The Toxicity and Risk of Chemical Mixtures

The evaluation assumes that the hazard and possible risk of the defined (top-ten) mixture of chemicals is representative for the hazard and risk of the entire complex mixture. For some mixtures that are relatively easily available (e.g., combustion fumes, food products, pesticide mixtures), this assumption could be validated by comparing the toxicity of the top-ten mixture with the toxicity of the original complex mixture in short-term test. 

The review presented in the previous sections shows an enormous diversity in risk assessment methods and procedures for chemical mixtures. This diversity is characteristic for the current state of the art. The awareness that mixtures may cause risks that are not fully covered by single compound evaluations is growing, but the knowledge required to accurately assess the risks of chemical mixtures is still limited. The scientific community is attempting to unravel the mechanisms involved in mixture exposure and toxicity, and over recent decades, a multitude of new techniques to assess mixture risks have been developed. However, a comprehensive and solid conceptual framework to evaluate the risks of chemical mixtures is still lacking. The framework outlined in Section 5.4 can be considered a first step toward such a conceptual framework. The framework recognizes that the problem definitions vary greatly (between protective and retrospective assessments, for humans and ecosystems), and that each question has resulted in a different type of approach. 

EPA recommends three approaches (1) if the toxicity data on mixture of concern are available, the quantitative risk assessment is done directly form these preferred data (2) when toxicity data are not available for the mixture of concern, data of a sufficiently similar mixture can be used to derive quantitative risk assessment for mixture of concern and (3) if the data are not available for both mixture of concern and the similar mixture, mixture effects can be evaluated from the toxicity data of components. According to EPA, the dose-additive models reasonably predict the systemic toxicity of mixtures composed of similar (dose addition) and dissimilar (response addition) compounds. Therefore, the potential health risk of a mixture can be estimated using a hazard index (HI) derived by summation of the ratios of the actual human exposure level to estimated maximum acceptable level of each toxicant. A HI near to unity is suggestive of concern for public health. This approach will hold true for the mixtures that do not deviate from additivity and do not consider the mode of action of chemicals. Modifications of the standard HI approach are being developed to take account of the data on interactions. 

Safe, S. (1998) Hazard and Risk Assessment of Chemical Mixtures Using the Toxic Equivalency Factor Approach. Environmental Health Perspectives, 106(Suppl. 4), 1051-1058. 

Mineral Oil Hydraulic Fluids and Polyalphaolefin Hydraulic Fluids. Limited information about environmentally important physical and chemical properties is available for the mineral oil and water-in-oil emulsion hydraulic fluid products and components is presented in Tables 3-4, 3-5, and 3-7. Much of the available trade literature emphasizes properties desirable for the commercial end uses of the products as hydraulic fluids rather than the physical constants most useful in fate and transport analysis. Since the products are typically mixtures, the chief value of the trade literature is to identify specific chemical components, generally various petroleum hydrocarbons. Additional information on the properties of the various mineral oil formulations would make it easier to distinguish the toxicity and environmental effects and to trace the site contaminant s fate based on levels of distinguishing components. Improved information is especially needed on additives, some of which may be of more environmental and public health concern than the hydrocarbons that comprise the bulk of the mineral oil hydraulic fluids by weight. For the polyalphaolefin hydraulic fluids, basic physical and chemical properties related to assessing environmental fate and exposure risks are essentially unknown. Additional information for these types of hydraulic fluids is clearly needed. 

The immediate future in risk assessment will focus on the difficult but necessary task of integrating experimental data from all levels into the risk assessment process. A continuing challenge to toxicologists engaged in hazard or risk assessment is that of risk from chemical mixtures. Neither human beings nor ecosystems are exposed to chemicals one at a time, yet logic dictates that the initial assessment of toxicity start with individual chemicals. The resolution of this problem will require considerable work at all levels, in vivo and in vitro, into the implications of chemical interactions for the expression to toxicity, particularly chronic toxicity. 

Safe S. 1998. Hazard and risk assessment of chemical mixtures using the toxic equivalency factor approach. Environ Hlth Perspect 106 1051-1062. 

As described, living organisms are constantly exposed to vast amounts of chemicals, that is, to 1 big chemical mixture. We lack the information on how to properly capture the entire exposure, on how to address the toxicity, and how to evaluate the associated risk. Therefore, the initial approach is to properly define mixtures on a smaller scale. These are the mixtures of concern and are usually associated with a specific exposure scenario and possible health implications. Exposures to chemical mixtures of concern can range from simple and well-defined mixtures to complex and poorly defined mixtures. For example, morphine in combination with other epidural anesthetics is used in hospital settings for pain relief. The mixture can be characterized as simple (<10 chemicals), and in some cases such mixtures can be well defined because it is easier to identify the chemicals involved and know their dose, toxicity, and potential interactions. In contrast, complex mixtures are composed of many (>10) chemicals. Their composition may be largely known or at least reproducible (e.g.,... 

This section gives a nonexhaustive overview of the regulatory state of the art on human risk assessment of chemical mixtures in the United States, the European Union (EU), and other nations and (international agencies. The focus is on regulations for environmental pollution, but when available and relevant, mixture regulations from other policy areas have also been included in the overview, for example, for food quality and the workplace. The reader is referred to McCarty and Borgert (2006) and Monosson (2005) for a more extensive overview of mixture toxicity regulations related to human health. 

Ecological risk assessment of chemical mixtures may be conducted using the same types of data sources and approaches as in human risk assessment of mixtures. Available data and approaches are, however, different in kind and numbers. The vast majority of data are from laboratory toxicity tests with mostly binary mixtures... 

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