Metal ions affecting the hematological system.

Many metals are essential elements and necessary for proper biological function at low intake levels. However, exposure to high intake levels of these metals may result in adverse effects. In addition, exposures to mixtures of metals may produce interactions that result in synergistic or antagonistic effects. This chapter focuses on metals that affect the hematological system and how exposures to mixtures of metals may contribute to their hematotoxicity. Exposure to arsenic, cadmium, copper, lead, mercury, tin or zinc has been shown to produce some effect on the hematological system. Binary interactions resulting from exposure to combinations of metals may increase or decrease the hematotoxicity induced by individual metals. For example, copper, iron, and zinc have been shown to have a protective effect on the hematotoxicity of lead. In contrast, co-exposure to manganese may increase the hematotoxicity of lead.

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.

ATSDR evaluation of potential for human exposure to zinc.

As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of portions of the toxicological profile for zinc. The primary purpose of this article is to provide interested individuals with environmental information on zinc that includes production data, environmental fate, potential for human exposure, analytical methods and a listing of regulations and advisories.

ATSDR evaluation of the health effects of zinc and relevance to public health.

As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites, which have the greatest public health impact. These profiles comprehensively summarise toxicological and environmental information. This article constitutes the release of portions of the Toxicological Profile for Zinc. The primary purpose of this article is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of zinc. It contains descriptions and evaluations of toxicological studies and epidemiological investigations, and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health.

Interaction profile for lead, manganese, zinc, and copper.

This interaction profile discusses and evaluates the evidence for joint toxic action among lead, manganese, zinc, and copper. The interaction profile recommends how to incorporate concerns about possible interactions or additivity into public health assessments of hazardous waste sites where people might be exposed to mixtures of these chemicals. The profile recommends using endpoint-specific hazard indexes and a hazard quotient to screen for potential health effects. The qualitative weight-of-evidence (WOE) approach is then used to predict the impact of interactions on the endpoint-specific hazard indexes and hazard quotient.

Six interaction profiles for simple mixtures.

The Agency for Toxic Substances and Disease Registry (ATSDR) has a program for chemical mixtures that encompasses research on chemical mixtures toxicity, health risk assessment, and development of innovative computational methods. ATSDR prepared a guidance document that instructs users on how to conduct health risk assessment on chemical mixtures (Guidance Manual for the Assessment of Joint Toxic Action of Chemical Mixtures). ATSDR also developed six interaction profiles for chemical mixtures. Two profiles were developed for persistent environmental chemicals that are often found in contaminated fish and also can be detected in human breast milk. The mixture included chlorinated dibenzo-p-dioxins, hexachlorobenzene, dichlorodiphenyl dichloroethane, methyl mercury, and polychlorinated biphenyls. Two profiles each were developed for mixtures of metals and mixtures of volatile organic chemicals (VOCs) that are frequently found at hazardous waste sites. The two metal profiles dealt with (a) lead, manganese, zinc, and copper; and (b) arsenic, cadmium, chromium, and lead; the two VOCs mixtures dealt with (a) 1,1,1-trichloroethane, 1,1-dichloroethane, trichloroethylene, and tetrachloroethylene; and (b) benzene, ethylbenzene, toluene, and xylenes (BTEX). Weight-of-evidence methodology was used to assess the joint toxic action for most of the mixtures. Physiologically based pharmacokinetic modeling was used for BTEX. In most cases, a target-organ toxicity dose modification of the hazard index approach is recommended for conducting exposure-based assessments of noncancer health hazards.