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July 19, 2012

Why Chemicals in Plastics May Have Worse Effects at Lower Doses

 

Why is there so much debate about whether plastic chemicals like Bisphenol-A (BPA) or phthalates are harmful to humans in the amounts at which we’re exposed to them?  And why is it so difficult to pass regulations in the United States to protect us from these chemicals?  One reason is that regulators are accustomed to following the age-old adage that “the dose makes the poison.”  But on a conference call this morning with the Collaborative on Health and the Environment (CHE),  I learned how it is that endocrine-disrupting chemicals like those found in plastics and pesticides actually do their most long-term and lasting damage at levels considered to be non-toxic.  But first, here’s a little basic biology:

The Endocrine System

To understand what endocrine-disrupting chemicals do, it’s important to understand what the endocrine system is in the first place.  According to The Endocrine Disruption Exchange:

The endocrine system is the exquisitely balanced system of glands and hormones that regulates such vital functions as body growth, response to stress, sexual development and behavior, production and utilization of insulin, rate of metabolism, intelligence and behavior, and the ability to reproduce.  Hormones are chemicals such as insulin, thyroxin, estrogen, and testosterone that interact with specific target cells. The interactions occur through a number of mechanisms, the easiest of which to conceptualize is the lock and key.

We hear about hormones most often in relation to women’s monthly cycles or adolescent sexual development.  But hormones regulate a whole lot more.  And when the natural action of hormones is disrupted by synthetic chemicals that mimic hormones, a whole host of disorders can result.

Too Many Keys; Not Enough Locks

During the conference call, I asked for a layman’s explanation of how endocrine-disrupting chemicals work and why they are so harmful at lower levels.  Dr. Laura Vandenberg, co-author of a review of the low dose effects of endocrine-disrupting chemicals published in March of this year, explained it this way:

The cells in our body contain hormone receptors, molecules that bind to a particular hormone.  You can think of the mechanism as a lock and key system, with the receptors being the locks and the hormones being the keys to specific locks.  Chemicals that mimic hormones in the body will bind to those receptors and create effects in the body similar to hormones.  Those effects can increase the likelihood of diseases like obesity, cardio vascular disease, reproductive disorders, behavioral disorders, autism, diabetes, and various cancers.  But the important thing to note is that the body only has so many hormone receptors.  So once a high enough dose of a chemical is reached, the receptors will be saturated, meaning that no further hormone response will be seen, no matter how much higher the dose of the chemical.  At high doses, it becomes toxic for the receptor to keep responding, so it shuts down.

For hormone receptors located on the outside of cells, there is another mechanism that limits the amount of hormone response.  To do their work, these receptors bind to a hormone and then enter the cell, move down into the cell, and then move back up and out again to bind to more hormone.  This movement takes time, so there are only so many receptors that can be bound, no matter how much more of the chemical is in the system.

Harmful below toxic levels

At high enough levels, hormones are toxic and will cause damage and death to cells.  Traditionally, regulatory toxicologists (the people who study chemicals to make decisions on how they should be regulated) study chemicals at high doses to see what the toxic affects are and decrease the dose until they don’t see anymore toxic affects on the cells.  They then assume that below that threshold, a chemical is safe.  But unfortunately, they don’t test below the toxic threshold to take into consideration the hormonal responses that are taking place.  And it’s those hormonal responses that have long term effects and different effects at different stages of development in a person’s life.

What amount of a particular chemical will cause disruption of the endocrine system is very specific to each chemical.  But the general point is that toxicologists need to change their assumptions because low dose effects of a chemical cannot necessarily be predicted based on high dose effects.  The low dose effects are simply different.  According to the researchers on the conference call, we need a paradigm shift in regulatory toxicology.

Chemical Cocktail

Another listener on the call today asked about the effects of multiple endocrine-disrupting chemicals.  None of us is exposed to one chemical at a time but a whole Long Island Iced Tea of chemicals on a daily basis.  So while each chemical itself might be below the threshold for observed effects, the combination of chemicals can increase their effects.  In a 2002 study published in Environmental Health Perspectives, 11 different estrogen-mimicking chemicals were tested at very low levels.  The dose of each chemical was so low, no estrogenic effects could be observed.  But combined, the additive effect of the 11 chemicals led to “a dramatic enhancement of the hormone’s action.”

What does this mean for us?

The bottom line is that chemicals like BPA, phthalates, parabens, PCB, DDT,and other endocrine-disruptors can be dangerous for us no matter what the dose.  At high levels, they are acutely toxic.  At low levels, they disrupt the endocrine system.  And at very low levels, they can still combine with other chemicals in the environment to disrupt the endocrine system.  As citizens, we need to understand how these chemicals work so that we are not mislead when the chemical industry claims that a particular product is safe because the amount of a particular chemical in it is too low to make a difference.   That kind of reasoning is just too simplistic.



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