benzo[a]pyrene

The Dose Makes the Poison – or does it?

By Kacee Deener

Three images arranged horizontally: grade school students in classroom; girl with arms raised; bicyclists at sunrise

 

When I was a graduate student, one of the first lectures in my toxicology class was about the history and basic principles of toxicology. We learned about Paracelsus, the 16th century physician-alchemist known as the father of toxicology, and how he coined the phrase “the dose makes the poison.” This has been a central tenant of toxicology and an important concept in human health risk assessment. The more we learn about the health effects of chemicals, however, the more we realize things may not be quite this simple.

I recently wrote about identifying the hazards of chemicals. Once we know what such hazards are, how do we know what levels of exposure will cause those health effects in humans? This is a really important question. To answer it, scientists do something called dose-response analysis, the next step in the human health risk assessment process. To do this, scientists calculate how different amounts (exposures or doses) of a chemical can impact health effects (responses) in humans.

Scientists measure these amounts both externally (outside the body) and internally (inside the body). External measurements, exposure levels, are the amount of a chemical in an external media, such as air, water, or soil. Internal dose refers to the amount of a chemical that actually gets into a person’s body after ingesting or inhaling something (like food or air) that contains the chemical.

Often, as the internal dose or exposure level increases, the response or health effect also increases—though there are exceptions to this. Additionally, sometimes we don’t have data about effects at doses lower than what might be tested in studies, so we have to mathematically extrapolate to estimate the effects below the observed data. Traditionally we have done this using different approaches for cancer versus other health effects, but this may change as our scientific understanding of disease processes improves.

Why is dose-response assessment important? First, it helps us understand what happens in the human body at different levels of exposure to a chemical, and it allows us to see that relationship presented graphically. Second, it allows us to derive toxicity values (described in the table below) that become important when we develop a complete risk assessment.

Toxicity Value Name Description
Reference Dose (oral exposures) The amount of a substance that one can ingest every day for a lifetime that is not anticipated to cause harmful health effects.
Reference Concentration (inhalation exposures) The amount of a substance that one can breathe every day for a lifetime that is not anticipated to cause harmful health effects.
Oral Slope Factor An estimate of the increased cancer risk from a lifetime of oral exposure to a substance.
Inhalation Unit Risk An estimate of the increased cancer risk from a lifetime of inhalation exposure to a substance.

 

We want to make sure we are protective of sensitive groups of people when we calculate toxicity values. To do that we may apply scientifically-based factors to account for uncertainty in various areas, such as differences between animals and humans (if we start with animal data), differences among humans (such as genetics, life stages, etc.), and scientific data gaps (for example, certain health endpoints that have not been evaluated). In EPA’s Integrated Risk Information System (IRIS) Program, we’ve started developing multiple toxicity values for different organ systems or health effects seen in the data.

The toxicity values resulting from dose-response assessment are used as part of a larger calculation to estimate risk from exposure to environmental contaminants. I’ll talk more about that in a few weeks. Until then, check out an example of dose-response assessment in Section 2 of the IRIS assessment of benzo[a]pyrene. And read more about dose-response assessment on the Agency’s risk assessment website.

About the Author: Kacee Deener is the Communications Director in EPA’s National Center for Environmental Assessment.  She joined EPA 13 years ago and has a Masters degree in Public Health.

Editor's Note: The opinions expressed here are those of the author. They do not reflect EPA policy, endorsement, or action.

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100 Days of EPA Science, and Beyond

By Kacee Deener

Numeral 100 with clouds and sky in backgroundEPA recently highlighted some of the Agency’s achievements during Gina McCarthy’s first 100 days as Administrator, noting that we have made significant strides towards improving the health of American families and protecting the environment across the country.

One of the seven highlighted examples is “Taking Action on Toxics and Chemical Safety” – which includes strengthening chemical assessments through changes to the Agency’s Integrated Risk Information System (IRIS) Program.  In a recent blog post, I described these changes and why they make sense for the IRIS Program, the Agency, and the American people.  But the IRIS Program hasn’t stopped there.  We’ve been moving forward implementing the changes.  Since August, we have:

  1. Released early materials for several chemical assessments.  These materials highlight our thought process for determining which studies are most important for the assessment, help make sure we didn’t miss any important research, and help identify potential scientific controversies early on.
  2. Scheduled the first IRIS public bimonthly meeting (Dec. 12-13).  At this meeting we will discuss the early materials for three chemicals (ETBE, tert-butanol, and RDX) and the draft assessments and peer review charges for two chemical assessments (ethylene oxide and benzo[a]pyrene).
  3. Held a public scientific workshop to discuss the IRIS assessment of hexavalent chromium.  An important component of determining the cancer causing potential of ingested hexavalent chromium is understanding the rates at which this metal is effectively detoxified in the gastrointestinal tract.  EPA convened an expert panel to discuss this issue in September; more than 200 stakeholders participated!
  4. Scheduled a scientific workshop on mouse lung tumors.  At this workshop, which will be held in early 2014, experts will discuss the available data from studies of mouse lung tumors following exposure to chemicals and discuss the relevance of these tumors in mice to assessing human cancer risk.
  5. Released final IRIS assessments for biphenyl, 1,4-dioxane (inhalation update), and methanol (noncancer). These final assessments provide information on the health effects of these chemicals and toxicity values that risk assessors can use (along with exposure and other information) to make decisions to protect public health.
  6. Announced a workshop on formaldehydeThis workshop, which will be held in spring 2014, will focus on several scientific issues pertinent to assessing the potential health effects of inhaled formaldehyde.  We’re taking input on speakers/panelists and topics for three theme areas – you can send us your suggestions here.

I think you’ll agree we’ve been making tremendous progress!  These activities illustrate our commitment to scientific integrity, public input, and transparency as we work together to produce the highest quality scientific assessments to inform decisions to protect public health.

About the Author: Kacee Deener is the Communications Director in EPA’s National Center for Environmental Assessment, home of the IRIS Program.  She joined EPA 12 years ago and has a Masters degree in Public Health.

Editor's Note: The opinions expressed here are those of the author. They do not reflect EPA policy, endorsement, or action.

Please share this post. However, please don't change the title or the content. If you do make changes, don't attribute the edited title or content to EPA or the author.