Expert Report

Phthalates and Cumulative Risk Assessment: The Tasks Ahead (2008)



People are exposed to a variety of chemicals throughout their daily lives. To protect public health, regulators use risk assessments to examine the effects of chemical exposures. At the request of the U.S. Environmental Protection Agency, the National Research Council convened a committee to provide guidance for assessing the risk of phthalates, chemicals found in many consumer products that have been shown to affect the development of the male reproductive system of laboratory animals. The committee's report concludes that, because people are exposed to multiple phthalates and other chemicals that affect male reproductive development, a cumulative risk assessment should be conducted that evaluates the combined effects of exposure to all these chemicals. The report sets out a new vision of cumulative risk assessment that can also serve as a model for evaluating the health risks of other types of chemicals.

Key Messages

  • Any agent that can produce androgen insufficiency or block androgen-receptor signaling in the developing male fetus would have effects that are included in the array of malformations known to be caused by phthalates.
  • Focus in cumulative risk assessment should be on the health outcomes and not on the pathways that lead to them, whether defined as mechanisms of action or as modes of action.
  • 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.
  • The committee concluded that EPA's more recent stipulations on when dose-addition methods should be used are too restrictive. Phthalates may not all act by the same mechanisms, and they do not have parallel dose-response curves. However, those facts do not negate the appropriateness of using general dose-addition methods in a cumulative risk assessment.
  • The conceptual approach taken for phthalates should be applicable to other agents.
  • The exposures contribute to common adverse outcomes. However, the committee emphasizes that not all phthalates are equivalent in the severity of their effects. 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.
  • There are exposures to multiple phthalates. Not only concurrent exposure, but concurrent exposure at all life stages, has been demonstrated.
  • There are several approaches for conducting cumulative risk assessment with the dose-addition approach.