Phthalates and Cumulative Risk Assessment The Tasks Ahead (2008) / Chapter Skim
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From page 3... ...
In this context, EPA asked the National Research Council to review independently the health effects of phthalates, determine whether cumulative risk assessment of this chemical class should be conducted, and, if so, indicate approaches that could be used for the assessment. The applicability of such approaches to other chemical classes and to cumulative risk assessment generally was also to be considered.
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From page 4... ...
Multiple pathways can lead to a common outcome, and a focus on only a specific pathway can lead to too narrow an approach in conducting a cumulative risk assessment. Accordingly, the chemicals that should be considered for cumulative risk assessment should be ones that cause the same health outcomes or the same types of health outcomes, such as a specific set of effects on male reproductive development, not ones that cause the health outcomes only by a specific pathway.
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From page 5... ...
Not only concurrent exposure, but concurrent exposure at all life stages, has been demonstrated. The second question concerns whether exposures to multiple phthalates contribute to common adverse outcomes.
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From page 6... ...
The phthalates that are most potent in causing effects on the development of the male reproductive system are generally those with ester chains of four to six carbon atoms; phthalates with shorter or longer chains typically exhibit less severe or no effects. Furthermore, the age of the animals at the time of Human Testicular Phthalate Syndrome Dysgenesis Syndrome Disturbance of Androgen Action Fetal Germ Hypospadias Testicular Germ Cell Effects Cell Cancer Cryptorchidism Other reproductive tract malformations ↓LC function, [↑Tumors]
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From page 7... ...
On the basis of the findings summarized above, the committee recommends that a cumulative risk assessment be conducted for phthalates and that the assessment include other antiandrogens, as described further in the next section. CONSIDERATIONS FOR CONDUCTING CUMULATIVE RISK ASSESSMENT One approach to cumulative risk assessment of a mixture is to consider the mixture as a single agent and develop toxicity data on the mixture.
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From page 8... ...
Where single-chemical risk assessments might yield the verdict "absence of risk," dose addition might yield the opposite conclusion. Specifically, there is an expectation with dose addition that every component at any dose contributes, in proportion to its prevalence, to the overall mixture toxicity.
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From page 9... ...
The stipulations have affected how EPA evaluates chemicals for cumulative risk assessment, for example, grouping structurally related chemicals on the assumption that they act by the same mechanisms. For cumulative risk assessment, the committee strongly recommends that EPA group chemicals that cause common adverse outcomes and not focus exclusively on structural similarity or on similar mechanisms of action.
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From page 10... ...
The committee emphasizes that the conceptual approach taken for phthalates should be applicable to other agents. FUTURE DIRECTIONS The current practice of restricting cumulative risk assessment to structurally or mechanistically related chemicals ignores the important fact that different chemical exposures may result in the same common adverse outcomes.
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From page 11... ...
To cite another example, EPA could evaluate combined exposures to lead, methylmercury, and polychlorinated biphenyls because all contribute to cumulative risk of cognitive deficits consistent with IQ reduction in children, although the deficits are produced by different mechanisms of action. Cumulative risk assessment based on common adverse outcomes is a feasible and physiologically relevant approach to the evaluation of the multiplicity of human exposures and directly reflects EPA's mission to pro
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From page 12... ...
However, a focus on common adverse outcomes actually facilitates the process by defining the groups of agents that should be included for a given outcome.
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