Hana R. Pohl

Vitamin C intake influences the bleomycin-induced chromosome damage assay: implications for detection of cancer susceptibility and chromosome breakage syndromes.

Supplementation with 1 g of vitamin C (ascorbic acid) per day decreased the amount of chromosome damage induced in lymphocytes by an exposure to bleomycin during the last 5 h of cell culture. We did not see such changes in lymphocytes from control individuals samples at the same time but not taking vitamin C supplements. This bleomycin assay has been proposed as a test for cancer susceptibility. A similar assay for genetic instability may be useful in detecting heterozygotes for chromosome-breakage syndromes (for example, Fanconi anemia or ataxia telangiectasia). Even though our sample size is small and our results should be interpreted cautiously, statistically significant effects were found with vitamin C supplementation. It would, therefore, be prudent to consider dietary and perhaps other lifestyle factors when interpreting of results from this bleomycin assay and related assays for genetic instability.

10:Metal Ions Affecting the Neurological System

Several individual metals including aluminum, arsenic, cadmium, lead, manganese, and mercury were demonstrated to affect the neurological system. Metals are ubiquitous in the environment. Environmental and occupational exposure to one metal is likely to be accompanied by exposure to other metals, as well. It is, therefore, expected that interactions or “joint toxic actions” may occur in populations exposed to mixtures of metals or to mixtures of metals with other chemicals. Some metals seem to have a protective role against neurotoxicity of other metals, yet other interactions may result in increased neurotoxicity. For example, zinc and copper provided a protective role in cases of lead-induced neurotoxicity. In contrast, arsenic and lead co-exposure resulted in synergistic effects. Similarly, information is available in the current literature on interactions of metals with some organic chemicals such as ethanol, polychlorinated biphenyls, and pesticides. In depth understanding of the toxicity and the mechanism of action (including toxicokinetics and toxicodynamics) of individual chemicals is important for predicting the outcomes of interactions in mixtures. Therefore, plausible mechanisms of action are also described.

Mixtures and their risk assessment in toxicology.

For communities generally and for persons living in the vicinity of waste sites specifically, potential exposures to chemical mixtures are genuine concerns. Such concerns often arise from perceptions of a sites higher than anticipated toxicity due to synergistic interactions among chemicals. This chapter outlines some historical approaches to mixtures risk assessment. It also outlines ATSDRs current approach to toxicity risk assessment. The ATSDRs joint toxicity assessment guidance for chemical mixtures addresses interactions among components of chemical mixtures. The guidance recommends a series of steps that include simple calculations for a systematic analysis of data leading to conclusions regarding any hazards chemical mixtures might pose. These conclusions can, in turn, lead to recommendations such as targeted research to fill data gaps, development of new methods using current science, and health education to raise awareness of residents and health care providers. The chapter also provides examples of future trends in chemical mixtures assessment.

13. Historical View on Lead: Guidelines and Regulations

Lead has been used in many commodities for centuries. As a result, human exposure has occurred through the production and use of these lead-containing products. For example, leaded gasoline, lead-based paint, and lead solder/pipes in water distribution systems have been important in terms of exposure potential to the general population. Worker exposures occur in various industrial activities such as lead smelting and refining, battery manufacturing, steel welding or cutting operations, printing, and construction. Some industrial locations have also been a source of exposure to the surrounding communities. While the toxicity of relatively high lead exposures has been recognized for centuries, modern scientific studies have shown adverse health effects at very low doses, particularly in the developing nervous system of fetuses and children. This chapter reflects on historical and current views on lead toxicity. It also addresses the development and evolution of exposure prevention policies. As discussed here, these lead policies target a variety of potential exposure routes and sources. The changes reflect our better understanding of lead toxicity. The chapter provides lead-related guidelines and regulations currently valid in the U. S. and in many countries around the world. The reader will learn about the significant progress that has been made through regulations and guidelines to reduce exposure and prevent lead toxicity.

Interspecies Uncertainty in Molecular Responses and Toxicity of Mixtures

Most of the experimental toxicity testing data for chemicals are generated through the use of laboratory animals, namely, rodents such as rats and mice or other species. Interspecies extrapolation is needed to nullify the differences between species so as to use such data for human health/risk assessment. Thus, understanding of interspecies differences is important in extrapolating the laboratory results to humans and conducting human risk assessments based on current credible scientific knowledge. Major causes of interspecies differences in anatomy and physiology, toxicokinetics, injury repair, molecular receptors, and signal transduction pathways responsible for variations in responses to toxic chemicals are outlined. In the risk assessment process, uncertainty associated with data gaps in our knowledge is reflected by application of uncertainty factors for interspecies differences. Refinement of the risk assessment methods is the ultimate goal as we strive to realistically evaluate the impact of toxic chemicals on human populations. Using specific examples from current risk assessment practice, this chapter illustrates the integration of interspecies differences in evaluation of individual chemicals and chemical mixtures.