Peter A. Valberg

Workgroup report : Base stations and wireless networks-radiofrequency (RF) exposures and health consequences

Radiofrequency (RF) waves have long been used for different types of information exchange via the airwaves—wireless Morse code, radio, television, and wireless telephony (i.e., construction and operation of telephones or telephonic systems). Increasingly larger numbers of people rely on mobile telephone technology, and health concerns about the associated RF exposure have been raised, particularly because the mobile phone handset operates in close proximity to the human body, and also because large numbers of base station antennas are required to provide widespread availability of service to large populations. The World Health Organization convened an expert workshop to discuss the current state of cellular-telephone health issues, and this article brings together several of the key points that were addressed. The possibility of RF health effects has been investigated in epidemiology studies of cellular telephone users and workers in RF occupations, in experiments with animals exposed to cell-phone RF, and via biophysical consideration of cell-phone RF electric-field intensity and the effect of RF modulation schemes. As summarized here, these separate avenues of scientific investigation provide little support for adverse health effects arising from RF exposure at levels below current international standards. Moreover, radio and television broadcast waves have exposed populations to RF for > 50 years with little evidence of deleterious health consequences. Despite unavoidable uncertainty, current scientific data are consistent with the conclusion that public exposures to permissible RF levels from mobile telephony and base stations are not likely to adversely affect human health.

Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity

Submicrometer magnetic particles, ingested by cells and monitored via the magnetic fields they generate, provide an alternative to optical microscopy for probing movement and viscosity of living cytoplasm, and can be used for cells both in vitro and in vivo. We present methods for preparing lung macrophages tagged with magnetic particles for magnetometric study. Interpretation of the data involves fitting experimental remanent-field decay curves to nonlinear mechanistic models of intracellular particle motion. The model parameters are sensitive to mobility and apparent cytoplasmic viscosity experienced by particle-containing organelles. We present results of parameter estimation for intracellular particle behavior both within control cells and after (a) variable magnetization duration, (b) incubation with cytochalasin D, and (c) particle twisting by external fields. Magnetometric analysis showed cytoplasmic elasticity, dose-dependent motion inhibition by cytochalasin D, and a shear-thinning apparent viscosity.

Magnetic particle motions within living cells. Physical theory and techniques

Body tissues are not ferromagnetic, but ferromagnetic particles can be present as contaminants or as probes in the lungs and in other organs. The magnetic domains of these particles can be aligned by momentary application of an external magnetic field; the magnitude and time course of the resultant remanent field depend on the quantity of magnetic material and the degree of particle motion. The interpretation of magnetometric data requires an understanding of particle magnetization, agglomeration, random motion, and both rotation and translation in response to magnetic fields. We present physical principles relevant to magnetometry and suggest models for intracellular particle motion driven by thermal, elastic, or cellular forces. The design principles of instrumentation for magnetizing intracellular particles and for detecting weak remanent magnetic fields are described. Such magnetic measurements can be used for noninvasive studies of particle clearance from the body or of particle motion within body tissues and cells. Assumptions inherent to this experimental approach and possible sources of artifact are considered and evaluated.

Critical review of the human data on short-term nitrogen dioxide (NO2) exposures: Evidence for NO2 no-effect levels

Nitrogen dioxide (NO2) is a ubiquitous atmospheric pollutant due to the widespread prevalence of both natural and anthropogenic sources, and it can be a respiratory irritant when inhaled at elevated concentrations. Evidence for health effects of ambient NO2 derives from three types of studies: observational epidemiology, human clinical exposures, and animal toxicology. Our review focuses on the human clinical studies of adverse health effects of short-term NO2 exposures, given the substantial uncertainties and limitations in interpretation of the other lines of evidence. We examined more than 50 experimental studies of humans inhaling NO2, finding notably that the reporting of statistically significant changes in lung function and bronchial sensitivity did not show a consistent trend with increasing NO2 concentrations. Functional changes were generally mild and transient, the reported effects were not uniformly adverse, and they were not usually accompanied by NO2-dependent increases in symptoms. The available human clinical results do not establish a mechanistic pathway leading to adverse health impacts for short-term NO2 exposures at levels typical of maximum 1-h concentrations in the present-day ambient environment (i.e., below 0.2 ppm). Our review of these data indicates that a health-protective, short-term NO2 guideline level for susceptible (and healthy) populations would reflect a policy choice between 0.2 and 0.6 ppm. Extended abstract Nitrogen dioxide (NO2) is a ubiquitous atmospheric pollutant due to the widespread prevalence of both natural and anthropogenic sources, and it can be a respiratory irritant when inhaled at elevated concentrations. Natural NO2 sources include volcanic action, forest fires, lightning, and the stratosphere; man-made NO2 emissions derive from fossil fuel combustion and incineration. The current National Ambient Air Quality Standard (NAAQS) for NO2, initially established in 1971, is 0.053 ppm (annual average). Ambient concentrations monitored in urban areas in the United States are ~0.015 ppm, as an annual mean, i.e., below the current NAAQS. Short-term (1-h peak) NO2 concentrations outdoors are not likely to exceed 0.2 ppm, and even 1-h periods exceeding 0.1 ppm are infrequent. Inside homes, 1-h NO2 peaks, typically arising from gas cooking, can range between 0.4 and 1.5 ppm. The health effects evidence of relevance to ambient NO2 derives from three lines of investigation: epidemiology studies, human clinical studies, and animal toxicology studies. The NO2 epidemiology remains inconsistent and uncertain due to the potential for exposure misclassification, residual confounding, and co-pollutant effects, whereas animal toxicology findings using high levels of NO2 exposure require extrapolation to humans exposed at low ambient NO2 levels. Given the limitations and uncertainties in the other lines of health effects evidence, our review thus focused on clinical studies where human volunteers (including asthmatics, children, and elderly) inhaled NO2 at levels from 0.1 to 3.5 ppm during short-term (½–6-h) exposures, often combined with exercise, and occasionally combined with co-pollutants. We examined the reported biological effects and classified them into (a) lung immune responses and inflammation, (b) lung function changes and airway hyperresponsiveness (AHR), and (c) health effects outside the lungs (extrapulmonary). We examined more than 50 experimental studies of humans inhaling NO2, finding that such clinical data on short-term exposure allowed discrimination of NO2 no-effect levels versus lowest-adverse-effects levels. Our conclusions are summarized by these six points: For lung immune responses and inflammation: (1) healthy subjects exposed to NO2 below 1 ppm do not show pulmonary inflammation; (2) at 2 ppm for 4 h, neutrophils and cytokines in lung-lavage fluid can increase, but these changes do not necessarily correlate with significant or sustained changes in lung function; (3) there is no consistent evidence that NO2 concentrations below 2 ppm increase susceptibility to viral infection; (4) for asthmatics and individuals having chronic obstructive pulmonary disease (COPD), NO2-induced lung inflammation is not expected below 0.6 ppm, although one research group reported enhancement of proinflammatory processes at 0.26 ppm. With regard to NO2-induced AHR: (5) studies of responses to specific or nonspecific airway challenges (e.g., ragweed, methacholine) suggest that asthmatic individuals were not affected by NO2 up to about 0.6 ppm, although some sensitive subsets may respond to levels as low as 0.2 ppm. And finally, for extra-pulmonary effects: (6) such effects (e.g., changes in blood chemistry) generally required NO2 concentrations above 1–2 ppm. Overall, our review of data from experiments with humans indicates that a health-protective, short-term-average NO2 guideline level for susceptible populations (and healthy populations) would reflect a policy choice between 0.2 and 0.6 ppm. The available human clinical results do not establish a mechanistic pathway leading to adverse health impacts for short-term NO2 exposures at levels typical of maximum 1-h concentrations in the present-day ambient environment (i.e., below 0.2 ppm).

Carbon Black and Soot: Two Different Substances

Carbon blacks are manufactured under controlled conditions for commercial use primarily in the rubber, painting, and printing industries. In contrast, soots are unwanted byproducts from the combustion of carbon-based materials for the generation of energy or heat, or for the disposal of waste. Unfortunately, the terms carbon black and soot often have been used interchangeably; however, carbon black is physically and chemically distinct from soot. Greater than 97% of carbon black consists of elemental carbon arranged as aciniform particulate. Depending on the type of soot, the relative amount of carbon (< 60% of the total particle mass), the type of particulate carbon, and particle characteristics (size, shape, and heterogeneity) can vary considerably. For both carbon black and soot, other elements and chemical compounds are associated with the particulate carbon. Total inorganics (ash) represent < 1% of the carbon black particle mass. Organic compounds can be extracted from particle surfaces (solvent extractable fraction [SOF]), and for carbon black, also are < 1% of the particle mass. Soots have much greater percentages of ash, SOF, or both, than carbon black. There has been concern about the adsorbed organic compounds because of potential biologic activity. For carbon black, the SOF is strongly adherent to carbon surfaces and is not released by biological fluids. The types of organic compounds consist primarily of unsubstituted polycyclic aromatic hydrocarbons and are not as biologically potent as those compounds present in soot. Thus, carbon black is distinctly different from soot, and when discussing potential health effects, care must be taken to differentiate between the two types of carbon-based particles.

A Critical Assessment of Studies on the Carcinogenic Potential of Diesel Exhaust

After decades of research involving numerous epidemiologic studies and extensive investigations in laboratory animals, a causal relationship between diesel exhaust (DE) exposure and lung cancer has not been conclusively demonstrated. Epidemiologic studies of the transportation industry (trucking, busing, and railroad) show a small elevation in lung cancer incidence (relative risks [RRs] generally below 1.5), but a dose response for DE is lacking. The studies are also limited by a lack of quantitative concurrent exposure data and inadequate or lack of controls for potential confounders, particularly tobacco smoking. Furthermore, prior to dieselization, similar elevations in lung cancer incidence have been reported for truck drivers, and in-cab diesel particulate matter (DPM) exposures of truck drivers were comparable to ambient highway exposures. Taken together, these findings suggest that an unidentified occupational agent or lifestyle factor might be responsible for the low elevations in lung cancer reported in the transportation studies. In contrast, underground miners, many of whom experience the highest occupational DPM exposures, generally do not show elevations in lung cancer. Laboratory studies must be interpreted with caution with respect to predicting the carcinogenic potential of DE in humans. Tumors observed in rats following lifetime chronic inhalation of very high levels of DPM may be attributed to species-specific overload mechanisms that lack relevance to humans. Increased tumor incidence was not observed in other species (hamsters or mice) exposed to DPM at very high levels or in rats exposed at lower levels (≤2000 μg/m3). Although DPM contains mutagens, mutagenicity studies in which cells were exposed to concentrated extracts of DPM also have limited application to human risk assessment, because such extracts can be obtained from DPM only by using strong organic solvents, agitation, and heat. Most studies have shown that whole DPM itself is not mutagenic because the adsorbed organic compounds are minimally bioavailable in aqueous-based fluids. In the past two decades, dramatic changes in diesel engine technology (e.g., low-sulfur fuel and exhaust after-treatment) have resulted in >99% reduction in DPM and other quantitative and qualitative changes in the chemical and physical characteristics of diesel exhaust. Thus, the current database, which is focused almost entirely on the potential health effects of traditional diesel exhaust (TDE), has only limited utility in assessing the potential health risks of new-technology diesel exhaust (NTDE). To overcome some of the limitations of the historical epidemiologic database on TDE and to gain further insights into the potential health effects of NTDE, new studies are underway and more studies are planned.

Carbon black vs. black carbon and other airborne materials containing elemental carbon: Physical and chemical distinctions

Airborne particles containing elemental carbon (EC) are currently at the forefront of scientific and regulatory scrutiny, including black carbon, carbon black, and engineered carbon-based nanomaterials, e.g., carbon nanotubes, fullerenes, and graphene. Scientists and regulators sometimes group these EC-containing particles together, for example, interchangeably using the terms carbon black and black carbon despite one being a manufactured product with well-controlled properties and the other being an undesired, incomplete-combustion byproduct with diverse properties. In this critical review, we synthesize information on the contrasting properties of EC-containing particles in order to highlight significant differences that can affect hazard potential. We demonstrate why carbon black should not be considered a model particle representative of either combustion soots or engineered carbon-based nanomaterials. Overall, scientific studies need to distinguish these highly different EC-containing particles with care and precision so as to forestall unwarranted extrapolation of properties, hazard potential, and study conclusions from one material to another.

Non-cancer health effects of diesel exhaust: a critical assessment of recent human and animal toxicological literature.

We reviewed laboratory and clinical studies bearing on the non-cancer health effects of diesel exhaust (DE) published since the 2002 release of the US EPA Health Assessment Document for Diesel Engine Exhaust. We critically evaluated over 100 published articles on experimental research, focusing on their value for predicting the risk of non-cancer health effects in humans exposed to DE. Human controlled-exposure studies provide new evidence of lung inflammatory effects and thrombogenic and ischemic effects of inhaled DE, albeit for older-model diesel engines and concentrations that are much higher (~300 μg/m3) than typical ambient or even occupational levels. Recent animal studies provide insight into the potential mechanisms underlying observed respiratory and cardiovascular health responses; however, because of unrealistically high DE concentrations, the mechanisms elucidated in these studies may not be relevant at lower DE exposure levels. Although larger in number, and suggestive of possible mechanisms for non-cancer health effects at elevated DE levels, interpretation of this recent group of clinical-study findings and laboratory-animal results remains hindered by inconsistencies and variability in outcomes, potentially irrelevant DE-exposure compositions, limitations in exposure protocols and pathways, and uncertainties in extrapolation and generalization. A mechanism of action that allows reliable prediction of adverse health effects at DE-exposure levels typical of the present-day ambient and occupational environment has not emerged. Because of changing diesel-engine technology, inhalation studies using realistic environmental and occupational exposures of new-technology diesel exhaust are of critical importance.

Correlation between the behavior of magnetic iron oxide particles in the lungs of rabbits and phagocytosis

Five New Zealand white male rabbits were exposed (30 min; 300 mg/m3) to a submicrometric magnetic iron oxide aerosol (gamma-Fe2O3) produced by burning iron pentacarbonyl in a reducing atmosphere. After aerosol inhalation, an external magnetic field was applied to the rabbits to magnetize and align the ferrimagnetic particles within their lungs. After removal of the external field, a remanent magnetic field was detectable at the body surface. Using a flux-gate magnetometer probe in an enclosure shielded against external magnetic noise, the peak remanent field after magnetization was measured periodically during the next 6 weeks. After each magnetization, the strength of the remanent field decayed rapidly with time (relaxation). The mechanism responsible is particle rotation caused by tissue, cell, organelle, or Brownian movement. The rate of relaxation changed with time after particle inhalation, especially during the first day; changes in the relaxation rate correlated with an estimate of in situ particle phagocytosis during that time. Analysis of pulmonary lavage fluid from 15 rabbits into which radioactive gold-198 had been intratracheally instilled showed that, at 1 hr after instillation, 27% of the gold had been phagocytized, whereas at 16 hr 91% had been ingested. The strength of the magnetic field immediately after each magnetization (that is, before relaxation) was used to estimate the amount of iron oxide in the lungs. At 1 day after exposure, 96.8 +/- 8.8% (mean +/- standard error) of the initial dust was still present; at 10 days, 67.9 +/- 16.2%; and at 40 days, 16.0 +/- 4.6%. It is concluded that ferrimagnetic particles can serve as an easily measured, long-lasting marker that can be used for noninvasive studies of clearance and of particle phagocytosis and as a probe for intracellular processes such as organelle motion.

Health effects research and regulation of diesel exhaust: an historical overview focused on lung cancer risk.

The mutagenicity of organic solvent extracts from diesel exhaust particulate (DEP), first noted more than 55 years ago, initiated an avalanche of diesel exhaust (DE) health effects research that now totals more than 6000 published studies. Despite an extensive body of results, scientific debate continues regarding the nature of the lung cancer risk posed by inhalation of occupational and environmental DE, with much of the debate focused on DEP. Decades of scientific scrutiny and increasingly stringent regulation have resulted in major advances in diesel engine technologies. The changed particulate matter (PM) emissions in “New Technology Diesel Exhaust (NTDE)” from today’s modern low-emission, advanced-technology on-road heavy-duty diesel engines now resemble the PM emissions in contemporary gasoline engine exhaust (GEE) and compressed natural gas engine exhaust more than those in the “traditional diesel exhaust” (TDE) characteristic of older diesel engines. Even with the continued publication of epidemiologic analyses of TDE-exposed populations, this database remains characterized by findings of small increased lung cancer risks and inconsistent evidence of exposure–response trends, both within occupational cohorts and across occupational groups considered to have markedly different exposures (e.g. truckers versus railroad shopworkers versus underground miners). The recently published National Institute for Occupational Safety and Health (NIOSH)-National Cancer Institute (NCI) epidemiologic studies of miners provide some of the strongest findings to date regarding a DE-lung cancer association, but some inconsistent exposure–response findings and possible effects of bias and exposure misclassification raise questions regarding their interpretation. Laboratory animal studies are negative for lung tumors in all species, except for rats under lifetime TDE-exposure conditions with durations and concentrations that lead to “lung overload.” The species specificity of the rat lung response to overload, and its occurrence with other particle types, is now well-understood. It is thus generally accepted that the rat bioassay for inhaled particles under conditions of lung overload is not predictive of human lung cancer hazard. Overall, despite an abundance of epidemiologic and experimental data, there remain questions as to whether TDE exposure causes increased lung cancers in humans. An abundance of emissions characterization data, as well as preliminary toxicological data, support NTDE as being toxicologically distinct from TDE. Currently, neither epidemiologic data nor animal bioassay data yet exist that directly bear on NTDE carcinogenic potential. A chronic bioassay of NTDE currently in progress will provide data on whether NTDE poses a carcinogenic hazard, but based on the significant reductions in PM mass emissions and the major changes in PM composition, it has been hypothesized that NTDE has a low carcinogenic potential. When the International Agency for Research on Cancer (IARC) reevaluates DE (along with GEE and nitroarenes) in June 2012, it will be the first authoritative body to assess DE carcinogenic health hazards since the emergence of NTDE and the accumulation of data differentiating NTDE from TDE.