Exposure to Outdoor Particulate Matter Air Pollution and Risk of Gastrointestinal Cancers in Adults: A Systematic Review and Meta-Analysis of Epidemiologic Evidence.

BACKGROUND: Outdoor air pollution is a known lung carcinogen, but research investigating the association between particulate matter (PM) and gastrointestinal (GI) cancers is limited. OBJECTIVES: We sought to review the epidemiologic literature on outdoor PM and GI cancers and to put the body of studies into context regarding potential for bias and overall strength of evidence. METHODS: We conducted a systematic review and meta-analysis of epidemiologic studies that evaluated the association of fine PM [PM with an aerodynamic diameter of ≤2.5µm (PM2.5)] and PM10 (aerodynamic diameter ≤10µm) with GI cancer incidence or mortality in adults. We searched five databases for original research published from 1980 to 2021 in English and summarized findings for studies employing a quantitative estimate of exposure overall and by specific GI cancer subtypes. We evaluated the risk of bias of individual studies and the overall quality and strength of the evidence according to the Navigation Guide methodology, which is tailored for environmental health research. RESULTS: Twenty studies met inclusion criteria and included participants from 14 countries; nearly all were of cohort design. All studies identified positive associations between PM exposure and risk of at least one GI cancer, although in 3 studies these relationships were not statistically significant. Three of 5 studies estimated associations with PM10 and satisfied inclusion criteria for meta-analysis, but each assessed a different GI cancer and were therefore excluded. In the random-effects meta-analysis of 13 studies, PM2.5 exposure was associated with an increased risk of GI cancer overall [risk ratio (RR)=1.12; 95% CI: 1.01, 1.24]. The most robust associations were observed for liver cancer (RR=1.31; 95% CI: 1.07, 1.56) and colorectal cancer (RR=1.35; 95% CI: 1.08, 1.62), for which all studies identified an increased risk. We rated most studies with "probably low" risk of bias and the overall body of evidence as "moderate" quality with "limited" evidence for this association. We based this determination on the generally positive, but inconsistently statistically significant, effect estimates reported across a small number of studies. CONCLUSION: We concluded there is some evidence of associations between PM2.5 and GI cancers, with the strongest evidence for liver and colorectal cancers. Although there is biologic plausibility for these relationships, studies of any one cancer site were few and there remain only a small number overall. Studies in geographic areas with high GI cancer burden, evaluation of the impact of different PM exposure assessment approaches on observed associations, and investigation of cancer subtypes and specific chemical components of PM are important areas of interest for future research. https://doi.org/10.1289/EHP9620.

The Pebble Remains in the Master's Hand: Two Careers Spent Learning (Still) from John Evans.

In this article, we discuss four vexing problems in risk-based decision making that John Evans has addressed over the last nearly 40 years and has perennially challenged the two of us and others to think about. We tackle the role in decision making of potential thresholds in dose-response functions, how the lack of health reference values for many chemicals may distort risk management, the challenge of model uncertainty for risk characterization, and the yet-untapped potential for value-of-information analysis to enhance public health decision making. Our theme is that work remains to be done on each of these, but that some of that work would merely involve listening to ideas that John has already offered.

Pesticide interactions and risks of sperm chromosomal abnormalities.

Disentangling the separate and synergistic effects of chemicals poses methodological challenges for accurate exposure assessment and for investigating epidemiologically how chemicals affect reproduction. We investigated combined exposures to ubiquitous contemporary use pesticides, specifically organophosphates (OP) and pyrethroids (PYR), and their association with germ cell abnormalities among adult men. Fluorescence in situ hybridization was used to determine disomy in sperm nuclei and urine was analyzed for concentrations of PYR metabolites (3-phenoxybenzoic acid; 3PBA) and OP dialkyl phosphate (DAP) metabolites. Incidence rate ratios using Poisson models were estimated for each disomy type by exposure quartile of DAP metabolites and 3PBA, controlling for confounders. The shape of the associations between PYRs, OPs and disomy were frequently nonmonotonic. There were consistent interactions between OP and PYR metabolite concentrations and the risk for sperm abnormalities. Taking both chemicals into account simultaneously resulted in quantitatively different associations than what was reported previously for OPs and PYRs separately, demonstrating the importance of modeling multiple concentrations simultaneously. Methods investigating interactions using Poisson models are needed to better quantify chemical interactions and their effects on count-based health outcomes, the importance of which was shown here for germ cell abnormalities.

Challenges and Considerations When Balancing the Risks of Contaminants with the Benefits of Fruits and Vegetables for Infants and Toddlers.

BACKGROUND: Fruits and vegetables are key to a healthy diet, particularly in children; however, parents may be concerned about contaminants found in fruits and vegetables. Making informed food choices for children requires understanding and balancing the risks of contaminant exposure with the importance of providing a healthy diet. The objective of this work is to identify fruits and vegetables commonly consumed by infants and toddlers; identify potential contaminants in fruits and vegetables; and outline considerations in assessing contaminant risks in food categories with a critical role in a healthy diet. METHOD: Commonly consumed fruits and vegetables were obtained from the Feeding Infants & Toddlers Study (FITS 2016). The US Food and Drug Administration Total Diet Study was reviewed for contaminant occurrence, and multiple experts were consulted on considerations in assessing risk of certain contaminants. RESULTS: FITS data show eight fruits and nine vegetables account for over 80% of consumption in infants and toddlers. Several contaminants have been detected in fruits and vegetables. Questions to be addressed prior to establishing contaminant guidance were identified. CONCLUSION: Contaminant guidance for fruits and vegetables consumed by infants and toddlers raises several challenges. Expertise from multiple disciplines is required to find an approach that maximizes public health benefit.

An Overview of Occupational Risks From Climate Change.

Changes in atmosphere and temperature are affecting multiple environmental indicators from extreme heat events to global air quality. Workers will be uniquely affected by climate change, and the occupational impacts of major shifts in atmospheric and weather conditions need greater attention. Climate change-related exposures most likely to differentially affect workers in the USA and globally include heat, ozone, polycyclic aromatic hydrocarbons, other chemicals, pathogenic microorganisms, vector-borne diseases, violence, and wildfires. Epidemiologic evidence documents a U-, J-, or V-shaped relationship between temperature and mortality. Whereas heat-related morbidity and mortality risks are most evident in agriculture, many other outdoor occupational sectors are also at risk, including construction, transportation, landscaping, firefighting, and other emergency response operations. The toxicity of chemicals change under hyperthermic conditions, particularly for pesticides and ozone. Combined with climate-related changes in chemical transport and distribution, these interactions represent unique health risks specifically to workers. Links between heat and interpersonal conflict including violence require attention because they pose threats to the safety of emergency medicine, peacekeeping and humanitarian relief, and public safety professionals. Recommendations for anticipating how US workers will be most susceptible to climate change include formal monitoring systems for agricultural workers; modeling scenarios focusing on occupational impacts of extreme climate events including floods, wildfires, and chemical spills; and national research agenda setting focusing on control and mitigation of occupational susceptibility to climate change.

The work environment disability-adjusted life year for use with life cycle assessment: a methodological approach.

BACKGROUND: Life cycle assessment (LCA) is a systems-based method used to determine potential impacts to the environment associated with a product throughout its life cycle. Conclusions from LCA studies can be applied to support decisions regarding product design or public policy, therefore, all relevant inputs (e.g., raw materials, energy) and outputs (e.g., emissions, waste) to the product system should be evaluated to estimate impacts. Currently, work-related impacts are not routinely considered in LCA. The objectives of this paper are: 1) introduce the work environment disability-adjusted life year (WE-DALY), one portion of a characterization factor used to express the magnitude of impacts to human health attributable to work-related exposures to workplace hazards; 2) outline the methods for calculating the WE-DALY; 3) demonstrate the calculation; and 4) highlight strengths and weaknesses of the methodological approach. METHODS: The concept of the WE-DALY and the methodological approach to its calculation is grounded in the World Health Organization's disability-adjusted life year (DALY). Like the DALY, the WE-DALY equation considers the years of life lost due to premature mortality and the years of life lived with disability outcomes to estimate the total number of years of healthy life lost in a population. The equation requires input in the form of the number of fatal and nonfatal injuries and illnesses that occur in the industries relevant to the product system evaluated in the LCA study, the age of the worker at the time of the fatal or nonfatal injury or illness, the severity of the injury or illness, and the duration of time lived with the outcomes of the injury or illness. RESULTS: The methodological approach for the WE-DALY requires data from various sources, multi-step instructions to determine each variable used in the WE-DALY equation, and assumptions based on professional opinion. CONCLUSIONS: Results support the use of the WE-DALY in a characterization factor in LCA. Integrating occupational health into LCA studies will provide opportunities to prevent shifting of impacts between the work environment and the environment external to the workplace and co-optimize human health, to include worker health, and environmental health.

What do we learn from emissions reporting? Analytical considerations and comparison of pollutant release and transfer registers in the United States, Canada, England, and Australia.

Pollutant release and transfer registers (PRTRs) are becoming a popular measure for addressing industrial pollution in many countries. PRTRs require reporting of emissions from specific industrial sectors and making the information publicly available. This article suggests a framework for comparing PRTRs in order to determine whether they attain their declared goals and which factors, if any, influence their effectiveness. The challenges to such a comparison can be divided into three groups. The first refers to changes that are directly linked to the characteristics of PRTRs: both the changes within a specific system over time and variations among different systems. The second refers to parameters that affect the outcomes of the systems without being directly a part of them. The third involves the relations between the emissions reported to the PRTRs and the associated environmental risk. We suggest an approach that relies on relative comparison, commensurate with the unique characteristics of each PRTR, that compares their actual outcomes. Such an approach is necessary both due to significant variations among current PRTRs as well as for following the unique policy objectives that are manifested in different PRTRs. Application of this comparative approach in the United States, England, Canada, and Australia demonstrates significant differences in PRTR systems across countries and suggests that the mere presence of a PRTR may not lead to reduced industrial emissions. The analysis also demonstrates that emission reductions do not correlate with reductions in risk-related measures. The article proposes several simple modifications to the composition of current PRTR databases that may facilitate more accurate analysis of results and effective oversight of implementation.

Measured concentrations of VOCs in several non-residential microenvironments in the United States.

Individuals spend about 25% of their time in non-residential indoor microenvironments. For some of these microenvironments, particularly stores and restaurants, exposures to volatile organic compounds (VOCs), have not been well characterized. In the Boston Exposure Assessment in Microenvironments (BEAM) study, sampling using scripted activities was conducted in stores, restaurants, and transportation in the summer of 2003 and winters of 2004 and 2005. A suite of VOCs including hydrocarbons, several chlorinated compounds, and aldehydes was analyzed. Nine store types were sampled using a composite design to enable a greater number of stores to be visited. Stores had higher concentrations of formaldehyde, toluene, ethylbenzene, xylenes, and styrene than other microenvironments, particularly in certain store types. Geometric mean formaldehyde levels were highest in the housewares stores, at 53 microg/m3 (95% CI = 43, 66). Geometric mean toluene levels were highest in multipurpose stores, at 76 microg/m3 (95% CI = 50, 118). The levels observed in stores were several times higherthan levels found in transportation microenvironments, and indicate strong indoor sources. In contrast, benzene did not have significantly higher levels in stores than typically found outdoors. Concentrations of formaldehyde and benzene, ethylbenzene, xylenes, and styrene were strongly influenced by the presence of smoking in the dining microenvironment. Chloroform levels were higher in restaurants than in other microenvironments, with a geometric mean of 1.1 microg/m3 (95% CI = 0.7, 1.8). The VOC concentrations found in stores and restaurants in this study are a potentially important source of exposure for sensitive individuals or people who work in these microenvironments.

A quantitative risk-benefit analysis of changes in population fish consumption.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish, while recommendations encourage fish consumption among the general population because of nutritional benefits. To investigate the aggregate impacts of hypothetical shifts in fish consumption, the Harvard Center for Risk Analysis convened an expert panel (see acknowledgements). Effects investigated include prenatal cognitive development, coronary heart disease mortality, and stroke. Substitution of fish with high MeHg concentrations with fish containing less MeHg among women of childbearing age yields substantial developmental benefits and few negative impacts. However, if women instead decrease fish consumption, countervailing risks substantially reduce net benefits. If other adults (mistakenly and inappropriately) also reduce their fish consumption, the net public health impact is negative. Although high compliance with recommended fish consumption patterns can improve public health, unintended shifts in consumption can lead to public health losses. Risk managers should investigate and carefully consider how populations will respond to interventions, how those responses will influence nutrient intake and contaminant exposure, and how these changes will affect aggregate public health.

A quantitative analysis of fish consumption and coronary heart disease mortality.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of fish consumption on coronary heart disease (CHD) mortality and nonfatal myocardial infarction (MI). Other papers quantify stroke risk and the impacts of both prenatal MeHg exposure and maternal intake of n-3 PUFAs on cognitive development. This analysis identified articles in a recent qualitative review appropriate for the development of a dose-response relationship. Studies had to satisfy quality criteria, quantify fish intake, and report the precision of the relative risk estimates. Relative risk results were averaged, weighted proportionately by precision. CHD risks associated with MeHg exposure were reviewed qualitatively because the available literature was judged inadequate for quantitative analysis. Eight studies were identified (29 exposure groups). Our analysis estimated that consuming small quantities of fish is associated with a 17% reduction in CHD mortality risk, with each additional serving per week associated with a further reduction in this risk of 3.9%. Small quantities of fish consumption were associated with risk reductions in nonfatal MI risk by 27%, but additional fish consumption conferred no incremental benefits.

A quantitative analysis of fish consumption and stroke risk.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of fish consumption on stroke risk. Other papers quantify coronary heart disease mortality risk and the impacts of both prenatal MeHg exposure and maternal intake of n-3 PUFAs on cognitive development. This analysis identified articles in a recent qualitative literature review that are appropriate for the development of a dose-response relationship between fish consumption and stroke risk. Studies had to satisfy quality criteria, quantify fish intake, and report the precision of the relative risk estimates. The analysis combined the relative risk results, weighting each proportionately to its precision. Six studies were identified as appropriate for inclusion in this analysis, including five prospective cohort studies and one case-control study (total of 24 exposure groups). Our analysis indicates that any fish consumption confers substantial relative risk reduction compared to no fish consumption (12% for the linear model), with the possibility that additional consumption confers incremental benefits (central estimate of 2.0% per serving per week).

Food safety: risk assessment methodology and decision-making criteria.

As our scientific technology grows, risk assessment methods become more complex and, therefore, open to greater scientific debate. Risk assessment has always been a part of the regulatory notification and approval process for foods. However, the methodologies applied to risk assessment and decision-making have become diverse, dependent on a number of features, including the areas of the world in which one operates, the need to use cumulative risk assessment for pesticides and other ingredients or alternative risk assessment considerations for evaluating nontraditional or bioengineered foods. Diverse institutional structures within a single federal regulatory authority may tend to lead to diversity in risk outcomes that creates policy decisions that complicate and confuse the risk management process. On top of this challenge, decisions become more complicated by the need to examine beneficial factors of foods rather than the adverse effects of foods and food additives. Foods are a complex mixture of ingredients. Regulatory groups recognize the need to use new approaches for evaluating the safety and risks associated with foods and food additives, and to do so in a timely manner. The United States Food and Drug Administration (US FDA) in its need to ensure standards of "reasonable certainty of no harm" continues to explore alternative means to be responsive to petitioners as well as continue to examine scientifically validated means, e.g., quantitative structure-activity relationship (QSAR), and computer-assisted programs, within the approval process to assist in the evaluation of risks. Another means to improve the risk management process would include the cumulative risk assessment of pesticides that will, no doubt, be the beginning of more intensive efforts to understand cumulative exposures and the inherent risks from multiple pathways of exposure. The passage of the Food Quality Protection Act (FQPA) resulted in developing additional risk assessment methodologies and approaches to assess the potential for multiple exposures and risks. Addressing the international criteria used in decision-making related to foods safety assessment has resulted in acceptable intake values for food ingredients for carcinogens and noncarcinogens that, in general, tend to be more stringent in the United States compared to Europe. Clearly, the need for harmonization of risk assessment criteria and the impact of the decision process on regulatory approvals and safety assessment is a future need for the continued assurances of food safety. The topics presented in this paper are based on a symposium held in November 2002 at the annual meeting of the American College of Toxicology.

The effect of different tumor groupings on findings of anticarcinogenic responses in long-term rodent bioassays.

Many investigators have found that there is a decrease in tumor rates at some sites when rodents are exposed to some chemicals. The generality of this finding of anticarcinogenicity has been questioned. In this study, we evaluate the effect of several alternative ways of grouping the 3000 tumor types in the Cancer Bioassay Data System (CBDS) database of carcinogenesis test results into a limited number of classes on findings of anticarcinogenicity. We also study the influence of random variation of tumor rate on the apparent anticarcinogenic effects of specific chemicals. We compare the numbers of chemicals classified as anticarcinogenic in (1) our "standard" classification system, (2) a modification of that system to correct some deficiencies in the CBDS database pointed out by Dr. J. Haseman, (3) an alternative classification system developed by Dr. K. S. Crump and colleagues, (4) the number of animals displaying at least one tumor, or (5) the total number of tumors appearing in all animals in control and dosed groups. Although there is a difference in the number of chemicals classified as anticarcinogens by these alternative classification schemes, all of them show a statistically significant increase in the number of anticarcinogenic responses above the random rate predicted by a Monte Carlo simulation of the rodent bioassay. The number of anticarcinogenic responses is similar in our standard classification, our modified classification, and a classification scheme developed by Crump, though specific site/organs may differ. This arises because these schemes use approximately the same number of tumor groups (about 100). If the number of tumor groups decreases (for example, in the total tumors or tumor-bearing animal schemes), the number of anticarcinogenic responses decreases because of the decrease in overall sensitivity of the test. A scheme which combines tumor types can be useful by integrating carcinogenic and anticarcinogenic responses to exposure. At the same time, combination may hide important biological information. We urge consideration of both increases and decreases when evaluating the likely human effects of exposure.

Dealing with the dangers of fear: the role of risk communication.

Among the many lessons of the homeland terrorist attacks of 2001 was that fear has powerful public health implications. People chose to drive instead of flying, thereby raising their risk of injury or death. Thousands took broad-spectrum antibiotics to prevent possible anthrax infections, thereby accelerating antimicrobial resistance. Such potentially harmful actions were taken by people seeking a sense of safety because they were afraid. This essay argues for greater emphasis on risk communication to help people keep their fears in perspective. Effective communication, not only through what the government says but implicit in the actions it takes, empowers people to make wiser choices in their own lives, and to support wise choices by society in applying limited resources to maximize public and environmental health.