Lifelong, the general population is exposed to mixtures of chemicals. Most often, risk assessment is performed to estimate the probability of adverse effects in the population using external exposures to a single chemical and considering one route of exposure. To estimate whole exposure to a chemical, human biomonitoring studies are used to measure chemical concentrations in biological matrices. The limitations of these studies are that it is not possible to distinguish the sources or the routes of exposure. Moreover, only the concentrations of a limited number of chemicals are usually determined due to the associated cost. In this study, a methodology has been developed to estimate the internal exposures of the population to a mixture of trace elements (inorganic As, Cd, Pb and Hg) throughout lifetime. This methodology uses realistic lifetime exposure trajectories coupled to physiological based kinetic modeling, considering several sources of exposure. Then, the estimated biomarkers of exposure were compared to human biomonitoring data to estimate the robustness of the methodology. Finally, risk characterization was performed based on the simulated biomarkers of exposure considering an additive effect of chemicals. This methodology allows to determine the contribution of chemicals to the overall risk of renal effect.

Bisphenol A (BPA) is ubiquitous in plastics, which can modify and improve the applicability and durability of plastics. Previous laboratory studies have shown that BPA can trigger cognitive impairment and depression. The olfactory bulb (OB) is significantly related to cognition and depression. However, there is a deficiency in information on BPA-induced OB neurotoxicity. Therefore, we analyzed the OB tissues of male mice at the transcriptional level after BPA poisoning at four different levels of concentration (0, 0.01, 0.1, and 1 μg/mL). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and weighted gene co-expression network analysis (WGCNA) were used to screen critical pathways and core genes. The result demonstrated that the PI3K-AKT signaling pathway might play a crucial role in the effects of BPA on the OB. In addition, two genes of the PI3K-AKT signaling pathway, the colony stimulating factor-1 receptor (Csf1r) and the toll-like receptor 2 (Tlr2), were screened by the protein-protein interaction networks. Furthermore, molecular docking identified ceftolozane as a potential drug candidate that could counteract BPA-related OB neurotoxicity. Conclusively, our results confirmed that BPA induced OB damage in male mice through the PI3K-AKT pathway and proposed that ceftolozane might reduce BPA-induced OB neurotoxicity.

Cottonseed meal (CSM) is an ideal source of protein feed ingredients. However, the gossypol contained in it has toxic effects on animals, limiting its use in livestock production. The underlying mechanisms remain largely unknown. This study aimed to investigate the adverse effects of gossypol exposure and assess whether melatonin, a natural antioxidant, could alleviate oocyte damage induced by gossypol. Porcine cumulus oocyte complexes (COCs) were treated with gossypol alone or co-treated with melatonin for 44 h during in vitro maturation. The results demonstrated that gossypol exposure induced oxidative stress and mitochondrial dysfunction, leading to oocyte maturation failure. Conversely, melatonin co-treatment mitigated these detrimental effects, by promoting oocyte mitophagy, as evidenced by the upregulation of PINK1, Parkin, and LC3 expressions, along with the downregulation of P62. Further investigation revealed that gossypol treatment significantly decreased SIRT1 protein expression, while melatonin co-treatment markedly increased it. Using the SIRT1 inhibitor Ex527 confirmed that melatonin enhances mitophagy through SIRT1, improving mitochondrial function and rescuing oocyte maturation. This study revealed the potential harm of gossypol on mammalian reproductive health, provided experimental reference for the protective effect of melatonin, and provided theoretical basis for the effective prevention and treatment of reproductive damage caused by gossypol.

Hexafluoropropylene oxide trimer acid (HFPO-TA), a novel alternative to perfluorooctanoic acid (PFOA), has been widely used and ubiquitously detected in aquatic environments. However, its potential effects on sex differentiation of aquatic organisms are not well known. Therefore, in this study, zebrafish were exposed to HFPO-TA at different development stages (0-21, 21-42, and 42-63 dpf) to investigate the effects on sex differentiation and its underlying mechanisms. All three exposures to HFPO-TA resulted in the feminization of zebrafish, and the impact of Stage II was most significant. The transcription levels of key genes related to female differentiation (bpm15, cyp19a1a, esr1, vtg1, and sox9b) were up-regulated, while those of key genes related to male differentiation (dmrt1, gata4, amh, and sox9a) were down-regulated, which could lead to the feminization. In addition, it was found that the dysregulations of these genes were prolonged in adult zebrafish even through a long recovery, which could cause sex imbalance in populations. Therefore, HFPO-TA might not be a safe alternative to PFOA, and more evidences from multi- and transgenerational toxicology are warranted.

Ochratoxin A (OTA) is a mycotoxin widely found in foodstuffs that is suspected to pose adverse health effects on humans. As one of the biggest coffee-producing countries, Indonesia face challenges in managing the OTA contamination at reasonable levels in coffee. A favorable climate for fungi growth and inappropriate food safety practices are several issues faced in Indonesia for managing the OTA contamination in coffee products. Nevertheless, studies about risk analysis exposure of OTA from coffee consumption in Indonesia is limited. Hence, the present study aimed to evaluate the risk of exposure to OTA from coffee consumption using the Margin of Exposure Approach (MOE) based on coffee provincial consumption data. Risk assessment using the MOE approach revealed that the OTA exposure from coffee consumption in Indonesia is generally of concern. The MOE values derived in the present study were generally below 1000. Several Indonesian provinces even have MOE values below 200, indicating a greater concern of exposure. Overall, the present study highlights the importance of food safety management in Indonesian coffee production to minimize the OTA exposure from coffee consumption.

Chlorate, mainly used in the production of fireworks, herbicides and other products, is an inorganic pollutant, which easily dissolves in water and is difficult to degrade. Chlorate has a potential toxic risk to the thyroid function, kidneys, and blood system, which could pose a potential threat to human health. However, studies focusing on human exposure to chlorate are scarce, especially via food consumption. This study aimed to investigate the concentrations of chlorate in six types of foods (n=531) from south China, and evaluate potential exposure risks for local residents. The detection rates of chlorate in all six types of foods were greater than 50 %, indicating the ubiquitous occurrence of chlorate in foods. Among the six types of foods, vegetables exhibited the highest concentrations of chlorate (p < 0.05), mainly attributed to the direct exposure to the environment compared with other foods. The hazard quotient (HQ) values by using EFSA reference dose (RfD) of chlorate via foods and water consumption existed greater than 1 in different age groups, indicating a potential health risks to human in south China.

A comprehensive survey was conducted by investigating 25 emerging and traditional organophosphate esters (OPEs) in 182 dairy products collected in China. The concentration of total OPEs (ΣOPEs) ranged from 0.0261 to 1178 ng/g wet weight (ww) in all the dairy samples. The major contaminants were triethyl phosphate (proportion: 93 %) and tris(1-chloro-2-isopropyl) phosphate (proportion: 2 %). Among types of dairy products, the concentrations of ΣOPEs decreased in the following order: milk powder (mean: 80.8 ng/g ww, proportion: 86 %) > cheese (9.43 ng/g ww, 10 %) > milk tablets (2.72 ng/g ww, 3 %) > liquid dairy (1.05 ng/g ww, 1 %). The significant correlation between emerging and traditional OPEs suggests that they likely share similar sources or are used together in commercial applications. OPEs contamination was related to the OPEs properties, local OPEs production and application, and dairy types. For the general Chinese population, the average and high estimated daily intakes of ΣOPEs via dairy products were 31.5 and 83.6 ng/kg bw/day, respectively. Dairy exposure in toddlers and children were higher than other age groups. Although the high-exposure risk of ΣOPEs was 3.50 × 10, potentially toxic tris(1-chloro-2-isopropyl) phosphate accounted for 38 % of the total hazard quotients.

Gardenia blue (GB), a widely used plant-derived food color is prepared by reaction of genipin, the aglycone of geniposide, with protein hydrolysate. Recent animal studies investigating GB toxicity have indicated blue coloration in the gastrointestinal tract, kidneys and mesenteric lymph nodes in rodents following dietary administration. This study investigated the uptake and disposition of [C]GB in male and female rats and mice administered 100 or 1000 mg/kg by gavage. [C]GB was prepared by reaction of [2-C]genipin with soy protein hydrolysate. Following administration in rats, C was eliminated primarily in feces (89-97% of administered dose), exhaled volatile organic chemical (VOC) and CO traps contained no radioactivity, and urine contained 0.2-0.4 %. In bile-duct-cannulated rats (100 mg/kg [C]GB), 0.25% of dose was recovered in bile, and in urine, 0.5%. The percent of the dose absorbed was 0.9%, based on radioactivity in urine, bile, and carcass minus digestive tract contents. The highest level of radioactivity in tissues was in kidney; however renal recovery was low, with only 0.02-0.04% of the dose recovered in kidney. Repeated dosing indicated that C accumulated in kidney, and was slowly removed following cessation of dosing, consistent with previous studies, in the absence of any functional or histopathological changes.

This work evaluated the effects of the consumption of a plant-based beverage (Cyperus esculentus L., Adansonia digitata L., and thermal water) on the physiological parameters of mice over a 28-day period. Thirty-two female FVB/n mice (n = 8) were randomly assigned to one of four groups divided into two experimental protocols: Group 1 drank water and Group 2 drank a plant-based beverage for 24 h; in the second experimental protocol, Group 3 consumed water and Group 4 consumed plant-based beverage for a limited time (4 h). Two experimental protocols were conducted to assess whether the exposure time to the beverage affects the animals' physiological parameters, to determine if there is a possible daily limit for consumption of the product and to analyze their adverse effects. The mice consuming a beverage ingested a larger amount of drink and a smaller amount of food. Histologically there are no pathological changes in collected organs. The consumption of a plant-based beverage has been shown to have a positive effect on oxidative markers and can have a diuretic action. According to results, no behavioral changes or clinical signs of disease were observed throughout both experimental protocols, and no mortality was recorded.

Rutin (Rut) is a flavonoid with pharmacological activities such as anti-inflammatory and antioxidant. Acrylamide (ACR) is a toxic substance widely found in human life that can induce neurotoxicity. Some studies have confirmed that neurotoxicity caused by ACR induces myelin damage, which in turn causes neurological dysfunction. Therefore, we established a rutin intervention model to investigate the protective effect of Rut on ACR-induced sciatic nerve injury in rats and its mechanism. The results showed that superoxide dismutase (SOD) activity and glutathione (GSH) content increased and lactate dehydrogenase (LDH) activity decreased in the middle and high dose groups of Rut compared with the ACR group, and the expression of Myelin basic protein (MBP), Extracellular-regulated kinase 1/2(ERK1/2), Phosphorylated extracellular regulated kinase 1/2 (P-ERK1/2), and Nuclear factor E-2-associated factor (Nrf2) was promoted in the Rut-protected group, which suggests that Rutin has a protective effect on ACR-induced sciatic nerve injury and that the mechanism of Rutin's protective effect is related to activation of the ERK1/2 pathway and alleviation of oxidative stress injury.

Organophosphate esters (OPEs) and their metabolites (mOPEs) are emerging pollutants. In this study, 18 OPEs and 10 mOPEs were measured in the 6th and 7th Beijing total diet studies (TDSs), and the dietary intakes of these pollutants by Beijing adults were estimated to assess related health concerns. Most OPEs and mOPEs had high detecting frequencies in both TDSs, which indicated that various foods in Beijing have been universally contaminated with OPEs and mOPEs. Statistical analysis further confirmed that the levels of both ∑OPEs and ∑mOPEs in the 7th Beijing TDS were significantly higher than those in the 6th study, indicating heavier contamination of both OPEs and their metabolites with time. Along with increasing OPE/mOPE contamination level and food consumption values, significant increases of EDIs were observed during the two studies, with the average EDIs of ∑OPEs increasing from 5.07 to 24.1 ng/kg bw/day, and that of ∑mOPEs increasing from 2.07 to 7.23 ng/kg bw/day. Although a comparison between EDIs and reference of doses (RfDs) indicated that current intakes of OPEs could still not cause significant health risks, the sharply increasing contamination levels and EDIs suggested the necessity to continuously monitor these emerging food contaminants.

To evaluate the safety of alpha- glycerylphosphorylcholine (α-GPC) as a novel food, the study of acute oral toxicity, subchronic toxicity, teratogenic toxicity and genotoxicity were conducted. In acute oral toxicity, no toxic effects were observed in rats of both genders administrated 10.0g/kg BW α-GPC. In 90-day oral toxicity, female high-dose group (2,000mg/kg) had lower body weight, body weight gain, empty stomach body weight, total protein (TP), albumin (ALB), and higher alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) in contrast to control group. In teratogenic toxicity, the body weights of pregnant rats on the 9th day (d9), the 12th day (d12), the 15th day (d15), and the 20th day (d20), body weight gains, and net body weight gains in high-dose group (2,000mg/kg) decreased, the other parameters had no difference compared to control group. In genotoxicity tests (Mammalian erythrocyte micronucleus, Chromosome aberration and Ames test), all dose groups didn't display significant change compared with negative control group. Based on above results, α-GPC is actually low hazard novel food, has a NOAEL of 1,000mg/kg BW for female rats and 2,000mg/kg BW for male rats following 13-week oral exposure, has a NOAEL of 1,000mg/kg BW for pregnant rats and 2,000mg/kg BW for fetal rats in teratogenic toxicity, has no genotoxicity in vitro or in vivo.