Extended Analysis and Evidence Integration of Chloroprene as a Human Carcinogen.

β-Chloroprene is used in the production of polychloroprene, a synthetic rubber. In 2010, Environmental Protection Agency (EPA) published the Integrated Risk Information System "Toxicological Review of Chloroprene," concluding that chloroprene was "likely to be carcinogenic to humans." This was based on findings from a 1998 National Toxicology Program (NTP) study showing multiple tumors within and across animal species; results from occupational epidemiological studies; a proposed mutagenic mode of action; and structural similarities with 1,3-butadiene and vinyl chloride.

Cancer Risk Associated With Exposure to Bitumen and Bitumen Fumes: An Updated Systematic Review and Meta-Analysis.

Objective: To evaluate whether cancer risks are increased among bitumen (asphalt) workers.

Methods: Systematic review and meta-analysis of cancer risks (lung, upper aerodigestive tract (UADT), esophagus, bladder, kidney, stomach, and skin) and bitumen exposure. Certainty in the epidemiological evidence that bitumen-exposed workers experience increased cancer risks was rated using Grading of Recommendations Assessment, Development and Evaluation criteria.

Short-term ozone exposure and asthma severity: Weight-of-evidence analysis.

To determine whether evidence indicates that short-term exposure to ambient concentrations of ozone in the United States can affect asthma severity, we systematically reviewed published controlled human exposure, epidemiology, and animal toxicity studies. The strongest evidence for a potential causal relationship came from epidemiology studies reporting increased emergency department visits and hospital admissions for asthma following elevated ambient ozone concentrations. However, while controlled exposure studies reported lung function decrements and increased asthma symptoms following high ozone exposures 160-400 parts per billion [ppb]), epidemiology studies evaluating similar outcomes reported less consistent results.

Particle size distributions of lead measured in battery manufacturing and secondary smelter facilities and implications in setting workplace lead exposure limits.

Inhalation plays an important role in exposures to lead in airborne particulate matter in occupational settings, and particle size determines where and how much of airborne lead is deposited in the respiratory tract and how much is subsequently absorbed into the body. Although some occupational airborne lead particle size data have been published, limited information is available reflecting current workplace conditions in the U.S.

Rethinking Meta-Analysis: Applications for Air Pollution Data and Beyond.

Meta-analyses offer a rigorous and transparent systematic framework for synthesizing data that can be used for a wide range of research areas, study designs, and data types. Both the outcome of meta-analyses and the meta-analysis process itself can yield useful insights for answering scientific questions and making policy decisions. Development of the National Ambient Air Quality Standards illustrates many potential applications of meta-analysis.

Ozone exposure and systemic biomarkers: Evaluation of evidence for adverse cardiovascular health impacts.

The US Environmental Protection Agency (EPA) recently concluded that there is likely to be a causal relationship between short-term (< 30 days) ozone exposure and cardiovascular (CV) effects; however, biological mechanisms to link transient effects with chronic cardiovascular disease (CVD) have not been established. Some studies assessed changes in circulating levels of biomarkers associated with inflammation, oxidative stress, coagulation, vasoreactivity, lipidology, and glucose metabolism after ozone exposure to elucidate a biological mechanism. We conducted a weight-of-evidence (WoE) analysis to determine if there is evidence supporting an association between changes in these biomarkers and short-term ozone exposure that would indicate a biological mechanism for CVD below the ozone National Ambient Air Quality Standard (NAAQS) of 75 parts per billion (ppb).

Are the elements of the proposed ozone National Ambient Air Quality Standards informed by the best available science?

The United States Environmental Protection Agency (US EPA) issues National Ambient Air Quality Standards (NAAQS) for six criteria pollutants, including ozone. Each standard has four elements: an indicator, level, averaging time, and form. Ozone levels (i.

Providing perspective for interpreting cardiovascular mortality risks associated with ozone exposures.

When identifying standards for air pollutants based on uncertain evidence, both science and policy judgments play critical roles. Consequently, critical contextual factors are important for understanding the strengths, limitations, and appropriate interpretation of available science, and potential benefits of risk mitigation alternatives. These factors include the relative magnitude and certainty of the risks posed by various factors and the impacts of other risk factors on air pollutant epidemiology study findings.

Weight-of-evidence evaluation of long-term ozone exposure and cardiovascular effects.

We conducted a weight-of-evidence (WoE) analysis to assess whether the current body of research supports a causal relationship between long-term ozone exposure (defined by EPA as at least 30 days in duration) at ambient levels and cardiovascular (CV) effects. We used a novel WoE framework based on the United States Environmental Protection Agency's National Ambient Air Quality Standards causal framework for this analysis. Specifically, we critically evaluated and integrated the relevant epidemiology and experimental animal data and classified a causal determination based on categories proposed by the Institute of Medicine's 2008 report, Improving the Presumptive Disability Decision-making Process for Veterans.

Weight-of-evidence evaluation of short-term ozone exposure and cardiovascular effects.

There is a relatively large body of research on the potential cardiovascular (CV) effects associated with short-term ozone exposure (defined by EPA as less than 30 days in duration). We conducted a weight-of-evidence (WoE) analysis to assess whether it supports a causal relationship using a novel WoE framework adapted from the US EPA's National Ambient Air Quality Standards causality framework. Specifically, we synthesized and critically evaluated the relevant epidemiology, controlled human exposure, and experimental animal data and made a causal determination using the same categories proposed by the Institute of Medicine report Improving the Presumptive Disability Decision-making Process for Veterans ( IOM 2008).

Evaluation of the causal framework used for setting national ambient air quality standards.

Abstract A scientifically sound assessment of the potential hazards associated with a substance requires a systematic, objective and transparent evaluation of the weight of evidence (WoE) for causality of health effects. We critically evaluated the current WoE framework for causal determination used in the United States Environmental Protection Agency's (EPA's) assessments of the scientific data on air pollutants for the National Ambient Air Quality Standards (NAAQS) review process, including its methods for literature searches; study selection, evaluation and integration; and causal judgments. The causal framework used in recent NAAQS evaluations has many valuable features, but it could be more explicit in some cases, and some features are missing that should be included in every WoE evaluation.

Evaluation of adverse human lung function effects in controlled ozone exposure studies.

The US EPA is evaluating controlled human ozone exposure studies to determine the adequacy of the current ozone National Ambient Air Quality Standard of 75 ppb. These studies have shown that ozone exposures of 80 ppb and greater are associated with lung function decrements. Here, we critically review studies with exposures below 80 ppb to determine the lowest ozone concentration at which decrements are causally associated with ozone exposure and could be considered adverse using the Adverse Effects/Causation Framework.

Particulate matter in new technology diesel exhaust (NTDE) is quantitatively and qualitatively very different from that found in traditional diesel exhaust (TDE).

Diesel exhaust (DE) characteristic of pre-1988 engines is classified as a "probable" human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC), and the U.S. Environmental Protection Agency has classified DE as "likely to be carcinogenic to humans.

Non-chemical stressors and cumulative risk assessment: an overview of current initiatives and potential air pollutant interactions.

Regulatory agencies are under increased pressure to consider broader public health concerns that extend to multiple pollutant exposures, multiple exposure pathways, and vulnerable populations. Specifically, cumulative risk assessment initiatives have stressed the importance of considering both chemical and non-chemical stressors, such as socioeconomic status (SES) and related psychosocial stress, in evaluating health risks. The integration of non-chemical stressors into a cumulative risk assessment framework has been largely driven by evidence of health disparities across different segments of society that may also bear a disproportionate risk from chemical exposures.

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 (approximately 300 microg/m(3)) than typical ambient or even occupational levels.

Trends in the elemental composition of fine particulate matter in Santiago, Chile, from 1998 to 2003.

Santiago, Chile, is one of the most polluted cities in South America. As a response, over the past 15 yr, numerous pollution reduction programs have been implemented by the environmental authority, Comisión Nacional del Medio Ambiente. This paper assesses the effectiveness of these interventions by examining the trends of fine particulate matter (PM(2.

Measurement of particle concentrations in a dental office.

Particles in a dental office can be generated by a number of instruments, such as air-turbine handpieces, low-speed handpieces, ultrasonic scalers, bicarbonate polishers, polishing cups, as well as drilling and air sprays inside the oral cavity. This study examined the generation of particles during dental drilling and measured particle size, mass, and trace elements. The air sampling techniques included both continuous and integrated methods.

Integrating studies on carcinogenic risk of carbon black: epidemiology, animal exposures, and mechanism of action.

Objective: We sought to address the toxicology literature on carbon black (CB) since 1996, when IARC reclassified CB from group 3 to group 2B.

Methods: We reviewed epidemiology and laboratory studies from 1996 to 2006, focusing on new analyses of worker populations, on species differences in tumorigenicity of poorly soluble particles, and on the role of particle-bound organics in tumorigenicity.

Results: Some epidemiology studies have reported positive associations between cancer risk and worker's possible exposure to CB, but larger studies, in more highly exposed populations, have not shown consistent patterns of either elevated risk or dose-response.

A cancer risk assessment of inner-city teenagers living in New York City and Los Angeles.

Background: The Toxics Exposure Assessment Columbia-Harvard (TEACH) project assessed exposures and cancer risks from urban air pollutants in a population of high school teenagers in New York City (NYC) and Los Angeles (LA). Forty-six high school students participated in NYC and 41 in LA, most in two seasons in 1999 and 2000, respectively.

Methods: Personal, indoor home, and outdoor home 48-hr samples of volatile organic compounds (VOCs), aldehydes, particulate matter with aerodynamic diameter < or = 2.

Modeling time-location patterns of inner-city high school students in New York and Los Angeles using a longitudinal approach with generalized estimating equations.

The TEACH Project obtained subjects' time-location information as part of its assessment of personal exposures to air toxics for high school students in two major urban areas. This report uses a longitudinal modeling approach to characterize the association between demographic and temporal predictors and the subjects' time-location behavior for three microenvironments--indoor-home, indoor-school, and outdoors. Such a longitudinal approach has not, to the knowledge of the authors, been previously applied to time-location data.

Analysis of PM10, PM2.5, and PM2 5-10 concentrations in Santiago, Chile, from 1989 to 2001.

Daily particle samples were collected in Santiago, Chile, at four urban locations from January 1, 1989, through December 31, 2001. Both fine PM with da < 2.5 microm (PM2.

Steel dust in the New York City subway system as a source of manganese, chromium, and iron exposures for transit workers.

The United States Clean Air Act Amendments of 1990 reflected increasing concern about potential effects of low-level airborne metal exposure on a wide array of illnesses. Here we summarize results demonstrating that the New York City (NYC) subway system provides an important microenvironment for metal exposures for NYC commuters and subway workers and also describe an ongoing pilot study of NYC transit workers' exposure to steel dust. Results from the TEACH (Toxic Exposure Assessment, a Columbia and Harvard) study in 1999 of 41 high-school students strongly suggest that elevated levels of iron, manganese, and chromium in personal air samples were due to exposure to steel dust in the NYC subway.