Low-level Lead Research Articles

Blood pressure and renal function responses in workers exposed to lead for up to six years

Abstract Background Lead is a widespread environmental toxicant. However, there is currently no consensus whether low-level lead exposure raises blood pressure (BP) or induces kidney dysfunction. Purpose The Study for Promotion of Health in Recycling Lead (SPHERL) assessed the BP and renal function (RF) responses for up to six years in the workers without previous occupational lead exposure. Methods BP was the average of 5 consecutive readings and the estimated glomerular filtration rate was derived from serum creatinine (eGFRcrt) and cystatin C (eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 mg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis. Results The 234 workers analyzed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 µg/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92-6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p≥0.51 and p≥0.18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were -0.25/-0.12 mm Hg (CI: -0.94 to 0.44/-0.66 to 0.42 mm Hg). Accordingly, the incidence of stage-1 or -2 hypertension was not associated with the BL change (p≥0.063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 3-fold BL increment were not significant, amounting to -0.70 mL/min/1.73 m2(CI: -1.70 to 0.30 mL/min/1.73 m2) and -1.06 ml/min/1.73 m2 (-2.16 to 0.03 mL/min/1.73 m2). Conclusion The BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.Figure 1Figure 2

Selenium-containing peptides as effective alleviators for low-level lead induced neural damage

The TSeMMM and SeMDPGQQ, two selenium-containing peptides derived from Se-enriched rice protein hydrolysates, have previously been demonstrated to show neuroprotective properties against high-dose lead exposure. However, the potential toxicological effects of these functional peptides on low-dose lead-induced neurotoxicity remain poorly understood. The present study aimed to investigate the protective mechanism of two selenium-containing peptides in mitigating low-dose Pb2+-induced damage in HT22 cells. Results showed that treatment with 40 μmol/L Pb2+ significantly reduced cell viability and increased apoptosis, both of which were alleviated by 40 μmol/L TSeMMM and SeMDPGQQ treatment. Furthermore, two peptides exhibited antioxidant potentials by reducing reactive oxygen species levels to 32.19% and 79.29% of the model group, respectively. They also enhanced antioxidant enzyme activities and mitigated oxidative stress through activation of the Keap1/Nrf2 pathway. Additionally, two peptides improved mitochondrial function by elevating mitochondrial membrane potential, ATP production while dramatically reducing reactive oxygen species levels. Interestingly, TSeMMM exhibited superior neurointerventional effects compared to SeMDPGQQ. The RNA sequencing analysis revealed that TSeMMM modulated gene expressions related to oxidative stress and neuroprotective function. The study provides insights into the protective mechanism underlying selenium-containing peptides for mitigating neuronal damage.

Assessment of Lead and Iron Concentration in Cosmetics Traded in the AL-Ajilat City Market

This study examined the concentrations of heavy metals, namely lead (Pb) and iron (Fe), in lipsticks, foundations, and face powders to ensure compliance with international safety standards and assess potential health risks. Using atomic absorption spectroscopy (AAS), samples were analyzed for heavy metal content and compared to WHO, FDA, and Health Canada guidelines. Results included that lead levels in lipsticks ranged from 0.03 to 6.15 ppm, with one sample exceeding the WHO limit of 0.01 ppm, raising safety concerns. Iron levels were alarmingly high, with a maximum of 2,566 ppm, well above the WHO guideline of 0.3 ppm. Baseline samples consistently showed low levels of lead at 0.03 ppm, but iron concentrations reached 5,735 ppm, indicating significant safety deviations. Lead concentrations in the face powders ranged from 0.03 to 2.14 ppm, with some exceeding the WHO limit, while iron levels averaged 2,613 ppm, well above acceptable limits. The study concluded that high iron levels in these cosmetic products pose health risks, stressing the need for stricter regulatory oversight and quality control in the cosmetics industry.

Lead Poisoning in a Mother and Her Four Children Using a Traditional Eye Cosmetic - New York City, 2012-2023.

Even low levels of lead in children's blood are associated with developmental delays, difficulty learning, and behavioral issues. Adults are also vulnerable to the detrimental health effects of lead exposure. The New York City (NYC) Department of Health and Mental Hygiene receives blood lead test results for NYC residents and conducts investigations of lead poisoning cases. Blood lead testing of a child aged 4 years in 2012 led to the discovery of blood lead levels above the CDC blood lead reference value of 3.5 μg/dL in the child as well as four other family members over a period of 11 years, including the child's mother and three younger siblings born during 2012-2016. The only potential source of lead exposure identified for all cases was the use of surma, a traditional eye cosmetic, which was found to contain 390,000 ppm lead. The cases in this report highlight the challenges of risk communication when deeply ingrained cultural practices, such as the use of surma, persist despite health warnings. Moreover, they highlight the intergenerational nature of such practices and the need for comprehensive family follow-up once a member is identified as being at risk. These products continue to be available globally, even in places such as the United States where sales are prohibited. Multistakeholder efforts involving local and global engagement could promote reformulation of these products at the countries of origin to eliminate lead as an ingredient.

Non-Invasive Raman Classification Comparison with pXRF of Monochrome and Related Qing Porcelains: Lead-Rich-, Lead-Poor-, and Alkali-Based Glazes.

Chinese porcelain with an optically clear colored glaze, imported to Europe from the Kangxi period (1662-1722, Qing Dynasty) onwards was highly collected by the French Elite of the 18th century. The bright colors with a clear, shiny glaze were unlike anything produced in Europe at that time. The colors of enamelled artifacts (on biscuits or already glazed porcelain) can be fully monochrome or consist of associations of large monochromatic areas with or without application of gilding. Non-invasive portable XRF and mobile Raman analyses have previously shown their effectiveness in the characterization of (colored) glassy silicates. In this study, we compare the Raman signatures of twenty-one Chinese artifacts fully-or with major monochrome area (sancai)-decorated with blue, turquoise (or celectian blue), honey-yellow, green, eggplant, and red color. Different types of glazes are identified and confirmed by pXRF: lead-rich, lead-poor-alkali, lead-doped alkali, and alkali-based compositions. However, an unexpected low level of lead is observed in the turquoise glazes, likely to optimize the gloss. Raman spectroscopy appears more reliable to compare the Pb content than pXRF. This work presents Raman spectral signatures of glazes that can potentially be used for non-invasive object classification and counterfeit detection.

Pb Pollution Stress in Alnus cremastogyne Monitored by Antioxidant Enzymes

Lead (Pb) is a common toxic heavy metal element that can be absorbed by plant roots and enter the food chain, damaging human health. Alnus cremastogyne has a wide native range, is fast growing, has a wide range of timber uses, and has rhizomatous roots that can improve planted soils. In this study, we evaluated whether Alnus cremastogyne has the potential to remediate Pb-contaminated soils through a 6-month pot experiment in soils with different Pb concentrations (0, 50, 100, 200, and 400 mg/kg). Our results indicate that Alnus cremastogyne plant height, basal diameter, and organ biomass decreased, H2O2 and MDA content increased, and the activities of antioxidant enzymes and osmotic regulators increased and then decreased with increasing lead concentrations. The Pb bioconcentration factor of Alnus cremastogyne was less than 1 at all Pb concentrations, and Pb accumulated mainly in the root system. This indicates that Alnus cremastogyne is not a Pb-enriched plant and does not have outstanding Pb transport capacity. The growth of Alnus cremastogyne was not significantly affected at low Pb concentrations, and its plant height, basal diameter, and biomass were significantly suppressed under high Pb stress. Therefore, Alnus cremastogyne is not a suitable species for the remediation of lead-contaminated soils but can be used as a silvicultural species in environments with low lead levels.

Research for the Common Good: Unreliable Lead-Free Marketing for Tableware

Tableware often contains glazes that may contain lead and other toxins. Inadequate firing processes can result in lead seepage into food, posing health risks upon ingestion. 1. Besides glaze, the ceramic material itself may contain heavy metals, such as lead. Even exposure to very low levels of lead can significantly impact childhood IQ, which has been a public issue since the 1960s. Near-zero levels of exposure to toxins are essential to protect public health. 2. Health organizations have published recommended “safe” levels of lead and other toxins. For example, California Proposition 65: <0.1 ppm; Massachusetts 105 CMR 460.200 Lead Poisoning and Control: <2 ppm; Food and Drug Administration (FDA): <0.5 ppm for mugs. In this study, ceramic cups specifically advertised as lead- and cadmium-free were tested. While the primary goal was to verify the legitimacy of lead- and cadmium-free advertisements as an educational service to consumers, levels of chromium and zinc were also tested. Specifically, the level of toxins within the ceramic, the amount of toxins leaching into the consumable liquids, and changes in leached levels over time were investigated. Samples were examined by using Inductively Coupled Plasma (ICP) analysis. Our findings show a wide range of toxin exposure, indicating that the marketing is false.

Lead exposure and source attribution for a mammalian scavenger before and after a culling program

Lead-based ammunition is a significant source of environmental lead and threatens species that scavenge lead-shot carcasses, particularly in areas with intensive shooting. With the impacts of lead on avian scavengers well established, there is increasing focus on the effects of lead on mammalian scavengers. We investigated lead exposure in a morphologically specialized mammalian scavenger, the Tasmanian devil (Sarcophilus harrisii), by analyzing their blood lead levels (BLLs) before and after a marsupial culling program using linear mixed effects models. We compared lead isotope signatures in devil blood to those in the culling ammunition to inform potential source attributions. We sampled 23 devils before culling and 15 after culling, finding no significant difference in mean BLLs pre and post-culling. However, devils captured closer to forestry coupes where culling had occurred had higher BLLs, and a greater proportion of devils displayed elevated BLLs post-culling (33 % compared to 18 % pre-culling). The highest BLL (7.93 μg/dL) was found in a devil post-culling and this individual had lead isotope signatures that matched the ammunition samples analyzed, suggesting the individual was exposed to lead from scavenging on culled carcasses. While 18 % of the devil blood lead samples had isotope signatures consistent with the ammunition samples, most were measurably different, indicating other sources of lead in the landscape. BLLs in our study landscape were similar to published BLLs for wild devils across Tasmania. That said, lead isotope signatures in the blood of individual devils sampled both before and after culling shifted closer to those of ammunition samples post-culling. Our results indicate that while some individual devils may have been exposed to lead from culling, most devils in the landscape did not show evidence of recent exposure. However, even low lead levels can adversely impact wildlife health and immunity, a particular concern for devils, a species endangered by disease.

Assessment of urban air quality in Abidjan in terms of trace metals (copper, lead, zinc) by arborescent vegetation: Case of the species Hibiscus tiliaceus rubra.

Urban air quality is closely linked to human activities. Policies aimed at reducing or monitoring this form of pollution therefore have a dual benefit for health and the environment. Biomonitoring of air quality is one possible scientific approach. In this study, the woody species Hibiscus tiliaceus rubra was used as a biomonitor of air quality in the city of Abidjan. The leaves of the woody species were used to quantify the bioaccumulation of three trace metals: copper, lead and zinc. The assessment was carried out on five main road sections: "Adjamé-Cocody", " Adjamé-Yopougon", "Cocody-Bingerville", abobo-Anyama” and " Adjamé-Plateau". The results obtained show that the content of these trace metals varies according to the road. High levels of copper and zinc and very low levels of lead were initially found in the leaves of the species. The Adjamé-Cocody axis and the Adjamé-Yopougon axis recorded the highest levels of lead. The Adjamé-Plateau axis remains the least contaminated, with relatively low levels of lead.

Evaluating metal cookware as a source of lead exposure.

We previously demonstrated that aluminum cookware brought from Afghanistan by resettled families as well as some aluminum cookware available for purchase in the United States represent a previously unrecognized source of lead exposure. However, the extent to which this cookware represents a source of lead exposure to other United States residents is unclear. To test additional cookware for lead content and its propensity to leach lead and other toxic metals. This will further our understanding of the extent to which this cookware represents a lead poisoning risk in the United States and elsewhere. We screened an additional 28 pieces of aluminum cookware and 5 brass items for lead content using an X-ray fluorescence (XRF) analyzer and used our leachate method to estimate the amount of lead that migrates into food. We also tested 17 additional stainless steel items to determine whether they would be safer alternatives. Many aluminum cookware products contained in excess of 100 parts per million (ppm) of lead. Many also leached enough lead under simulated cooking and storage conditions to exceed recommended dietary limits. One hindalium appam pan (an Indian frying pan/wok) leached sufficient lead to exceed the childhood limit by 1400-fold. Brass cookpots from India also yielded high lead levels, with one exceeding the childhood limit by over 1200-fold. In contrast, stainless steel cookware leached much lower levels of lead. Aluminum and brass cookware available for purchase in the United States represents a previously unrecognized source of lead exposure.

Quality Evaluation, health risk Assessment, and geographic origin tracing of Ophiocordyceps sinensis through mineral element analysis

Ophiocordyceps sinensis (OS) is a unique and precious medicinal fungus endemic to the Tibetan Plateau, growing underground for the majority of its lifecycle. The mineral composition of OS is a distinctive feature, yet there is currently a lack of comprehensive mineral profiles. The concerns regarding excessive heavy metals and associated health risks significantly impact the development of the OS industry. Furthermore, OS samples from various production areas exhibit distinct qualities, resulting in significant price differences. Mineral profiles hold great potential for origin tracing. Consequently, there is an urgent need for quality evaluation, health risk assessment, and geographic origin tracing of OS by mineral element analysis. Here, 96 OS samples were collected from the representative producing areas in China to investigate their mineral profiles by inductively coupled plasma-optical emission spectrometry (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS). Potassium (K) was found to be the most abundant mineral in the OS samples, with a mean content of 10.73 g/kg. High levels of phosphor (P), sulfur (S) and magnesium (Mg) were also detected with concentrations exceeding 1 g/kg. The mean concentrations of total arsenic in all OS samples were determined to be 8.33 mg/kg. The OS from Nagqu exhibited a relatively high quality with lower levels of lead (Pb), cadmium (Cd) and arsenic. Health risk assessment based on the total target hazard quotient (THQ) value of heavy metals of Zn, Mn, Fe, copper (Cu), nickel (Ni), chromium (Cr), Pb and Cd indicated that consumption of OS from China did not pose an obvious risk to human health at the ingestion rate declared by the Chinese Pharmacopeia. Finally, three orthogonal partial least squares discriminant analysis (OPLS-DA) models were constructed using 75 samples to trace the geographic origins. These models successfully authenticated OS samples from six producing areas and confirmed by 21 blind test samples with 90.48 % accuracy. These results affirmed that OS from different regions possessed distinct metal profiles, which could be utilized to authenticate the geographic origins of O. sinensis.

Multiple prenatal exposures and acute-care clinical encounters for asthma among children born to mothers living near a Superfund site.

Prenatal exposures are associated with childhood asthma, and risk may increase with simultaneous exposures. Pregnant women living in lower-income communities tend to have elevated exposures to a range of potential asthma risk factors, which may interact in complex ways. We examined the association between prenatal exposures and the risk of childhood acute-care clinical encounters for asthma (hospitalizations, emergency department visits, observational stays) using conditional logistic regression with a multivariable smoothing term to model the interaction between continuous variables, adjusted for maternal characteristics and stratified by sex. All births near the New Bedford Harbor (NBH) Superfund site (2000-2006) in New Bedford, Massachusetts, were followed through 2011 using the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System to identify children aged 5-11 years with acute-care clinical asthma encounters (265 cases among 7787 children with follow-up). Hazard ratios (HRs) were higher for children living closer to the NBH site with higher umbilical cord blood lead levels than in children living further away from the NBH site with lower lead levels (P<.001). HRs were higher for girls (HR=4.17; 95% CI, 3.60-4.82) than for boys (HR=1.72; 95% CI, 1.46-2.02). Our results suggest that prenatal lead exposure in combination with residential proximity to the NBH Superfund site is associated with childhood asthma acute-care clinical encounters. This article is part of a Special Collection on Environmental Epidemiology.

Gender-Specific Effects on the Cardiorespiratory System and Neurotoxicity of Intermittent and Permanent Low-Level Lead Exposures.

Lead exposure is a significant health concern, ranking among the top 10 most harmful substances for humans. There are no safe levels of lead exposure, and it affects multiple body systems, especially the cardiovascular and neurological systems, leading to problems such as hypertension, heart disease, cognitive deficits, and developmental delays, particularly in children. Gender differences are a crucial factor, with women's reproductive systems being especially vulnerable, resulting in fertility issues, pregnancy complications, miscarriages, and premature births. The globalization of lead exposure presents new challenges in managing this issue. Therefore, understanding the gender-specific implications is essential for developing effective treatments and public health strategies to mitigate the impact of lead-related health problems. This study examined the effects of intermittent and permanent lead exposure on both male and female animals, assessing behaviours like anxiety, locomotor activity, and long-term memory, as well as molecular changes related to astrogliosis. Additionally, physiological and autonomic evaluations were performed, focusing on baro- and chemoreceptor reflexes. The study's findings revealed that permanent lead exposure has more severe health consequences, including hypertension, anxiety, and reactive astrogliosis, affecting both genders. However, males exhibit greater cognitive, behavioural, and respiratory changes, while females are more susceptible to chemoreflex hypersensitivity. In contrast, intermittent lead exposure leads to hypertension and reactive astrogliosis in both genders. Still, females are more vulnerable to cognitive impairment, increased respiratory frequency, and chemoreflex hypersensitivity, while males show more reactive astrocytes in the hippocampus. Overall, this research emphasizes the importance of not only investigating different types of lead exposure but also considering gender differences in toxicity when addressing this public health concern.

Reductions in spice lead levels in the republic of Georgia: 2020–2022

Spice adulteration using yellow lead chromate-based pigments has been documented as a growing global health concern. Spices from the Republic of Georgia with extremely high levels of lead, up to an order of magnitude higher than any other spices worldwide, have been implicated as sources of child lead poisoning. The objectives of this study were to 1) evaluate lead concentrations in spices sampled across the country of Georgia between 2020 and 2022, and 2) assess factors associated with spice adulteration, specifically the role of spice quality and regulatory enforcement. Spice samples were collected from 29 cities nationwide. The most populous cities were selected in each administrative region as well as those of importance to the spice supply chain. Sampling was carried out at the largest spice bazaars in each city. The regions of Adjara and Imereti were the focus of qualitative interviews conducted in 2021 with key businesspeople selling spices with very high and low levels of lead. The same cities and bazaars were visited at each of three sampling periods between 2020 and 2022. In total, 765 spice samples were collected. Lead concentrations in spices decreased over time, with a maximum of 14,233 μg/g in 2020 down to 36 μg/g in the final sampling round of 2022. A logistic regression determined that sampling round, region and spice type were associated with elevated lead in samples. Samples from Adjara and those containing marigold had the highest lead levels. Interviews with eighteen prominent spice vendors revealed difficulties sourcing sufficient quantities of high quality, brightly colored marigold, and concerns about adulteration. Interviews with two authorities from the National Food Authority highlighted the increased attention on regulating lead in spices since 2018. Continued monitoring and periodic regulatory enforcement may adequately disincentivize further adulteration with lead chromate in the spice industry in Georgia.

Effects of chronic low-level lead (Pb) exposure on cognitive function and hippocampal neuronal ferroptosis: An integrative approach using bioinformatics analysis, machine learning, and experimental validation

Lead (Pb), a pervasive and ancient toxic heavy metal, continues to pose significant neurological health risks, particularly in regions such as Southeast Asia. While previous research has primarily focused on the adverse effects of acute, high-level lead exposure on neurological systems, studies on the impacts of chronic, low-level exposure are less extensive, especially regarding the precise mechanisms linking ferroptosis — a novel type of neuron cell death — with cognitive impairment. This study aims to explore the potential effects of chronic low-level lead exposure on cognitive function and hippocampal neuronal ferroptosis. This research represents the first comprehensive investigation into the impact of chronic low-level lead exposure on hippocampal neuronal ferroptosis, spanning clinical settings, bioinformatic analyses, and experimental validation. Our findings reveal significant alterations in the expression of genes associated with iron metabolism and Nrf2-dependent ferroptosis following lead exposure, as evidenced by comparing gene expression in the peripheral blood of lead-acid battery workers and workers without lead exposure. Furthermore, our in vitro and in vivo experimental results strongly suggest that lead exposure may precipitate cognitive dysfunction and induce hippocampal neuronal ferroptosis. In conclusion, our study indicates that chronic low-level lead exposure may activate microglia, leading to the promotion of ferroptosis in hippocampal neurons.

Maternal prenatal lead levels and neonatal brain volumes: Testing moderations by maternal depressive symptoms and family income

There is considerable evidence that prenatal lead exposure is detrimental to child cognitive and socio-emotional development. Further evidence suggests that the effects of prenatal lead on developmental outcomes may be conditional upon exposure to social stressors, such as maternal depression and low socioeconomic status. However, no studies have examined associations between these co-occurring stressors during pregnancy and neonatal brain volumes. Leveraging a sample of 101 mother-infant dyads followed beginning in mid-pregnancy, we examined the main effects of prenatal urinary lead levels on neonatal lateralized brain volumes (left and right hippocampus, amygdala, cerebellum, frontal lobes) and total gray matter. We additionally tested for moderations between lead and depressive symptoms and between lead and family income relative to the federal poverty level (FPL) on the same neurodevelopmental outcomes. Analyses of main effects indicated that prenatal lead was significantly (ps < 0.05) associated with reduced right and left amygdala volumes (βs = −0.23- -0.20). The testing and probing of cross-product interaction terms using simple slopes indicated that the negative effect of lead on the left amygdala was conditional upon mothers having low depressive symptoms or high income relative to the FPL. We interpret the results in the context of trajectories of prenatal and postnatal brain development and susceptibility to low levels of prenatal lead in the context of other social stressors.

Genetic susceptibility to low-level lead exposure in men: Insights from ALAD polymorphisms

The genetic susceptibility to low-level lead (Pb) exposure in general populations has been poorly investigated and is limited to the single nucleotide polymorphism (SNP) rs1800435 in the delta-aminolevulinic acid dehydratase gene (ALAD). This study explored associations between ten selected ALAD SNPs with Pb concentrations in blood (BPb) and urine (UPb) among 281 men aged 18–49 years from Slovenia, including 20 individuals residing in a Pb-contaminated area. The geometric mean (range) of BPb and UPb were 19.6 (3.86–84.7) μg/L and 0.69 (0.09–3.82) μg/L SG, respectively. The possible genetic influence was assessed by examining SNP haplotypes, individual SNPs, and the combination of two SNPs using multiple linear regression analyses. While no significant associations were found for haplotypes, the presence of variant alleles of rs1800435 and rs1805312 resulted in an 11% and 13% decrease in BPb, respectively, while the presence of variant allele of rs1139488 (homozygous only) exhibited significant 20% increase in BPb, respectively. Additionally, variant allele of rs1800435 resulted in lower UPb. Individual SNPs in the model explained only around 1 additional percentage point of BPb variability. In contrast, combination analyses identified six combinations of two SNPs, which significantly explained 3–22 additional percentage points of BPb variability, with the highest explanatory power observed for the rs1800435-rs1139488 and rs1139488-rs1805313 combinations. Moreover, excluding participants from the Pb-contaminated area indicated that exposure level influenced SNPs-Pb associations.Our results confirm the importance of the ALAD gene in Pb kinetics even at low exposure levels. Additionally, we demonstrated that identifying individuals with specific combinations of ALAD SNPs explained a larger part of Pb variability, suggesting that these combinations, pending confirmation in other populations and further evaluation through mechanistic studies, may serve as superior susceptibility biomarker in Pb exposure compared to individual SNPs.

Transcriptomic and behavioral analyses reveal unique target tissues and molecular pathways associated with embryonic exposure to low level glyphosate and metal mixtures in zebrafish

Investigation of developmental molecular events following exposure to environmentally relevant agrochemical mixtures is critical to predicting their potential long-term ecological and human health risks. Here, we sought to uncover transcriptomic changes during zebrafish (Danio rerio) embryonic development following exposure to glyphosate and co-exposure to metals. Glyphosate is widely used globally with an allowable drinking water limit of 700 ppb. We examined effects of glyphosate (10 ppb) alone and when co-exposed to a metal mixture containing low levels of arsenic (4 ppb), lead (5 ppb), cadmium (2 ppb), and vanadium (15 ppb). This mixture was derived based on behavioral and morphological toxicity findings and environmentally relevant concentrations found in agricultural regions where glyphosate and metals are ubiquitously present. Gene expression patterns coupled to a single-cell transcriptomic dataset revealed that developmental exposure (28–72 h post fertilization) to glyphosate dysregulates expression of developmental genes specific to the central nervous system. Subsequent studies indicated significant suppression of larval zebrafish movement with 10 ppb glyphosate exposure. Studies with glyphosate + metals mixture and metals mixture alone showed unique developmental transcriptomic patterns and behavioral changes compared to glyphosate exposure alone. However, some outcomes (e.g., changes in expression of genes involved in epigenetic regulation and extracellular matrix patterning) were common across all three exposures compared to the control. Notably, glyphosate + metals co-exposure distinctly suppresses lysosomal transcripts and targets renal developmental genes. While further studies are required to uncover the precise nature of the interactions between glyphosate and metals, our study shows that glyphosate at very low levels is a behavioral and neurotoxicant that changes when metals are present. Given this herbicide affects distinctive physiological processes, including renal development and lysosomal dysregulation when co-exposed with metals, we conclude that environmental cation levels should be considered in glyphosate toxicity and risk assessment.

Maternal suboptimal selenium intake and low-level lead exposure affect offspring’s microglial immune profile and its reactivity to a subsequent inflammatory hit

Micronutrients such as selenium (Se) are essentials since prenatal life to support brain and cognitive development. Se deficiency, which affects up to 1 billion people worldwide, can interact with common adverse environmental challenges including (Pb), exacerbating their toxic effects. Exploiting our recently validated rat model of maternal Se restriction and developmental low Pb exposure, our aims were to investigate: (i) the early consequences of suboptimal Se intake and low-Pb exposure on neuroinflammation in neonates’ whole brains; (ii) the potential priming effect of suboptimal Se and low-Pb exposure on offspring’s glial reactivity to a further inflammatory hit. To these aims female rats were fed with suboptimal (0.04 mg/kg; Subopt) and optimal (0.15 mg/kg; Opt) Se dietary levels throughout pregnancy and lactation and exposed or not to environmentally relevant Pb dose in drinking water (12.5 µg/mL) since 4 weeks pre-mating. We found an overall higher basal expression of inflammatory markers in neonatal brains, as well as in purified microglia and organotypic hippocampal slice cultures, from the Subopt Se offspring. Subopt/Pb cultures were highly activated than Subopt cultures and showed a higher susceptibility to the inflammatory challenge lipopolysaccharide than cultures from the Opt groups. We demonstrate that even a mild Se deficiency and low-Pb exposure during brain development can influence the neuroinflammatory tone of microglia, exacerbate the toxic effects of Pb and prime microglial reactivity to subsequent inflammatory stimuli. These neuroinflammatory changes may be responsible, at least in part, for adverse neurodevelopmental outcomes.

Change of the retinoic acid pathway in hypothalamus and pituitary damage induced by combined exposure to low-level Pb~(2+) and 1-nitropyrene in mice

To observe the expression of the retinoic acid(RA) pathway in hypothalamus and pituitary damage induced by combined exposure of low-level lead and 1-nitropyrene in mice, and to explore the relationship between the changes of RA pathway and hypothalamus and pituitary damage. A total of 84 4-week-old ICR mice were randomly divided into the control group, Pb~(2+) tainted group(0.008 mg/L), 1-NP tainted group(0.1 mg/kg), low(0.008 mg/L Pb~(2+)+0.004 mg/kg 1-NP), medium(0.008 mg/L Pb~(2+)+0.02 mg/kg 1-NP), and high-dose co-toxicity group(0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP) according to body weight, with 14 mice in each group. Among them, Pb~(2+) was provided by lead acetate, added to deionized water and ingested by mice drinking freely, 1-NP was given by intraperitoneal injection, 1-NP was administered by intraperitoneal injection. Record daily water intake and food intake. After 21 consecutive days of exposure, body mass was measured, histological changes in the hypothalamus and pituitary were observed under an optical microscope, and lead content in brain tissue was measured by atomic absorption spectrometry. The real-time fluorescence quantitative PCR was used to detect the abundance of retinoic acid pathway members and c-Jun N-terminal kinases genes(Jnks), and the western blot method was used to detect expression levels of acetaldehyde dehydrogenase 2(ALDH2), cytochrome P450 family member 26A1(CYP26a1) proteins. There was no difference in the mean weekly water intake and food intake of the mice in each group. The body weight of the high-dose co-toxicity group mice((27.4±1.9)g) was lower than that of the control group((29.8±2.3)g)(P&lt;0.05). The level of serum follicle-stimulating hormone(FSH) in the middle and high dose co-toxicity groups((265.01±2.99), (260.42±3.61)pg/mL, respectively) was lower than that in the control group((279.00±1.30)pg/mL, P&lt;0.05). The content of Pb~(2+) in the brain of each group containing Pb~(2+) was higher than that of the control group. In the hypothalamic and pituitary tissues, the abundance of Adh1, Adh2, Rar and Rxr, and ALDH2 levels in the medium and high dose co-toxicity groups were higher than those in the control group(P&lt;0.05). Cyp26a1 gene abundance and protein levels were lower in the medium and high dose co-toxicity groups than in the control group(P&lt;0.05). The abundance of Jnks in the high-dose co-toxicity group was higher than that in the control group(P&lt;0.05). Continuous exposure to 0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP for 21 days can cause damage to the hypothalamus and pituitary of mice, and activate the RA signaling pathway.