A Meta-Analysis of Stressors from the Total Environment Associated with Children's General Cognitive Ability.

General cognitive ability, often referred to as 'general intelligence', comprises a variety of correlated abilities. Childhood general cognitive ability is a well-studied area of research and can be used to predict social outcomes and perceived success. Early life stage (e.g., prenatal, postnatal, toddler) exposures to stressors (i.e., chemical and non-chemical stressors from the total (built, natural, social) environment) can impact the development of childhood cognitive ability. Building from our systematic scoping review (Ruiz et al., 2016), we conducted a meta-analysis to evaluate more than 100 stressors related to cognitive development. Our meta-analysis identified 23 stressors with a significant increase in their likelihood to influence childhood cognitive ability by 10% or more, and 80 stressors were observed to have a statistically significant effect on cognitive ability. Stressors most impactful to cognition during the prenatal period were related to maternal health and the mother's ability to access information relevant to a healthy pregnancy (e.g., diet, lifestyle). Stressors most impactful to cognition during the early childhood period were dietary nutrients (infancy), quality of social interaction (toddler), and exposure to toxic substances (throughout early childhood). In conducting this analysis, we examined the relative impact of real-world exposures on cognitive development to attempt to understand the inter-relationships between exposures to both chemical and non-chemical stressors and early developmental life stages. Our findings suggest that the stressors observed to be the most influential to childhood cognitive ability are not permanent and can be broadly categorized as activities/behaviors which can be modified to improve childhood cognition. This meta-analysis supports the idea that there are complex relationships between a child's total environment and early cognitive development.

A Systematic Review and Meta-Analysis Investigating the Relationship between Exposures to Chemical and Non-Chemical Stressors during Prenatal Development and Childhood Externalizing Behaviors.

Childhood behavioral outcomes have been linked to low quality intrauterine environments caused by prenatal exposures to both chemical and non-chemical stressors. The effect(s) from the many stressors a child can be prenatally exposed to may be influenced by complex interactive relationships that are just beginning to be understood. Chemical stressors influence behavioral outcomes by affecting the monoamine oxidase A (MAOA) enzyme, which is involved in serotonin metabolism and the neuroendocrine response to stress. Non-chemical stressors, particularly those associated with violence, have been shown to influence and exacerbate the externalizing behavioral outcomes associated with low MAOA activity and slowed serotonin metabolism. The adverse developmental effects associated with high stress and maternal drug use during pregnancy are well documented. However, research examining the combined effects of other non-chemical and chemical stressors on development and childhood outcomes as a result of gestational exposures is scarce but is an expanding field. In this systematic review, we examined the extant literature to explore the interrelationships between exposures to chemical and non-chemical stressors (specifically stressful/traumatic experiences), MAOA characteristics, and childhood externalizing behaviors. We observed that exposures to chemical stressors (recreational drugs and environmental chemicals) are significantly related to externalizing behavioral outcomes in children. We also observed that existing literature examining the interactions between MAOA characteristics, exposures to chemical stressors, and traumatic experiences and their effects on behavioral outcomes is sparse. We propose that maternal stress and cortisol fluctuations during pregnancy may be an avenue to link these concepts. We recommend that future studies investigating childhood behaviors include chemical and non-chemical stressors as well as children's inherent genetic characteristics to gain a holistic understanding of the relationship between prenatal exposures and childhood behavioral outcomes.

Nonlinear patterns in mercury bioaccumulation in American alligators are a function of predicted age.

Mercury is a widespread, naturally occurring contaminant that biomagnifies in wetlands due to the methylation of this element by sulfate-reducing bacteria. Species that feed at the top trophic level within wetlands are predicted to have higher mercury loads compared to species feeding at lower trophic levels and are therefore often used for mercury biomonitoring. However, mechanisms for mercury bioaccumulation in sentinel species are often poorly understood, due to a lack of long-term studies or an inability to differentiate between confounding variables. We examined mercury bioaccumulation patterns in the whole blood of American alligators (Alligator mississippiensis) from a long-term mark-recapture study (1979-2017) in South Carolina, USA. Using a growth model and auxiliary information on predicted age at first capture, we differentiated between age- and size-related variation in mercury bioaccumulation, which are often confounded in alligators due to their determinate growth pattern. Contrary to predictions that the oldest or largest individuals were likely to have the highest mercury concentrations, our best-supported model indicated a peak in mercury concentration at 30-40 years of age, depending on the sex, and lower concentrations in the youngest and oldest animals. To evaluate the robustness of our findings, we re-analyzed data from a previously published study of mercury in alligators sampled at Merritt Island National Wildlife Refuge in Florida. Unlike the South Carolina data, the data from Florida contained minimal auxiliary information regarding age, yet the best supported model similarly indicated a peaked rather than increasing relationship between mercury and body size, a less-precise indicator of age. These findings highlight how long-term monitoring can differentiate between confounding variables (e.g., age and size) to better elucidate complex relationships between contaminant exposure and demographic factors in sentinel species.

Examining maternal and environmental transfer of mercury into American alligator eggs.

American alligators are exposed to mercury (Hg) throughout their natural range and may maternally transfer Hg into their eggs. Wildlife species are highly sensitive to Hg toxicity during embryonic development and neonatal life, and information on Hg transfer into eggs is critical when attempting to understand the effects of Hg exposure on developing oviparous organisms. To examine Hg transfer in alligators, the objectives of the present study were to 1) determine Hg concentrations in yolk (embryonic and neonatal food source) from wild alligator eggs collected from three locations - Yawkey Wildlife Center SC (YWC), Lake Apopka FL (LA), and Lake Woodruff FL (LW); 2) examine the relationship between THg concentrations in wild alligator nest material and egg yolk at Merritt Island National Wildlife Refuge, FL; 3) examine the Hg concentrations in wild maternal female alligators (blood) and the THg in corresponding egg yolks and embryos across three nesting seasons at a single location (YWC), and evaluate the relationship between nesting female THg concentrations (blood) and their estimated age and number of nesting years (YWC); and 4) assess the transfer of biologically-relevant Hg concentrations (based on Hg measured in maternal female blood) into embryos using an egg-dosing experiment. Mean total Hg (THg) concentrations observed at each site were 26.3 ng/g ± 11.0 ng/g (YWC), 8.8 ng/g ± 5.1 ng/g (LA), and 22.6 ng/g ± 6.3 ng/g (LW). No relationship was observed between THg in alligator nest material and corresponding yolk samples, nor between THg in maternal alligator blood and estimated age and number of nesting years of these animals. However, significant positive relationships were observed between THg in blood of nesting female alligators and THg in their corresponding egg yolk. We observed that 12.8% of the maternal blood THg is found in the corresponding egg yolk, and a highly significant correlation was observed between the two sample types (r = 0.66; p < 0.0001). The egg dosing experiment revealed that Hg did not transfer through the eggshell at developmental stage 19. Overall, this study provides new information regarding Hg transfer in American alligators which can improve biomonitoring efforts and may inform ecotoxicological investigations and population management programs in areas of high Hg contamination.

A systematic review and meta-analysis examining the interrelationships between chemical and non-chemical stressors and inherent characteristics in children with ADHD.

Children may be more vulnerable to the combined interactions of chemical and non-chemical stressors from their built, natural, and social environments when compared to adults. Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed childhood neurodevelopmental disorder and is considered a major public health issue, as 75% of childhood cases persist into adulthood. ADHD is characterized by developmentally inappropriate levels of hyperactivity, impulsivity, and inattention, with the neurotransmitter serotonin regulating these symptoms. Monoamine oxidase A (MAOA) aids in serotonin uptake and is often implicated in behavioral and emotional disorders, including ADHD. When children are exposed to cigarette smoke, bisphenol A (BPA), or organophosphate pesticides, MAOA activity is inhibited. Non-chemical stressors, such as traumatic childhood experiences, and lifestyle factors, complicate the relationship between genotype and exposures to chemical stressors. But the co-occurrence among outcomes between exposures to chemical stressors, non-chemical stressors, and the low activity MAOA genotype suggest that mental illness in children may be influenced by multiple interacting factors. In this systematic review, we examine the existing literature that combines exposures to chemical and non-chemical stressors (specifically childhood trauma), MAOA characteristics, and ADHD diagnosis to investigate the interrelationships present. We observe that chemical (lead [Pb], phthalates/plasticizers, persistent organic pollutants, and cigarette smoke) exposure is significantly related to ADHD in children. We also observed that existing literature examining the interaction between MAOA, exposures to chemical stressors, and traumatic experiences and their effect on ADHD outcomes is sparse. We recommend that future studies investigating childhood ADHD include chemical and non-chemical stressors and inherent characteristics to gain a holistic understanding of childhood mental health outcomes.

Examining toxic trace element exposure in American alligators.

Toxic trace element exposure occurs through release of the ubiquitous and naturally occurring elements arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg). The unique environmental conditions of the wetland ecosystems along the southeastern Atlantic coast of the United States lead to the accumulation of Hg which is greater than in most other ecosystems in the country. There are also point sources of As, Cd, and Pb in this region. To effectively monitor trace element concentrations, and consequently the potential human exposure, accessible local sentinel species are needed. In this study, concentrations of As, Cd, Pb, Hg and six other trace elements (Al, Ni, Cu, Zn, Se, Mo) were examined in American alligators (Alligator mississippiensis) from seven wetland sites in South Carolina and Florida and assessed for their utility as a sentinel species for human trace element exposure. Alligators were chosen as a potential sentinel as they share a common exposure with the local human population through their aquatic diet, and they are directly consumed commercially and through recreation hunting in this region. Sex was significantly related to the concentration of Zn, Mo, and Al, but not As, Pb, Hg, Cd, Se, or Cu. Site specific differences in element concentrations were observed for As, Pb, Hg, Cd, Se, Zn, and Mo. Size/age was significantly related to the element Hg and Pb concentrations observed. The observed concentration ranges for the four toxic elements, As (6-156 ng/g), Cd (0.3-1.3 ng/g), Pb (3-4872 ng/g), and Hg (39-2765 ng/g), were comparable to those previously reported in diverse human populations. In this region alligators are hunted recreationally and consumed by the local community, making them a vehicle of direct human toxic element exposure. We propose that the similarity in As, Cd, Pb, and Hg concentrations between alligators observed in this study and humans underscores how alligators can serve as a useful sentinel species for toxic element exposure.

Evaluating mercury concentrations and body condition in American alligators (Alligator mississippiensis) at Merritt Island National Wildlife Refuge (MINWR), Florida.

Concentrations of mercury (Hg) are not well studied in free-ranging wildlife. Atmospheric deposition patterns of Hg have been studied in detail and have been modeled for both global and specific locations and often correlate to environmental impact. However, monitoring the impact of Hg deposition in wildlife is complicated due to local environmental conditions that can affect the transformation of atmospheric Hg to the biologically available forms (e.g., rainfall, humidity, pH, the ability of the environment to methylate Hg), as well as affect the accessibility to organisms for sampling. In this study, Hg concentrations in blood samples from a population of American alligators (Alligator mississippiensis) at Merritt Island National Wildlife Refuge (MINWR), FL, USA, over a seven-year period (2007 to 2014; n=174 individuals) were examined to assess Hg variation in the population, as well as the difference in Hg concentration as a function of health status. While most of this population is healthy, 18 individuals with low body mass indices (BMI, defined in this study) were captured throughout the sampling period. These alligators exhibited significantly elevated Hg concentrations compared to their age/sex/season matched counterparts with normal BMI, suggesting that health status should be taken into account when examining Hg concentrations and effects. Alligator blood Hg concentrations were related to the interaction of age/size, sex, and season. This study illustrates the value of a routinely monitored population of large predators in a unique coastal wetland ecosystem, and illuminates the value of long-term environmental exposure assessment.

Trace element biodistribution in the American alligator (Alligator mississippiensis).

Routine monitoring of contaminant levels in wildlife is important for understanding chemical exposure and ultimately the link to ecosystem and human health. This is particularly important when the monitored species is recreationally hunted for human consumption. In the southeastern United States, recreational alligator harvesting takes place annually and in locations that are known to be contaminated with environmental pollutants. In this study, we investigated the biodistribution of trace elements in the American alligator (Alligator mississippiensis) from five sites in Florida, USA. These sites are locations where annual recreational alligator harvesting is permitted and two of the sites are identified as having high mercury contamination with human consumption advisories in effect. We utilized routinely collected monitoring samples (blood and scute), a commonly consumed tissue (muscle), and a classically analyzed tissue for environmental contaminants (liver) to demonstrate how the trace elements were distributed within the American alligator. We describe elemental tissue compartmentalization in an apex predator and investigate if noninvasive samples (blood and scute) can be used to estimate muscle tissue concentrations for a subset of elements measured. We found significant correlations for Hg, Rb, Se, Zn and Pb between noninvasive samples and consumed tissue and also found that Hg was the only trace metal of concern for this population of alligators. This study fills a gap in trace elemental analysis for reptilian apex predators in contaminated environments. Additionally, comprehensive elemental analysis of routinely collected samples can inform biomonitoring efforts and consumption advisories.

Variation in perfluoroalkyl acids in the American alligator (Alligator mississippiensis) at Merritt Island National Wildlife Refuge.

This study aimed to quantify concentrations of fifteen perfluoroalkyl acids (PFAAs) in the plasma of American alligators (Alligator mississippiensis) inhabiting wetlands surrounding the Kennedy Space Center (KSC) in Florida, USA located at Merritt Island National Wildlife Refuge (MINWR). Approximately 10 male and 10 female alligators (ntotal = 229) were sampled each month during 2008 and 2009 to determine if seasonal or spatial trends existed with PFAA burden. PFOS represented the highest plasma burden (median 185 ng/g) and PFHxS the second highest (median 7.96 ng/g). While no significant seasonal trends were observed, unique spatial trends emerged. Many of the measured PFAAs co-varied strongly together and similar trends were observed for PFOS, PFDA, PFUnA, and PFDoA, as well as for PFOA, PFHxS, PFNA, PFTriA, and PFTA, suggesting more than one source of PFAAs at MINWR. Higher concentrations of PFOS and the PFAAs that co-varied with PFOS were collected from animals around sites that included the Shuttle Landing Facility (SLF) fire house and the Neil Armstrong Operations and Checkout (O&C) retention pond, while higher concentrations of PFOA and the PFAA that co-varied with PFOA were sampled from animals near the gun range and the old fire training facility. Sex-based differences and snout-vent length (SVL) correlations with PFAA burden were also investigated.

Global DNA methylation loss associated with mercury contamination and aging in the American alligator (Alligator mississippiensis).

Mercury is a widespread environmental contaminant with exposures eliciting a well-documented catalog of adverse effects. Yet, knowledge regarding the underlying mechanisms by which mercury exposures are translated into biological effects remains incomplete. DNA methylation is an epigenetic modification that is sensitive to environmental cues, and alterations in DNA methylation at the global level are associated with a variety of diseases. Using a liquid chromatography tandem mass spectrometry-based (LC-MS/MS) approach, global DNA methylation levels were measured in red blood cells of 144 wild American alligators (Alligator mississippiensis) from 6 sites with variable levels of mercury contamination across Florida's north-south axis. Variation in mercury concentrations measured in whole blood was highly associated with location, allowing the comparison of global DNA methylation levels across different "treatments" of mercury. Global DNA methylation in alligators across all locations was weakly associated with increased mercury exposure. However, a much more robust relationship was observed in those animals sampled from locations more highly contaminated with mercury. Also, similar to other vertebrates, global DNA methylation appears to decline with age in alligators. The relationship between age-associated loss of global DNA methylation and varying mercury exposures was examined to reveal a potential interaction. These findings demonstrate that global DNA methylation levels are associated with mercury exposure, and give insights into interactions between contaminants, aging, and epigenetics.

Use of indicator chemicals to characterize the plastic fragments ingested by Laysan albatross.

Laysan albatross (Phoebastria immutabilis) ingest plastic marine debris of a wide range of shape, sizes and sources. To better characterize this plastic and provide insights regarding its provenance and persistence in the environment, we developed a simple method to classify plastic fragments of unknown origin according to the resin codes used by the Society of Plastics Industry. Known plastics were analyzed by gas chromatography-mass spectroscopy (GC-MS) to identify indicator chemicals characteristic of each plastic resin. Application of this method to fragments of ingested plastic debris from boluses of Laysan albatross from Kure Atoll, Hawai'i, yielded proportions of 0.8% High Density Polyethylene, 6.8% Polystyrene, 8.5% Polyethylene Terephthalate, 20.5% Polyvinyl Chloride and 68.4% Polypropylene. Some fragments were composed of multiple resin types. These results suggest that infrequently recycled plastics are the dominant fragments ingested by albatross, and that these are the most prevalent and persistent resin types in the marine environment.

Investigating the potential role of persistent organic pollutants in Hawaiian green sea turtle fibropapillomatosis.

It has been hypothesized for decades that environmental pollutants may contribute to green sea turtle fibropapillomatosis (FP), possibly through immunosuppression leading to greater susceptibility to the herpesvirus, the putative causative agent of this tumor-forming disease. To address this question, we measured concentrations of 164 persistent organic pollutants (POPs) and halogenated phenols in 53 Hawaiian green turtle (Chelonia mydas) plasma samples archived by the Biological and Environmental Monitoring and Archival of Sea Turtle Tissues (BEMAST) project at the National Institute of Standards and Technology Marine Environmental Specimen Bank. Four groups of turtles were examined: free-ranging turtles from Kiholo Bay (0% FP, Hawaii), Kailua Bay (low FP, 8%, Oahu), and Kapoho Bay (moderate FP, 38%, Hawaii) and severely tumored stranded turtles that required euthanasia (high FP, 100%, Main Hawaiian Islands). Four classes of POPs and seven halogenated phenols were detected in at least one of the turtles, and concentrations were low (often <200 pg/g wet mass). The presence of halogenated phenols in sea turtles is a novel discovery; their concentrations were higher than most man-made POPs, suggesting that the source of most of these compounds was likely natural (produced by the algal turtle diet) rather than metabolites of man-made POPs. None of the compounds measured increased in concentration with increasing prevalence of FP across the four groups of turtles, suggesting that these 164 compounds are not likely primary triggers for the onset of FP. However, the stranded, severely tumored, emaciated turtle group (n=14) had the highest concentrations of POPs, which might suggest that mobilization of contaminants with lipids into the blood during late-stage weight loss could contribute to the progression of the disease. Taken together, these data suggest that POPs are not a major cofactor in causing the onset of FP.