Hygienic and toxicological aspects of occupational and environmental exposure to beryllium

As the production of missile, nuclear devices and electronics grew and modern industrial technologies emerged the risk of the occupational exposure to beryllium has become increasingly common and widespread. The environmental burden of beryllium is also on the increase, not only as a result of emissions from plants producing and processing beryllium, or its alloys and compounds, but also from burning coal of higher beryllium content in some localities. This article discusses primarily the hygienic and toxicologic aspects of beryllium and its threat to human health. The following topics are included in this review: occurrence, production and uses of beryllium; its metabolism and experimental toxicology; clinical toxicology and pathogenesis of berylliosis; hygienic and epidemiologic aspects of berylliosis; berylliosis treatment and prevention. Berylliosis is here characterized as a disease combining clinical manifestations of pneumosclerosis, allergy to beryllium and, in its granulomatous form, autoimmune reactions. Importantly, the available technical means and measures can ensure that the both occupational and environmental exposure to beryllium can be kept below the established MAC values. If occasionally impossible, special preventive measures should be adopted. It is essential that all persons with allergy be prophylactically excluded from work at risk of exposure to beryllium.     

Interactions of chromium with microorganisms and plants

Chromium is a highly toxic non-essential metal for microorganisms and plants. Due to its widespread industrial use, chromium (Cr) has become a serious pollutant in diverse environmental settings. The hexavalent form of the metal, Cr(VI), is considered a more toxic species than the relatively innocuous and less mobile Cr(III) form. The presence of Cr in the environment has selected microbial and plant variants able to tolerate high levels of Cr compounds. The diverse Cr-resistance mechanisms displayed by microorganisms, and probably by plants, include biosorption, diminished accumulation, precipitation, reduction of Cr(VI) to Cr(III), and chromate efflux. Some of these systems have been proposed as potential biotechnological tools for the bioremediation of Cr pollution. In this review we summarize the interactions of bacteria, algae, fungi and plants with Cr and its compounds.     

Genetic toxicology: Findings and challenges

The review highlights the history of genetic toxicology as a distinct research area, as well as the issues of genetic toxicology and development of its methodology. The strategies and testing patterns of genotoxic compounds are discussed with the purpose of identifying potential human carcinogens, as well as compounds capable of inducing heritable mutations in humans. The main achievements of genetic toxicology in the 20th century are summarized and the challenges of the 21st century are discussed.     

Actual problems of genetic toxicology

The review deals with current issues of genetic toxicology and aims to develop this science at the contemporary stage. We study general approaches to assessing the genotoxic and mutagenic activity of environmental factors; to constructing a regulatory system of chemical compounds that considers the mutagenic effect in Russia and abroad; and to determining modern methods for assessing the organ specificity of mutagens, alternative methods of genetic toxicology, the mutagenic action of various factors in the survey of population, and the abilities of toxicogenomics to identify the mutagenic properties of the environment.     

Effect of Rhamnolipids on Chromium-Contaminated Kaolinite

Hexavalent chromium Cr(VI) is a common environmental pollutant that is treated by its reduction to the trivalent form Cr(III). The latter can be re-oxidized to the toxic form, Cr(VI), under specific conditions. A study was conducted on the removal of Cr(III) to eliminate the hazard imposed by its presence in soil as there has been some evidence that organic compounds can decrease its sorption. The effect of addition of negatively-charged biosurfactants (rhamnolipids) on chromium contaminated kaolinite was studied. Results showed that the rhamnolipids have the capability of extracting 25% portion of the stable form of chromium, Cr(III), from the kaolinite, under optimal conditions. The removal of hexavalent chromium was also enhanced compared to water by a factor of 2 using a solution of rhamnolipids. Results from the sequential extraction procedure showed that rhamnolipids remove Cr(III) mainly from the carbonate and oxide/hydroxide portions of the kaolinite. The rhamnolipids had also the capability of reducing close to 100% of the extracted Cr(VI) to Cr(III) over a period of 24 days. This study indicated that rhamnolipids could be beneficial for the removal or long–term conversion of chromium Cr(VI) to Cr(III).     

Insolubilization of hexavalent chromium in highly alkaline cement sludge by anaerobic bioremediation

Chemical treatment using reducing agents such as ferrous sulfate is the most popular method for remediation of hexavalent chromium–contaminated sludge. However, the use of such chemical agents poses the risk of secondary pollution through the elution of other heavy metals. Therefore, a bioremediation method was developed to remediate high-alkali cement sludge containing hexavalent chromium. When a biomediator mainly composed of lignocellulose and lignoarabinoxylan was added to hexavalent chromium–contaminated sludge under anaerobic conditions, the amount of hexavalent chromium eluted from the treated sludge decreased significantly to below the level of the environmental standard value in Japan and its pH was reduced to 8. Moreover, the oxidation-reduction potential of the treated sludge decreased and its microbiota changed. These results indicate that anaerobic microbes can facilitate the change of hexavalent chromium to an immobilized form of trivalent chromium. Nucleotide sequence analysis suggested that anaerobic microbes activated in the sludge were Exiguobacterium aurantiacum, which are known to tolerate high pH environments and produce organic acids, even in the cement sludge. Finally, treated sludge did not elute hexavalent chromium during shaking in acid or alkaline solution.     

Reduction of Toxic Chromium and Partial Localization of Chromium Reductase Activity in Bacterial Isolate DM1

Summary With advances in biotechnology, bioremediation has become one of the most rapidly developing fields in environmental restoration, utilizing microorganism to reduce the concentration and toxicity of heavy metals. Hexavalent chromium reducing bacterial culture (DM1) was isolated from the contaminated sites of chemical industries and its ability to reduce hexavalent chromium to trivalent chromium, a detoxification process in cell suspension and cell extract was examined. Based on the biochemical analysis DM1 was identified as Ochrobactrum sp. It could tolerate chromium upto a maximum concentration of 300 ppm, optimum temperature and pH being 35 °C and 7 respectively for maximum chromium reduction. Assay with the permeabilized cells (treated with toluene and Triton X-100) and cell free extract demonstrated that the hexavalent chromium reduction is mainly associated with the soluble fraction of the cell. The chromium reducing activity is inducible. The presence of an induced protein having molecular weight around 30 kDa in the presence of chromium and absence in cells without chromium points out a possible role of this protein in chromium reduction. The bacterial isolate DM1 can be exploited for bioremediation of hexavalent chromium containing wastes, since it seems to have the potential to reduce the toxic hexavalent form of chromium to its nontoxic trivalent form.     

Emerging issues: nutritional awareness in environmental toxicology

Based on recent evidence, we hypothesize that nutrition can modulate the toxicity of environmental pollutants and thus modulate health and disease outcome associated with chemical insults. For example, certain dietary fats may increase the risk to environmental insult induced by polychlorinated biphenyls (PCBs), and fruits and vegetables, rich in antioxidant and anti-inflammatory nutrients or bioactive compounds, may provide protection. Nutritional awareness in environmental toxicology is critical, because of opportunities to develop dietary guidelines which specifically target exposed populations. Nutrition may provide the most sensible means to develop primary prevention strategies of diseases associated with environmental toxicology.     

Perfluorinated compounds: occurrence and risk profile

Perfluorinated compounds (PFCs) such as perfluoro-octane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) are emerging environmental pollutants, arising mainly from their use as surface treatment chemicals, polymerization aids and surfactants. They are ubiquitous, persistent and bioaccumulative in the environment. Perfluorinated compounds are being proposed as a new class of POPs. Although tests in rodents have demonstrated numerous negative effects of PFCs, it is unclear if exposure to perfluorinated compounds may affect human health. This review provides an overview of the recent toxicology and toxicokinetics, monitoring data now available for the environment, wildlife, and humans and attempts to explain the mechanisms of action of PFCs.     

Environmental enrichment of laboratory animals used in regulatory toxicology studies

There is a wealth of information in the published literature which describes a multitude of approaches to enriching the environment of laboratory animals. This paper attempts to review the various methods of enrichment through social contact, enhancement of the environment and diet, and improvements in husbandry. It attempts to place the various enrichment initiatives within the context of a laboratory which conducts regulatory toxicology, describes some of the experiences in the author's own laboratory and attempts to highlight those ideas which might prove practical to implement in the future. The aim is to demonstrate that a creative approach to environmental enrichment is indeed compatible with regulatory toxicology. It is hoped that this will encourage those responsible for the care and welfare of animals in such a laboratory to challenge historical practices and include environmental enrichment as a fundamental necessity of study design.     

代谢组学及其在环境毒理学中的应用

代谢组学作为系统生物学的一部分,因其具有分析速度快的特点,被广泛用于生物医学等方面的研究。目前代谢组学在环境毒理学方面的研究主要针对单一污染物,但也需要考虑到被污染地的复杂情况。通过介绍代谢组学及其发展历程,总结了目前主流代谢组学技术的各自特点,讨论了代谢组学在环境重金属、有机污染物和抗生素中的毒性评估以及环境胁迫耐受性中的评价等方面内容,综述了其在环境毒理学中的应用,并指出其应用不足,旨在为代谢组学应用于环境毒理学的研究提供参考。     

Killing of Chromium-Damaged Cells by Mismatch Repair and its Relevance to Carcinogenesis

Hexavalent chromium compounds are widespread environmental contaminants that are well recognized as human carcinogens and potent respiratory toxicants. Intracellular metabolism of chromium(VI) leads to the production of numerous chromium-DNA adducts that are primarily formed at the phosphate groups. The mechanism of toxicity of these DNA modifications in human cells has been uncertain for a long time because chromium and other phosphate-based adducts did not block DNA replication with purified polymerases. Our recent studies identified mismatch repair proteins as activators of toxic responses to chromium-DNA damage, which resolved an apparent discrepancy in genotoxic activity of chromium adducts in cells and in vitro. The discovered mechanism of toxicity provided the basis for a novel model of chromium carcinogenesis based on the selection of resistant clones that lack mismatch repair and progress to cancer due to high levels of spontaneous mutagenesis.     

DNA microarray technology in toxicogenomics of aquatic models: methods and applications

Toxicogenomics represents the merging of toxicology with genomics and bioinformatics to investigate biological functions of genome in response to environmental contaminants. Aquatic species have traditionally been used as models in toxicology to characterize the actions of environmental stresses. Recent completion of the DNA sequencing for several fish species has spurred the development of DNA microarrays allowing investigators access to toxicogenomic approaches. However, since microarray technology is thus far limited to only a few aquatic species and derivation of biological meaning from microarray data is highly dependent on statistical arguments, the full potential of microarray in aquatic species research has yet to be realized. Herein we review some of the issues related to construction, probe design, statistical and bioinformatical data analyses, and current applications of DNA microarrays. As a model a recently developed medaka (Oryzias latipes) oligonucleotide microarray was described to highlight some of the issues related to array technology and its application in aquatic species exposed to hypoxia. Although there are known non-biological variations present in microarray data, it remains unquestionable that array technology will have a great impact on aquatic toxicology. Microarray applications in aquatic toxicogenomics will range from the discovery of diagnostic biomarkers, to establishment of stress-specific signatures and molecular pathways hallmarking the adaptation to new environmental conditions.     

Toxicity,bioavailability and metal speciation

1. Environmental toxicology emphasizes the difference from traditional toxicology in which pure compounds of interest are added to purified diets, or injected into the test animals. When the objective is to study the fate and effects of trace elements in the environment, knowledge of the speciation of the elements and their physico-chemical forms is important.2. Cadmium salts such as the sulfides, carbonates or oxides, are practically insoluble in water. However, these can be converted to water-soluble salts in nature under the influence of oxygen and acids. Chronic exposure to Cd is associated with renal toxicity in humans once a critical body burden is reached.3. The solubility of As(III) oxide in water is fairly low, but high in either acid or alkali. In water, arsenic is usually in the form of the arsenate or arsenite. As(III) is systemically more poisonous than the As(V), and As(V) is reduced to the As(III) form before exerting any toxic effects. Organic arsenicals also exert their toxic effects in vivo in animals by first metabolizing to the trivalent arsenoxide form. Some methyl arsenic compounds, such as di- and trimethylarsines, occur naturally as a consequence of biological activity. The toxic effect of arsenite can be potentiated by dithiols, while As has a protective effect against the toxicity of a variety of forms of Se in several species.4. Selenium occurs in several oxidation states and many selenium analogues of organic sulfur compounds exist in nature. Selenium in selenate form occurs in alkaline soils, where it is soluble and easily available to plants. Selenite binds tightly to iron and aluminum oxides and thus is quite insoluble in soils. Hydrogen selenide is a very toxic gas at room temperature. The methylated forms of Se are much less toxic for the organism than selenite. However, the methylated Se derivatives have strong synergistic toxicity with other minerals such as arsenic.5. Aquatic organisms absorb and retain Hg in the tissues, as methylmercury, although most of the environmental Hg to which they are exposed is inorganic. The methylmercury in fish arises from the bacterial methylation of inorganic Hg. Methylmercury in the human diet is almost completely absorbed into the bloodstream. The nervous system is the principal target tissue affected by methylmercury in adult human beings, while kidney is the critical organ following the ingestion of Hg(II) salts.     

Role of physiological antioxidants in chromium(VI)-induced cellular injury.

Chromium(VI) compounds are well known to be potent toxic and carcinogenic agents. Because chromium(VI) is easily taken up by cells and is subsequently reduced to the trivalent form, the formation of chromium(III) or other intermediate oxidation states such as chromium(V) and (IV) is believed to play a role in the adverse biological effects of chromium(VI) compounds. Recent in vitro studies have shown that this reduction process generates free radical species such as active oxygen radicals. Furthermore, physiological antioxidants are reported to modify the genotoxic and toxic effects of chromate. This article reviewed the recent in vitro and in vivo studies of the effects of antioxidants including active oxygen scavengers; glutathione; vitamins B2, E, and C, on chromate-induced injury such as DNA lesions; lipid peroxidation; enzyme inhibition; cytotoxicity; mutation; and so on. In addition, the mechanism of action of these antioxidants was discussed with respect to the formation of active oxygen radicals and paramagnetic chromium such as chromium(V) and (III). Such studies may help elucidate the mechanism of chromium(VI) toxicity as well as the mechanism of protection.     

In vivo reduction of chromium (VI) and its related free radical generation

Chromium (VI) compounds are widely recognized as human carcinogens. Extensive studies in vitro and in model systems indicate that the reactive intermediate, Cr (V), generated by cellular reduction of Cr (VI), is likely the candidate for the ultimate carcinogenic form of chromium compounds. Here we review our current understanding of the in vivo reduction of Cr (VI) and its related free radical generation. Our results demonstrate that Cr (V) is indeed generated from the reduction of Cr (VI) in vivo, and that Cr (V) thus formed can mediate the generation of free radicals. Cr (V) and its related free radicals are very likely to be involved in the mechanism of Cr (VI)induced toxicity and carcinogenesis. These studies also illustrate that in vivo EPR spectroscopy and magnetic resonance imaging can be very useful and powerful tools for studying paramagnetic metal ions in chemical and biochemical reactions occurring in intact animals.     

Hygienic-toxicological aspects of exposure to lead. A critical review

This review on hygienic, toxicologic and ecologic aspects of environmental burden of lead deals with the following topics: occurrence, production and use of lead; metabolism of lead and experimental toxicology of lead; toxicity of lead to man; hygienic and ecologic aspects of lead pollution. Lead ore mining and processing, production of lead-acid batteries and combustion of gasoline containing tetraethyl-lead as an anti-knock ingredient constitute at present the most important sources of lead pollution. The last named source of lead pollution in urban atmosphere is most hazardous to human health. Attempts to reduce this health hazard include use of additive-free gasoline, or replacement of tetraethyl lead by other anti-knock agents, e. g. by tetraethylcopper. The experiments with the use of organic compounds of manganese have failed to succeed. The possibility of biological monitoring of occupational and nonoccupational exposures to lead is discussed in detail in this review.     

Chromium metabolism

The trivalent state of chromium (Cr³⁺) is that encountered in biological milieus and is responsible for its nutritional activity. The principal route by which trivalent chromium enters the body is the digestive system. Chromium in foods is present both in the inorganic form and as organic complexes. Intestinal absorption of chromium is low (0.5–2%), and the mechanism has not yet been fully elucidated. Absorbed chromium circulates as free Cr³⁺, as Cr³⁺ bound to transferrin or other plasma proteins, or as complexes, such as glucose tolerance factor (GTF)-Cr. Circulating trivalent chromium can be taken up by tissues, and its distribution in the body depends on the species, age, and chemical form. It is excreted primarily in the urine by glomerular filtration or bound to a low-mol-wt organic transporter. Chromium metabolism is still imperfectly understood. The use of⁵¹Cr has nevertheless furnished valuable data concerning its transport and excretion.     

From quantal counts to mechanisms and systems: the past, present, and future of biometrics in environmental toxicology

As appreciation for human impact on the environment has developed, so have the experimental systems and associated statistical tools that quantify this impact. Toxicological study in particular has grown in its complexity and its need for advanced statistical support. Within this perspective, we describe statistical practice in environmental toxicology and risk assessment. We present two case studies, one from mammalian toxicology and one from aquatic toxicology, that highlight the evolution of statistical practice in environmental toxicology.