Environmental Chemicals: Evaluating Low-Dose Effects

By Birnbaum, Linda S. | Environmental Health Perspectives, April 2012 | Go to article overview

Environmental Chemicals: Evaluating Low-Dose Effects


Birnbaum, Linda S., Environmental Health Perspectives


Around the world, large-scale biomonitoring programs have provided extensive information about human exposure to a large number of environmental chemicals (Barr et al. 2010; Bilau et al. 2008; Churchill et al. 2001; Woodruff et al. 2011). As these programs extend to look at vulnerable populations, including pregnant women, fetuses, and the elderly, our knowledge of the widespread distribution of many of these chemical--including hundreds that have been classified as endocrine disruptors--continues to climb. However, the mere presence of a chemical in humans is not necessarily cause for concern. What is concerning is the increasing number of epidemiological studies showing associations between the concentration of these chemicals in the general population and adverse health end points (Braun and Hauser 2011; Crain et al. 2008). Although high exposures following accidental or occupational exposures to endocrine disruptors, industrial chemicals, pesticides, and pharmaceuticals have shown striking effects, epidemiological studies suggest that low doses may also be unsafe, even for populations that are not typically considered "vulnerable."

Making connections between the exposome and risk assessment is a difficult but important venture (Paustenbach and Galbraith 2006; Rappaport and Smith 2010). Risk assessments typically examine the effects of high doses of administered chemicals to determine the lowest observed adverse effect levels (LOAELs) and no observed adverse effect levels (NOAELs); reference doses, which are assumed safe for human exposure, are then calculated from these doses using a number of safety factors. Thus, human exposures to thousands of environmental chemicals fall in the range of nonnegligible doses that are thought to be safe from a risk assessment perspective. Yet the ever-increasing data from human biomonitoring and epidemiological studies suggests otherwise: Low internal doses of endocrine disruptors found in typical human populations have been linked to obesity (Carwile and Michels 2011), infertility (Meeker and Stapleton 2010), neurobehavioral disorders (Swan et al. 2010), and immune dysfunction (Miyashita et at 2011), among others.

For several decades, environmental health scientists have been dedicated to addressing the "low-dose hypothesis," which postulates that low doses of chemicals can have effects that would not necessarily be predicted from their effects at high doses. More than 10 years ago, a National Toxicology Program expert panel concluded that there was evidence for low-dose effects for a select number of well-studied endocrine disruptors (Melnick et al. 2002). Now, a diverse group of scientists has reexamined this large body of literature, finding examples of low-dose effects for dozens of chemicals across a range of chemical classes, including industrial chemicals, plastic components and plasti-cizers, pesticides, phytoestrogens, preservatives, surfactants and detergents, flame retardants, and sunblock, among others (Vandenberg et al. 2012). Vandenberg et al. selected several examples of controversial low-dose test cases and applied an analytical weight-of-evidence approach to determine whether there was sufficient evidence to conclude that particular environmental chemicals had effects on specific biological end points. Their analysis addresses how experimental design, choice of animal strain/species, study size, and inclusion of appropriate controls affect the outcome and interpretation of studies on bisphenol A (BPA), atrazine, dioxin, and perchlorate. Their study provides important insight into the effects of environmental chemicals on health-related end points and addresses the mechanistic questions of how chemicals with hormonal activity can have effects at external doses that are often considered safe by the regulatory community.

Vandenberg et al. (2012) have also collected several hundred examples of nonmonotonic dose response curves (representing many classes of environmental chemicals) that have been observed in cultured cells, animals, and even human populations, Most important, they reviewed the voluminous endocrine literature on how and why nonlinear responses manifest at different levels of biological complexity, including the combination of competing monotonic responses (such as enhanced cell proliferation and cytotoxicity), the expression of cell-and tissue-specific cofactors and receptors, and receptor down-regulation, desensitization, and competition. …

The rest of this article is only available to active members of Questia

Sign up now for a free, 1-day trial and receive full access to:

  • Questia's entire collection
  • Automatic bibliography creation
  • More helpful research tools like notes, citations, and highlights
  • Ad-free environment

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this article

This article has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this article

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited article

Environmental Chemicals: Evaluating Low-Dose Effects
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Full screen

matching results for page

Cited passage

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited passage

Welcome to the new Questia Reader

The Questia Reader has been updated to provide you with an even better online reading experience.  It is now 100% Responsive, which means you can read our books and articles on any sized device you wish.  All of your favorite tools like notes, highlights, and citations are still here, but the way you select text has been updated to be easier to use, especially on touchscreen devices.  Here's how:

1. Click or tap the first word you want to select.
2. Click or tap the last word you want to select.

OK, got it!

Thanks for trying Questia!

Please continue trying out our research tools, but please note, full functionality is available only to our active members.

Your work will be lost once you leave this Web page.

For full access in an ad-free environment, sign up now for a FREE, 1-day trial.

Already a member? Log in now.