toxicology

‘Dr. Lowry, I read on the internet that I shouldn’t feed my child rice cereal. Is this true?’

Introduction by LaTonya Sanders

October is Children’s Health Month. In 1992, the American Academy of Pediatrics established October as Child Health Month in order to focus national attention on children’s health issues. This month and throughout the year, EPA works with parents, teachers, health providers and other partners to promote healthy environments where children live, learn and play.

Only through partnerships and collaboration can we make a difference and leverage the needed resources and support to guard all children against environmental health threats.

PEHSUEPA is proud to partner with people and organizations that are on the forefront in protecting children’s health and the environment, which is consistently true for Dr. Jennifer Lowry and the Mid-America Pediatric Environmental Health Specialty Unit. Dr. Lowry is a crucial partner to EPA, and her work is instrumental in creating a healthier future for our children.

By Jennifer Lowry, MD

Jennifer Lowry, MDPediatricians love children. We love helping children become the best people they can be. We love doing what is needed to make the world a better place for children to be healthy.

What pediatricians don’t love is being caught unaware of the latest blog, internet chat, or media storm regarding environmental health issues. Media and other news outlets often inform parents of possible environmental exposures that can cause harm to children.

Unfortunately, not all of the information is true, which causes undo concern for parents and confusion to pediatricians who are asked about these effects.

A World of Stuff

What is a pediatrician or family to do? It is important to realize we are surrounded by stuff. We, or the people who have come before us, have made choices that puts stuff in our world that is supposed to make things “better” or “easier.” Unfortunately, not all of the stuff we encounter fits both descriptions.

Cell phones, plastics, better beef, lead in paint, and synthetic athletic fields are just a few examples that may make life easier, but might not (or definitely not in some cases) make life better. But today, everywhere you turn, someone is saying our children’s lives are being damaged by the chemicals we have in the environment. Is this true?

A Matter of the Dose

As a toxicologist, I have been taught “Everything is a poison. It is just a matter of the dose.” Paracelsus was a Swiss-German Renaissance physician, botanist, alchemist, astrologer and general occultist. Born in 1493, he founded the discipline of toxicology. Paracelsus rejected the medical conditions of the time, and pioneered the use of chemicals and minerals in medicine. He is credited with the phrase “the dose makes the poison,” but is also known to have said: If given in small doses, “what makes a man ill also cures him.” Thus, he realized medicines can be beneficial at low doses, but cause harm at higher doses.

Paracelsus, founder of toxicology

Paracelsus, founder of toxicology

But what about chemicals and metals, both synthetic and natural? What about plants? Is it true there is no harm at low levels? Well, it depends. Medications used to treat illnesses are rigorously tested for safety and efficacy. Chemicals used in the environment are not. Alternative medications (dietary supplements) are not.

We know some medications have benefits at very low doses (micrograms), but can cause toxicity at the milligram dose (or 1,000 times the microgram dose). Some medications have no efficacy at the milligram dose and require much higher doses (grams or 1000 times the milligram dose) to have effect.

Why would we expect plants, supplements, chemicals or metals to be any different? Each chemical is different and has a different profile for efficacy and toxicity. Some chemicals (botulinum toxin, for example) are toxic at even lower doses. Unfortunately, we are finding out doses that were presumed safe were really not safe to begin with.

Arsenic and Lead

Chemical symbols for arsenic and lead

Chemical symbols for arsenic and lead

At one time, we erroneously thought because arsenic was “natural,” it could be placed in soil as a pesticide. However, arsenic is relatively immobile so anything that grows where it was placed (such as rice fields) can incorporate it into the food. Thus, higher levels of arsenic are found in foods grown where arsenic was used.

The same is true about lead. Pediatricians know that children are not little adults. But the level associated with toxicity in adults was applied to children early in the 1900s. However, it was soon realized children were more vulnerable and action was required at lower levels. Lead has not become more toxic over time. Our recognition of the toxicity of lead has changed for us to realize that even low levels of blood lead may result in harm.

So What Do We Do?

Can a 6-month-old child eat rice cereal? YES. Should they only eat rice cereal? NO. Does it have to be the first cereal they eat? NO. Can my teenager have a cell phone? YES. Should they be on it all the time? NO. Should they carry it in their pants or in their bra? NO. Should an infant or toddler play with a cell phone or tablet as their entertainment? NO.

How do you discover these answers? Great resources are available to help you sort this out:

  • Pediatric Environmental Health Specialty Units (PEHSUs) – Staffed by health care professionals who are experts in pediatric environmental health, they can help to best inform health care providers and the public on how to keep children safe from environmental toxins.
  • American Academy of Pediatrics – Through the Council on Environmental Health, health care professionals can learn about the latest science on pediatric environmental health and how to incorporate this knowledge into their practice. This website is a great resource for families to find out what experts in children advise.
  • Poison Control Centers – Staffed by health care professionals, they are best able to help you with acute exposures. Some PEHSUs collaborate with poison control centers. Call 1-800-222-1222.

Lastly, be smart. Do you really need that stuff? Do you really need to throw it away? Reduce, reuse and recycle. It is easy to blame others before us for where we are now. But who will our children blame with what we leave them?

About the Introducer: LaTonya Sanders serves as the children’s health coordinator in EPA Region 7’s Office of Public Affairs in Lenexa, Kan. Her EPA career expands over 20 years in public affairs, communications, outreach, education and congressional relations.

About the Author: Jennifer Lowry, MD, is the medical director of the Mid-America Pediatric Environmental Health Specialty Unit at Children’s Mercy Hospital in Kansas City, among several other prestigious titles. She served on EPA’s Children’s Health Protection Advisory Committee from 2012 to 2014.

Editor's Note: The opinions expressed here are those of the author. They do not reflect EPA policy, endorsement, or action, and EPA does not verify the accuracy or science of the contents of the blog.

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Which Ounces of Prevention? Predictive Toxicology Using Organotypic Models

By Shane Hutson

VPROMPT team members (left-to-right) Shane Hutson, Dmitry Markov, John Wikswo and Lisa McCawley. Photo courtesy of Vanessa Allwardt.

VPROMPT team members (left-to-right) Shane Hutson, Dmitry Markov, John Wikswo and Lisa McCawley. Photo courtesy of Vanessa Allwardt.

Everyone knows that “an ounce of prevention is worth a pound of cure,” but think about that saying’s application to environmental chemical exposure. There are tens of thousands of chemicals in common use. If we don’t prioritize that list, it quickly adds up to a few tons of prevention.

There is no doubt that prevention is the best medicine when you know exactly what needs to be prevented, but how do we know? How do we predict which chemicals are toxic – and at which exposure levels? Those questions are why I became involved in toxicology research.

For 40+ years, the gold standard for those questions has been expensive, time consuming, animal-based (primarily mice and rats) laboratory exposure studies where results are not clearly predictive of effects in humans. Are we stuck with such studies? A large number of scientists are working to answer that question with “No, we can do better.”

I became involved in this effort during a year at EPA’s National Center for Computational Toxicology. My interests lie in developmental toxicity – understanding how chemical exposures affect the developing fetus – so I worked with EPA researchers on the Virtual Embryo Project to build computational models of specific developmental events and how they go awry during chemical exposure. When combined with high-throughput screening efforts such as ToxCast, computational models do have some predictive ability. But we still have a lot to learn.

That brings me to my current efforts. I’ve teamed up with a talented group of colleagues at Vanderbilt and the University of Pittsburgh to found VPROMPT – Vanderbilt-Pittsburgh Resource for Organotypic Models for Predictive Toxicology.

The word “models” pops up again here, but these are not computational. VPROMPT is using diverse expertise in biology, chemistry, physics and engineering to grow “models” that are three dimensional assemblies of multiple human cell types in carefully perfused microfluidic chambers. Such models are designed to be “organotypic,” that is, matching the microenvironment that cells experience in a living organ. This will enable our model to more closely mimic human responses to chemical exposure.

Our plans focus on developmental toxicity with models for liver, mammary gland, developing limb, and fetal membrane. The latter is a key model for investigating chemicals’ links to preterm birth.

VPROMPT is just getting started. We have lots to do in terms of engineering, fabricating and validating our models, but we also have high hopes for their predictivity. Will they help us make sure we only need that reasonable ounce of prevention? Stay tuned and let’s see where the science takes us!

About the Author: Shane Hutson is an Associate Professor of Physics at Vanderbilt University and Deputy Director of the Vanderbilt Institute for Integrative Biosystems Research & Education.

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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Globally Linking Scientific Knowledge through the Adverse Outcome Pathways Wiki

By Steve Edwards, Ph.D.

I am thrilled to announce that on September 25th, we and our partners released the online Adverse Outcome Pathway (AOP) Wiki—an interactive, virtual encyclopedia for the development and evaluation of adverse outcome pathways.

An AOP is a conceptual framework that shows what is known about the “pathways,” or links between a chemical and how it: interacts with a biological process, initiates direct changes on a molecular level, and leads to an environmental and human health risk, or “adverse outcome.”

It is important for us to understand and map AOPs in order to incorporate toxicological data into chemical risk assessments and regulatory decision-making.

Our goal for the AOP Wiki was to create an easy-to-use tool that will stimulate, capture, and use crowd-sourced knowledge from the scientific community. Using the Wiki’s user-friendly interface and standardization guidance, we have created a tool to allow scientists from all industries and disciplines to develop, evaluate, and use adverse outcome pathways.

All AOPs within the wiki are constructed using guidance from two reports of the Organization for Economic Co-operation and Development’s (OECD) Extended Advisory Group on Molecular Screening and Toxicogenomics (Guidance on Developing and Assessing Adverse Outcome Pathways and the AOP Developers’ User Handbook). What I find particularly helpful about the guidance and wiki design is that it provides a user-friendly experience with consistent terminology and useful widgets for navigation and development. This way AOP developers and other users without extensive experience with Wiki language can take full advantage of the available information.

AOP Knowledge Base

AOP Knowledge Base

Our Wiki is the first publicly released module of the larger AOP Knowledge Base (AOP KB). This international collaboration will provide a consolidated, comprehensive knowledge base on how chemicals can induce adverse effects. Through quality user engagement, we want the knowledge base to evolve and become the focal point for AOP development and dissemination. Our next step is to integrate the wiki with the other AOP KB modules in development:

  • AOP Xplorer
    A graphic computer module that will allow scientists worldwide to create graphics that highlight how several different AOPs might interconnect and adversely affect the same biological system. (Expected release later this year.)
  • Intermediate Effects Database
    Will host chemical-related data derived from non-traditional methods.
  • Effectopedia
    Will bring together scientists and studies from different disciplines to share data about different species and biological organization, chemical exposure routes and durations, and much more.

With these tools, we are taking strides toward connectingthe sequence of events that unfold after chemical interaction sparks changes on the molecular level of a biological system, and cascades on until an adverse health outcome. The Advanced Outcome Pathway Wiki is a collaborative effort of the EPA, the OECD, the international scientific community, the European Joint Research Center, and the U.S. Army Corp of Engineers. For more information on this project, please see our fact sheet.

About the Author: EPA systems biologist Stephen Edwards is developing a framework to improve the scientific underpinnings of the Agency’s human and ecological risk assessments. He serves as a senior Agency advisor on the development of predictive toxicology models of disease using genomics, proteomics, and metabolomics.

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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Education Outreach: Fun for All!

By Maureen Gwinn, Ph.D., DABT

Since 2007, the Girl Scouts Council Nation’s Capital Chapter has organized a Girl Scout Science Day to give local Girl Scouts an opportunity to learn more about science in a fun and friendly environment. 

I first became involved as a friend of the troop leader in charge of the event.  She and I would work on ideas, adapt experimental protocols and talk our science friends into volunteering at the event. 

EPA's Maureen Gwinn: "I enjoy every opportunity I have to encourage kids to have fun with science."

From the beginning, experiments have been led by Cadette or Senior Girl Scouts with the assistance of volunteers, including troop ‘moms’ and ‘dads’ and area scientists. We have hands-on experiments that address concepts of chemistry, microbiology, genetics, and toxicology.  We have had discussions related to what goes into your personal hygiene products, why DNA is unique to each of us, and how forensic science can help to solve a crime.

The Cadette and Senior Girl Scouts running the experiments at a recent event were the 4th graders who participated five years ago.  It has been a pleasure to see these girls not only learn the scientific concepts well enough to teach them to the new Brownie and Junior Girl Scouts, but to watch them take on more responsibility for the event itself.  Through my involvement in this event, I have been privileged to watch those young, giggly ten-year-old girls turn into responsible young ladies – that still giggle, but do so while teaching or setting up for the next group of girls. 

This event inspired me to volunteer in education outreach at other events, including the Society of Toxicology Annual meeting, EPA’s Earth Day celebrations, and the USA Science & Engineering Festival

Volunteering in education outreach was not something I had considered in the past, but after participating in the Girl Scout Science Day for the past five years, I enjoy every opportunity I have to encourage kids to have fun with science, to ask questions about how things work, and to work together to solve scientific problems. 

The Society of Toxicology Education Committee has ways to help support these types of opportunities, and for K-12 in particular we are putting together a website of ideas, experiments, and how-to’s to get you started in the new year. 

Are you interested in getting involved in education outreach, but don’t know where to start? Or are you already involved and have some tips or favorite resources to share? Please post your questions or suggestions in the comments section below so we can join forces.

The impact these events have on the kids is worth the effort. 

About the Author:  Maureen Gwinn is a biologist in EPA’s National Center for Environmental Assessment and works as an Associate National Program Director for Sustainable and Healthy Communities.  She is currently serving in her final year as the K-12 Subcommittee Chair for the Society of Toxicology and is always looking for ideas for scientific outreach.

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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