Is PM More Toxic Than the Sum of Its Parts? Risk-Assessment Toxicity Factors vs. PM-Mortality “Effect Functions”

Abstract

Epidemiology studies of populations living in areas with good air quality report correlations between levels of ambient particulate matter (PM) and mortality rates. These associations occur at low PM concentrations that are below current air quality standards. Can such concentrations cause mortality, given the toxicity of PM chemical constituents? We examined chemical-specific, dose-response data typically used in U.S. EPA human health risk assessments. These assessments rely on established, no-effect thresholds for noncancer health endpoints. We found that chemicals identified as constituents of ambient PM are present at concentrations considerably below the regulatory thresholds used in risk assessment (i.e., below the RfCs and RfDs that identify levels for which no adverse health effects are anticipated). From the perspective of risk assessment, exposure to the concentrations of chemicals in ambient PM (e.g., sulfate, nitrate, and elemental carbon) cannot be expected to cause death. Hence, the health effects attributed to ambient PM in “regulatory impact analyses” appear to be at odds with what would be predicted from a standard U.S. EPA health-risk assessment for PM chemicals. Four possible resolutions of this paradox are that (1) the mixtures of chemicals present in ambient PM are vastly more toxic than the sum of individual components, (2) small portions of the general population are vastly more sensitive to certain ambient PM chemicals than reflected in U.S. EPA toxicity factors, (3) the toxicity of ambient PM is unrelated to its chemical constituents, or (4) PM mass concentration is not the causal factor in the reported associations. The associations may arise because ambient PM concentrations (1) are a surrogate for unmeasured copollutants (e.g., HAPs), (2) covary with confounding factors that cannot be fully controlled (e.g., weather, demographics), or (3) covary with unmeasured (e.g., societal, behavioral, or stress) factors.

The preparation and presentation of this article were self-funded in part and supported in part by overhead funds from Gradient Corporation. The author is indebted to many critical and constructive comments from colleagues and thoughtful reviewers.

Presented at the AAAR Conference on Particulate Matter: Atmospheric Sciences, Exposure, and the Fourth Colloquium on PM and Human Health, Pittsburgh, PA, 31 March to 4 April 2003.

Notes

* The criteria pollutants studied include particulate matter (PM), sulfur dioxide (SO₂), ozone (O₃), nitrogen oxides (NO_x), and carbon monoxide (CO).

* Of 2,400,000 annual deaths, the leading cause of death is heart disease (710,000 deaths), and the second leading cause is cancer (550,000 deaths) (Jemal et al., 2003). Of course, one might argue that the “PM deaths” are contained within these heart disease and cancer deaths.

* “Secondary PM” is defined as that component of ambient particulate matter that is created in the atmosphere via chemical reactions between pollutants that were originally emitted as gases. The prime examples of secondary PM are the ammonium nitrate and ammonium sulfate particles in the air, whose precursors were originally emitted as gases, that is, nitrogen oxides or sulfur dioxide, respectively.

* If a chemical dose is below threshold for damage via one mechanism, it would not be expected to lower the threshold dose of another chemical acting via a separate mechanism. However, one mechanism may be in the causal chain for several separate adverse health outcomes.

* In comparison, the annual background incidence of cancer in the United States is about 1,280,000 new cases per year in a population of 287,000,000, which is an annual cancer risk of about 1 in 220.

† Both the Six Cities cohort and the ACS cohort studies show an intriguing trend for all-cause mortality risk and lung-cancer mortality risk associated with PM to decline with educational level. For lung cancer the PM-2.5 relative risk for those with less than a high school education is 1.41 (ACS) and 2.69 (Six Cities), whereas for those with more than a high school education the relative risk for lung cancer is 0.66 (ACS) and 1.08 (Six Cities).

* To estimate lifetime mortality risk per 1 μ g/m³, we take the excess risk, divide by the concentration causing that risk, and multiply that by the fraction of all deaths that are caused by cause of death analyzed in the epidemiologic studies, that is, (0.37/18.6)(0.07) = 14 × 10^{− 4} and (0.08/10)(0.07) = 5.6 × 10^{− 4}.

* The “Six Cities” include Boston, St. Louis, Knoxville, Madison, Steubenville, and Topeka, and they have been the focus of both time-series and cohort epidemiologic studies on the effects of air pollution.