Drinking Water and Health, Volume 9 Selected Issues in Risk Assessment (1989) / Chapter Skim
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3 Risk Assessment of Mixtures of Systemic Toxicants in Drinking Water
3 Risk Assessment of Mixtures of Systemic Toxicants in Drinking Water
Pages 121-132
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From page 121... ...
With the goal of providing adequate but not excessively conservative exposure standards for health protection, this chapter presents various approaches to using incomplete empirical information and scientific judgment to assess the health risks associated with exposure to mixtures in drinking water. The dominant concern with mixtures, as noted earlier, is unexpected amplification of toxicity arising from combinations of mixture components.
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From page 122... ...
To model interaction requires precise definition of the term "interaction." As described in the 1988 publication by the Committee on Methods for the In Vivo Toxicity Testing of Complex Mixtures (NRC, 1988, p. 1001: Int~r~rtinn char Hill rPfP~rPA to tic clPvi~tinn from Alla Lo V__~lJ 4~ V ~ A- I -- -- .
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From page 123... ...
Compounds of the heavy metals mercury and cadmium disrupt renal cellular function and produce renal necrosis. "Commonality" does not now translate readily into any simple arithmetic manipulations, but Figure 3-1 is an attempt to illustrate the concept.
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From page 124... ...
However, such doseadditive models as are implied by the hazard index might not provide the most biologically plausible approach to describing the effects of a complex mixture of toxicants if the compounds do not have the same mode of toxic action.
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From page 125... ...
A water quality or hazard index similar to the EPA index would be defined under some assumptions of additivity. Given that ADIs already incorporate uncertainty factors, usually of 100, and given that only one study (Murphy et al., 1959)
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From page 126... ...
Such a margin, however, would be excessive in most cases. That is, just as it seems unreasonable to expect totally independent actions of the agents identified in a drinking water source, it seems equally unreasonable to expect complete overlap in toxic targets, so even the additivity alternative already embodies this additional but unrecognized safety factor.
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From page 127... ...
Modifying HI by using the weighting factor Wij takes into account the possibly different toxic spectra of different materials, avoids the lumping together of unrelated toxicities, and still incorporates all reported toxicities into a unified measure. Grouping Agents with Common Toxicities With a small number of agents, it might be possible to invoke expert opinion to separate components of toxic mixtures into clusters and to assign
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From page 128... ...
Incorporating an Uncertainty Factor for Synergism The issue of toxic interactions synergistic or antagonistic is central in the development of a risk assessment strategy for chemical mixtures in drinking water. Even though the concentrations of contaminants in most sources of drinking water for the general public are likely to be very low, there is insufficient evidence about the toxicity of chemical mixtures after long-term, low-dose exposure to support a definite conclusion that toxic interactions are absent under these conditions.
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From page 129... ...
From a different perspective, however, the incorporation of a UF is not intended to trigger regulatory action every time contaminants are detected in drinking water sources. The hazard index in the new approach must be assessed in actual situations.
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From page 130... ...
referred briefly to the potential applicability of response-surface methods for describing the effects of combinations of toxicants The methods include experimental design, statistical inference? and mathematical techniques that, when combined, enable an experimenter to explore empirically the process of interest.
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From page 131... ...
1983. TLVs: Threshold Limit Values for Chemical Substances and Physical Agents in the Work Environment, with Intended Changes for 1983-1984.
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From page 132... ...
1982. Viability of embryos of the winter flounder Pseudopleuronectes americanus exposed to mixtures of cadmium and silver in combination with selected fixed sabinities.
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