Nitrate ingestion from drinking water has been associated with an increased risk of adverse birth outcomes as well as elevated risk of colorectal cancer and several other cancers. Yet, to date, no studies have attempted to quantify the health and economic impacts due to nitrate in drinking water in the United States. This study presents a first-of-its-kind comprehensive assessment of nitrate exposure from drinking water for the entire United States population. This exposure assessment serves as the basis for our analysis of the annual nitrate-attributable disease cases in the United States and the associated economic losses due to medical costs and lost productivity. Additionally, through a meta-analysis of studies on drinking water nitrate and colorectal cancer, we examine the exposure-response relationship for nitrate and cancer risk. On the basis of national nitrate occurrence data and relative risk ratios reported in the epidemiology literature, we calculated that annually, 2939 cases of very low birth weight, 1725 cases of very preterm birth, and 41 cases of neural tube defects could be related to nitrate exposure from drinking water. For cancer risk, combining nitrate-specific risk estimates for colorectal, ovarian, thyroid, kidney, and bladder cancers results in a range of 2300 to 12,594 annual nitrate-attributable cancer cases (mean: 6537 estimated cases). For medical expenditures alone, this burden of cancer corresponds to an annual economic cost of 250 million to 1.5 billion U.S. dollars, together with a potential 1.3 to 6.5 billion dollar impact due to lost productivity. With the meta-analysis of eight studies of drinking water nitrate and colorectal cancer, we observed a statistically significant positive association for nitrate exposure and colorectal cancer risk and calculated a one-in-one million cancer risk level of 0.14 mg/L nitrate in drinking water. Health and economic analyses presented here suggest that lowering exposure to nitrate in drinking water could bring economic benefits by alleviating the impacts of nitrate-associated diseases.

Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.

Exposure to cleaning products has been associated with harm to the respiratory system, neurotoxicity, harm to the reproductive system, and elevated risk of cancer, with greatest adverse impacts for workers exposed in an occupational setting. Social and consumer interest in cleaning products that are safer for health created a market category of "green" products defined here as products advertised as healthier, non-toxic, or free from harmful chemicals as well as products with a third-party certification for safety or environmental features. In the present study we examined the air quality impacts of cleaning products and air fresheners, measuring the number, concentrations, and emission factors of volatile organic compounds (VOCs) in an air chamber following product application. Across seven common product categories, 30 products were tested overall including 14 conventional, 9 identified as "green" with fragrance, and 7 identified as "green" and fragrance-free. A total of 530 unique VOCs were quantified with 205 additional VOCs detected below the limits of quantification. Of the quantifiable VOCs, 193 were considered hazardous according to either the California's Department of Toxic Substances Control Candidate Chemicals List or the European Chemical Agency's Classification and Labeling Inventory. The total concentration of VOCs and total emission factors across all products with detections ranged from below limits of detection to 18,708 μg/m³, 38,035 μg/g product and 3803 μg/application. Greater total concentration, total emission factors, and numbers of VOCs were generally observed in conventional cleaning products compared to products identified as "green", particularly compared to fragrance-free products. A hazard index approach was utilized to assess relative risk from measured VOC emissions. The five products with the highest hazard indices were conventional products with emissions of 2-butoxyethanol, isopropanol, toluene and chloroform. Overall, this analysis suggests that the use of "green" cleaning products, especially fragrance-free products, may reduce exposure to VOC emissions.

The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

Application of agricultural pesticides poses health concerns for farmworkers and for local communities due to pesticide drift from spraying or fumigation, pesticide volatilization into the air, contamination of household dust, as well as direct exposure for people who work in agriculture and their families. In this analysis of pesticide use records for Ventura County, California (USA) from 2016 to 2018, we identified the most prevalent toxicological effects of the pesticides applied. We also developed a cumulative toxicity index that incorporates specific toxicity endpoints for individual pesticides, the severity and strength of association for each endpoint, and the reliability of the data sources. Combining the toxicity index for each pesticide with the pounds applied within each square mile section in Ventura County, we calculated the total toxicity-weighted pesticide use and identified pesticides associated with higher potential risk to health. Analysis of U.S. Census data for Ventura County found a greater percentage of Hispanic/Latino, African American and Asian community members in township sections with a greater volume of pesticides applied and higher toxicity-weighted pesticide use. Similarly, areas with limited economic and social resources had elevated pesticide application overall and elevated toxicity-weighted pesticide use. The combination of toxicological and demographic analyses presented in this study provides information that can support the development of policies to protect public health from excessive exposure to pesticides and better environmental health protection for socially vulnerable populations.