activity in several of the DNA-repair proficient and p53-mutant cancer models, while showing improved tolerability in mice by 32-fold compared to the parent platinum-acridine (P1-A1). The distribution and DNA/RNA adduct levels produced by the acridine- and benz[c]acridine-based analogues in NCI-H460 cells (confocal microscopy, ICP-MS), and their ability to bind G-quadruplex forming DNA sequences (CD spectroscopy, HR-ESMS) were studied. P1-B1 emerges as a less genotoxic, more tolerable, and potentially more target-selective hybrid agent than P1-A1.

Determination of Mercury in an Assortment of Dietary Supplements Using an Inexpensive Combustion Atomic Absorption Spectrometry Technique

The concentrations of mercury in forty, commercially available dietary supplements, were determined using a new, inexpensive analysis technique. The method involves thermal decomposition, amalgamation, and detection of mercury by atomic absorption spectrometry with an analysis time of approximately six minutes per sample. The primary cost savings from this approach is that labor-intensive sample digestion is not required prior to analysis, further automating the analytical procedure. As a result, manufacturers and regulatory agencies concerned with monitoring lot-to-lot product quality may find this approach an attractive alternative to the more classical acid-decomposition, cold vapor atomic absorption methodology. Dietary supplement samples analyzed included astragalus, calcium, chromium picolinate, echinacea, ephedra, fish oil, ginger, ginkgo biloba, ginseng, goldenseal, guggul, senna, St Johns wort, and yohimbe products. Quality control samples analyzed with the dietary supplements indicated a high level of method accuracy and precision. Ten replicate preparations of a standard reference material (NIST 1573a, tomato leaves) were analyzed, and the average mercury recovery was 109% (2.0% RSD). The method quantitation limit was 0.3 ng, which corresponded to 1.5 ng/g sample. The highest found mercury concentration (123 ng/g) was measured in a concentrated salmon oil sample. When taken as directed by an adult, this product would result in an approximate mercury ingestion of 7 μg per week.