Toxic Tuesdays

Dealing with Uncertainty When Evaluating Toxicity​

Toxic Tuesdays

CHEJ highlights several toxic chemicals and the communities fighting to keep their citizens safe from harm.

Dealing with Uncertainty When Evaluating Toxicity

In a recent issue, we discussed the many challenges in evaluating the adverse health effects that result from exposure to a mixture of toxic chemicals. Despite this, scientists still estimate and assess risks by attempting to compensate for these uncertainties.

This is done by assigning an uncertainty factor (UF) to the different uncertainties. How well these uncertainty factors fill in the gap in what we do not know is a matter of controversy and opinion. Especially when you acknowledge that we only have good toxicity information on about 1% of the more than 80,000 chemicals that are in use.

Consider just a few of the uncertainties. The first step in assessing risks is to determine what substances a person was exposed to, at what concentration and for how long. Rarely is this information ever available, so assumptions need to be made to estimate this critical information. Sometimes, there is limited air, soil or water data. This data is often collected for a different purpose, such as to evaluate the need for remediation as opposed to evaluating public health risks. There are also uncertainties in how the samples were collected, the accuracies of and precision of the analytical measurements and the thoroughness of the sampling (were the samples taken at the right places, analyzed for the right substances and at relevant concentrations). At times, modeling is used to estimate how much of a chemical a person was exposed to (usually after making assumptions about even what kind of chemicals a person was exposed to), how long they were exposed and at what concentration.

The next step is to evaluate the toxicity information available on the chemical in question. This would include information from animal studies, clinical trials and epidemiological studies involving people. Since most of the data that exists is from animal studies, this step already creates enormous uncertainties. These uncertainties include extrapolating results in animals to people; the variability in response among people; the sensitivity in response among people; estimating acute or short-term responses in people when the only data you have is from chronic or long-term exposure, and vice versa. These examples just touch the surface of the many uncertainties in our understanding of how chemicals affect a person’s health. 

Another factor that comes into play is the health status of the individual who was exposed. People who are generally healthy and without pre-existing conditions respond differently to toxic chemicals than people with prior exposures, poor immune or nutritional status, or pre-existing health problems.

To address these many uncertainties, scientists have developed what were originally called safety factors, but now are referred to simply as uncertainty factors (UF). These uncertainty factors can range from 1 to 10 and often are multiplied together to yield a composite uncertainty factor that can be as high as 100 (10 x 10). These UFs are included in the estimate of the risks a person or group of people face.

Scientists give an UF to each specific uncertainty trying to compensate for the uncertainty. Doing this requires making many assumptions about areas of knowledge that very little is known about. These assumptions are made by “scientific experts” who very quickly become convinced that they “know” the health risks that a person or a group of people face. Of course, they do not really know. Instead, what they have is an opinion based on multiple assumptions, typically for a single substance.

What compounds this process is that the people who make these risk assessment estimates are scientific experts, and do not include the people who have to bear the risks of the chemical exposures. That’s not right! The people who bear the risks need to be involved in the risk assessment and health evaluation process because of the many uncertainties that exist in estimating exposures and in extrapolating what little data exist to evaluate adverse health effects resulting from exposures to low level mixtures of toxic chemicals.

For more about uncertainties when evaluating the adverse effects from chemical exposures, see Environmental Decisions in the Face of Uncertainty, by the Institute of Medicine of the National Academies, 2013.

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Toxic Tuesdays

Epigenetic Toxicity

Toxic Tuesdays

CHEJ highlights several toxic chemicals and the communities fighting to keep their citizens safe from harm.

Epigenetic Toxicity

The way scientists think about how chemicals cause their toxic effects is changing. Recent scientific research tells us that the traditional notion of how chemicals act is being replaced by a better understanding of the actual features of exposures that influence how chemicals express their adverse effects in people. These features include the timing and vulnerability of exposures, exposures to mixtures, effects at low doses and genetic alterations called epigenetics.

It wasn’t too long ago that scientists believed that the DNA in our cells was set for life, that our genes would be passed on from one generation to the next, and that it would take generations to change our genetic makeup. This is no longer the case.

A new research area, called epigenetics, is perhaps the fastest growing field in toxicology and it is changing the way we think about chemical exposures and the risks they pose. Epigenetics is the study of changes in DNA expression (the process of converting the instructions in DNA into a final product, such as blue eyes or brown hair) that are independent of the DNA sequence itself.

Researchers are learning is that the “packaging” of the DNA is just as important as a person’s genetic make-up in determining a person’s observable traits, such as eye color, or their susceptibility to diseases such as adult on-set diabetes or lupus.

We are learning that the environment is a critical factor in the control of these packaging processes. We may be born with our genes, but epigenetic changes can occur because of environmental influences and exposures during development and throughout life. These influences include reactions to the chemicals in the food we eat, the air we breathe, the water we drink, and they appear to contribute to the development of cancer and other diseases.

Researchers have found that the genome, which is a person’s complete set of DNA, responds to toxic chemicals in the environment that a person is exposed to. It can lead to changes in gene expression, not by mutating the genes, but by sending subtle signals that stops gene activity or turns them on at the wrong times. Researchers believe that the genome has evolved from adapting to stressful survival situations to becoming more vulnerable to adverse environmental exposures, which leads to direct changes in people’s health based on how they respond to toxic chemicals in their environment. Linda Birnbaum, the former director of the National Institute of Environmental Health Sciences and the National Toxicology Program, put it this way: exposure to gene-altering substances, particularly in the womb and shortly after birth, “can lead to increased susceptibility to disease. The susceptibility persists long after the exposure is gone, even decades later. Glands, organs, systems can be permanently altered.”

This growing field of epigenetic toxicity may explain the long-term effects of chemical substances and the predisposition to disease that some people have due to environmental factors including exposure to chemicals. Epigenetics may also help to explain why certain people develop diseases and others do not, or why the person who smoked for 30 years never developed lung cancer.

There is still much to learn, but an early lesson to take away from this emerging science is that we need to rethink our traditional ideas of how chemicals affect our health. This is especially true since regulators and public health scientists who make decisions about safe levels of exposure to toxic chemicals are not considering epigenetic toxicity in their evaluations and are missing a critically important piece of the toxic chemical exposure puzzle. This may help explain why government is constantly telling people that the testing that has been done shows no cause for concern, while the people who have been exposed have symptoms and illnesses with no explanation for why they are sick.  

For more information on epigenetic toxicity, see these resources:



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Backyard Talk

Linking Adverse Health Effects and Chemical Exposures

One of the most common questions I get asked is about the health effects of toxic chemicals. Will the chemicals in the landfill harm my children? Will the emissions from the plant cause my family to get cancer? Did the chemicals off-gassing from the PVC flooring cause my son’s asthma? The questions continue every day from people across the country.

Most of what we know about the toxicity of chemicals comes from animal studies and from studies of workers who manufacture the chemicals. From this experience, we’ve learned that dusty air causes lung cancer, benzene causes leukemia, radioactive paint causes bone cancer, vinyl chloride, liver cancer, and certain pesticides cause muscle weakness and paralysis. There’s also limited evidence from studies in communities, especially among children who are highly susceptible to toxic chemicals. At Love Canal, for example, there were high rates of miscarriages and children born with birth defects; in Tucson, AZ, children whose parents drank water contaminated with trichloroethylene (TCE) were born with 2-1/2 times more heart defects than normal; in Toms River, NJ, high rates of childhood cancer was linked to drinking water contaminated with TCE and other solvents; and in Woburn, MA, increased rates of childhood leukemia were associated with drinking contaminated water.

There is no question that exposure to toxic chemicals causes adverse health effects. But for nearly all chemicals there is not enough information on what happens when people are exposed. At best, there’s good information on the toxicity of only about 10% of over 80,000 chemicals in use today.

This makes it very difficult to say with certainty what health effects will occur following exposure to toxic chemicals. Among the uncertainties are how an individual body responds to exposure (this varies quite a lot from person to person), how long exposures occur, how many chemicals you’re exposed to and the actual toxicity of the substance. In most instances, these factors are unknown.

Another confounding factor is that many symptoms or diseases are not specific to a particular chemical. In most instances, there can be many causes of the symptoms that people are having. And since few physicians know much about toxic chemicals, they often tend to blame the victim for his or her situation rather than looking at chemicals as a possible explanation. For example, many physicians will diagnose a person who is fatigued, moody and without appetite as “depressed,” likely to have a problem at home or at work. Seldom is exposure to toxic chemicals considered, even when raised by the patient.

Still another problem is determining the “normal” rate of an illness or disease in a community or in a group of people. Scientists simply can’t decide amongst themselves what is normal, in large part because of the many uncertainties already mentioned.

As a result, evaluating chemical exposures is largely a matter of opinion, not fact. Scientists can give you estimates of risk, or tell you what adverse effects are typically associated with exposure to a chemical, but they cannot tell you with any certainty whether your child will develop cancer because of his/her exposure to TCE or other chemicals in your drinking water. They can give you their opinion, but it’s only an opinion.

This is very frustrating for people. How can we be smart enough to put a man on the moon and bring him back, yet we don’t know much about the toxicity of the sea of chemicals that we live in every day? This speaks volumes about the power of the chemical industry to control government regulations and research agendas.

Backyard Talk

New Dioxin Report: What it means

Several weeks ago EPA released the non-cancer portion of the EPA’s health assessment for the chemical known as dioxin. The event passed without industry collapsing, without the public going into panic as was anticipated by the food industry, and basically without the world coming to an end. The myriad forecasts of doom that industry and its apologists predicted did not come to pass. In fact, the media barely took notice. Why? – Because the reassessment did not set any new standards or introduce any new regulations.  It simply provided the scientific basis for determining the risks that dioxin poses, though in this case, just the non-cancer risks (EPA is still working on the cancer report).

The non-cancer effects of dioxin as described in the report are quite serious. In a recent review paper, Dr. Linda Birnbaum, Director of the NIEHS, summarized the adverse health effects of dioxin exposure in humans as including “cardiovascular disease, diabetes, cancer, porphyria, endometriosis, early menopause, reduced testosterone and thyroid hormones, altered immune responses, skin, tooth, and nail abnormalities, altered growth factor signaling, and altered metabolism.”

Most notably, the non-cancer assessment included for the first time a value called the reference dose.  This is a number used to evaluate non-cancer risks and is generally defined as “a level below which exposures are generally considered to be safe.” The EPA’s Reference Dose for dioxin is 0.7 picograms TEQ per kilogram per day (pg/kg/d) which was derived by evaluating developmental and reproductive effects in a community in Italy (Seveso) exposed to dioxin caused by an accident at a pesticide manufacturing plant.

What’s remarkable about the EPA reference dose is when you compare this number to the average daily exposure of the American public to dioxin (defined as the daily intake from all sources, 90% of which comes from food).  Using the most recent data from EPA (see Lorber et al. 2009) the average daily exposure is 0.54 pg TEQ/kg/d compared to EPA’s reference dose of 0.7 pg TEQ/kg/d.  So the average person gets a daily dose of dioxin that’s 77% of EPA’s new reference dose. That’s the good news; the bad news is that the average is so very close to the EPA reference dose and that some groups, especially children, are exposed to higher levels that exceed the new EPA reference dose. This is because children have different eating habits than adults. They tend to eat more diary products that are high in dioxin. Dioxin is prevalent in foods that are high in saturated fat, primarily meat and dairy.

A 2003 study conducted by a National Academy of Sciences Committee on Dioxin in Food bears this out. The committee found that children ages 1 to 5 were exposed to 1.09 pg TEQ/kg/day and children ages 6-11 years old were exposed to 0.69 pg TEQ/kg/day. This analysis shows that dioxin exposure in children 1 to 5 years old exceeds EPA’s reference or safe dose and that children 6 to 11 years old have dioxin exposure that is virtually identical to the EPA reference dose.

As a practical matter, this means that the best risk estimate we have on dioxin shows that the public, especially children are being exposed to unacceptable levels of dioxin that may be causing subtle adverse effects. These subtle effects likely include developmental effects that Dr. Birnbaum described in her review paper as posing the greatest concern “in part because the effects occur at the high end of the background range for the general population.”  These exposures may exceed the EPA’s reference does and even approach the levels observed in the study of Seveso, Italy.    The developmental effects may include altered thyroid and immune status, altered neurobehavior at the level of hearing, psychomotor function, and gender-related behaviors, altered cognition, dentition, and development of reproductive organs, and delays in breast development, in addition to altered sex ratios among exposed offspring.

While no exposure to dioxin is the ideal, we are not there yet.  In the meantime, exposure to dioxin in food, especially for children remains too high and needs to be addressed by EPA, FDA, and USDA. CHEJ strongly urges the EPA to finish and release their review on dioxin and cancer, and to develop a comprehensive action plan to further reduce dioxin emissions and exposures.

For a copy of EPA’s new dioxin health report, visit

To see CHEJ’s press release about this report, visit