BackgroundElectronic cigarettes (EC) deliver aerosol by heating fluid containing nicotine. Cartomizer EC combine the fluid chamber and heating element in a single unit. Because EC do not burn tobacco, they may be safer than conventional cigarettes. Their use is rapidly increasing worldwide with little prior testing of their aerosol.ObjectivesWe tested the hypothesis that EC aerosol contains metals derived from various components in EC.MethodsCartomizer contents and aerosols were analyzed using light and electron microscopy, cytotoxicity testing, x-ray microanalysis, particle counting, and inductively coupled plasma optical emission spectrometry.ResultsThe filament, a nickel-chromium wire, was coupled to a thicker copper wire coated with silver. The silver coating was sometimes missing. Four tin solder joints attached the wires to each other and coupled the copper/silver wire to the air tube and mouthpiece. All cartomizers had evidence of use before packaging (burn spots on the fibers and electrophoretic movement of fluid in the fibers). Fibers in two cartomizers had green deposits that contained copper. Centrifugation of the fibers produced large pellets containing tin. Tin particles and tin whiskers were identified in cartridge fluid and outer fibers. Cartomizer fluid with tin particles was cytotoxic in assays using human pulmonary fibroblasts. The aerosol contained particles >1 µm comprised of tin, silver, iron, nickel, aluminum, and silicate and nanoparticles (<100 nm) of tin, chromium and nickel. The concentrations of nine of eleven elements in EC aerosol were higher than or equal to the corresponding concentrations in conventional cigarette smoke. Many of the elements identified in EC aerosol are known to cause respiratory distress and disease.ConclusionsThe presence of metal and silicate particles in cartomizer aerosol demonstrates the need for improved quality control in EC design and manufacture and studies on how EC aerosol impacts the health of users and bystanders.

Generally, e-cigarettes required stronger vacuums (suction) to smoke than conventional brands, and the effects of this on human health could be adverse. The amount of aerosol produced by e-cigarettes decreased during smoking, which necessitated increasing puff strength to produce aerosol. The decreased efficiency of aerosol production during e-cigarette smoking makes dosing nonuniform over time and calls into question their usefulness as nicotine delivery devices.

Indole-3-carbinol (I3C) and 3,3-diindolylmethane (DIM) are promising cancer chemopreventive agents in rodent models, but there is a paucity of data on their pharmacokinetics and tissue disposition. The disposition of I3C and its acid condensation products, DIM, [2-(indol-3-ylmethyl)-indol-3-yl]indol-3-ylmethane (LTr 1 ), indolo[3,2b]carbazole (ICZ) and 1-(3-hydroxymethyl)-indolyl-3-indolylmethane (HI-IM) was studied, after oral administration of I3C (250 mg/kg) to female CD-1 mice. Blood, liver, kidney, lung, heart, and brain were collected between 0.25 and 24 h after administration and the plasma and tissue concentrations of I3C and its derivatives determined by high-performance liquid chromotography. I3C was rapidly absorbed, distributed, and eliminated from plasma and tissues, falling below the limit of detection by 1 h. Highest concentrations of I3C were detected in the liver where levels were approximately 6-fold higher than those in the plasma. Levels of DIM, LTr 1 , and HI-IM were much lower, although they persisted in plasma and tissues for considerably longer. DIM and HI-IM were still present in the liver 24 h after I3C administration. Tissue levels of DIM and LTr 1 were found to be in equilibrium with plasma at almost every time point measured. In addition to acid condensation products of I3C, a major oxidative metabolite (indole-3-carboxylic acid) and a minor oxidative metabolite (indole-3-carboxaldehyde) were detected in plasma of mice after oral administration of I3C. ICZ was also tentatively identified in the liver of these mice. This study shows for the first time that, after oral administration to mice, I3C, in addition to its acid condensation products, is absorbed from the gut and distributed systemically into a number of well-perfused tissues, thus allowing the possibility for some pharmacological activity of the parent compound in vivo.

ObjectiveOur purpose was to quantify 36 inorganic chemical elements in aerosols from disposable electronic cigarettes (ECs) and electronic hookahs (EHs), examine the effect of puffing topography on elements in aerosols, and identify the source of the elements.MethodsThirty-six inorganic chemical elements and their concentrations in EC/EH aerosols were determined using inductively coupled plasma optical emission spectroscopy, and their source was identified by analyzing disassembled atomizers using scanning electron microscopy and energy dispersive X-ray spectroscopy.ResultsOf 36 elements screened, 35 were detected in EC/EH aerosols, while only 15 were detected in conventional tobacco smoke. Some elements/metals were present in significantly higher concentrations in EC/EH aerosol than in cigarette smoke. Concentrations of particular elements/metals within EC/EH brands were sometimes variable. Aerosols generated at low and high air-flow rates produced the same pattern of elements, although the total element concentration decreased at the higher air flow rate. The relative amount of elements in the first and last 60 puffs was generally different. Silicon was the dominant element in aerosols from all EC/EH brands and in cigarette smoke. The elements appeared to come from the filament (nickel, chromium), thick wire (copper coated with silver), brass clamp (copper, zinc), solder joints (tin, lead), and wick and sheath (silicon, oxygen, calcium, magnesium, aluminum). Lead was identified in the solder and aerosol of two brands of EHs (up to 0.165 μg/10 puffs).ConclusionThese data show that EC/EH aerosols contain a mixture of elements, including heavy metals, with concentrations often significantly higher than in conventional cigarette smoke. While the health effects of inhaling mixtures of heated metals is currently not known, these data will be valuable in future risk assessments involving EC/EH elements/metals.

The combination of gemcitabine and docetaxel administered on days 1 and 8 every 21 days was feasible and well tolerated in patients with advanced malignancies. The sequence of administration had no significant effect on the toxicity or pharmacokinetics of either drug. Minimally pretreated patients tolerated higher doses of this combination without significant toxicities. This schedule and combination demonstrated activity in a variety of solid tumors, and merits further evaluation.