Association between exposure to mixture of heavy metals and hyperlipidemia risk among U.S. adults: A cross-sectional study.

Previous studies have suggested that exposure to heavy metals might increase the risk of hyperlipidemia. However, limited research has investigated the association between exposure to mixture of heavy metals and hyperlipidemia risk. To explore the independent and combined effects of heavy metal exposure on hyperlipidemia risk, this study involved 3293 participants from the National Health and Nutrition Examination Survey (NHANES), including 2327 with hyperlipidemia and the remaining without. In the individual metal analysis, the logistic regression model confirmed the positive effects of barium (Ba), cadmium (Cd), mercury (Hg), Lead (Pb), and uranium (U) on hyperlipidemia risk, Ba, Cd, Hg and Pb were further validated in restricted cubic splines (RCS) regression model and identified as positive linear relationships. In the metal mixture analysis, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and quantile-based g computation (qgcomp) models consistently revealed a positive correlation between exposure to metal mixture and hyperlipidemia risk, with Ba, Cd, Hg, Pb, and U having significant positive driving roles in the overall effects. These associations were more prominent in young/middle-aged individuals. Moreover, the BKMR model uncovered some interactions between specific heavy metals. In conclusion, this study offers new evidence supporting the link between combined exposure to multiple heavy metals and hyperlipidemia risk, but considering the limitations of this study, further prospective research is required.

Associations between urinary heavy metals and anxiety among adults in the National Health and Nutrition Examination Survey (NHANES), 2007-2012.

BACKGROUND: Few studies have investigated the associations between heavy metals and anxiety. The purpose of this study was to examine the associations between single and combined exposure to heavy metals and anxiety. METHODS: This study employed data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Anxiety was assessed by patients self-reporting the number of anxious days per month. First, we evaluated the associations between 10 heavy metals single exposure and anxiety by multivariable logistic regression. We then selected 5 heavy metals (cadmium, antimony, cobalt, tungsten, and uranium) for further analysis by elastic net regression. Subsequently, principal component analysis (PCA), weighted quantile regression (WQS), and Bayesian kernel machine regression (BKMR) were utilized to evaluate the associations between 5 heavy metals co-exposure and anxiety. RESULTS: This study included 4512 participants, among whom 1206 participants were in an anxiety state. Urinary cadmium and antimony were separately related to an increased risk of anxiety (p for trend <0.01 and < 0.01, respectively). In PCA analysis, PC1 was associated with an increased risk of anxiety (p for trend <0.001). In WQS analysis, the positive WQS index was substantially linked with the risk of anxiety (OR (95%CI): 1.23 (1.04,1.39)). In BKMR analysis, the overall effects of co-exposure to heavy metals were positively connected with anxiety. CONCLUSION: Our study identified a positive correlation between individual exposure to cadmium and antimony and the risk of anxiety. Additionally, the co-exposure to cadmium, antimony, cobalt, tungsten, and uranium was associated with an increased risk of anxiety.

Essential metal mixtures exposure and NAFLD: A cohort-based case-control study in northern Chinese male adults.

Epidemiologic evidence on metal mixtures and non-alcoholic fatty liver disease (NAFLD) is limited. We aimed to assess the relationship between multiple metal co-exposure and NAFLD among male adults in Northern China. We conducted a cohort-based case-control study with 648 NAFLD and 648 non-NAFLD males. Seven metal concentrations (calcium, copper, iron, magnesium, manganese, selenium, and zinc) were determined in the blood. We used logistic regression and restricted cubic splines (RCS) to estimate the associations between the single metal and NAFLD. The impact of metal mixtures was quantified by the environmental risk score (ERS) in the adaptive elastic-net regression, and the association with NAFLD was estimated by logistic regression. Age-adjusted RCS showed linear relationships between blood calcium, selenium, and NAFLD. Blood copper, iron, magnesium, and manganese were non-linearly associated with NAFLD. Single metal analysis observed significant relationships between calcium, copper, manganese, and NAFLD, with the adjusted odds ratio (95% confidence interval) for quartile 1 vs. quartile 4 of 1.99 (1.30, 3.05), 2.36 (1.52, 3.64), and 1.77 (1.22, 2.55), respectively. However, metal mixtures analysis revealed one squared term (copper [ß = -0.146]) and five metal-metal interactions (calcium × copper [ß = 0.200], copper × magnesium [ß = 0.188], copper × selenium [ß = 0.188], iron × magnesium [ß = 0.143], magnesium × selenium [ß = -0.297]) except the three main effects. Higher ERS indicated a higher risk for NAFLD when exposed to metal mixtures, with an adjusted odds ratio = 6.50 (95% confidence interval: 4.36-9.69) for quartile 4 vs. quartile 1. Mediation analysis suggested that 11.66% of the effect of ERS on NAFLD was suppressed by fasting blood glucose. Our results show that exposure to metal mixtures is associated with a higher risk for NAFLD than the single metal. Interactions between metals suggest the importance of balancing the various metals for health benefits. Prospective cohorts and mechanism studies need to confirm the findings.

Mercury and selenium co-ingestion assessment via rice consumption using an in-vitro method: Bioaccessibility and interactions.

Mercury (Hg) was reported to accumulate in rice grains, and, together with the selenium (Se) was found in rice, the co-exposure of Hg-Se via rice consumption may present significant health effects to human. This research collected rice samples containing high Hg:high Se and high Se:low Hg concentrations from high Hg and high Se background areas. The physiologically based extraction test (PBET) in vitro digestion model was utilized to obtain bioaccessibility data from samples. The results showed relatively low bioaccessible for Hg (<60%) and Se (<25%) in both rice sample groups, and no statistically significant antagonism was identified. However, the correlations of Hg and Se bioaccessibility showed an inverse pattern for the two sample groups. A negative correlation was detected in the high Se background rice group and a positive correlation in the high Hg background group, suggesting various micro forms of Hg and Se in rice from different planting locations. In addition, when the benefit-risk value (BRV) was calculated, some "fake" positive results showed while Hg and Se concentrations were directly used, which indicated that bioaccessibility should not be neglected in benefit-risk assessment.

Associations of exposure to blood and urinary heavy metal mixtures with psoriasis risk among U.S. adults: A cross-sectional study.

Accumulating evidence showed that environmental exposure to toxic metals was harmful to human health. However, information about the effects of exposure to metal mixtures on psoriasis was scarce. To investigate the independent and comprehensive associations between heavy metal co-exposure and psoriasis in adults, data of 6534 adults aged 20-80 years from the National Health and Nutrition Examination Survey (NHANES) were used. Among them, 187 (2.86 %) were diagnosed with psoriasis and the rest were participants without psoriasis. We examined the independent and combined associations of 3 blood metals and 11 urinary metals with psoriasis risk. In the single-metal analyses, urinary barium (Ba), cesium (Cs), antimony (Sb), uranium (Ur), and cadmium (Cd) were positively correlated with psoriasis risk, while urinary molybdenum (Mo) was identified as a protective factor for psoriasis. Moreover, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models consistently revealed the positive effect of urinary metal co-exposure on psoriasis risk. The associations were more evident in the young and middle-aged group than the elderly group. In the urinary mixtures, Ba was the highest weighted metal in the whole population and the young and middle-aged people, whereas Sb was the top weighted metal in the elderly group. Additionally, BKMR analysis revealed the potential interaction between certain components of urinary metal mixtures in psoriasis. The results of quantile-based g computation (qgcomp) model further proved the toxic effect of urinary metal mixtures on psoriasis, and the positive linear relationship between urinary Ba and psoriasis risk was identified by restricted cubic splines (RCS) regression. We concluded that co-exposure to multiple heavy metals was associated with psoriasis risk. Given the limitations of the NHANES study, further prospective designed studies are warranted.

Co-exposure to commercial food product ingredient E341 and E551 triggers cytotoxicity in human mesenchymal stem cells.

Several nano-toxicological studies have assessed the prospective health risks of engineered nanostructures. Still, nanoscale ingredients from food products are not explored well, and only a few have attended to the possible effects of food additive-based nanoparticles in food. The physicochemical properties of food additives and their fate on human health are still unknown. To fill this knowledge gap, we examined the physicochemical characteristics of food product isolate E341/E551. Additionally, we assessed the consequence of these nanoscale E341 and E551 as co-exposure on human mesenchymal stem cells (hMSCs). The transmission electron microscope (TEM) images revealed that food product isolate (E341/E551) consists of nanoscale particles. The E551 and E341 have 20-50 nm and 70-200 nm diameters, respectively. Co-exposure of food additives SiO2 (E551) and Tricalcium phosphate (E341) effect on the cell viability, morphology, mitochondrial membrane potential, and reactive oxygen species (ROS) level of hMSCs were studied. The cell viability reduction, mitochondrial membrane potential loss, and ROS generation in E341/E551 co-exposed cells were observed. Our study suggests that E341/E551 co-exposure elevated the ROS level and mitochondrial membrane potential depletion at a high dose. The oxidative stress-related genes MDM3, TNFSF10, and POR have exhibited significant upregulation in the E341/E551 treatment group. These results conclude that long-term over-exposure to E341/E551 may be triggers health risks in a human. Further in vivo studies are required for food industry implications due to nanoscale ingredients in E341 and E551.

Analysis of the of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. by PBET digestion in vitro/Caco-2 cell model and their cumulative risk assessment / 药学学报

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

Cocktails of Mycotoxins, Phytoestrogens, and Other Secondary Metabolites in Diets of Dairy Cows in Austria: Inferences from Diet Composition and Geo-Climatic Factors.

Dairy production is a pivotal economic sector of Austrian and European agriculture. Dietary toxins and endocrine disruptors of natural origin such as mycotoxins and phytoestrogens can affect animal health, reproduction, and productivity. This study characterized the profile of a wide spectrum of fungal, plant, and unspecific secondary metabolites, including regulated, emerging, and modified mycotoxins, phytoestrogens, and cyanogenic glucosides, in complete diets of lactating cows from 100 Austrian dairy farms. To achieve this, a validated multi-metabolite liquid chromatography/electrospray ionization−tandem mass spectrometric (LC/ESI−MS/MS) method was employed, detecting 155 of >800 tested metabolites. Additionally, the most influential dietary and geo-climatic factors related to the dietary mycotoxin contamination of Austrian dairy cattle were recognized. We evidenced that the diets of Austrian dairy cows presented ubiquitous contamination with mixtures of mycotoxins and phytoestrogens. Metabolites derived from Fusarium spp. presented the highest concentrations, were the most recurrent, and had the highest diversity among the detected fungal compounds. Zearalenone, deoxynivalenol, and fumonisin B1 were the most frequently occurring mycotoxins considered in the EU legislation, with detection frequencies >70%. Among the investigated dietary factors, inclusion of maize silage (MS) and straw in the diets was the most influential factor in contamination with Fusarium-derived and other fungal toxins and metabolites, and temperature was the most influential among the geo-climatic factors.

Novel Integrated Tiered Cumulative Risk Assessment of Heavy Metals in Food Homologous Traditional Chinese Medicine Based on a Real-Life-Exposure Scenario.

In order to serve population health better, the first integrated tiered decision tree for cumulative risk assessment of co-exposure of Pb-, Cd-, and As-associated health risks in food homologous traditional Chinese medicine (TCM) was designed, after measuring their concentrations by inductively coupled plasma-mass spectroscopy (ICP-MS). Basically, our three-step decision tree involving hazard quotient (HQ), hazard index (HI), and target-organ toxicity dose (TTD) modification of the HI method was developed to evaluate the potential risks of 949 batches of 15 types of food homologous TCM. To acquire a real-life exposure scenario, the cumulative risk assessment model was established by optimizing key parameters, such as ingestion rates, frequency, and duration of exposure to food homologous TCM based on questionnaire data. As a result, the mean concentrations of Pb, Cd, and As in 949 batches of food homologous TCM were 0.896, 0.133, and 0.192 mg/kg, respectively. The HQ values of As for Angelica sinensis (Oliv.) Diels and Houttuynia cordata Thunb. were 1.04 and 1.01, respectively, for females. Other HQs of Pb, Cd, or As in food homologous TCM were lower than 1 for both males and females. However, after rapid screening of the co-exposure health risks of heavy metals by the HI method, cumulative risk assessment results acquired by TTD modification of the HI method implied that the potential health risks associated with the co-exposure of Pb, Cd, and As in Lonicera japonica Thunb. and Houttuynia cordata Thunb. ingested as both TCM and food were of concern in the clinic. Additionally, the cumulative risks of Pb, Cd, and As in Mentha canadensis L., Chrysanthemum indicum L., and Zaocys dhumnades (Cantor) only used as food exceeded the human tolerance dose. Collectively, our innovation on the tiered strategy of decision tree based on a real-life exposure scenario provides a novel approach engaging in the cumulative risk assessment of heavy metals in food homologous TCM. All in all, such effort attempts to scientifically guide the rational use of TCM in the treatment of the complex diseases and the improvement of population health.

Co-exposure of chronic stress and alumina nanoparticles aggravates hippocampal microglia pyroptosis by activating cathepsin B/NLRP3 signaling pathway.

Combined exposure of chronic stress and alumina nanoparticles (AlNPs) aggravates hippocampal injury, but the pathogenesis is unevaluated. This study aimed to investigate the effect and mechanism of co-exposure to chronic stress and AlNPs on hippocampal microglia pyroptosis. In this study, chronic restraint stress (CRS) alone caused NLRP3-mediated hippocampal microglia pyroptosis, but AlNPs did not. Moreover, co-exposure to CRS and AlNPs exacerbated hippocampal microglia pyroptosis, resulting in more severe hippocampal damage and behavioral deficits in rats. Protein-protein interaction network predicted that cathepsin B was a potential regulatory protein of NLRP3. CRS up-regulated cathepsin B expression which had a more pronounced increase in co-exposure group. Whereas, caspase-1 inhibitor VX-765 alleviated hippocampal microglia pyroptosis and behavioral deficits in rats. Consistent with in vivo results, co-exposure of corticosterone and AlNPs aggravated NLRP3-mediated pyroptosis and cathepsin B expression in HAPI cells. Nevertheless, the pyroptosis of HAPI cells was inhibited by cathepsin B inhibitor CA-074Me and NLRP3 knockout, respectively. NLRP3 agonist nigericin failed to promote the pyroptosis of HAPI cells in the presence of cathepsin B inhibition. These results demonstrated that co-exposure to chronic stress and AlNPs could aggravate hippocampal microglia pyroptosis by activating cathepsin B/NLRP3 signaling pathway, resulting in hippocampal damage and behavioral deficits.

Understanding the translocation and bioaccumulation of cadmium in the Enshi seleniferous area, China: Possible impact by the interaction of Se and Cd.

Selenium (Se) plays an indispensable role in minimizing cadmium (Cd) hazards for organisms. However, their potential interactions and co-exposure risk in the naturally Se-Cd enriched paddy field ecosystem are poorly understood. In this study, rice plants with rhizosphere soils sampled from the Enshi seleniferous region, China, were investigated to resolve this confusion. Here, translocation and bioaccumulation of Cd showed some abnormal patterns in the system of soil-rice plants. Roots had the highest bioaccumulation factors of Cd (range: 0.30-57.69; mean: 11.86 ± 14.32), and the biomass of Cd in grains (range: 1.44-127.70 µg, mean: 36.55 ± 36.20 µg) only accounted for ∼10% of the total Cd in whole plants (range: 14.67-1363.20 µg, mean: 381.25 ± 387.57 µg). The elevated soil Cd did not result in the increase of Cd concentrations in rice grains (r2 = 0.03, p > 0.05). Most interestingly, the opposite distribution between Se and Cd in rice grains was found (r2 = 0.24, p < 0.01), which is contrary to the positive correlation for Se and Cd in soil (r2 = 0.46, p < 0.01). It is speculated that higher Se (0.85-11.46 µg/g), higher Se/Cd molar ratios (mean: 5.42 ≫1; range: 1.50-12.87), and higher proportions of reductive Se species (IV, 0) of the Enshi acidic soil may have the stronger capacity of favoring the occurrence of Se binding to Cd ions by forming Cd-Se complexes (Se2- + Cd2+ =CdSe) under reduction conditions during flooding, and hence change the Cd translocation from soil to roots. Furthermore, the negative correlation (r2 = 0.25, p < 0.05) between the Cd translocation factor (TFwhole grains/root) and the roots Se indicates that Cd translocation from the roots to rice grains was suppressed, possibly by the interaction of Se and Cd. This study inevitably poses a challenge for the traditional risk assessment of Cd and Se in the soils-crops-consumers continuum, especially in the seleniferous area.

The Effects of Lead and Cadmium Co-exposure on Serum Ions in Residents Living Near a Mining and Smelting Area in Northwest China.

In this study, we investigated the associations between cadmium (Cd) and lead (Pb) co-exposure, and serum ion levels in two populations living near a mining/smelting area and a nature reserve (control area), respectively. A total of 445 participants were included in this study. Their blood cadmium (BCd), blood lead (BPb), and serum ion levels were determined, and the association between exposure levels and serum ion levels was analyzed. The exposure levels of subjects living in the polluted area were significantly higher (p < 0.001). Lower levels of potassium, inorganic phosphorus, and iron were observed in subjects from the polluted area, whereas their sodium and chloride levels were higher (p < 0.01). The anion gap in their serum was also significantly lower. We observed positive dose-effect relationships between Cd and/or Pb exposure and serum sodium and chloride, and negative dose-effect relationships between Cd and/or Pb exposure and serum inorganic phosphorus, iron, as well as the anion gap. High Cd-Pb, high Cd, and high Pb exposure led to modification effects in potassium, calcium, inorganic phosphorus, and iron levels, and the anion gap. No synergistic effects were observed in our results. In conclusion, our data demonstrate that Cd and Pb exposure, alone or in combination, can lead to serum ion imbalances.

Co-exposure of serum calcium, selenium and vanadium is nonlinearly associated with increased risk of type 2 diabetes mellitus in a Chinese population.

BACKGROUND: Metals play an important role in type 2 diabetes mellitus (T2DM). This study aimed to explore the association of T2DM risk with single metal exposure and multi-metal co-exposure. METHODS: A case-control study with 223 T2DM patients and 302 controls was conducted. Serum concentrations of 19 metals were determined by inductively coupled plasma mass spectrometry (ICP-MS). Those metals with greater effects were screened out and co-exposure effects of metals were assessed by least absolute shrinkage and selection operator (LASSO) regression. RESULTS: Serum calcium (Ca), selenium (Se) and vanadium (V) were found with greater effects. Higher levels of Ca and Se were associated with increased T2DM risk (OR = 2.23, 95%CI: 1.38-3.62, Ptrend = 0.002; OR = 3.16, 95%CI: 1.82-5.50, Ptrend < 0.001), but higher V level was associated with decreased T2DM risk (OR = 0.58, 95%CI: 0.34-0.97, Ptrend < 0.001). Serum Ca and V concentrations were nonlinearly associated with T2DM risk (Poverall < 0.001, Pnonliearity < 0.001); however, Se concentration was linearly associated with T2DM risk (Poverall < 0.001, Pnonliearity = 0.389). High co-exposure score of serum Ca, Se and V was associated with increased T2DM risk (OR = 3.50, 95%CI: 2.08-5.89, Ptrend < 0.001) as a non-linear relationship (Poverall < 0.001, Pnonliearity = 0.003). CONCLUSIONS: This study suggest that higher levels of serum Ca and Se were associated with increased T2DM risk, but higher serum V level was associated with decreased T2DM risk. Moreover, co-exposure of serum Ca, Se and V was nonlinearly associated with T2DM risk, and high co-exposure score was positively associated with T2DM risk.

Rare cases of severe life-threatening lead poisoning due to accident or chronic occupational exposure to lead and manganese: Diagnosis, treatment, and prognosis.

BACKGROUND: Chronic long-term, low-dose environmental and occupational exposure to lead (Pb) has been extensively studied in large cohorts worldwide among general populations, miners, smelters, or battery workers. However, studies on severe life-threatening Pb poisoning due to accidental or chronic occupational exposure to Pb and manganese (Mn) were rarely reported. METHODS: We present one case of acute severe Pb poisoning and compare it with another severe chronic occupational exposure case involving Pb and Mn. A 27-year-old woman mistakenly took a large quantity of pure Pb powder as an herbal remedy; she developed abdominal colic, severe nausea, vomiting, fatigue, and cutaneous and sclera icterus. Laboratory tests showed her blood lead level (BLL) of 173.5 µg dL-1 and urinary lead level (ULL) of 1240 µg dL-1. The patient was diagnosed with acute Pb poisoning and acute liver failure. In another chronic exposure case, a 56-year-old man worked in a Pb and Mn smelting factory for 15 years. He was brought to the emergency room with severe nausea, vomiting, and paroxysmal abdominal colic, which was intolerable during the onset of pain. His BLL was 64.8 µg dL-1 and ULL was 38 µg dL-1, but his blood and urinary Mn levels were normal. The patient was diagnosed with chronic Pb poisoning. Both patients received chelation therapy with calcium disodium ethylene-diamine-tetraacetate (CaNa2EDTA). The woman with acute severe Pb intoxication recovered well and was discharged from the hospital after treatment, and the man who survived severe Pb poisoning was diagnosed with lung cancer. CONCLUSION: Clinical manifestations of acute and chronic severe Pb poisoning are different. Chelation therapy with CaNa2EDTA is proven to be an effective life-saving therapy in both cases by reducing BLL. Occupational exposure to both Pb and Mn does not appear to increase Mn neurotoxicity; however, the probability that co-exposure to Mn may increase Pb toxicity in the same patient cannot be excluded.

Systematic probabilistic risk assessment of pesticide residues in tea leaves.

Multiple pesticide residues are frequently present in tea leaves and while the majority of residues satisfy Taiwan's current health regulations, there are potential health effects from pesticide exposure that are of great concern for tea drinkers. We undertook a systematic probabilistic risk assessment of 59 pesticides in tea leaves from 1629 tea leaf samples obtained by Taiwan's Food and Drug Administration in two monitoring surveys in 2015. Bayesian statistics used a Markov Chain Monte Carlo approach to estimate posterior distributions of pesticide residues in tea leaves, lifetime average daily doses and hazard quotients (HQs) of evaluated pesticides. We classified 95th percentile values of HQs into three categories: 0 < HQ < 0.5, 0.5 ≤ HQ ≤ 1 and 1 < HQ. The 95th percentiles of HQs for triazophos (3.39), carbofuran (2.04) and endosulfan (1.80) exceeded 1 in the adult population; the HQ for 3-OH carbofuran was 0.97 and was less than 0.5 for the remaining 55 pesticides. The health risk posed by pesticide residues for tea drinkers is negligible, if triazophos, carbofuran, endosulfan, and 3-OH carbofuran residues satisfy regulatory standards. However, five legacy pesticides, DDT, methomyl, carbofuran, dicofol and endosulfan, were identified. To reduce uncertainties, this study combined Bayesian statistics with a mode of action approach for systematic risk assessment of co-exposure to multiple pesticide residues in tea leaf samples. Measuring pesticide transfer rates will improve the quality of future risk assessments concerning residues in tea leaves. Appropriate management of pesticides in Taiwanese tea farms and monitoring of pesticide residues in imported tea is warranted to protect Taiwan's tea drinkers.

Co-administration of a Rhododendron tomentosum extract does not affect mercury tissue concentrations and excretion rate in methylmercury-treated adult male rats.

OBJECTIVES: Consumption of fish/seafood is clearly linked to higher mercury levels in human tissue samples. However, correlations between methylmercury (MeHg) intakes calculated from dietary surveys and mercury body burdens are usually weak and can vary across populations. Different factors may affect MeHg absorption, distribution, metabolism and excretion, including co-exposures to phytochemicals and antibiotics, which were shown to affect mercury body burdens in rodents. Based on the observation that rat pups developmentally exposed to MeHg and a Rhododendron tomentosum extract (Labrador Tea) presented significantly higher blood mercury levels at weaning compared to pups exposed to MeHg alone, the modulation of MeHg toxicokinetics by Labrador Tea was further investigated in adult rats. RESULTS: Total mercury levels were quantified in the blood, liver, kidney and feces of adult male rats exposed to MeHg (1.2 mg/kg bodyweight/day, for 3 weeks) administered either alone or in combination with Labrador Tea (100 mg/kg bodyweight/day) or with an antibiotics cocktail (to inhibit MeHg demethylation by gut bacteria). While the reduced fecal excretion and higher blood mercury levels expected from antibiotics-treated rats were observed, mercury levels in samples from Labrador Tea-treated rats were not significantly different from those measured in samples from rats exposed to MeHg alone.

Neurobehavioral and oxidative stress alterations following methylmercury and retinyl palmitate co-administration in pregnant and lactating rats and their offspring.

Fish consumption and ubiquitous methylmercury (MeHg) exposure represent a public health problem globally. Micronutrients presented in fish affects MeHg uptake/distribution. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. The present study aimed to examine the effects of both MeHg and retinyl palmitate administered to pregnant and lactating rats. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/Kg/day) and retinyl palmitate (7500 µg RAE1/Kg/day), either individually or in combination from the gestational day 0 to weaning. In dams, maternal behavior was scored. In neonatal and infant offspring, associative learning and neurodevelopment were evaluated. Further periadolescent male and female pups were assessed for open field, habituation and object recognition using episodic-like memory paradigm. Maternal and offspring redox parameters were evaluated. Our results showed no effects of MeHg-VitA co-administration in the quality of maternal care but showed subtle alterations in the pro-oxidant response of the hippocampus. In offspring, MeHg-VitA co-exposure affected early associative learning in neonatal pups, with no further modifications in neurodevelopment, and no locomotor or exploratory alterations in later developmental stages. Habituation was altered in a sex-dependent manner, but no overall memory disturbances were encountered. Finally, MeHg-VitA co-administration reduced lipoperoxidation in male offspring hippocampus. In conclusion, VitA co-administration in dams, under our exposure protocol, can counteract the deleterious neurodevelopmental effects solely attributed to low-dose MeHg in a tissue-specific mechanism, suggesting a protective effect of VitA against MeHg-induced oxidative damage in the central nervous system, especially in the offspring. Further work is needed to confirm our findings and elucidate the molecular mechanisms of MeHg-VitA modulation. Pre-clinical assays are necessary to demonstrate the potential therapeutical use of VitA in populations directly or indirectly exposed to MeHg.

Effects of methylmercury and retinol palmitate co-administration in rats during pregnancy and breastfeeding: Metabolic and redox parameters in dams and their offspring.

Ubiquitous low-dose methylmercury (MeHg) exposure through an increased fish consumption represents a global public health problem, especially among pregnant women. A plethora of micronutrients presented in fish affects MeHg uptake/distribution, but limited data is available. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. Therefore, the present study aimed to examine the effects of both MeHg and retinyl palmitate administered on pregnant and lactating rats in metabolic and redox parameters from dams and their offspring. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/kg/day) and retinyl palmitate (7500 µg RAE/kg/day) via gavage, either individually or in combination from the gestational day 0 to weaning. For dams (150 days old) and their offspring (31 days old), glycogen accumulation (hepatic and cardiac) and retinoid contents (plasma and liver) were analyzed. Hg deposition in liver tissue was quantified. Redox parameters (liver, kidney, and heart) were evaluated for both animals. Cytogenetic damage was analyzed with micronucleus test. Our results showed no general toxic or metabolic alterations in dams and their offspring by MeHg-VitA co-administration during pregnancy and lactation. However, increased lipoperoxidation in maternal liver and a disrupted pro-oxidant response in the heart of male pups was encountered, with apparently no particular effects in the antioxidant response in female offspring. GST activity in dam kidney was altered leading to possible redox disruption of this tissue with no alterations in offspring. Finally, the genomic damage was exacerbated in both male and female pups. In conclusion, low-dose MeHg exposure and retinyl palmitate supplementation during gestation and lactation produced a potentiated pro-oxidant effect, which was tissue-specific. Although this is a pre-clinical approach, we recommend precaution for pregnant women regarding food consumption, and we encourage more epidemiological studies to assess possible modulations effects of MeHg-VitA co-administration at safe or inadvertently used doses in humans, which may be related to specific pathologies in mothers and their children.

Combined effects of cadmium and tetrabromobisphenol a (TBBPA) on development, antioxidant enzymes activity and thyroid hormones in female rats.

Tetrabromobisphenol A (TBBPA) is one of the world's most widely used brominated flame retardants (BFRs) and considered as persistent halogenated contaminant. E-wastes contain a range of toxic chemicals, including BFRs and heavy metals, exerting adverse impacts to human health and environment. Nevertheless, comprehensive evaluation on combined toxicity of these co-existing pollutants is limited. This study conducted a subchronic effects of cadmium and TBBPA on the development and antioxidative defense system as well as thyroid functions in female rats through single and combined exposure at environmentally relevant doses for a 20-day consecutive administration. Body indexes, histopathology, redox status, and thyroid hormones levels were assessed. Slower body weight gains and reduced ovary weight (20.8% and 32.4% for combined and single-Cd exposures, respectively) were observed with significant variation from controls in high dose treatments. Co-exposure resulted in a slight enhancement in TSH levels compared to control (by 7.6% for high dose) without significance. TBBPA-Cd interactions are involved in the changes of kidney weight as well as the induction of SOD activities and MDA levels. The disturbances in the redox status may be a result of an independent effect of Cd and/or TBBPA and also of their interaction. The results implied under these treatment, kidney was more sensitive with significant increased organ coefficient and alteration for antioxidative indices (increasing by 46% for SOD activity). This study represents the toxic effects of Cd and TBBPA co-exposure through oral administration in pubertal rats, which may provide useful information for health risk assessment for young exposed individuals.

Thyroid disrupting pesticides impair the hypothalamic-pituitary-testicular axis of a wildlife bird, Amandava amandava.

The effect of two thyroid disrupting pesticides (TDPs) mancozeb (MCZ) and imidacloprid (IMI) on the hypothalamic-pituitary-gonadal/testicular (HPG) axis of a seasonally breeding bird, Amandava amandava has been evaluated. Male birds (n=8/group) were exposed to each of the pesticide (0.25% LD50 of respective pesticide) as well as to their two equimixture doses (0.25% of LD50 of each and 0.5% LD50 of each) through food for 30d during pre-breeding stage of the reproductive cycle. Reduction in weight, volume and other histopathological features revealed testicular regression. Suppression of gonadotropin releasing hormone, increased expression of gonadotropin inhibitory hormone in the hypothalamus of exposed groups as well as impairment of plasma levels of the reproduction related hormones indicated the disruption of the HPG axis. The pesticides interference of the thyroid function during the critical phase of reproductive development impaired the HPG axis; more significantly in co-exposed groups suggesting the cumulative toxicity.