Physico-chemical features of engineered nanoparticles relevant to their toxicity

Abstract

Nanotoxicology studies require investigations of several physico-chemical aspects of the particle/body fluid interaction, here described by reviewing recent literature in the light of new experimental data. Current characterization mostly covers morphology and metric-related characteristics (form, chemical composition, specific surface area, primary particle size and size distribution), and is mandatory in any experimental study. To unveil toxicity mechanisms, several other physico-chemical properties relevant to (geno) toxicity need to be assessed, typically the release or quenching of radical/ROS (Reactive Oxygen Species), the presence of active metal ions, evidence of structural defects. Major tasks for physical chemists working on nanoparticles-induced genotoxicity are described with some examples: (i), Tailored preparation of the same material in different sizes; (ii) particle modification changing a single property at a time; and (iii) identification of appropriate reference materials. Phenomena occurring during the contact between nanoparticles and cellular media or biological fluids (dispersion, agglomeration/aggregation, protein adsorption) are discussed in relation to the surface properties of the nanoparticles considered.     

太和胶囊毒理学安全性研究

目的 评价太和胶囊作为新资源食品的食用安全性。方法 采用小鼠急性经口毒性试验、小鼠骨髓微核试验、小鼠精子畸形试验、Ames试验和30d喂养试验进行检测。结果 雌雄小鼠急性经口最大耐受剂量(MTD)均大于15．0g/kg体重，属无毒级；骨髓微核试验、精子畸形试验、Ames试验3项遗传毒性试验均为阴性；30d喂养试验未显示明显毒性。结论 太和胶囊属安全性食品。     

饮用水中非挥发性有机物的遗传毒性及脂质过氧化作用

用ＳＯＳ显色法研究了３种不同水源自来水中非挥发性有机物的遗传毒性，以大鼠肝微粒体系统为模型研究了自来水非挥发性有机物的脂质过氧化作用。结果表明：以Ｄ湖水为水源的自来水中非挥发性有机物具有遗传毒性、且能使大鼠肝微粒体的脂质过氧化作用显著增强。     

化学诱变剂在实验海洋食物链中的流动以及遗传毒性的检测——Ⅱ.有机诱变剂苯并[a]芘

采用高压液相色谱(HPLC)测定的方法研究了有机诱变剂苯并[a]芘在实验海洋食物链(从浮游藻类褐指藻Phaeodactylum tricornutum Bohlin经中国对虾Penaeueus orientalis Kishinouye到欧氏六线鱼Hexagrammos otakii Jordan et Starks)中的流动,并对积累苯并]a[芘的中国对虾和欧氏六线鱼内脏和肌肉进行了紫露草微核(Trad-MCN)的测定,结果如下:①苯并]a[芘具有延缓褐指藻生长的作用。褐指藻中苯并[a]芘的吸着量随剂量的增大而增大。苯并[a]芯的测定量小于加入量,其损失量与剂量之间具有一定的相关性。②鱼虾内脏中积累的苯并[a]芘的浓度高于肌肉中的浓度。苯并[a]芘在中国对虾到欧氏六线鱼的传递中浓度减少,在鱼肉中很难检测到。通过显著性t测检发现,处理组和对照组虾肉之间的诱变性差异显著(P<0.05),处理组和对照组虾内脏之间的违变性差异亦显著)P<0.005)。     

Genotoxicity of Acqueous Elutions of Industrial Soils

The genotoxicity of industrial soils was evaluated. A single cell electrophoresis assay or comet assay, using eleocyte cells of Eisenia foetida, was performed to assess the genotoxicity of aqueous elutions. These were obtained from industrial soils containing metals. All soil samples meet the environmental quality guidelines for metal concentrations. However, elutions have produced genotoxic effects at dilutions as low as 6%. Total metal concentrations for each aqueous elution could express synergistic effects of these compounds.     

Cytotoxic and genotoxic potential of the type I photoinitiators BAPO and TPO on human oral keratinocytes and V79 fibroblasts

Objectives

Phenylbis(acyl) phosphine oxide (BAPO) and diphenyl(acyl) phosphine oxide (TPO) are alternative photoinitiators to camphorquinone (CQ) in dental resinous materials. Aim of this study was to investigate their cytotoxic/genotoxic potential in human oral keratinocytes (OKF6/Tert2) and Chinese hamster lung fibroblasts (V79) in comparison to CQ.

Genotoxicity of trichloroethylene in the natural milieu

Trichloroethylene (TCE) is a suspected genotoxic and carcinogenic compound which is usually present in the air, soil and water as pollutant. To estimate the genotoxic potential of TCE in a pure chemical form as well as an ingredient of the complex sample, Ames fluctuation test using TA98 and TA100 strains and Allium cepa genotoxicity assay were performed. For the genotoxicity analysis of TCE in natural milieu, the above mentioned tests were performed on the waste waters collected from two different stations of northern India namely Saharanpur and Aligarh, U.P., and these waste waters were supplemented with 50 and 100 mg/l of trichloroethylene. TCE alone was found to be non-genotoxic by both the testing system up to the range of 1000 mg/l concentration (data not shown). However, the test water samples supplemented with 100 mg/l of TCE, exhibited a significant increase in the genotoxicity compared with control by both the testing systems. In Ames fluctuation test, Mi(f) value was found to be increased by 41% and 53% with 100 mg/l of TCE supplemented Saharanpur and Aligarh waste water samples respectively, in the presence of S9 fraction compared with their respective controls. Allium cepa genotoxicity test also showed around 25% increase in total chromosomal aberration frequency following 100 mg/l TCE supplementation. However, supplementation of 50 mg/l TCE to the test water samples could not enhance the genotoxicity to a significant extent. From these results, we can conclude that TCE itself was non-genotoxic but it may promote mutation and/or DNA damage at a concentration of 100 mg/l under certain environmental conditions. We suggest that some chemicals in the test water samples might be interacting with TCE and/or metabolite(s) to cause the enhancement in genotoxicity. The mechanism of these synergistic effects should be explored further.     

城市生活垃圾健康危害研究进展

人类目前正承受着垃圾处理的巨大压力,特别是城市垃圾的问题已严重困扰城市。垃圾对人们日常生活特别是身体健康方面的影响也越来越受到重视。本文就垃圾产生遗传毒性,发育毒性甚至诱发肿瘤等方面的研究展开综述。     

P-postlabeling analysis of DNA adducts formed in vitro and in rat skin by methylenediphenyl-4,4'-diisocyanate (MDI)

The ³²P-postlabeling method was adapted for the detection of DNA adducts formed by methylenediphenyl-4,4'-diisocyanate (MDI). Incubation of the 3'-phosphates of the deoxyribosides of cytosine (C), adenine (A), guanine (G) and thymine (T) with MDI in Tris buffer resulted in the formation of 5, 7, 8, and 2 reaction products, respectively. Incubation of DNA with MDI resulted in detectable levels of 5, 2, and 1 adducts attributable to C, A, and G. Analysis of DNA isolated from the epidermis of rats treated dermally with 9 mg MDI showed an adduct pattern similar to the one seen in the in vitro DNA incubation. A total adduct level of 7 per 10⁸ nucleotides was measured, the limit of detection was 2 adducts per 10¹⁰ nucleotides. The data indicate that a minute fraction of MDI can reach DNA in vivo in a chemically reactive form. In comparison with the genotoxic skin carcinogen 7,12-dimethylbenz[a]anthracene on the other hand, the DNA-binding potency of MDI was more than 1000-fold lower.     

In vivo micronucleus test in mice with 1-phenylethanol

1-Phenylethanol is one of the major primary phase-I metabolites of ethylbenzene. In principle it may yield an electrophilic intermediate by phase-II metabolism. Because of the extensive use of ethylbenzene as a solvent, 2-year carcinogenicity inhalation studies were carried out leading to renal hyperplasia and tubular neoplasms both in male and female rats and alveolar/bronchiolar neoplasms in male mice and hepatocellular neoplasms in female mice. Whereas the mechanism underlying the increased renal tumor incidences in rats has been clarified, the mechanism of tumor formation (genotoxic or nongenotoxic mode of action) in the lung and liver of mice is still unclear. The genotoxicity data available to date for 1-phenylethanol include in vitro studies using either bacteria (Salmonella reverse mutation assay, E. coli Pol A⁺/Pol A⁻ test) or mammalian cells (mouse lymphoma assay, chromosome aberration test and sister chromatid exchanges using CHO cells). These experiments, however, did not always follow current standard procedures and some of the data obtained are compromised and not always convincing. The present database thus does not allow a definitive assessment of the in vitro genotoxic potential of 1-phenylethanol. The in vitro database suggests that clastogenicity may be the most relevant genetic end point, and therefore an in vivo micronucleus assay in mouse bone marrow was carried out. The animals were given 1-phenylethanol in single oral doses up to the maximum tolerated dose of 750 mg/kg body weight. Bone marrow was sampled 24 and 48 h after treatment. Under the experimental conditions used, there was no evidence of increased micronuclei frequencies at any dose or sampling time. These findings indicate that 1-phenylethanol is not clastogenic in vivo. This information, together with other negative or inconclusive genotoxicity data available so far, suggests a nongenotoxic mode of action responsible for the lung and liver tumors observed in mice following 2 years of inhalation exposure to ethylbenzene.