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Fish early life stages are well known for their sensitivity to crude oil exposure. However, the effect of crude oil exposure on adults and their gametes during their spawning period is not well studied. Polar cod, a key arctic fish, may be at risk for crude oil exposure during this potentially sensitive life stage. Additionally, this species experiences lower food availability during their spawning season, with unknown combined consequences. In the present study, wild-caught polar cod were exposed to decreasing levels of a water-soluble fraction (WSF) of crude oil or control conditions and fed either at a low or high feed ration to assess the combined effect of both stressors. Samples were taken during late gonadal development, during active spawning (spawning window), and in the post-spawning period. Histology analysis of gonads from fish sampled during the spawning window showed that oil-exposed polar cod were more likely to have spawned compared to controls. Oil-exposed females had 947 differentially regulated hepatic genes, and their eggs had a higher polycyclic aromatic hydrocarbon body burden compared to controls. Feed ration did not consistently affect polar cod's response to oil exposure for the endpoints measured, however, did alone result in decreases in some sperm motility parameters. These results suggest that polar cod's spawning period is a sensitive life event to crude oil exposure, while feed limitation may play a minor role for this supposedly capital breeder. The effects of adult exposure to crude oil on gamete quality and the next generation warrant further investigation. [ABSTRACT FROM AUTHOR]

Short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) are environmental contaminants known for their persistence and bioaccumulation in fatty tissues. SCCPs are considered potential carcinogens and endocrine disruptors, with similar effects expected for MCCPs. This study investigated the body burden of SCCPs and MCCPs in residents of two regions of the Czech Republic with different levels of industrial pollution. Blood serum samples from 62 individuals in Ceske Budejovice (control area) and Ostrava (industrial area) were analysed. The results showed higher concentrations of SCCPs (<120–650 ng/g lipid weight (lw)) and MCCPs (<240–1530 ng/g lw) in Ostrava compared to Ceske Budejovice (SCCPs: <120–210 ng/g lw, MCCPs: <240–340 ng/g lw). The statistical analysis revealed no significant correlations between chemical concentrations and demographic variables such as age, BMI, or gender. The findings are consistent with European and Australian studies but significantly lower than levels reported in China. This is the first comprehensive survey of SCCPs and MCCPs in human blood serum in the Czech Republic and the second study in Europe. The data collected in this study are essential for assessing SCCPs and MCCPs. They will contribute to a better understanding the potential health risks associated with exposure to these chemicals. [ABSTRACT FROM AUTHOR]

The relationship between breastfeeding duration and maternal mixtures of organochlorine pesticides (OCP) biological concentrations has not been documented. For that reason, our objective was to evaluate the association between lactation duration and mixtures of OCP serum concentrations and their principal metabolites, as well as to identify the primary contributors within these mixtures. Consequently, we conducted a secondary analysis of 878 women over 18 years old who had at least one living child and served as controls in a population-based study from 2007 to 2011 in Northern Mexico. Through direct interviews, we collected data on breastfeeding duration, sociodemographic characteristics, and medical history. We determined serum concentrations of 24 OCP, including some metabolites, using gas chromatography with an electron microcapture detector. We applied Weighted Quantile Sum (WQS) regression models with binomial family specification to assess the relationship between breastfeeding duration (both for the first child and all children) and mixtures of OCP serum concentrations and their metabolites of interest. We identified a mixture of OCP negatively associated with breastfeeding the first child (OR = 0.63, 95% CI 0.52–0.77) and all children (OR = 0.59, 95% CI 0.46–0.75). The significant OCP or metabolites in both mixtures included p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), trans-nonachlor, β-hexachlorocyclohexane (β-HCH), p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), heptachlor, and hexachlorobenzene (HCB). Our results suggest serum concentrations of OCP mixtures in women who breastfed for at least 12 months are lower than those who breastfed for less than that time. Future studies are needed to evaluate the risk–benefit of multiple OCP in breast milk for maternal and child health. [ABSTRACT FROM AUTHOR]

Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction. The body burden of Cd at which these outcomes occur is not, however, reliably defined. Here, multiple-regression and mediation analyses were applied to data from 737 non-diabetic Thai nationals, of which 9.1% had an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 (a low eGFR). The excretion of Cd (ECd), and renal-effect biomarkers, namely β2-microglobulin (Eβ2M), albumin (Ealb), and N-acetylglucosaminidase (ENAG), were normalized to creatinine clearance (Ccr) as ECd/Ccr Eβ2M/Ccr, Ealb/Ccr, and ENAG/Ccr. After adjustment for potential confounders, the risks of having a low eGFR and albuminuria rose twofold per doubling ECd/Ccr rates and they both varied directly with the severity of β2-microglobulinuria. Doubling ECd/Ccr rates also increased the risk of having a severe tubular injury, evident from ENAG/Ccr increments [POR = 4.80, p = 0.015]. ENAG/Ccr was strongly associated with ECd/Ccr in both men (β = 0.447) and women (β = 0.394), while showing a moderate inverse association with eGFR only in women (β = −0.178). A moderate association of ENAG/Ccr and ECd/Ccr was found in the low- (β = 0.287), and the high-Cd body burden groups (β = 0.145), but ENAG/Ccr was inversely associated with eGFR only in the high-Cd body burden group (β = −0.223). These discrepancies together with mediation analysis suggest that Cd-induced nephron destruction, which reduces GFR and the tubular release of NAG by Cd, involves different mechanisms and kinetics. [ABSTRACT FROM AUTHOR]

Introduction: More than half of humans' Polychlorinated Biphenyl (PCB) exposure comes from dietary ingestion. This study investigated the dietary pattern of Malaysian adults and its association with the detection of 5 PCB congeners in the plasma. Materials and methods: A cross-sectional study was conducted among 129 patients with Metabolic Syndrome (MetS) attending the UiTM Primary Care Medicine (PCM) clinic. The participant's diet was assessed using a 128-item food frequency questionnaire. Results: PCB 206 was the most prevalent congener (74.4%) in the plasma of adults with MetS attending the UiTM PCM clinic, followed by PCB 180 (68.2%). The subjects' dietary patterns did not align with the Malaysia Healthy Plate concept, where consuming fruit and vegetables, grains, and proteins accounted for one-third portion of the plate each. Fish consumption significantly predicted PCB 180 level (AO: 1.0880, 95% CI: 1.0064, 1.0996, p=0.043). Meanwhile, the detection of PCB 206 in the plasma was influenced by dairy product consumption (AO: 1.0065, 95% CI: 1.0009, 1.0128, p=0.032) as well as fruits and vegetables consumption (AOR: 0.9982, 95% CI: 0.9968, 0.9996, p=0.014). Conclusion: The threat of PCBs is still prevalent in the population. A more effective strategy is needed to raise awareness and promote adherence to the Malaysian Healthy Plate concept among adults. [ABSTRACT FROM AUTHOR]

Aquatic insects serve as vital inter‐habitat linkages between aquatic and terrestrial ecosystems, as their life cycle includes both aquatic and terrestrial stages. They facilitate the flow of energy and nutrients and play an important role in the transport of waterborne contaminants to terrestrial environments. This study focused on the under‐investigated environmental fate of emerging contaminants (ECs), particularly pharmaceuticals (PhACs) and endocrine‐disrupting compounds (EDCs), which originate from wastewater effluents and accumulate in aquatic insects.Using an in situ study of a highly abundant caddisfly species (Trichoptera), Silo nigricornis (Pictet, 1834), inhabiting a wastewater‐impacted drainage ditch, we examined the bioaccumulation and bioamplification of PhACs and EDCs across the aquatic and terrestrial life stages of the caddisfly.We observed variations in the highest concentrations of PhACs and EDCs in different sample types, including water, biofilm and different life stages of S. nigricornis. Adult S. nigricornis exhibited the highest total concentrations of ECs among the different life stages, with 17 different ECs bioaccumulated in caddisfly tissues. Most of these ECs had higher concentrations in terrestrial adults compared to aquatic larvae and pupae. The total concentration of ECs increased significantly with development, revealing a 41% higher concentration in adult terrestrial caddisflies compared to pupae and larvae.Bioamplification factors provided insights into the increased body burden of the majority of compounds during at least one stage of metamorphosis in S. nigricornis. Evidence of bioamplification was observed in both metamorphosis stages, with certain compounds, such as antibiotics (azithromycin and tilmicosin), endocrine disruptors (TCPP – tris[1‐chloro‐2‐propyl]phosphate and parabens; methylparaben, propylparaben), consistently exhibiting increased concentrations from larval to pupal and from pupal to adult stages. The observed pattern of increasing body burden of contaminants during the caddisfly life cycle emphasises the effects of metamorphosis on the concentration of PhACs and EDCs in adult holometabolous aquatic insects.Our results emphasise the importance of adult caddisflies for the transport of waterborne contaminants such as PhACs and EDCs from aquatic to terrestrial environments. Therefore, our results emphasise the need to include adult trichopterans in the assessment of habitat quality, as their influence extends beyond the boundaries of the aquatic ecosystem. [ABSTRACT FROM AUTHOR]

Background and Aim: The existing data demonstrate that gut microbiota is involved in regulating mineral metabolism in cattle, although the data are quite contradictory. The study aimed to evaluate Saccharomyces cerevisiae-based probiotic's effects on gut microbiota, systemic metabolism, and dairy cows' essential trace element and mineral body burden. Materials and Methods: Fifteen cows received a daily supplement of a 50 g S. cerevisiae-based probiotic, fortified with methionine, choline, eugenol, cinnamaldehyde, and Capsicum oleoresin, for a month. 16S metagenomic sequencing was used to evaluate the taxonomic features of fecal microbiota. Serum trace elements and minerals levels were determined through inductively coupled plasma mass spectrometry. Results: Supplementation with S. cerevisiae-based probiotic complex significantly increased alpha and beta diversity, as well as the abundance of Mediterranea and Clostridium IV within the Bacillota phylum, whereas that of Bacteroidota and specifically unclassified Bacteroidales and unclassified Oscillospiraceae decreased. Following probiotic supplementation with the S. cerevisiae-based complex, gut microbiota modulation led to a significant boost in circulating levels of calcium, copper, selenium, and zinc. Creatinine levels decreased while total cholesterol levels increased within normal limits in the serum analysis. Conclusion: The observed improvement in trace elements and minerals in dairy cows might be due to changes in intestinal microflora caused by supplementation. Therefore, probiotic supplementation in cattle may be considered a potential tool for improvement of mineral nutrition in cattle. However, the influence of probiotic treatment and modulation of mineral metabolism on milk productivity and overall performance in cattle is yet to be estimated. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a pathological state that involves the dysregulation of different metabolic pathways and adipose tissue cells, constituting a risk factor for the development of other diseases. Bariatric surgery is the most effective treatment. The study of the behavior of pollutants in situations of extreme weight loss can provide biomonitoring information and tools to manage diseases of environmental etiology. Aim: To determine the prevalence of serum persistent and non-persistent pollutants in obese patients subjected to bariatric surgery and analyze the impact of sociodemographic variables on these changes. Methods: GC-MS/MS and UHPLC-MS/MS were utilized to determine the detection rates and concentrations of 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticide, in serum samples of 59 obese patients before and after undergoing bariatric surgery. Results: Detection rates of p,p'-DDE, HCB, β-HCH, naphthalene, phenanthrene and PCB congeners 138, 153 and 180 significantly increased due to surgery-induced weight loss. Serum levels of p,p'-DDE, PCB-138, PCB-153 and PCB-180 also increased after surgery. Correlations between naphthalene levels, weight loss, variation of total lipids and time after surgery were found. Additionally, correlations were observed between concentrations of PCB-138 and weight loss, and between phenanthrene levels and reduction of total lipids. No statistically significant differences were observed for other groups of contaminants, pharmaceuticals and other chemicals included in the quantification methods. Conclusions: Increment of POPs was observed after bariatric surgery. Serum concentrations of POPs after surgery were influenced by adiposity-related variables. Although biomonitoring studies show a decreasing tendency of exposure, rapid weight loss leads to an increase of circulating POPs. Further research on the interplay between adipose tissue, POPs and peripheral organs is required. [ABSTRACT FROM AUTHOR]

Zinc (Zn) and copper (Cu) are common contaminants of inland water bodies under severe anthropogenic pressure. The main aim of this study was to test the influence of environmental aqueous concentrations of Zn and Cu on the fitness-related life history traits of the cosmopolitan freshwater ostracod Heterocypris incongruens. Overall, eight subchronic laboratory experiments were conducted to test the effects of exposure to two Cu (260 and 460 µg Cu L−1) and Zn (230 and 410 µg Zn L−1) concentrations compared to the control conditions using asexual individuals originating from a wild population and from a commercial toxicity test (Ostracodtoxkit f). The response of ostracods to exposure to Zn and Cu differed considerably. The Cu treatments significantly reduced the total hatching success and hatching dynamics of resting eggs, increased the mortality of juveniles and reduced the survival of adults, dramatically decreasing the fitness of ostracods. On the other hand, the Zn treatments were less harmful and did not affect adult survival or the timing of juvenile hatching from subitaneous eggs but extended the timing of laying eggs at lower concentrations and stimulated hatching dynamics and success at higher concentrations. It seems that the increased Zn body burden did not strongly impact the fitness of the studied specimens. Moreover, the different responses of the laboratory and wild populations in the Zn experiments may suggest a genetic variation in the tolerance of ostracods to metals. Therefore, experiments involving laboratory H. incongruens as analogues of wild ostracods should be cautiously interpreted. We concluded that the major toxicant in our study was Cu, while Zn could be considered a micronutrient even supporting ostracod fitness, although its higher levels are likely to exert strong toxic effects. [ABSTRACT FROM AUTHOR]

Nanomaterials (NMs) are in high demand for a wide range of practical applications; however, comprehensively understanding the toxicity of these materials is a complex challenge, due to the limited availability of epidemiological evidence on the human health effects arising from workplace exposures. The aim of this work is to assess whether and how urinary metal concentrations could be reliable and useful in NM biomonitoring. In the framework of "NanoExplore Project" [EU LIFE17 Grant ENV/GR/000285], 43 not-exposed subjects and 40 exposed workers were recruited to measure exposure to NMs (PCN and LDSA) in the proximity of the workstations and biological biomarkers (urinary metal concentrations—Aluminum (Al), Silica (Si), Titanium (Ti), and Chromium (Cr); urinary OS biomarkers—TAP, Isop, and MDA). The results showed that Si and Ti were directly associated with NM exposure (both PCN and LDSA), as well as with OS biomarkers, especially in exposed workers. Moreover, the mediation analyses showed that Si could account for about 2.8% in the relationship between LDSA and OS biomarkers, possibly by decreasing OS antioxidant defenses in exposed people. In conclusion, our study provides evidence that occupational exposure to mixtures containing NMs can represent an underestimated hazard for exposed people, increasing the body burden and the oxidative balance. [ABSTRACT FROM AUTHOR]

Purpose: Adding organic soil amendments, like animal manure, can alleviate the mobility of lead (Pb). However, there is a scarcity of in vivo studies examining the impact of animal manure as a soil amendment on mammals. Methods: Six C57BL/6 mice per group were raised for 30 and 98 days on soil containing 3000 mg Pb/kg. On Pb-spiked soil, chicken manure (40 t/ha) was applied as an immobilizer. Pb concentrations in the tissues were analyzed using ICP-MS after microwave digestion. RT-PCR was used to measure the mRNA expression of antioxidant and cell apoptosis genes in the liver, kidneys, and brain. Results: When chicken manure was used as the immobilizer in Pb-spiked soil, Pb concentrations in the brain, kidneys, and lungs at day 30 were significantly different (p < 0.05) with reduction percentages of 28.58, 26.63, and 25.62, respectively. The brain, kidneys, liver, and bone, except for the lungs and trachea, also showed a similar reducing phenomenon on day 98, with percentages of 11.82, 4.63, 29.87, and 14.54, respectively. There was a significant difference in the levels of Nrf2, HMOX1, SOD1, CAT, BCL2, and Bax in the brain between Pb-exposed and remediated groups after 98 days of exposure. Conclusions: This study highlights that the utilization of chicken manure reduced Pb accumulation in tissues (6.25–28.58% at 30 days and 4.63–29.87% at 98 days). This reduction in Pb accumulation subsequently alleviated the body burden by activating antioxidant genes in the brain, notably HMOX1, SOD1, and CAT. [ABSTRACT FROM AUTHOR]

Benzotriazole ultraviolet (UV) stabilizers (BUVSs) are used in great quantities during industrial production of a variety of consumer and industrial goods. As a result of leaching and spill, BUVSs are detectable ubiquitously in the environment. As of May 2023, citing concerns related to bioaccumulation, biomagnification, and environmental persistence, (B)UV(S)‐328 was recommended to be listed under Annex A of the Stockholm Convention on Persistent Organic Pollutants. However, a phaseout of UV‐328 could result in a regrettable substitution because the replacement chemical(s) could cause similar or unpredicted toxicity in vivo, relative to UV‐328. Therefore, the influence of UV‐327, a potential replacement of UV‐328, was investigated with respect to early life development of newly fertilized rainbow trout embryos (Oncorhynchus mykiss), microinjected with environmentally relevant concentrations of UV‐327. Developmental parameters (standard length), energy consumption (yolk area), heart function, blue sac disease, mortality, and behavior were investigated. Alevins at 14 days posthatching, exposed to 107 ng UV‐327 g−1 egg, presented significant signs of hyperactivity; they moved on average 1.8‐fold the distance and at 1.5‐fold the velocity of controls. Although a substantial reduction in body burden of UV‐327 was observed at hatching, it is postulated that UV‐327, due to its lipophilic properties, interfered with neurological development and signaling from the onset of neurogenesis. If these results hold true across multiple taxa and species, a potential contributor to neurodevelopmental disorders might have been identified. These findings suggest that UV‐327 poses an unknown hazard to rainbow trout embryos and alevins, rendering UV‐327 a potential regrettable substitution to UV‐328. However, a qualified statement on a regrettable substitution requires a comparative investigation on the teratogenic effects between the two BUVSs. Environ Toxicol Chem 2024;43:762–771. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a metal with no nutritional value or physiological role. However, it is found in the body of most people because it is a contaminant of nearly all food types and is readily absorbed. The body burden of Cd is determined principally by its intestinal absorption rate as there is no mechanism for its elimination. Most acquired Cd accumulates within the kidney tubular cells, where its levels increase through to the age of 50 years but decline thereafter due to its release into the urine as the injured tubular cells die. This is associated with progressive kidney disease, which is signified by a sustained decline in the estimated glomerular filtration rate (eGFR) and albuminuria. Generally, reductions in eGFR after Cd exposure are irreversible, and are likely to decline further towards kidney failure if exposure persists. There is no evidence that the elimination of current environmental exposure can reverse these effects and no theoretical reason to believe that such a reversal is possible. This review aims to provide an update on urinary and blood Cd levels that were found to be associated with GFR loss and albuminuria in the general populations. A special emphasis is placed on the mechanisms underlying albumin excretion in Cd-exposed persons, and for an accurate measure of the doses–response relationships between Cd exposure and eGFR, its excretion rate must be normalised to creatinine clearance. The difficult challenge of establishing realistic Cd exposure guidelines such that human health is protected, is discussed. [ABSTRACT FROM AUTHOR]

This article analyzes nail technicians' occupational health experiences using body and hazard mapping – a visual, low-cost, and worker-centred approach. Thirty-seven Toronto-based nail technicians from predominantly Vietnamese, Chinese, and Korean communities identified various occupational illnesses, injuries, and symptoms on visual representations of human bodies (body mapping) and linked these to their hazard sources in the nail salon (hazard mapping). The impacts identified include musculoskeletal aches and pains, stress and mental health concerns, various symptoms linked to chemical exposure, and concerns about cancer and reproductive health. Rather than a conventional occupational health approach, this work draws on Vanessa Agard-Jones' expansion of the "body burden" as more than the bioaccumulation of chemical agents. As such, this article asserts that nail technicians' body burden encompasses various types of occupational illnesses and injuries. In addition, nail technicians are exposed to broader "toxic" systemic inequities and structural conditions that allow these workplace exposures to occur and persist. By illustrating the embodied and experiential knowledges of nail technicians and contextualizing this lived experience, the body and hazard maps illuminate vast layers of harm – or multiscalar toxicities – borne by nail technicians. Moreover, as a group-based method, body and hazard mapping allow collective reflection and can spur worker mobilization toward safer and fairer nail salons. [ABSTRACT FROM AUTHOR]

Gases from the breath exhalation can be used for the detection and estimation of associated contaminant in the human body. For the estimation of 226Ra body burden through the analyses of radon (222Rn) in the exhaled breath, similar technique has been considered for uranium miners in India. Initial experiments for Jaduguda underground uranium mine workers were based on qualitative approach due to the limitations of the sensitivity of the then available techniques. The inert gas 222Rn after its formation is soluble in the blood, may escape from the human body like other dissolved gases at lung/blood interface which can be removed through exhalation. Using a sensitive device that can effectively analyze the low activity concentration of radon, 226Ra body burden of the uranium miner can be estimated. The working principle, description and utility of the device as well as estimated 226Ra body burden are provided in the paper. Examination results of 244 subjects of uranium mines have shown a variation in the radium (226Ra) body burden from 0.54 to 3.75 kBq. The inexpensive technique can effectively be used in the field conditions due to high sensitivity, portability, low sampling time and minimal instrumentation requirements. [ABSTRACT FROM AUTHOR]

Although extensive research has been carried out on the occurrence of mercury (Hg) in biota, bioaccumulation and tissue distribution of Hg in songbirds have not been well characterized. In the present study, Hg was investigated in insects and barn swallows (Hirundo rustica) to explore the bioaccumulation characteristics of Hg. Hg in swallow feathers and tissues including muscle, liver, and bone was investigated to determine the tissue distribution of Hg. The concentrations of Hg were 1.39 ± 1.01 μg/g, 0.33 ± 0.09 μg/g, 0.47 ± 0.10 μg/g, and 0.23 ± 0.09 μg/g in feather, muscle, liver, and bone samples, respectively. The trophic magnification factor of Hg in swallows and insects was higher than 1. However, the Hg concentrations in swallow feathers were not significantly correlated with stable isotope values of carbon or nitrogen, which implies the complex food sources and exposure processes of Hg for swallows. Feathers had significantly higher concentrations of Hg than liver, muscle, and bone samples (p < 0.01 for all comparisons). Feather, muscle, bone, and other organs had fractions of 64.4 ± 11.9%, 6.07 ± 2.06%, 20.0 ± 8.19%, and 9.56 ± 2.96% in total body burden of Hg in swallows. Hg in feathers contributed more than half of Hg in the whole body for most swallow individuals. Swallows may efficiently eliminate Hg by molting, and the excretion flux of Hg and other contaminants via molting deserves more investigation. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is an environmental toxicant of worldwide public health significance. Diet is the main non-workplace Cd exposure source other than passive and active smoking. The intestinal absorption of Cd involves transporters for essential metals, notably iron and zinc. These transporters determine the Cd body burden because only a minuscule amount of Cd can be excreted each day. The International Agency for Research on Cancer listed Cd as a human lung carcinogen, but the current evidence suggests that the effects of Cd on cancer risk extend beyond the lung. A two-year bioassay demonstrated that Cd caused neoplasms in multiple tissues of mice. Also, several non-tumorigenic human cells transformed to malignant cells when they were exposed to a sublethal dose of Cd for a prolonged time. Cd does not directly damage DNA, but it influences gene expression through interactions with essential metals and various proteins. The present review highlights the epidemiological studies that connect an enhanced risk of various neoplastic diseases to chronic exposure to environmental Cd. Special emphasis is given to the impact of body iron stores on the absorption of Cd, and its implications for breast cancer prevention in highly susceptible groups of women. Resistance to cell death and other cancer phenotypes acquired during Cd-induced cancer cell transformation, under in vitro conditions, are briefly discussed. The potential role for the ZnT1 efflux transporter in the cellular acquisition of tolerance to Cd cytotoxicity is highlighted. [ABSTRACT FROM AUTHOR]

The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE‐28, ‐47, ‐49, ‐99, ‐100, ‐138, ‐153, ‐154, ‐183 and ‑209. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners (BDE‐47, ‐99, ‐153, ‐209) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint‐specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a pervasive toxic metal, present in most food types, cigarette smoke, and air. Most cells in the body will assimilate Cd, as its charge and ionic radius are similar to the essential metals, iron, zinc, and calcium (Fe, Zn, and Ca). Cd preferentially accumulates in the proximal tubular epithelium of the kidney, and is excreted in urine when these cells die. Thus, excretion of Cd reflects renal accumulation (body burden) and the current toxicity of Cd. The kidney is the only organ other than liver that produces and releases glucose into the circulation. Also, the kidney is responsible for filtration and the re-absorption of glucose. Cd is the least recognized diabetogenic substance although research performed in the 1980s demonstrated the diabetogenic effects of chronic oral Cd administration in neonatal rats. Approximately 10% of the global population are now living with diabetes and over 80% of these are overweight or obese. This association has fueled an intense search for any exogenous chemicals and lifestyle factors that could induce excessive weight gain. However, whilst epidemiological studies have clearly linked diabetes to Cd exposure, this appears to be independent of adiposity. This review highlights Cd exposure sources and levels associated with diabetes type 2 and the mechanisms by which Cd disrupts glucose metabolism. Special emphasis is on roles of the liver and kidney, and cellular stress responses and defenses, involving heme oxygenase-1 and -2 (HO-1 and HO-2). From heme degradation, both HO-1 and HO-2 release Fe, carbon monoxide, and a precursor substrate for producing a potent antioxidant, bilirubin. HO-2 appears to have also anti-diabetic and anti-obese actions. In old age, HO-2 deficient mice display a symptomatic spectrum of human diabetes, including hyperglycemia, insulin resistance, increased fat deposition, and hypertension. [ABSTRACT FROM AUTHOR]

Mercury is a ubiquitous environmental contaminant and can be found in inorganic (Hg0, Hg+ and Hg2+) and organic forms (chiefly CH3Hg+ or MeHg+). The main route of human, mammals and bird exposure occurs via predatory fish ingestion. Occupational exposure to Hg0 (and Hg2+) can also occur; furthermore, in gold mining areas the exposure to inorganic Hg can also be high. The toxicity of electrophilic forms of Hg (E+Hg) is mediated by disruption of thiol (-SH)- or selenol (-SeH)-containing proteins. The therapeutic approaches to treat methylmercury (MeHg+), Hg0 and Hg2+ are limited. Here we discuss the potential use of ebselen as a potential therapeutic agent to lower the body burden of Hg in man. Ebselen is a safe drug for humans and has been tested in clinical trials (for instance, brain ischemia, noise-induce hearing loss, diabetes complications, bipolar disorders) at doses varying from 400 to 3600 mg per day. Two clinical trials with ebselen in moderate and severe COVID are also approved. Ebselen can be metabolized to an intermediate with -SeH (selenol) functional group, which has a greater affinity to electrophilic Hg (E+Hg) forms than the available thiol-containing therapeutic agents. Accordingly, as observed in vitro and rodent models in vivo, Ebselen exhibited protective effects against MeHg+, indicating its potential as a therapeutic agent to treat MeHg+ overexposure. The combined use of ebselen with thiol-containing molecules (e.g. N-acetylcysteine and enaramide)) is also commented, because they can have synergistic protective effects against MeHg+. [ABSTRACT FROM AUTHOR]

Concentrations of selenium that exceed regulatory guidelines have been associated with coal mining activities and have been linked to detrimental effects on aquatic ecosystems and the organisms therein. Although the major route of selenium uptake in macroinvertebrates is via the diet, the uptake of waterborne selenite (HSeO3−), the prominent form at circumneutral pH, can be an important contributor to selenium body burden and thus selenium toxicity. In the current study, radiolabelled selenite (Se75) was used to characterize the mechanism of selenite uptake in the water flea, Daphnia magna. The concentration dependence (1–32 μM) of selenite uptake was determined in 1-hour uptake assays in artificial waters that independently varied in bicarbonate, chloride, sulphate, phosphate and selenate concentrations. At concentrations representative of those found in highly contaminated waters, selenite uptake was phosphate-dependent and inhibited by foscarnet, a phosphate transport inhibitor. At higher concentrations, selenite uptake was dependent on waterborne bicarbonate concentration and inhibited by the bicarbonate transporter inhibitor DIDS (4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid). These findings suggest that concentrations of phosphate in coal mining-affected waters could alter selenite uptake in aquatic organisms and could ultimately affect the toxic impacts of selenium in such waters. [ABSTRACT FROM AUTHOR]

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This paper reviewed various studies on the effects of endocrine disruptors on human health, focusing on accelerated aging in the younger generation. In particular, we analyzed how the modern lifestyle and ignorance of endocrine disruptors in the younger generation are accelerating aging, and how the concentration of endocrine disruptor exposure in the human body affects the body's burden. Based on existing papers, we conducted a systematic review using Web of Science, Google Scholar, and Scopus to comprehensively investigate and summarize the definition of endocrine disruptors, their effects on hormones, and the physical burden of continuous exposure to endocrine disruptors. Research has shown that persistent exposure to endocrine disruptors disrupts homeostasis in the body and creates oxidative stress that can lead to aging and chronic inflammation. These characteristics were also found to be significant in the observation of telomere length, which is a measure of aging. Therefore, in order to prevent accelerated aging in the younger generation, we can suggest ways to minimize exposure to endocrine disruptors and slow down normal aging in the entire public health, including the 3040s, in the long term. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic compounds (PACs) present in the water column are considered to be one of the primary contaminant groups contributing to the toxicity of a crude oil spill. Because crude oil is a complex mixture composed of thousands of different compounds, oil spill models rely on quantitative structure–activity relationships like the target lipid model to predict the effects of crude oil exposure on aquatic life. These models rely on input provided by single species toxicity studies, which remain insufficient. Although the toxicity of select PACs has been well studied, there is little data available for many, including transformation products such as oxidized hydrocarbons. In addition, the effect of environmental influencing factors such as temperature on PAC toxicity is a wide data gap. In response to these needs, in the present study, Stage I lobster larvae were exposed to six different understudied PACs (naphthalene, fluorenone, methylnaphthalene, phenanthrene, dibenzothiophene, and fluoranthene) at three different relevant temperatures (10, 15, and 20 °C) all within the biological norms for the species during summer when larval releases occur. Lobster larvae were assessed for immobilization as a sublethal effect and mortality following 3, 6, 12, 24, and 48 h of exposure. Higher temperatures increased the rate at which immobilization and mortality were observed for each of the compounds tested and also altered the predicted critical target lipid body burden, incipient median lethal concentration, and elimination rate. Our results demonstrate that temperature has an important influence on PAC toxicity for this species and provides critical data for oil spill modeling. More studies are needed so oil spill models can be appropriately calibrated and to improve their predictive ability. Environ Toxicol Chem 2023;42:2389–2399. © 2023 SETAC [ABSTRACT FROM AUTHOR]

The rapid trend of industrialization and urbanization can lead to greater exposure of the general population to chromium, cobalt, and nickel. Their total body burden from all routes of recent exposure, as well as interindividual variability in exposure levels, metabolism, and excretion rates, are reflected in the blood metal concentrations. The main goals in this study were as follows: observing the reference levels of chromium, cobalt, and nickel in the blood of the population living in Belgrade, identification of individual and sociodemographic factors that most affect their blood levels, and comprehension of recent exposure to chromium, cobalt, and nickel. Blood was sampled from 984 participants, voluntary blood donors, who agreed to participate in this study. Individual and sociodemographic data were collected using questionnaire adapted for different subpopulations. Blood metal analyses were measured using ICP-MS method (7700×, Agilent, USA). Our study provided reference values of chromium, cobalt, and nickel in blood for adult population (18–65 years) and confirmed that blood cobalt and nickel levels were mostly influenced by age and gender, and age, respectively. Furthermore, weight status affected blood chromium and cobalt levels, while national origin affected blood chromium levels. The present study highlighted the importance of human biomonitoring studies to monitor exposure status and identify subpopulations with increased exposure to chromium, cobalt, and nickel. [ABSTRACT FROM AUTHOR]

Guiyu has been one of the world's largest destinations for electronic waste (e-waste) recycling for decades. The recyling process in Guiyu relied on informal and family-based activities, which have led to severe environmental pollution and associated extensive health problems. This review examines the connections between exposure to persistent organic pollutants (POPs) and health outcomes, particularly in neonates, children and pregnant women. The residents in Guiyu exhibit high levels of contamination from POPs, especially PBDEs, PAHs and PCBs. Excessive exposure to these compounds have been associated with multi-system and long-term effects in children, changes in gestational age in pregnant mothers, and adverse birth outcomes in neonates. The findings raise concerns about the impact of POPs stemming from e-waste recycling on human health, and contribute to a better understanding of the need for monitoring sources, distribution, and effects of e-waste related-POPs in other regions of China and similar sites worldwide. Highlights: Guiyu is infamous for its involvement in primitive e-waste recycling processes. Elevated human body burden of PBDEs, PAHs, PCBs and PFOA in Guiyu residents. POPs exposure has adverse effects on multiple organ systems of neonates and children. The review highlights strong regulations should be organized to address the problems. [ABSTRACT FROM AUTHOR]

Honey bees (Apis mellifera L.) are important ecological and agricultural resources. They are among the most widely available pollinators and provide products as well as services. Unfortunately, honey bee populations are susceptible to several environmental threats, including heavy metal exposure. Honey bees can be exposed to heavy metals when foraging on contaminated honey and pollen resources, and in some cases by airborne exposure. We studied the joint acute and chronic effects of cadmium (Cd) and copper (Cu) on A. mellifera. A 1:1 solution of the two heavy metals increased larval developmental duration and the mortality of both larvae and foragers in a dose-dependent way, decreased forager feeding, increased body metal burdens, and disrupted the sucrose response behavior of foragers. In combination, Cd and Cu demonstrated a weakly synergistic effect on foragers, but for larvae an initially antagonistic effect at low doses changed to strongly synergistic response at higher concentrations. The sucrose response threshold of foragers decreased significantly when they were dosed with increasing concentrations of the metal mixtures. Overall, the fitness of honey bee larvae and foragers is detrimentally affected when these metals co-occur.

ObjectiveTo investigate the association between APOE genotype and β-amyloid (Aβ) burden, as measured by PET in patients with subcortical vascular cognitive impairment (SVCI) and those with Alzheimer disease-related cognitive impairment (ADCI).MethodsThis was a cross-sectional study of 310 patients with SVCI and 999 with ADCI. To evaluate the effects of APOE genotype or diagnostic group on Aβ positivity, we performed multivariate logistic regression analyses. Further distinctive underlying features of latent subgroups were examined by employing a latent class cluster analysis approach.ResultsIn comparison with ε3 homozygotes, in the ADCI group, ε2 carriers showed a lower frequency of Aβ positivity (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.23-0.79), while in the SVCI group, ε2 carriers showed a higher frequency of Aβ positivity (OR 2.26, 95% CI 1.02-5.01). In particular, we observed an interaction effect of ε2 carrier status and diagnostic group on Aβ positivity (OR 5.12, 95% CI 1.93-13.56), in that relative to ε3 homozygotes, there were more Aβ-positive ε2 carriers in the SVCI group than in the ADCI group. We also identified latent subgroups of Aβ-positive APOE ε2 carriers with SVCI and Aβ-positive APOE ε4 carriers with ADCI.ConclusionsOur findings suggest that APOE ε2 is distinctly associated with Aβ deposition in patients with SVCI and those with ADCI. Our findings further suggest that there is a distinctive subgroup of Aβ-positive APOE ε2 carriers with SVCI among patients with cognitive impairment.

Background/objectiveHuman exposure to per- and polyfluoroalkyl substances (PFAS) has changed since the early 2000s, in part, because of the phase-out and replacement of some long-chain PFAS. Studies of PFAS exposure and its temporal changes have been limited to date mostly to adults and pregnant women. We examined temporal trends and determinants of PFAS serum concentrations among mothers with a young child who participated in the CHARGE (CHildhood Autism Risk from Genetics and Environment) case-control study.MethodsWe quantified nine PFAS in serum samples collected from 2009 to 2016 in 450 Northern California mothers when their child was 2-5 years old. With five compounds that were detected in more than 50% of the samples, we performed multiple regression to estimate least square geometric means (LSGMs) of PFAS concentrations with adjustment for sampling year and other characteristics that may affect maternal concentrations (e.g., breastfeeding duration). We also used time-related regression coefficients to calculate percent changes over the study period.ResultsLSGM concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) decreased over the study period [percent change (95% confidence interval): -10.7% (-12.7%, -8.7%); -10.8% (-12.9%, -8.5%); -8.0% (-10.5%, -5.5%), respectively]. On the other hand, perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) showed mixed time trends. Among the selected covariates, longer breastfeeding duration was associated with decreased maternal serum concentrations of PFOA, PFOS, PFHxS, PFNA and PFDA.ConclusionsOur study demonstrated that body burden of some common long-chain PFAS among California mothers with a young child decreased over the study period and that breastfeeding appears to contribute to the elimination of PFAS in lactating mothers.

Modern nano-engineered pesticides have great promise for agriculture due to their extended, low dose release profiles that are intended to increase effectiveness but reduce environmental harm. Whether nanopesticides, including copper (Cu) formulations, cause reduced levels of toxicity to non-target aquatic organisms is unclear but important to assess. Predicting how aquatic species respond to incidental exposure to Cu-based nanopesticides is challenging because of the expected very low concentrations in the environment, and the two forms of exposure that may occur, namely to Cu ions and Cu nanoparticles. We conducted Cu speciation, tissue uptake, and 7-day toxicity laboratory experiments to test how a model estuarine organism, the amphipod Leptocheirus plumulosus, responded to two popular Cu-based nanopesticides, CuPRO and Kocide, and conventional CuCl2. Exposure concentrations ranged from 0 to 2.5 ppm, which were similar to those found in estuarine water located downstream of agricultural fields. Cu dissolution rates were much slower for the nanopesticides than the ionic formula, and Cu body burden in amphipods increased approximately linearly with the nominal exposure concentration. Amphipod survival declined in a normal dose-response manner with no difference among Cu formulations. Growth and movement rates after 7 days revealed no difference among exposure levels when analyzed with conventional statistical methods. By contrast, analysis of respiration rates, inferred from biomass measurements, with a bioenergetic toxicodynamic model indicated potential for population-level effects of exposure to very low-levels of the two nanopesticides, as well as the control contaminant CuCl2. Our results indicate that toxicity assessment of environmental trace pollutant concentrations may go undetected with traditional ecotoxicological tests. We present a process integrating toxicity test results and toxicodynamic modeling that can improve our capacity to detect and predict environmental impacts of very low levels of nanomaterials released into the environment.

BackgroundCadmium (Cd) is a developmental toxicant that is released into the environment during industrial processes. Previous animal studies suggest that Cd may impact the onset of puberty.ObjectivesTo determine whether Cd exposure, measured as urinary Cd concentration, was associated with ages at menarche and pubertal development.MethodsA cohort of 211 girls, ages 10-13 years at baseline, was followed for up to two years. Girls completed an interview and self-assessment of Tanner stages of breast development and pubic hair growth. They were followed monthly until menarche. Urinary Cd concentrations were measured in overnight urine specimens. Multivariable Cox regression was used to evaluate the association between urinary Cd and age at menarche and cumulative logit regression was used to evaluate the associations between urinary Cd and breast development and pubic hair growth.ResultsThe baseline geometric mean creatinine-adjusted Cd concentration was 0.22 μg/g creatinine (geometric standard deviation = 1.6) and decreased with increasing age (p-trend = 0.04). Cd levels were higher among Asian than White girls or girls of other/mixed race/ethnicity (p = 0.04). In multivariable analyses, girls with urinary Cd ≥ 0.4 μg/L were less likely to have attained menarche than girls with urinary Cd

Metalaxyl (MET) and myclobutanil (MYC) are two widely used chiral fungicides that may pose health risks to non-occupationally exposed populations. Here, the two fungicides were enantiomer-specific quantified in the dietary food and urine of residents in an Eastern China city, to determine the exposure and excretion of these contaminants in different populations. Results indicate that residues of MET and MYC varied with different food items at 0.42–0.86 ng/g fresh weight (FW) and 0.18–0.33 ng/g FW, respectively. In urine samples, the residual levels after creatinine adjusting (CR) ranged from 10.2 to 1715.4 ng/g CR for MET and were below the detection limit up to 320.7 ng/g CR for MYC. Significant age- and gender-related differences were separately found in urinary MET and MYC of different populations. Monte-Carlo simulations suggested that children had higher daily dietary intake (DDI) but lower urinary excretion (DUE) rates than youths, and thus may suffer higher body burdens. The residues of antifungally ineffective enantiomers (S-MET and R-MYC) were slightly higher than their antipodes in foods. Moreover, the enantiomer-selective urinary excretion resulted in higher retention of S-MET and R-MYC in the human body. Our results suggest that both dietary intake and urinary excretion should be enantiomer-specifically considered when assessing the exposure risk and body burden of chiral fungicides in the non-occupationally exposed population. Furthermore, substitutive application of enantiomer-enriched fungicide formulations can not only benefit the antifungal efficacy but also be safer for human health.

Despite limited biomonitoring studies suggesting extensive antibiotic exposure in general population, the body burden of antibiotics in young children and their potential health risks remain unclear. To assess the antibiotic exposure levels in young children, 508 preschoolers aged 3–6 years were recruited from eastern China in 2022, and a total of 50 representative antibiotics from 8 categories, including 17 human antibiotics (HAs), 4 antibiotics preferred as HAs (PHAs), 16 veterinary antibiotics (VAs), and 13 antibiotics preferred as VAs (PVAs), were analyzed by UPLC-MS/MS. Hazard quotient (HQ) and hazard index (HI) were calculated to evaluate the health risks, and multivariate logistic regression was applied to examine diet with antibiotic exposure. Our results showed that there were 41 antibiotics detected in children's urine, and the overall detection frequency was as high as 100%. Sulfonamides, macrolides, β-lactams, quinolones, and azoles were the predominant categories of antibiotic detected. Among the studied children, 6.5% had a sum of estimated daily intake (EDI) of all VAs and PVAs larger than 1 μg/kg/day. Notably, 10.0% of the children had a microbiological HI value exceeding 1, primarily contributed by ciprofloxacin. Children with higher consumption of seafood had a relatively increased exposure to multiple categories of antibiotics, including HAs, VAs, quinolones, azoles, and others. Principal component analysis suggested that "Aquatic products and viscera preferred dietary pattern" scores were positively correlated with the exposure levels of ciprofloxacin (OR: 1.23; 95% CI: 1.02–1.47) and carbadox (OR: 1.32; 95% CI: 1.10–1.59), and a relatively increased exposure of PHAs was realized in children with higher "Meat-egg preferred dietary pattern" scores (OR: 1.24; 95% CI: 1.03–1.50). In conclusion, there was a widespread exposure to antibiotics among preschool children from eastern China, and children who consumed more animal-derived foods may had an increased exposure to antibiotics. [ABSTRACT FROM AUTHOR]

Exposure to BTEX has been suggested to be a potential risk factor for asthma,[[1], [3]] a heterogeneous disease with unclear etiology, but its individual risk for adult asthma and its phenotypic clusters remains unclear. An hourly grid-scale model was utilized to estimate the residence-based ambient air BTEX levels and the time-lag effect (lag-0, lag-1, lag-2, lag-3, lag-4, and lag-5) on the daily asthma ERVs and outpatient visits. Abbreviations 2,4-DPMA N -acetyl- S -(2,4-dimethylbenzene)- l -cysteine 4-HNE 4-hydroxynonenal BMA N -acetyl- S -(benzyl)- l -cysteine BTEX benzene, toluene, ethylbenzene, and xylene C1P ceramide-1-phosphate ERV emergency room visit HEL N -(hexanoyl)-lysine LC-MS liquid chromatography-tandem mass spectrometry NHIRD National Health Insurance Research Database PGA phenylglyoxylic acid PMA N -acetyl- S -phenyl- l -cysteine RR relative risk S1P sphingosine-1-phosphate SL sphingolipid VOCs volatile organic compounds In a combined population-based and case-control study, exposure to benzene, toluene, ethylbenzene, and xylene (BTEX), particularly benzene, concomitant with increased oxidative stress and sphingolipid dysregulation, posed a significant, but differential, risk for current asthma, its severity, and phenotypic clusters. [Extracted from the article]

The excretion of β2-microglobulin (β2M) above 300 µg/g creatinine, termed tubulopathy, was regarded as the critical effect of chronic exposure to the metal pollutant cadmium (Cd). However, current evidence suggests that Cd may induce nephron atrophy, resulting in a reduction in the estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. Herein, these pathologies were investigated in relation to Cd exposure, smoking, diabetes, and hypertension. The data were collected from 448 residents of Cd-polluted and non-polluted regions of Thailand. The body burden of Cd, indicated by the mean Cd excretion (ECd), normalized to creatinine clearance (Ccr) as (ECd/Ccr) × 100 in women and men did not differ (3.21 vs. 3.12 µg/L filtrate). After adjustment of the confounding factors, the prevalence odds ratio (POR) for tubulopathy and a reduced eGFR were increased by 1.9-fold and 3.2-fold for every 10-fold rise in the Cd body burden. In women only, a dose–effect relationship was seen between β2M excretion (Eβ2M/Ccr) and ECd/Ccr (F = 3.431, η2 0.021). In men, Eβ2M/Ccr was associated with diabetes (β = 0.279). In both genders, the eGFR was inversely associated with Eβ2M/Ccr. The respective covariate-adjusted mean eGFR values were 16.5 and 12.3 mL/min/1.73 m2 lower in women and men who had severe tubulopathy ((Eβ2M/Ccr) × 100 ≥ 1000 µg/L filtrate). These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of Eβ2M/Ccr could be attributable mostly to Cd-induced impairment in the tubular reabsorption of the protein together with Cd-induced nephron loss, which is evident from an inverse relationship between Eβ2M/Ccr and the eGFR. [ABSTRACT FROM AUTHOR]

Acetochlor is a chloroacetanilide selective pre-emergent herbicide used for controlling grass and broadleaf weeds in crops. This study compared the acetochlor exposures of backpack and tractor sprayers and assessed whether dermal or air exposures were more important contributors to the overall body burden as measured by urinary metabolites. Sixty sugarcane farmers in Nakhonsawan province, Thailand participated in the study, and breathing zone air and dermal patch samples were collected during spraying. Urine samples were collected before spraying, at the end of the spraying task, and on the day after spraying. For backpack and tractor sprayers, there was no significant difference in their breathing zone air concentrations, total body dermal samples, or urinary 2-methy-6-methyaniline (EMA) concentrations on the day after spraying. In addition, although most backpack and tractor sprayers wore long pants and long sleeve shirts, they were still exposed to acetochlor, as evidenced by a significant increase in the urinary EMA from before spraying (GM = 11.5 µg/g creatinine) to after spraying (GM = 88.5 µg/g creatinine) to the next day (GM = 111.0 µg/g creatinine). Breathing zone air samples were significantly correlated with those of total body dermal patch samples and with urinary EMA concentrations after spraying. This suggests that both air and dermal exposure contribute to urinary EMA levels. [ABSTRACT FROM AUTHOR]

In determining the so-called "body burden", hair has been widely accepted for assessing toxic element exposure. However, its role in assessing essential elements is controversial. This study investigates the possible relationship between hair minerals, metabolic syndrome (MetS) and cardiovascular (CV) risk in non-occupationally exposed subjects with overweight–obesity. Ninety-five voluntary participants (aged 51 ± 12) were recruited in Northern Italy. Hair samples were collected and analysed via inductively coupled plasma mass spectrometry; the total toxicity index (TI) was calculated as well. To evaluate cardiovascular risk factors in the presence or absence of MetS, the following factors were considered via the innovative artificial neural network (ANN) method Auto-CM: hair mineralograms (31 elements) and 25 variables including blood pressure, anthropometric parameters, insulin resistance and biochemical serum markers assessing inflammation. The Framingham risk score, fatty liver index (FLI), visceral adiposity index and CV risk scores were also taken into consideration. As shown by the semantic map, which was subsequently confirmed by an activation and competition system (ACS), obesity parameters are strictly associated with CV risk factors, TI and inflammation; meanwhile, the single mineral elements seem to be unimportant. Data obtained via ANN demonstrate that MetS may be at least partly mediated by altered mineral levels also in the presence of obesity and that waist circumference is a crucial point to be monitored rather than BMI alone. Furthermore, the mineral body burden is one of the important factors for CV risk. [ABSTRACT FROM AUTHOR]

Nanomaterials (NMs) are in high demand for a wide range of practical applications; however, comprehensively understanding the toxicity of these materials is a complex challenge, due to the limited availability of epidemiological evidence on the human health effects arising from workplace exposures. The aim of this work is to assess whether and how urinary metal concentrations could be reliable and useful in NM biomonitoring. In the framework of “NanoExplore Project” [EU LIFE17 Grant ENV/GR/000285], 43 not-exposed subjects and 40 exposed workers were recruited to measure exposure to NMs (PCN and LDSA) in the proximity of the workstations and biological biomarkers (urinary metal concentrations—Aluminum (Al), Silica (Si), Titanium (Ti), and Chromium (Cr); urinary OS biomarkers—TAP, Isop, and MDA). The results showed that Si and Ti were directly associated with NM exposure (both PCN and LDSA), as well as with OS biomarkers, especially in exposed workers. Moreover, the mediation analyses showed that Si could account for about 2.8% in the relationship between LDSA and OS biomarkers, possibly by decreasing OS antioxidant defenses in exposed people. In conclusion, our study provides evidence that occupational exposure to mixtures containing NMs can represent an underestimated hazard for exposed people, increasing the body burden and the oxidative balance.

BackgroundModel-based compartmental analysis has been used to describe and quantify whole-body vitamin A metabolism and estimate total body stores (TBS) in animals and humans.ObjectivesWe applied compartmental modeling and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines.MethodsChildren ingested [13C10]retinyl acetate and 1 or 2 blood samples were collected from each child from 6 h to 28 d after dosing. Temporal data for fraction of dose in plasma [13C10]retinol were modeled using WinSAAM software and a 6-component model with vitamin A intake included as weighted data.ResultsModel-predicted TBS was 198, 533, and 1062 μmol for the Bangladeshi (age, 9-17 mo), Filipino (12-18 mo), and Guatemalan children (35-65 mo). Retinol kinetics were similar for Filipino and Guatemalan groups and generally faster for Bangladeshi children, although fractional transfer of plasma retinol to a larger exchangeable storage pool was the same for the 3 groups. Recycling to plasma from that pool was ∼2.5 times faster in the Bangladeshi children compared with the other groups and the recycling number was 2-3 times greater. Differences in kinetics between groups are likely related to differences in vitamin A stores and intakes (geometric means: 352, 727, and 764 μg retinol activity equivalents/d for the Bangladeshi, Filipino, and Guatemalan children, respectively).ConclusionsBy collecting 1 or 2 blood samples from each child to generate a composite plasma tracer data set with a minimum of 5 children/time, group TBS and retinol kinetics can be estimated in children by compartmental analysis; inclusion of vitamin A intake data increases confidence in model predictions. The super-child modeling approach is an effective technique for comparing vitamin A status among children from different populations. These trials were registered at www.clinicaltrials.gov as NCT03000543 (Bangladesh), NCT03345147 (Guatemala), and NCT03030339 (Philippines).

Kidney disease associated with chronic cadmium (Cd) exposure is primarily due to proximal tubule cell damage. This results in a sustained decline in glomerular filtration rate (GFR) and tubular proteinuria. Similarly, diabetic kidney disease (DKD) is marked by albuminuria and a declining GFR and both may eventually lead to kidney failure. The progression to kidney disease in diabetics exposed to Cd has rarely been reported. Herein, we assessed Cd exposure and the severity of tubular proteinuria and albuminuria in 88 diabetics and 88 controls, matched by age, gender and locality. The overall mean blood and Cd excretion normalized to creatinine clearance (Ccr) as ECd/Ccr were 0.59 µg/L and 0.0084 µg/L filtrate (0.96 µg/g creatinine), respectively. Tubular dysfunction, assessed by β2-microglobulin excretion rate normalized to Ccr(Eβ2M/Ccr) was associated with both diabetes and Cd exposure. Doubling of Cd body burden, hypertension and a reduced estimated GFR (eGFR) increased the risks for a severe tubular dysfunction by 1.3-fold, 2.6-fold, and 84-fold, respectively. Albuminuria did not show a significant association with ECd/Ccr, but hypertension and eGFR did. Hypertension and a reduced eGFR were associated with a 3-fold and 4-fold increases in risk of albuminuria. These findings suggest that even low levels of Cd exposure exacerbate progression of kidney disease in diabetics. [ABSTRACT FROM AUTHOR]

Organofluorines occur in human serum as complex mixtures of known and unidentified compounds. Human biomonitoring traditionally uses targeted analysis to measure the presence of known and quantifiable per- and polyfluoroalkyl substances (PFAS) in serum, yet characterization of exposure to and quantification of PFAS are limited by the availability of methods and analytical standards. Studies comparing extractable organofluorine (EOF) in serum to measured PFAS using organofluorine mass balance show that measurable PFAS only explain a fraction of EOF in human serum and that other sources of organofluorine may exist. The gap in fluorine mass balance has important implications for human biomonitoring because the total body burden of PFAS cannot be characterized and the chemical species that make up unidentified EOF are unknown. Many highly prescribed pharmaceuticals contain organofluorine (e.g., Lipitor, Prozac) and are prescribed with dosing regimens designed to maintain a therapeutic range of concentrations in serum. Therefore, we hypothesize organofluorine pharmaceuticals contribute to EOF in serum. We use combustion ion chromatography to measure EOF in commercial serum from U.S. blood donors. Using fluorine mass balance, we assess differences in unexplained organofluorine (UOF) associated with pharmaceutical use and compare them with concentrations of organofluorine predicted based on the pharmacokinetic properties of each drug. Pharmacokinetic estimates of organofluorine attributable to pharmaceuticals ranged from 0.1 to 55.6 ng F/mL. Analysis of 44 target PFAS and EOF in samples of commercial serum (n = 20) shows the fraction of EOF not explained by Σ44 PFAS ranged from 15% to 86%. Self-reported use of organofluorine pharmaceuticals is associated with a 0.36 ng F/mL (95% CL: −1.26 to 1.97) increase in UOF, on average, compared to those who report not taking organofluorine pharmaceuticals. Our study is the first to assess sources of UOF in U.S. serum and examine whether organofluorine pharmaceuticals contribute to EOF. Discrepancies between pharmacokinetic estimates and EOF may be partly explained by differences in analytical measurements. Future analyses using EOF should consider multiple extraction methods to include cations and zwitterions. Whether organofluorine pharmaceuticals are classified as PFAS depends on the definition of PFAS. [ABSTRACT FROM AUTHOR]

Chemical mixture risk assessment has, in the past, primarily focused on exposures quantified in the external environment. Assessing health risks using human biomonitoring (HBM) data provides information on the internal concentration, from which a dose can be derived, of chemicals to which human populations are exposed. This study describes a proof of concept for conducting mixture risk assessment with HBM data, using the population-representative German Environmental Survey (GerES) V as a case study. We first attempted to identify groups of correlated biomarkers (also known as 'communities', reflecting co-occurrence patterns of chemicals) using a network analysis approach (n = 515 individuals) on 51 chemical substances in urine. The underlying question is whether the combined body burden of multiple chemicals is of potential health concern. If so, subsequent questions are which chemicals and which co-occurrence patterns are driving the potential health risks. To address this, a biomonitoring hazard index was developed by summing over hazard quotients, where each biomarker concentration was weighted (divided) by the associated HBM health-based guidance value (HBM-HBGV, HBM value or equivalent). Altogether, for 17 out of the 51 substances, health-based guidance values were available. If the hazard index was higher than 1, then the community was considered of potential health concern and should be evaluated further. Overall, seven communities were identified in the GerES V data. Of the five mixture communities where a hazard index was calculated, the highest hazard community contained N-Acetyl-S-(2-carbamoyl-ethyl)cysteine (AAMA), but this was the only biomarker for which a guidance value was available. Of the other four communities, one included the phthalate metabolites mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) with high hazard quotients, which led to hazard indices that exceed the value of one in 5.8% of the participants included in the GerES V study. This biological index method can put forward communities of co-occurrence patterns of chemicals on a population level that need further assessment in toxicology or health effects studies. Future mixture risk assessment using HBM data will benefit from additional HBM health-based guidance values based on population studies. Additionally, accounting for different biomonitoring matrices would provide a wider range of exposures. Future hazard index analyses could also take a common mode of action approach, rather than the more agnostic and non-specific approach we have taken in this proof of concept. [ABSTRACT FROM AUTHOR]

The global prevalence of diabetes, and its major complication, diabetic nephropathy, have reached epidemic proportions. The toxic metal cadmium (Cd) also induces nephropathy, indicated by a sustained reduction in the estimated glomerular filtration rate (eGFR) and the excretion of β2-microglobulin (β2M) above 300 µg/day, which reflects kidney tubular dysfunction. However, little is known about the nephrotoxicity of Cd in the diabetic population. Here, we compared Cd exposure, eGFR, and tubular dysfunction in both diabetics (n = 81) and non-diabetics (n = 593) who were residents in low- and high-Cd exposure areas of Thailand. We normalized the Cd and β2M excretion rates (ECd and Eβ2M) to creatinine clearance (Ccr) as ECd/Ccr and Eβ2M/Ccr. Tubular dysfunction and a reduced eGFR were, respectively, 8.7-fold (p < 0.001) and 3-fold (p = 0.012) more prevalent in the diabetic than the non-diabetic groups. The doubling of ECd/Ccr increased the prevalence odds ratios for a reduced eGFR and tubular dysfunction by 50% (p < 0.001) and 15% (p = 0.002), respectively. In a regression model analysis of diabetics from the low-exposure locality, Eβ2M/Ccr was associated with ECd/Ccr (β = 0.375, p = 0.001) and obesity (β = 0.273, p = 0.015). In the non-diabetic group, Eβ2M/Ccr was associated with age (β = 0.458, p < 0.001) and ECd/Ccr (β = 0.269, p < 0.001). However, after adjustment for age, and body mass index (BMI), Eβ2M/Ccr was higher in the diabetics than non-diabetics of similar ECd/Ccr ranges. Thus, tubular dysfunction was more severe in diabetics than non-diabetics of similar age, BMI, and Cd body burden. [ABSTRACT FROM AUTHOR]

Inhalation exposure to cadmium at the workplace has been associated with an increased risk of lung cancer and non-cancer respiratory effects. To ensure levels of cadmium remain below effect levels, air quality is monitored and regulations specifying an air limit value are implemented. The EU Carcinogens and Mutagens Directive of 2019 recommended values for the inhalable fraction and the respirable fraction but the latter only for a transitional period. Cadmium exposure has also been associated with systemic effects, following its storage in the kidneys and due to its long half-life. The accumulation of cadmium occurs via different exposure routes and from different sources, including workplace dust and fumes, food, and smoking. Biomonitoring (in blood, urine) has been identified as the most appropriate method to follow up cumulative exposure and total cadmium body burden, as it conveniently reflects intakes by all routes. However, it is not systematically implemented. This paper has a double objective: first, proposing a possible limit value for the respirable fraction, using an approach integrating epidemiological data. Secondly, demonstrating that the implementation of both air and biological limit values is key to protecting workers' health in occupational settings. The paper summarizes the current knowledge on cadmium health effects and how biomarkers reflect those. It presents an approach to derive a respirable value, using recent human data, and describes how the combination of air monitoring and biomonitoring is applied by the EU industry to protect the workforce. While a respirable fraction value helps protect workers against local respiratory adverse health effects, air monitoring alone is not sufficient to protect workers against systemic effects of cadmium. Therefore, complementary biomonitoring and the implementation of a biological limit value is recommended. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are industrial products extensively used in the past. Because of their widespread presence and toxic effects, the international community adopted control measures to reduce their release into the environment. Currently, PCB concentrations are decreasing, but humans are still exposed. In this paper, we reported the results of a study concerning PCB concentrations in human serum samples collected in Italy over two decades. The aim of the study was to investigate the trend of major determinants of PCB human exposure, several decades after the end of their production. PCB concentrations ranged over three orders of magnitude (from 0.4 to 958 ng/g lipid), with a median value of 85 ng/g lipid. We identified age, sampling year, body mass index, sex, and living near hot spots or being occupationally exposed as relevant factors in determining body burden. Our results can give indications to refine regulatory policies on PCBs in Italy, with particular attention to the disposal of residue PCB-containing products. To improve control measures can further decrease the exposure of citizens to PCBs, limit health implications, and improve citizens' perception about chemical risk management. [ABSTRACT FROM AUTHOR]

Hair may be a potential biospecimen to discover biomarkers for Alzheimer's disease (AD) since it reflects the integral metabolic profiles of body burden over several months. Here, we described the AD biomarker discovery in the hair using a high-resolution mass spectrometry (HRMS)-based untargeted metabolomics approach. A total of 24 patients with AD and 24 age- and sex-matched cognitively healthy controls were recruited. The hair samples were collected 0.1-cm away from the scalp and further cut into 3-cm segments. Hair metabolites were extracted by ultrasonication with methanol/phosphate-buffered saline 50/50 (v/v) for 4 h. A total of 25 discriminatory chemicals in hair between the patients with AD and controls were discovered and identified. The AUC value achieved 0.85 (95% CI: 0.72~0.97) in patients with very mild AD compared to healthy controls using a composite panel of the 9 biomarker candidates, indicating high potential for the initiation or promotion phase of AD dementia in the early stage. A metabolic panel combined with the nine metabolites may be used as biomarkers for the early detection of AD. The hair metabolome can be used to reveal metabolic perturbations for biomarker discovery. Investigating perturbations of the metabolites will offer insight into the pathogenesis of AD. [ABSTRACT FROM AUTHOR]