Lead distribution in rats following respiratory exposure to lead-contaminated soils

Two preliminary experiments were performed to explore the use of an intratracheal instillation technique as a cost-effective method of determining the biokinetics of lead (Pb) following respiratory exposure to Pb-contaminated soils. A novel intratracheal instillation procedure was refined and used to deliver a defined dose of Pb-contaminated soil or PbAc to the lower respiratory tract of rats. In the first experiment, rats were sacrificed at numerous time intervals post-dosing, and liver, kidney, blood, and bone tissues were collected for Pb analysis. In the second experiment, rats were dosed with Pb-contaminated soil or PbAc via intratracheal instillation or gastric gavage. All rats were sacrificed 96 h after dose administration and tissues were collected for lead analysis. Data from these experiments indicate Pb is well-absorbed following intratracheal instillation of Pb-contaminated soil, and the intratracheal instillation technique could be used as a cost effective method for exploring the biokinetics of Pb in Pb-contaminated soils following respiratory tract exposure.     

环境中类固醇激素与斑马鱼(Danio rerio)体内有机阴离子转运多肽(Oatp1d1)的相互作用

环境中类固醇激素具有很高的生物活性,在水环境中又普遍存在,因而对鱼类健康造成威胁。目前,对鱼体内类固醇激素的吸收过程和毒代动力学知之甚少,特别是其中细胞膜转运体的作用。我们考察了17种内源性和环境中类固醇激素与斑马鱼体内有机阴离子摄取性转运体Oatp1d1的相互作用,Oatp1d1在斑马鱼的肝脏和肾脏中有显著表达。我们选择了不同类别的类固醇激素,包括雄烯二酮(A4)、黄体酮(P4)及其代谢物、糖皮质激素和螺旋内酯甾酮(竞争性抑制萤光黄(Lucifer Yellow, LY)的吸收)。半数抑制效应浓度(IC₅₀)通过S形抑制曲线获得,P4的IC₅₀最小,其他IC₅₀由大到小排列为:17α-羟基黄体酮>丙酸氯倍他索>螺旋内酯甾酮>21-羟基黄体酮>醋酸氟氢可的松和其他的糖皮质激素。类固醇激素的亲脂性与Oatp1d1相互作用的活性呈正相关关系。我们的数据表明不同类别的类固醇激素与Oatp1d1的相互作用活性不同,或为吸收,或为抑制,或吸收和抑制。如此可知类固醇激素会介入内源性底物的转运过程,以致相关的生理过程。同时,类固醇激素可通过竞争性抑制作用改变环境污染物的细胞贩运。 精选自Raffael Alois Willi, Karl Fent. Interaction of environmental steroids with organic anion transporting polypeptide (Oatp1d1) in zebrafish (Danio rerio). Environmental Toxicology and Chemistry,2018,37:2670-2676.
详情请见 https://doi.org/10.1002/etc.4231
     

Silica nanoparticles and silver-doped silica nanoparticles induce endoplasmatic reticulum stress response and alter cytochrome P4501A activity

Engineered silica nanoparticles (SiO₂-NPs) find widespread application and may lead to exposure of humans and the environment. Here we compare the effects of SiO₂-NPs and SiO₂-NPs doped with silver (SiO₂-Ag-NPs) on survival and cellular function of human liver cells (Huh7) and Pimephales promelas (fathead minnow) fibroblast cells (FMH). In Huh7 cells we investigate effects on the endoplasmatic reticulum (ER), including ER stress, and interactions of nanoparticles (NPs) with metabolizing enzymes and efflux transporters. The NPs formed agglomerates/aggregates in cell culture media as revealed by SEM and TEM. SiO₂ and SiO₂-1% Ag-NPs were taken up into cells as demonstrated by agglomerates occurring in vesicular-like structures or freely dispersed in the cytosol. Cytotoxicity was more pronounced in Huh7 than in FMH cells, and increased with silver content in silver-doped NPs. Dissolved silver was the most significant factor for cytotoxicity. At toxic and non-cytotoxic concentrations SiO₂-NPs and SiO₂-1% Ag-NPs induced perturbations in the function of ER. In Huh7 cells NPs induced the unfolded protein response (UPR), or ER stress response, as demonstrated in induced expression of BiP and splicing of XBP1 mRNA, two selective markers of ER stress. Additionally, SiO₂-1% Ag-NPs and AgNO₃ induced reactive oxygen species. Pre-treatment of Huh7 cells with SiO₂-1% Ag-NPs followed by exposure to the inducer benzo(a)pyrene caused a significant reduced induction of CYP1A activity. NPs did not alter the activity of ABC transporters. These data demonstrate for the first time that SiO₂-NPs and SiO₂-1% Ag-NPs result in perturbations of the ER leading to the ER stress response. This represents a novel and significant cellular signalling pathway contributing to the cytotoxicity of NPs.     

A pilot study of oral bioavailability of dioxins and furans from contaminated soils: Impact of differential hepatic enzyme activity and species differences

An in vivo pilot study of the oral bioavailability of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in two soils with distinct congener profiles (one dominated by PCDDs, the other by PCDFs) was conducted in rats and juvenile swine. The pilot study revealed potential confounding of relative bioavailability estimates compared to bioavailability in spiked corn oil gavage for tetrachlorodibenzofuran (TCDF) in the rat study due to differential EROD induction between groups receiving soil and those receiving spiked control PCDDs/PCDFs. A follow-up study in rats with the furan-contaminated soil was then conducted with reductions in the spiked control doses to 20%, 50% and 80% of the soil-feed dose in order to bracket hepatic enzyme induction levels in the soil group. When hepatic enzyme induction was matched between the soil and spiked control groups, the apparent relative bioavailability for TCDF was reduced significantly. Overall, after controlling for hepatic enzyme induction, estimates of relative bioavailability in rats and swine differed for the two soils. In the rat study, the relative bioavailability of the two soils were approximately 37% and 60% compared to corn oil administration for the PCDD- and PCDF- dominated soils, respectively, on a TEQ basis. In swine, both soils demonstrated relative bioavailability between 20% and 25% compared to administration in corn oil. These species differences and experimental design issues, such as controlling for differential enzyme induction between corn oil and soil-feed animals in a bioavailability study, are relevant to risk assessment efforts where relative bioavailability inputs are important for theoretical exposure and risk characterization.     

Widespread occurrence of estrogenic UV-filters in aquatic ecosystems in Switzerland

We performed a trace analytical study covering nine hormonally active UV-filters by LC-MS/MS and GC-MS in river water and biota. Water was analysed at 10 sites above and below wastewater treatment plants in the river Glatt using polar organic chemical integrative samplers (POCIS). Four UV-filters occurred in the following order of decreasing concentrations; benzophenone-4 (BP-4) > benzophenone-3 (BP-3) > 3-(4-methyl)benzylidene-camphor (4-MBC) > 2-ethyl-hexyl-4-trimethoxycinnamate (EHMC). BP-4 ranged from 0.27 to 24.0 μg/POCIS, BP-3, 4-MBC and EHMC up to 0.1 μg/POCIS. Wastewater was the most important source. Levels decreased with higher river water flow. No significant in-stream removal occurred. BP-3, 4-MBC and EHMC were between 6 and 68 ng/L in river water. EHMC was accumulated in biota. In all 48 macroinvertebrate and fish samples from six rivers lipid-weighted EHMC occurred up to 337 ng/g, and up to 701 ng/g in 5 cormorants, suggesting food-chain accumulation. UV-filters are found to be ubiquitous in aquatic systems.     

Quantitative monitoring of dermal and inhalation exposure to 1,6-hexamethylene diisocyanate monomer and oligomers

Respiratory sensitization and occupational asthma are associated with exposure to 1,6-hexamethylene diisocyanate (HDI) in both monomeric and oligomeric forms. The monomer and polymers of diisocyanates differ significantly in their rates of absorption into tissue and their toxicity, and hence may differ in their contribution to sensitization. We have developed and evaluated a liquid chromatography/mass spectrometry (LC-MS) method capable of quantifying HDI and its oligomers (uretidone, biuret, and isocyanurate) in air, tape-stripped skin, and paint samples collected in the automotive refinishing industry. To generate analytical standards, urea derivatives of HDI, biuret, and isocyanurate were synthesized by reaction with 1-(2-methoxyphenyl)piperazine and purified. The urea derivatives were shown to degrade on average by less than 2% per week at -20 degrees C over a 2 month period in occupational samples. The average recovery of HDI and its oligomers from tape was 100% and the limits of detection were 2 and 8 fmol microl(-1), respectively. Exposure assessments were performed on 13 automotive spray painters to evaluate the LC-MS method and the sampling methods under field conditions. Isocyanurate was the most abundant component measured in paint tasks, with median air and skin concentrations of 2.4 mg m(-3) and 4.6 microg mm(-3), respectively. Log-transformed concentrations of HDI (r = 0.79, p < 0.0001) and of isocyanurate (r = 0.71, p < 0.0001) in the skin of workers were correlated with the log-transformed product of air concentration and painting time. The other polyisocyanates were detected on skin for less than 25% of the paint tasks. This LC-MS method provides a valuable tool to investigate inhalation and dermal exposures to specific polyisocyanates and to explore relative differences in the exposure pathways.