Relation of blood lead levels and lead in gasoline: an updated systematic review.

BACKGROUND: Millions of tons of lead were added to gasoline worldwide beginning in 1922, and leaded gasoline has been a major source of population lead exposure. In 1960s, lead began to be removed from automotive gasoline. Removal was completed in 2021. OBJECTIVES: To determine whether removal of lead from automotive gasoline is associated with declines in population mean blood lead levels (BPb). METHODS: We examined published studies that reported population blood leaded levels for two or more years, and we calculated average concentrations of lead in gasoline corresponding to the years and locations of the blood lead level measurements. RESULTS: Removal of lead from gasoline is associated with declines in BPb in all countries examined. In some countries, BPb continues to fall after lead has been eliminated from gasoline. Following elimination of lead from gasoline, BPb less than 1 µg/dL have been observed in several European and North American countries, and BPb less than 3 µg/dL have been documented in several studies from South America. DISCUSSION: There remain many countries for which no multi-year studies of populations BPb have been identified, including all of Central America, high population countries including Pakistan and Indonesia, and major lead producers including Australia and Russia. CONCLUSION: Removal of lead from gasoline has been a public health success. Elimination of lead from gasoline has enabled many countries to achieve population mean BPb levels of 1 µg/dL or lower. These actions have saved lives, increased children's intelligence and created great economic benefit in countries worldwide.

A replicable strategy for mapping air pollution's community-level health impacts and catalyzing prevention.

BACKGROUND: Air pollution was responsible for an estimated 6.7 million deaths globally in 2019 and 197,000 deaths in the United States. Fossil fuel combustion is the major source. HYPOTHESIS: Mapping air pollution's health impacts at the community level using publicly available data and open-source software will provide a replicable strategy for catalyzing pollution prevention. METHODS: Using EPA's Environmental Benefits Mapping and Analysis (BenMAP-CE) software and state data, we quantified the effects of airborne fine particulate matter (PM2.5) pollution on disease, death and children's cognitive function (IQ Loss) in each city and town in Massachusetts. To develop a first-order estimate of PM2.5 pollution's impact on child IQ, we derived a concentration-response coefficient through literature review. FINDINGS: The annual mean PM2.5 concentration in Massachusetts in 2019 was 6.3 µg/M3, a level below EPA's standard of 12 µg/M3 and above WHO's guideline of 5 µg/M3. In adults, PM2.5 pollution was responsible for an estimated 2780 (Confidence Interval [CI] 2726 - 2853) deaths: 1677 (CI, 1346 - 1926) from cardiovascular disease, 2185 (CI, 941-3409) from lung cancer, 200 (CI, 66-316) from stroke, and 343 (CI, 222-458) from chronic respiratory disease. In children, PM2.5 pollution was responsible for 308 (CI, 105-471) low-weight births, 15,386 (CJ, 5433-23,483) asthma cases, and a provisionally estimated loss of nearly 2 million Performance IQ points; IQ loss impairs children's school performance, reduces graduation rates and decreases lifetime earnings. Air-pollution-related disease, death and IQ loss were most severe in low-income, minority communities, but occurred in every city and town in Massachusetts regardless of location, demographics or median family income. CONCLUSION: Disease, death and IQ loss occur at air pollution exposure levels below current EPA standards. Prevention of disease and premature death and preservation of children's cognitive function will require that EPA air quality standards be tightened. Enduring prevention will require government-incentivized transition to renewable energy coupled with phase-outs of subsidies and tax breaks for fossil fuels. Highly localized information on air pollution's impacts on health and on children's cognitive function has potential to catalyze pollution prevention.

Quantifying the climate benefits of a virtual versus an in-person format for an international conference.

BACKGROUND: Academic institutions across the globe routinely sponsor large conferences. During the COVID-19 pandemic, many conferences have used all- or partially virtual formats. The conversion of the 2021 Consortium of Universities for Global Health (CUGH) conference, originally planned in-person for Houston, TX USA to an all-virtual format provided an opportunity to quantify the climate-related impacts of in-person versus virtual conferences. METHODS: From the 2021 CUGH conference registration data, we determined each registrant's distance from Houston. Using widely available, open-source formulas, we calculated the carbon footprint of each registrant's round-trip drive or flight had they traveled to Houston. We assumed that registrants traveling more than 300 miles would have flown, with the remainder traveling by automobile. RESULTS: Of 1909 registrants, 1447 would have traveled less than 4000 miles, and 389 would have traveled more than 10,000 miles round trip. Total travel-related carbon emissions were estimated at 2436 metric tons of CO2, equivalent to the conservation of 2994 acres of forest for a year. CONCLUSIONS: Organizations can now readily quantify the climate cost of annual conferences. CUGH's annual international conference, when held in-person, contributes significantly to carbon emissions. With its focus on promoting global health equity, CUGH may play a lead role in understanding the pros and cons for planetary health of in-person versus virtual conferences. CUGH and other organizations could routinely measure and publish the climate costs of their annual conferences.

Aspartame and cancer - new evidence for causation.

BACKGROUND: Aspartame is one of the world's most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women. The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults. These findings generated intense controversy focused on the accuracy of RI's diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms. METHODS: To address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria. FINDINGS: This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection. INTERPRETATION: These new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies. These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame's health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame's carcinogenicity to humans.

Commentary: Novel strategies and new tools to curtail the health effects of pesticides.

BACKGROUND: Flaws in the science supporting pesticide risk assessment and regulation stand in the way of progress in mitigating the human health impacts of pesticides. Critical problems include the scope of regulatory testing protocols, the near-total focus on pure active ingredients rather than formulated products, lack of publicly accessible information on co-formulants, excessive reliance on industry-supported studies coupled with reticence to incorporate published results in the risk assessment process, and failure to take advantage of new scientific opportunities and advances, e.g. biomonitoring and "omics" technologies. RECOMMENDED ACTIONS: Problems in pesticide risk assessment are identified and linked to study design, data, and methodological shortcomings. Steps and strategies are presented that have potential to deepen scientific knowledge of pesticide toxicity, exposures, and risks. We propose four solutions: (1) End near-sole reliance in regulatory decision-making on industry-supported studies by supporting and relying more heavily on independent science, especially for core toxicology studies. The cost of conducting core toxicology studies at labs not affiliated with or funded directly by pesticide registrants should be covered via fees paid by manufacturers to public agencies. (2) Regulators should place more weight on mechanistic data and low-dose studies within the range of contemporary exposures. (3) Regulators, public health agencies, and funders should increase the share of exposure-assessment resources that produce direct measures of concentrations in bodily fluids and tissues. Human biomonitoring is vital in order to quickly identify rising exposures among vulnerable populations including applicators, pregnant women, and children. (4) Scientific tools across disciplines can accelerate progress in risk assessments if integrated more effectively. New genetic and metabolomic markers of adverse health impacts and heritable epigenetic impacts are emerging and should be included more routinely in risk assessment to effectively prevent disease. CONCLUSIONS: Preventing adverse public health outcomes triggered or made worse by exposure to pesticides will require changes in policy and risk assessment procedures, more science free of industry influence, and innovative strategies that blend traditional methods with new tools and mechanistic insights.

The interplay between environmental exposures and COVID-19 risks in the health of children.

BACKGROUND: An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution. OBJECTIVES: To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps. METHODS: An international group of researchers interested in children's environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps. DISCUSSION: Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a "dirty" environment in conveying protection - an example of the "hygiene hypothesis"; and what are the long term health effects of SARS-Cov-2 infection in early life. CONCLUSION: A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.

Probabilistic estimates of prenatal lead exposure at 195 toxic hotspots in low- and middle-income countries.

BACKGROUND: Prior estimates of pediatric lead-related disease burden in low- and middle-income countries (LMICs) used population estimates of maternal blood lead levels (BLLs). This approach may underestimate fetal BLLs by not considering potentially high prenatal lead exposure from toxic hotspots. OBJECTIVES: We developed a probabilistic approach to using the Adult Lead Methodology (ALM) to estimate fetal BLLs from prenatal exposure to lead-contaminated soil at hotspots in the Toxic Site Identification Program (TSIP). METHODS: We created distributions for each ALM parameter using published literature and extracted soil lead measurements from the TSIP database. Each iteration of the probabilistic ALM randomly selected values from the input distributions to generate a site-specific fetal BLL estimate. For each site, we ran 5000 model iterations, producing a site-specific fetal BLL distribution. RESULTS: 195 TSIP sites, in 33 LMICs, met our study inclusion criteria; an estimated 820,000 women of childbearing age are at risk for lead exposure at these sites. The predicted geometric means (GM) for site-specific fetal BLLs ranged from 3.3 µg/dL to 534 µg/dL, and 98% of sites had estimated GM fetal BLLs >5 µg/dL, the current reference level of the United States Centers for Disease Control and Prevention (CDC), while 11 sites had estimated GM fetal BLLs above the CDC chelation threshold of 45 µg/dL. DISCUSSION: The TSIP soil lead data and this probabilistic approach to the ALM show that pregnant women living near TSIP sites may have BLLs that put their fetus at risk for neurologic damage and other sequelae, underscoring the need for interventions to reduce lead exposure at toxic hotspots.

Building New York State Centers of Excellence in Children's Environmental Health: A Replicable Model in a Time of Uncertainty.

Public health programs may be seriously affected in periods of federal retrenchment. During these times, state-based strategies provide an alternate pathway for advancing public health.A 12-year campaign to secure state support for a network of Centers of Excellence in Children's Environmental Health (CEH) promoting health of children across New York State is described. It was driven by rising rates of asthma, birth defects, developmental disorders, and other noncommunicable diseases in children; growing evidence associating hazardous environmental exposures with these conditions; and recognition that federal resources in CEH are insufficient.Critical campaign elements were (1) formation of a statewide coalition of academic health centers, health care providers, public health officials, community advocates, and other stakeholders; (2) bipartisan collaborations with legislative champions and government leaders; (3) assessment of the burden of developmental disorders and noncommunicable diseases associated with environmental exposures among children; (4) maps documenting the presence of environmental hazards in every county statewide; (5) iterative charting of a changing political landscape; and (6) persistence. The 2017 award of a 5-year, $10 million contract to establish Centers of Excellence in CEH demonstrates the value of this statewide strategy.

The need for independent research on the health effects of glyphosate-based herbicides.

BACKGROUND: Glyphosate, formulated as Roundup, is the world's most widely used herbicide. Glyphosate is used extensively on genetically modified (GM) food crops designed to tolerate the herbicide, and global use is increasing rapidly. Two recent reviews of glyphosate's health hazards report conflicting results. An independent review by the International Agency for Research on Cancer (IARC) found that glyphosate is a "probable human carcinogen". A review by the European Food Safety Agency (EFSA) found no evidence of carcinogenic hazard. These differing findings have produced regulatory uncertainty. REGULATORY ACTIONS: Reflecting this regulatory uncertainty, the European Commission on November 27 2017, extended authorization for glyphosate for another 5 years, while the European Parliament opposed this decision and issued a call that pesticide approvals be based on peer-reviewed studies by independent scientists rather than on the current system that relies on proprietary industry studies. RAMAZZINI INSTITUTE RESPONSE: The Ramazzini Institute has initiated a pilot study of glyphosate's health hazards that will be followed by an integrated experimental research project. This evaluation will be independent of industry support and entirely sponsored by worldwide crowdfunding. The aim of the Ramazzini Institute project is to explore comprehensively the effects of exposures to glyphosate-based herbicides at current real-world levels on several toxicological endpoints, including carcinogenicity, long-term toxicity, neurotoxicity, endocrine disrupting effects, prenatal developmental toxicity, the microbiome and multi-generational effects.

The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation.

BACKGROUND: Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine. METHODS: We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA. RESULTS: Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA. CONCLUSIONS: Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model.

A comparative assessment of major international disasters: the need for exposure assessment, systematic emergency preparedness, and lifetime health care.

BACKGROUND: The disasters at Seveso, Three Mile Island, Bhopal, Chernobyl, the World Trade Center (WTC) and Fukushima had historic health and economic sequelae for large populations of workers, responders and community members. METHODS: Comparative data from these events were collected to derive indications for future preparedness. Information from the primary sources and a literature review addressed: i) exposure assessment; ii) exposed populations; iii) health surveillance; iv) follow-up and research outputs; v) observed physical and mental health effects; vi) treatment and benefits; and vii) outreach activities. RESULTS: Exposure assessment was conducted in Seveso, Chernobyl and Fukushima, although none benefited from a timely or systematic strategy, yielding immediate and sequential measurements after the disaster. Identification of exposed subjects was overall underestimated. Health surveillance, treatment and follow-up research were implemented in Seveso, Chernobyl, Fukushima, and at the WTC, mostly focusing on the workers and responders, and to a lesser extent on residents. Exposure-related physical and mental health consequences were identified, indicating the need for a long-term health care of the affected populations. Fukushima has generated the largest scientific output so far, followed by the WTCHP and Chernobyl. Benefits programs and active outreach figured prominently in only the WTC Health Program. The analysis of these programs yielded the following lessons: 1) Know who was there; 2) Have public health input to the disaster response; 3) Collect health and needs data rapidly; 4) Take care of the affected; 5) Emergency preparedness; 6) Data driven, needs assessment, advocacy. CONCLUSIONS: Given the long-lasting health consequences of natural and man-made disasters, health surveillance and treatment programs are critical for management of health conditions, and emergency preparedness plans are needed to prevent or minimize the impact of future threats.

Positive correlation between pesticide sales and central nervous system and cardiovascular congenital abnormalities in Brazil.

BACKGROUND: This study investigated the association between pesticide exposure in Brazil (2005-2013) with rates of central nervous system (CNS) and cardiovascular system (CVS) congenital abnormalities in 2014. METHOD: An exposure variable was established from data on production and sales of pesticides (kg) per crop area (ha) for 2012 and 2013 years. The Brazilian states were divided into three categories: high, medium, and low pesticide use and rate ratios were estimated for each group of states (CI: 95 %). RESULTS: In 2013 and 2014, the high use group presented a 100 and a 75 % increase, and the medium group a 65 and 23 % increase, respectively, in the risk of CNS and CVS congenital abnormalities at birth, compared to the low use group. CONCLUSION: These findings suggest that pesticide exposure could be associated with increased risk of congenital malformations at birth in Brazil.