A pilot study of chlormequat in food and urine from adults in the United States from 2017 to 2023.

Chlormequat chloride is a plant growth regulator whose use on grain crops is on the rise in North America. Toxicological studies suggest that exposure to chlormequat can reduce fertility and harm the developing fetus at doses lower than those used by regulatory agencies to set allowable daily intake levels. Here we report, the presence of chlormequat in urine samples collected from people in the U.S., with detection frequencies of 69%, 74%, and 90% for samples collected in 2017, 2018-2022, and 2023, respectively. Chlormequat was detected at low concentrations in samples from 2017 through 2022, with a significant increase in concentrations for samples from 2023. We also observed high detection frequencies of chlormequat in oat-based foods. These findings and chlormequat toxicity data raise concerns about current exposure levels, and warrant more expansive toxicity testing, food monitoring, and epidemiological studies to assess health effects of chlormequat exposures in humans. IMPACT: This study reports the detection of chlormequat, an agricultural chemical with developmental and reproductive toxicity, in the U.S. population and U.S. food supplies for the first time. While similar levels of the chemical were found in urine sampled from 2017 to 2022, markedly increased levels were found in samples from 2023. This work highlights the need for more expansive monitoring of chlormequat in U.S. foods and in human specimens, as well as toxicological and epidemiological study on chlormequat, as this chemical is an emerging contaminant with documented evidence of low-dose adverse health effects in animal studies.

Volatile organic compounds emitted by conventional and "green" cleaning products in the U.S. market.

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.

Discussion. Has the human population become a sentinel for the adverse effects of PFAS contamination on wildlife health and endangered species?

Global contamination with per- and polyfluoroalkyl substances (PFAS) poses a threat to both human health and the environment, with significant implications for ecological conservation policies. A growing list of peer-reviewed publications indicates that PFAS can harm wildlife health and that the adverse effects associated with PFAS exposure in wildlife are in concordance with human epidemiological studies. The correlation of cross-species data supports a unique perspective that humans can be regarded as a sentinel for PFAS effects in other species. The health harms due to PFAS are potentially most concerning for populations of endangered and threatened species that are simultaneously exposed to PFAS and other toxic pollutants, and also face threats to their survival due to habitat loss, degradation of ecosystems, and over-harvesting. Human epidemiological studies on the PFAS doses associated with health harm present a rich source of information about potential impacts on wildlife health due to PFAS. Our analysis suggests that national and international efforts to restrict the discharges of PFAS into the environment and to clean up PFAS-contaminated sites present an opportunity to protect wildlife from chemical pollution and to advance species conservation worldwide.

Locally caught freshwater fish across the United States are likely a significant source of exposure to PFOS and other perfluorinated compounds.

Per- and polyfluoroalkyl substances, or PFAS, gained significant public and regulatory attention due to widespread contamination and health harms associated with exposure. Ingestion of PFAS from contaminated food and water results in the accumulation of PFAS in the body and is considered a key route of human exposure. Here we calculate the potential contribution of PFOS from consumption of locally caught freshwater fish to serum levels. We analyzed data for over 500 composite samples of fish fillets collected across the United States from 2013 to 2015 under the U.S. EPA's monitoring programs, the National Rivers and Streams Assessment and the Great Lakes Human Health Fish Fillet Tissue Study. The two datasets indicate that an individual's consumption of freshwater fish is potentially a significant source of exposure to perfluorinated compounds. The median level of total targeted PFAS in fish fillets from rivers and streams across the United States was 9,500 ng/kg, with a median level of 11,800 ng/kg in the Great Lakes. PFOS was the largest contributor to total PFAS levels, averaging 74% of the total. The median levels of total detected PFAS in freshwater fish across the United States were 278 times higher than levels in commercially relevant fish tested by the U.S. Food and Drug Administration in 2019-2022. Exposure assessment suggests that a single serving of freshwater fish per year with the median level of PFAS as detected by the U.S. EPA monitoring programs translates into a significant increase of PFOS levels in blood serum. The exposure to chemical pollutants in freshwater fish across the United States is a case of environmental injustice that especially affects communities that depend on fishing for sustenance and for traditional cultural practices. Identifying and reducing sources of PFAS exposure is an urgent public health priority.

Racial and social disparities in Ventura County, California related to agricultural pesticide applications and toxicity.

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.

Laboratory testing of sunscreens on the US market finds lower in vitro SPF values than on labels and even less UVA protection.

BACKGROUND: New research has attributed increased significance to the causal link between ultraviolet A (UVA) radiation and immunosuppression and carcinogenesis. In the United States, sunscreens are labeled with only their sun protection factor (SPF) and an imprecise term "broad-spectrum protection." Sunscreen marketing and efficacy evaluations continue to be based primarily on skin redness (sunburn) or erythema. We sought to evaluate the ultraviolet (UV) protection offered by common sunscreen products on the US market using laboratory-measured UV-absorption testing and comparing with computer-modeled protection and the labeled SPF values. This approach enables an investigation of the relationship between the labeled SPF and measured UVA protection, a factor that is ignored in current regulations. METHODS: Fifty-one sunscreen products for sale in the United States with SPF values from 15 to 110 and labeled as providing broad-spectrum protection were tested using a commercial laboratory. All products were evaluated using the ISO 24443:2012 method for sunscreen effectiveness. The final absorbance spectra were used for analysis of in vitro UV protection. RESULTS: In vitro SPF values from laboratory-measured UV absorption and computer modeling were on average just 59 and 42 percent of the labeled SPF. The majority of products provided significantly lower UVA protection with the average unweighted UVA protection factor just 24 percent of the labeled SPF. CONCLUSION: Regulations and marketplace forces promote sunscreens that reduce sunburn instead of products that provide better, more broad-spectrum UV protection. The production and use of products with broad spectrum UV protection should be incentivized, removing the emphasis on sunburn protection and ending testing on people.

Community-Level Analysis of Drinking Water Data Highlights the Importance of Drinking Water Metrics for the State, Federal Environmental Health Justice Priorities in the United States.

Research studies analyzing the geospatial distribution of air pollution and other types of environmental contamination documented the persistence of environmental health disparities between communities. Due to the shortage of publicly available data, only limited research has been published on the geospatial distribution of drinking water pollution. Here we present a framework for the joint consideration of community-level drinking water data and demographic data. Our analysis builds on a comprehensive data set of drinking water contaminant occurrence for the United States for 2014-2019 and the American Community Survey 5-year estimates (2015-2019) from the U.S. Census Bureau. Focusing on the U.S. states of California and Texas for which geospatial data on community water system service boundaries are publicly available, we examine cumulative cancer risk for water served by community water systems of different sizes relative to demographic characteristics for the populations served by these water systems. In both California and Texas, greater cumulative cancer risk was observed for water systems serving communities with a higher percentage of Hispanic/Latino and Black/African American community members. This investigation demonstrates that it is both practical and essential to incorporate and expand the drinking water data metrics in the analysis of environmental pollution and environmental health. The framework presented here can support the development of public policies to advance environmental health justice priorities on state and federal levels in the U.S.

Packaged Foods Labeled as Organic Have a More Healthful Profile Than Their Conventional Counterparts, According to Analysis of Products Sold in the U.S. in 2019-2020.

The organic food market's recent rapid global growth reflects the public's interest in buying certified organic foods, including packaged products. Our analysis shows that packaged foods containing fewer ingredients associated with negative public health outcomes are more likely to be labeled organic. Previous studies comparing organic and conventional foods focused primarily on nutrient composition. We expanded this research by additionally examining ingredient characteristics, including processing and functional use. Our dataset included nutrition and ingredient data for 8240 organic and 72,205 conventional food products sold in the U.S. from 2019 to 2020. Compared to conventional foods, organic foods in this dataset had lower total sugar, added sugar, saturated fat and sodium content. Using a mixed effects logistic regression, we found that likelihood of classification as organic increased as sodium content, added sugar content and the number of ultra-processed ingredients and cosmetic additives on the product label decreased. Products containing no trans-fat ingredients were more likely to be labeled organic. A product was more likely to be classified "organic" the more potassium it contained. These features of organic foods sold in the U.S. are significant because lower dietary ingestion of ultra-processed foods, added sugar, sodium and trans-fats is associated with improved public health outcomes.

Development of health-based exposure limits for radiofrequency radiation from wireless devices using a benchmark dose approach.

BACKGROUND: Epidemiological studies and research on laboratory animals link radiofrequency radiation (RFR) with impacts on the heart, brain, and other organs. Data from the large-scale animal studies conducted by the U.S. National Toxicology Program (NTP) and the Ramazzini Institute support the need for updated health-based guidelines for general population RFR exposure. OBJECTIVES: The development of RFR exposure limits expressed in whole-body Specific Absorption Rate (SAR), a metric of RFR energy absorbed by biological tissues. METHODS: Using frequentist and Bayesian averaging modeling of non-neoplastic lesion incidence data from the NTP study, we calculated the benchmark doses (BMD) that elicited a 10% response above background (BMD10) and the lower confidence limits on the BMD at 10% extra risk (BMDL10). Incidence data for individual neoplasms and combined tumor incidence were modeled for 5% and 10% response above background. RESULTS: Cardiomyopathy and increased risk of neoplasms in male rats were the most sensitive health outcomes following RFR exposures at 900 MHz frequency with Code Division Multiple Access (CDMA) and Global System for Mobile Communications (GSM) modulations. BMDL10 for all sites cardiomyopathy in male rats following 19 weeks of exposure, calculated with Bayesian model averaging, corresponded to 0.27-0.42 W/kg whole-body SAR for CDMA and 0.20-0.29 W/kg for GSM modulation. BMDL10 for right ventricle cardiomyopathy in female rats following 2 years of exposure corresponded to 2.7-5.16 W/kg whole-body SAR for CDMA and 1.91-2.18 W/kg for GSM modulation. For multi-site tumor modeling using the multistage cancer model with a 5% extra risk, BMDL5 in male rats corresponded to 0.31 W/kg for CDMA and 0.21 W/kg for GSM modulation. CONCLUSION: BMDL10 range of 0.2-0.4 W/kg for all sites cardiomyopathy in male rats was selected as a point of departure. Applying two ten-fold safety factors for interspecies and intraspecies variability, we derived a whole-body SAR limit of 2 to 4 mW/kg, an exposure level that is 20-40-fold lower than the legally permissible level of 0.08 W/kg for whole-body SAR under the current U.S. regulations. Use of an additional ten-fold children's health safety factor points to a whole-body SAR limit of 0.2-0.4 mW/kg for young children.

Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food.

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.

Health and economic impact of nitrate pollution in drinking water: a Wisconsin case study.

Nitrate contamination of drinking water, common in agricultural areas, increases the risk of certain cancers and impacts fetal development during pregnancy. Building on previously published methodology, this study evaluates nitrate-attributable disease cases and adverse birth outcomes as well as their economic costs for Wisconsin, USA. Nitrate is the most common contaminant in groundwater in Wisconsin. Two-thirds of the state's residents use groundwater as the primary source of drinking water. Here, we analyze nitrate exposure from drinking water in Wisconsin based on nitrate test results for community water systems for the period of 2010-2017 and a novel methodology for estimating nitrate exposure for the 28% of state's residents who use private wells. We estimate that annually, 111-298 combined cases of colorectal, ovarian, thyroid, bladder, and kidney cancer in Wisconsin may be due to nitrate contamination of drinking water. Each year, up to 137-149 cases of very low birth weight, 72-79 cases of very preterm birth, and two cases of neural tube defects could be due to nitrate exposure from drinking water. The direct medical cost estimates for all nitrate-attributable adverse health outcomes range between $23 and $80 million annually. Simulating targeted reductions in the counties with the highest current drinking water nitrate concentrations resulted in similar reductions in adverse health outcomes as statewide reduction efforts, up to nitrate reductions of 20%. Time trend analysis suggests that groundwater nitrate concentrations are overall increasing. Thus, nitrate contamination of water supplies in Wisconsin is a public health problem that needs to be addressed.

Disposal of products and materials containing per- and polyfluoroalkyl substances (PFAS): A cyclical problem.

Per- and polyfluoroalkyl substances (PFAS), highly stable and persistent chemicals used in numerous industrial applications and consumer goods, pose an exceptionally difficult challenge for disposal. Three approaches are currently available for PFAS wastes: landfilling, wastewater treatment and incineration. Each disposal approach can return either the original PFAS or their degradation products back to the environment, illustrating that the PFAS problem is cyclical. Landfilling and wastewater treatment do not destroy PFAS and simply move PFAS loads between sites. Consumer products and various materials discarded in landfills leach PFAS over time, and landfill leachate is commonly sent to wastewater treatment plants. From wastewater treatment plants, PFAS are carried over to sludge and effluent. Sewage sludge can be landfilled, incinerated, or applied on agricultural fields, and PFAS from treated sludge (biosolids) can contaminate soil, water, and crops. Incineration of PFAS-containing wastes can emit harmful air pollutants, such as fluorinated greenhouse gases and products of incomplete combustion, and some PFAS may remain in the incinerator ash. Volatile PFAS are emitted into the air from landfills and wastewater treatment plants, and research is urgently needed on the potential presence of PFAS compounds in air emissions from commercially run incinerators. Monitoring of waste streams for PFAS, stopping PFAS discharges into water, soil and air and protecting the health of fence-line communities close to the waste disposal sites are essential to mitigate the impacts of PFAS pollution on human health.

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances.

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.

Analysis of Cumulative Cancer Risk Associated with Disinfection Byproducts in United States Drinking Water.

Hundreds of different disinfection byproducts form in drinking water following necessary treatment with chlorine and other disinfectants, and many of those byproducts can damage DNA and increase the risk of cancer. This study offers the first side-by-side comparison of cancer risk assessments based on toxicological and epidemiological studies of disinfection byproducts using a comprehensive contaminant occurrence dataset for haloacetic acids and trihalomethanes, two groups of disinfection byproducts that are regulated in drinking water. We also provide the first analysis of a new occurrence dataset for unregulated haloacetic acids that became available from the latest, fourth round of the U.S. EPA-mandated unregulated contaminant monitoring program (UCMR4). A toxicological assessment indicated that haloacetic acids, and in particular brominated haloacetic acids, are more carcinogenic and are associated with a greater number of attributable cancer cases than trihalomethanes. Based on the toxicological analysis, cumulative lifetime cancer risk due to exposure to trihalomethanes and haloacetic acids for community water systems monitored under UCMR4, estimated with standard default parameters for body weight and water intake, corresponds to 7.0 × 10-5 (3.5 × 10-5-1.3 × 10-4). The same analysis conducted with age sensitivity factors to account for elevated risk in infants and children yielded a cumulative risk estimate of 2.9 × 10-4 (1.7 × 10-4-6.2 × 10-4). Epidemiological data suggest that lifetime cancer risk from disinfection byproducts for the U.S. population served by community water systems is approximately 3.0 × 10-3 (2.1 × 10-4-5.7 × 10-3), or a lifetime cancer risk of three cases per thousand people. Overall, this analysis highlights the value of using human data in health risk assessments to the greatest extent possible.

Application of the Food Quality Protection Act children's health safety factor in the U.S. EPA pesticide risk assessments.

BACKGROUND: The Food Quality Protection Act of 1996, or FQPA, required the Environmental Protection Agency to set allowable levels for pesticides in a way that would "ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue." The act stipulated that an additional tenfold margin of safety for pesticide risk assessments shall be applied to account for pre- and postnatal toxicity and for any data gaps regarding pesticide exposure and toxicity, unless there are reliable data to demonstrate that a different margin would be safe for infants and children. DISCUSSION: To examine the implementation of the FQPA-mandated additional margin of safety, this analysis reviews 59 pesticide risk assessments published by the EPA between 2011 and 2019. The list includes 12 pesticides used in the largest amount in the U.S.; a group of 35 pesticides detected on fruits and vegetables; and 12 organophosphate pesticides. For the non-organophosphate pesticides reviewed here, the EPA applied an additional children's health safety factor in 13% of acute dietary exposure scenarios and 12% of chronic dietary exposure scenarios. For incidental oral, dermal and inhalation exposures, additional FQPA factors were applied for 15, 31, and 41%, respectively, of the non-organophosphate pesticides, primarily due to data uncertainties. For the organophosphate pesticides as a group, a tenfold children's health safety factor was proposed in 2015. Notably, in 2017 that decision was reversed for chlorpyrifos. CONCLUSIONS: For the majority of pesticides reviewed in this study, the EPA did not apply an additional FQPA safety factor, missing an opportunity to fully use the FQPA authority for protecting children's health.

Cumulative risk analysis of carcinogenic contaminants in United States drinking water.

Cumulative risk analysis of contaminant occurrence in United States drinking water for the period of 2010-2017 indicates that over 100,000 lifetime cancer cases could be due to carcinogenic chemicals in tap water. The majority of this risk is due to the presence of arsenic, disinfection byproducts and radioactive contaminants. For different states within the U.S., cumulative cancer risk for drinking water contaminants ranges between 1 × 10-4 and 1 × 10-3, similar to the range of cumulative cancer risks reported for air pollutants. Overall, national attributable risk due to tap water contaminants is approximately 4 × 10-4, which is two orders of magnitude higher than the de minimus cancer risk of one-in-a-million. Thus, decreasing the levels of chemical contaminants in drinking water represents an important opportunity for protecting public health.

Exposure-based assessment and economic valuation of adverse birth outcomes and cancer risk due to nitrate in United States drinking water.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Applying a cumulative risk framework to drinking water assessment: a commentary.

The health risks of drinking water contaminants and the economic benefits of drinking water standards are typically assessed one chemical at a time, an approach that misses the health impacts of co-occurring contaminants in drinking water. In contrast, a cumulative risk framework has become common in air quality evaluations such as the U.S. Environmental Protection Agency's National Air Toxics Assessment. We posit that the drinking water field would benefit from making the transition to a unified assessment framework for multiple contaminants that can overcome the long-standing challenge of treating cancer and non-cancer contaminants separately. Here we present a cumulative risk methodology that combines a risk-based cancer metric with a weighted health indicator index for non-cancer contaminants and incorporates disability weights from the Global Burden of Disease study. Our methodology generates a numeric toxicity score reflecting the potential health impacts for the sum of contaminants present in each sample of drinking water. Further research is needed to refine the risk and toxicity parameters for specific contaminants and to address the mode of interaction between co-occurring chemicals. As this cumulative risk model goes through future refinements, we anticipate that it would provide information that can help communities and policy makers evaluate different options for drinking water treatment.

KLRG1 binds cadherins and preferentially associates with SHIP-1.

The killer cell lectin-like receptor G1 (KLRG1) is a unique inhibitory receptor expressed on a phenotypically mature subset of resting NK cells as well as subsets of T cells in naive mice. In vivo, pathogenic immune system activation induces dramatic changes in the expression patterns of KLRG1 among the different cell subsets. In order to enhance our understanding of KLRG1 signaling properties and to clarify the functions of KLRG1 on these cells, we identified the broadly expressed N-cadherin molecule as a ligand for KLRG1. We further demonstrate that a second member of this superfamily of adhesion molecules, E-cadherin, binds to KLRG1. Additionally, we show that upon phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) tyrosine, KLRG1 recruits both SHIP-1 and SHP-2 but not SHP-1. We also delineate the key KLRG1 ITIM amino acid residues required for optimal association with these phosphatases. Finally, we demonstrate that KLRG1 engagement can inhibit sub-optimal TCR signaling. Taken together, our results indicate that KLRG1 may differentially regulate NK cell and T cell functions through the association with different ligands as well as the recruitment of distinct phosphatases.