Journal of Toxicology and Environmental Health, Part A最新文献

Plant species from the Ficus genus are widely used as food, and in folk medicine as anti-inflammatory, antioxidant and anticancer agents, although some of these species are known to produce adverse effects. The aim of this study was to determine and compare the chemical composition as well as in vitro antioxidant and mutagenic activity of the aqueous extracts of leaves from F. adhatodifolia and F. obtusiuscula. Phytochemical screening using thin-layer chromatography identified 6 classes of secondary metabolites in the extracts. Total phenolic content was estimated by the Folin-Ciocalteau method and the phenolic profile was determined by UPLC-DAD-ESI/MS/MS. Antioxidant activities were evaluated by the DPPH radical assay and by the β-carotene/linoleic acid system. Mutagenic activity was measured by the Salmonella typhimurium reverse mutation test with 4 strains, in both the presence and absence of metabolic activation. Flavonoids, coumarins, and tannins were detected in both extracts, and 6 major derivatives were identified as flavone compounds. Antioxidant activities were demonstrated for both extracts, while F. obtusiuscula contained higher concentrations of phenolic compounds. Mutagenic activity of the TA97 strain without metabolic activation was observed for both tested extracts, as well as the TA102 strain with metabolic activation. In addition, the extract of F. adhatodifolia was shown to be mutagenic to the TA102 strain without metabolic activation. Evidence indicates that the use of teas obtained from these two plant extracts in folk medicine may raise concerns and needs further investigation as a result of potential pro-oxidant mutagenic effects in the absence or presence of metabolic activation.

Nonnutritive sweeteners (NNS), including saccharin, sucralose, aspartame, and acesulfame-potassium, are commonly consumed in the general population, and all except for saccharin are considered safe for use during pregnancy and lactation. Sucralose (Splenda) currently holds the majority of the NNS market share and is often combined with acesulfame-potassium in a wide variety of foods and beverages. To date, saccharin is the only NNS reported to be found in human breast milk after maternal consumption, while there is no apparent information on the other NNS. Breast milk samples were collected from 20 lactating volunteers, irrespective of their habitual NNS intake. Saccharin, sucralose, and acesulfame-potassium were present in 65% of participants' milk samples, whereas aspartame was not detected. These data indicate that NNS are frequently ingested by nursing infants, and thus prospective clinical studies are necessary to determine whether early NNS exposure via breast milk may have clinical implications.

A lab-on-a-chip (LOC) is a microfluidic device (MFD) that integrates several lab functions into a single chip of only millimeters in size. LOC provides several advantages, such as low fluidic volumes consumption, faster analysis, compactness, and massive parallelization. These properties enable a microfluidic-based high-throughput drug screening (HTDS) system to acquire cell-based abundant cytotoxicity results depending on linear gradient concentration of drug with only few hundreds of microliters of the drug. Therefore, a microfluidic device was developed containing an array of eight separate microchambers for cultivating HepG2 cells to be exposed to eight different concentrations of acetaminophen (APAP) through a diffusive-mixing-based concentration gradient generator. Every chamber array with eight different concentrations (0, 5.7, 11.4, 17.1, 22.8, 28.5, 34.2, or 40 mM) APAP had four replicating cell culture chambers. Consequently, 32 experimental results were acquired with a single microfluidic device experiment. The microfluidic high-throughput cytotoxicity device (μHTCD) and 96-well culture system showed comparable cytotoxicity results with increasing APAP concentration of 0 to 40 mM. The HTDS system yields progressive concentration-dependent cytotoxicity results using minimal reagent and time. Data suggest that the HTDS system may be applicable as alternative method for cytotoxicity screening for new drugs in diverse cell types.

The general population is exposed to phthalates through consumer products, diet, and medical devices. Phthalic acid (PA) is a common final metabolite of phthalates, and its isomers include isophthalic acid (IPA), terephthalic acid (TPA), and phthalaldehyde (o-phthalic acid, OPA). The purpose of this study was to investigate whether PA and PA isomers exert reproductive toxicity, including altered sperm movement. In vitro cell viability assays were comparatively performed using Sertoli and liver cell lines. In animal experiments, PA or PA isomers (10, 100, or 1000 mg/kg) were administered orally to Sprague-Dawley (SD) rats, and semen samples were analyzed by computer-aided sperm analysis (CASA). PA treatment produced a significant effect on curvilinear velocity (VCL), straight-line velocity (VSL), mean velocity or average path velocity (VAP), amplitude of lateral head displacement (ALH), and frequency of head displacement or beat cross-frequency (BCF), whereas IPA, TPA, and OPA induced no marked effects. In vitro cell viability assays showed that mouse normal testis cells (TM4) and human testis cancer cells (NTERA 2 cl. D1) were more sensitive to PA and OPA than mouse liver normal cells (NCTC clone 1469) and human fetal liver cells (FL 62891). Our study suggests that PA and PA isomers specifically produced significant in vitro and in vivo reproductive toxicity, particularly sperm toxicity and testis cell cytotoxicity. Of the isomers examined, PA appeared to be the most toxic and may serve as a surrogate biomarker for reproductive toxicity following mixed exposure to phthalates.

The responses of biochemical and genetic parameters were evaluated in tissues of Poecilia reticulata exposed to sublethal and environmentally relevant concentrations of 0.005, 0.01, or 0.02 mg/L of the organophosphorous (OP) pesticide temephos (TE) for 168 h. Activities of enzymes brain acetylcholinesterase (AChE) and liver carboxylesterase (CbE) were determined. Nuclear abnormalities (NA) and micronucleus (MN) frequency in gill erythrocytes were also measured. No mortality was observed over the experimental period; however, brain AChE activities were decreased significantly in guppies in all TE treatment groups after 72 h of exposure. Hepatic CbE activities of fish were increased in all TE treatment groups at 96, 120, and 144 h of exposure. The frequencies of MN and NA in fish gill erythrocytes displayed a marked rise after 168 h of exposure to concentrations of 0.01 or 0.02 mg/L TE. Thus, determination of these parameters may be employed as potential indices of exposure to TE using this sentinel organism for monitorining.

Carbon tetrachloride (CCl4), a halogenated substance that generates free radical species during metabolism in vivo, induces hepatotoxicity, produces oxidative DNA damage, and increased levels of protein carbonyl, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE). In this study, Sprague-Dawley rats received single or repeated ip injections of carbon tetrachloride (CCl4), and formation and persistence of carbonyls, MDA, and 4-HNE in plasma were measured using gas chromatography-mass spectrometry. After a single injection of 500 mg/kg CCl4 the in vivo half-lives of MDA and carbonyl content were 1.5 d and 2 d, respectively, while that of 4-HNE was approximately 10 d. Treatment with CCl4 (50, 100, 500, or 1000 mg/kg) dose-dependently increased these oxidative biomarkers in blood. However, formation of protein carbonyls and MDA was less sensitive than 4-HNE to CCl4. Levels of serum glutamic oxaloacetic transaminase (SGOT) and glutamic pyruvic transaminase (SGPT) (hepatotoxicity markers) rose with CCl4 doses. After a single injection (500 mg/kg), the peak level of SGOT was observed after 8 h but SGPT after 24 h. Overall, 4-HNE was more dose-sensitive and showed greater formation subchronically than other biomarkers. Multiple ip treatments with 300 mg CCl4 /kg (d 1, 3, 6, 10, 14, and 21) demonstrated that 4-HNE formation was highest (18-fold, peak/control) and subchronic up to d 21 (last treatment day), unlike other biomarkers. Data suggest that 4-HNE, MDA, and carbonyl content may be useful oxidative biomarkers for exposure to free radical generating halogenated compounds. However, 4-HNE appears to be a more sensitive and sustainable biomarker for toxicological and risk assessments.

Dietary exposure to arsenic (AS), cadmium (Cd), and lead (Pb) of Brazilian schoolchildren living in Ribeirão Preto, Brazil, was assessed. Food samples including rice, beans, vegetables, fruits, and meat served daily by public schools were collected as presented in different seasons. Metallic elements were determined by inductively coupled plasma-mass spectrometry (ICP-MS).The main sources of As, Cd, and Pb were found to be rice, vegetables, and pork, respectively. Further, in some food types there were seasonal differences in the concentrations of metallic elements. The mean daily intakes of As, Cd, and Pb based upon the association between food consumption data and the observed concentrations of metals in their diet were 6.9 μg, 0.9 μg, and 0.6 μg for As, Cd, and Pb, respectively. These findings are below the toxicological reference values provided by the European Food Safety Authority (EFSA) and the World Health Organization (WHO).

Environmental contaminants known as endocrine-disrupting chemicals (EDC) have been associated with adverse effects on reproductive processes. These chemicals may mimic or antagonize endogenous hormones, disrupting reproductive functions. Although preliminary studies focused on environmental estrogens, the presence of compounds with androgenic activity has also been described. This study examines exposure of female pregnant and lactating rats to low doses of androgens and assesses potential effects on female offspring. Pregnant Wistar rats were exposed to testosterone propionate (TP) at doses of 0.05, 0.1, or 0.2 mg/kg or corn oil (vehicle), subcutaneously, to determine influence on reproductive health of female offspring. There were two exposure groups: (1) rats treated from gestational day (GD) 12 until GD 20; and (2) animals treated from GD 12 until the end of lactation. Perinatal exposure to TP produced increased anogenital distance after birth and diminished height of uterine glandular epithelium at puberty in animals exposed to 0.2 mg/kg. However, these alterations were not sufficient to impair sexual differentiation and normal physiology of the female rat reproductive tract.

The purpose of this study was to examine the effects of Ag nanoparticles (nAg) of two different sizes (20 and 80 nm) and Ag(+) on the immune system of the freshwater mussel Elliptio complanata. Mussels were exposed to increasing concentrations of nAg and dissolved Ag (AgNO3) for 48 h at 15°C and concentration of 0, 0.8, 4, or 20 μg/L. Immunocompetence was determined by hemocyte viability, phagocytosis, and cell cytotoxicity. Ag tissue loadings and levels of metallothioneins (MT), lipid peroxidation (LPO), and labile zinc (Zn) were also determined. Results revealed first that 20- and 80-nm nAg readily formed aggregates in freshwater. Ag was detected in soft tissues with each form of Ag with bioconcentration factors of 20, 9, and 7 for Ag(+), 20-nm nAg, and 80-nm nAg, respectively. Significant induction in phagocytosis and decreased cell cytotoxicity were observed. All forms of Ag were able to induce LPO in gills and digestive glands at concentrations below those from the initial fraction of dissolved Ag. The effects of nAg on MT levels in mussels were not discernible from those of dissolved Ag, but the 80-nm was 25-fold more potent than 20-nm nAg in inducing MT. Multivariate analysis revealed that the global responses of the 20- and 80-nm nAg were generally similar to those of dissolved Ag. Data also demonstrated that nAg are bioavailable for mussels where the immune system is a target during early exposure to nanoparticles.

A mouse assay for measuring the relative bioavailability (RBA) of arsenic (As) in soil was developed. In this study, results are presented of RBA assays of 16 soils, including multiple assays of the same soils, which provide a quantitative assessment of reproducibility of mouse assay results, as well as a comparison of results from the mouse assay with results from a swine and monkey assay applied to the same test soils. The mouse assay is highly reproducible; three repeated assays on the same soils yielded RBA estimates that ranged from 1 to 3% of the group mean. The mouse, monkey, and swine models yielded similar results for some, but not all, test materials. RBA estimates for identical soils (nine test soils and three standard reference materials [SRM]) assayed in mice and swine were significantly correlated (r = 0.70). Swine RBA estimates for 6 of the 12 test materials were higher than those from the mouse assay. RBA estimates for three standard reference materials (SRM) were not statistically different (mouse/swine ratio ranged from 0.86-1). When four test soils from the same orchard were assessed in the mouse, monkey, and swine assays, the mean soil As RBA were not statistically different. Mouse and swine models predicted similar steady state urinary excretion fractions (UEF) for As of 62 and 74%, respectively, during repeated ingestion doses of sodium arsenate, the water-soluble As form used as the reference in the calculation of RBA. In the mouse assay, the UEF for water soluble As(V) (sodium arsenate) and As(III) (sodium [meta] arsenite) were 62% and 66%, respectively, suggesting similar absolute bioavailabilities for the two As species. The mouse assay can serve as a highly cost-effective alternative or supplement to monkey and swine assays for improving As risk assessments by providing site-specific assessments of RBA of As in soils.