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Toxic Tuesdays

Cyanide

Toxic Tuesdays

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

Cyanide

Cyanide is a chemical usually found in compounds with other chemicals. Cyanide compounds can be found in some bacteria, fungi, algae, and the seeds of stone fruits. One of the most dangerous cyanide compounds is hydrogen cyanide, a colorless gas that smells like almonds. It is used in industrial processes such as electroplating, metallurgy, metal mining, plastics production, organic chemical production, and photographic developing. Hydrogen cyanide can enter the air surrounding industrial settings where it is used. It can also be produced by combustion engines, tobacco smoke, and the burning of acrylonitrile plastics. (CHEJ has previously written about acrylonitrile here). Because acrylonitrile is used in many consumer plastics, building fires are one of the most common ways people are exposed to hydrogen cyanide.

Breathing hydrogen cyanide for even short amounts of time is incredibly dangerous and can lead to death. When cyanide enters the body it stops cells from being able to produce energy, interfering with many life-sustaining functions of the brain and heart. Early symptoms of cyanide exposure occur within minutes and include headache, dizziness, elevated heart rate, shortness of breath, and vomiting. This can then progress to seizures, decreased heart rate, low blood pressure, coma, heart attack, and death. People who survive exposure can have lifelong neurological impairments. Factory workers who inhaled low levels of hydrogen cyanide over years have reported trouble breathing, chest pain, vomiting, and headaches. Exposure to other cyanide-containing compounds results in the same health effects. Because of the extreme toxicity of cyanide exposure, the use of cyanide-containing compounds and the use of compounds that can produce cyanide when burned should be restricted in order to protect public health.

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Cyanide

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Acknowledging the Limits to Assessing Low Dose Mixtures of Toxic Chemicals​

Toxic Tuesdays

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

Acknowledging the Limits to Assessing Low Dose Mixtures of Toxic Chemicals

Approximately 1 year ago a Norfolk Southern train carrying more than 150 cars, many of which containing toxic chemicals derailed in East Palestine, OH. Thirty-eight of the train cars derailed and a decision was made by Norfolk Southern to burn the contents of 5 tanker cars containing vinyl chloride and other toxic chemicals. This unleashed a huge black cloud of particulates that enveloped the surrounding neighborhoods and farms in both OH and PA.

Immediately after the burn, people in East Palestine began reporting adverse health symptoms including, headaches, nose bleeds, skin rashes, central nervous symptoms, thyroid problems and more. These and other adverse health problems have continued to plague the residents of this rural midwestern town.

EPA responded immediately by telling people that everything was alright, that there was no cause for alarm. EPA’s testing found no levels of “concern.” But the people in East Palestine could not accept this narrative because they knew things were not right. They knew the health effects they were suffering were real. They knew that EPA was not telling them the truth.

If EPA were honest with the people at East Palestine, they would have told them that they don’t understand why people are continuing to report so many illnesses while their data tells them that there should not be any adverse health problems in the community.

But if EPA did that, if they acknowledged how little is known about the link between adverse health effects and exposures to mixtures of chemicals, the people of East Palestine would demand action in the face of these uncertainties. Action like paying for people to relocate from the area so that they can stop being exposed to the toxic chemicals which are still in the air, getting the health care they need and moving on with lives.

It is clear from the situation in East Palestine that very little is known about how people respond to exposures to low level mixtures of toxic chemicals. It’s time to acknowledge that the scientific understanding does not exist to explain what is happening to the health of the people in East Palestine or other communities exposed to toxic chemicals. It’s time to recognize that we cannot rely on traditional toxicology to answer the questions people have about their exposures to low level chemical mixtures.

In an editorial about evaluating low dose exposures, Linda Birnbaum, former director of the National Institute for Environmental Health Sciences, described the traditional approach to evaluating health risks as “antiquated” and said that it needs to be replaced by a “better understanding of the actual characteristics of modern environmental chemicals.” Birnbaum went on to say that “It is time to start the conversation between environmental health scientists, toxicologists, and risk assessors to determine how our understanding of low doses effects and non-monotonic dose responses influence the way risk assessments are performed for chemicals with endocrine disrupting activities.”

It’s time to acknowledge that the tools we have are not able to answer the questions people ask about their exposures to toxic chemicals and give people the relief they are asking or, whether it’s cleanup, relocation, health care or something else.   

This is exactly what the government did for the Vietnam veterans exposed to Agent Orange; for the atomic bomb victims exposed to radiation fallout; for the 9/11 first responders in New York City; for the soldiers exposed to burn-pit smoke in Iraq and Afghanistan; and for the marines and their families at Camp Lejeune, North Carolina who drank contaminated water.

In each of these instances, the government recognized that the science linking exposure and health outcomes was impossible to assess and instead of requiring proof of cause and effect, they said, enough, we need to take care of our own and moved to a presumptive scientific approach that allowed veterans and first responders to get health care and other compensation. We should do the same for the people of East Palestine and in hundreds of other communities that have been exposed to low level mixtures of toxic chemicals.

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Cyanide

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Glyphosate Risks

Toxic Tuesdays

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

Glyphosate Risks

Glyphosate is a chemical found in weed killer products like RoundUpTM used on farms and home lawns. Because of its effectiveness, glyphosate has become the most widely used herbicide in the world. People who work with these products and people who live near farms where they are used can get exposed to glyphosate through the air. The International Agency for Research on Cancer (IARC) has concluded that glyphosate exposure probably causes blood cancers. 81% of American adults and children have detectable concentrations of glyphosate in their urine. While much is still unknown about the potential health risks of glyphosate exposure, two recently published studies illuminate how big a concern it may be for both workers and the public.

One study aimed at assessing the potential cancer risk posed to farmers who work with glyphosate-containing herbicides. The study used data from the Agricultural Health Study (AHS), which collected biological samples from private and commercial pesticide applicators in Iowa and North Carolina from 1993-1997. The study analyzed AHS participants who were male, above the age of 50, had no blood disorders, and had not been diagnosed with cancer, which created a sample of 1,681 people. The researchers analyzed the DNA of these participants to look for the loss of large portions of DNA in the Y chromosome. Significant loss of DNA portions can have a massive effect on how the body’s cells function and have been linked to increased risk for cancer. Losses of large portions of DNA in the Y chromosome have been specifically linked to blood cancers like those that may be caused by glyphosate exposure.

In the study, 21% of participants had lost large portions of the DNA in their Y chromosome in some of their cells. Statistical analysis found that using glyphosate-containing pesticides for either a longer period or with more intensity were both associated with more DNA loss in the Y chromosome. While these findings do not prove that occupational exposure to glyphosate causes cancer, they provide important biological evidence that glyphosate exposure can cause the kinds of largescale changes in DNA that are associated with cancer. It is the first study of agricultural workers to show this association between glyphosate and DNA loss.

A second study sought the extent of glyphosate exposure among people who live near farms where glyphosate is used. Some studies have shown that glyphosate exposure during pregnancy is associated with reduced fetal growth and pre-term birth. Thus, this study focused on measuring glyphosate levels of pregnant people in Idaho who live near farms that use glyphosate. The study included 40 participants in Idaho who were in their first trimester of pregnancy in 2021. Researchers collected weekly urine samples from participants until delivery. Half of participants lived near farms (less than 0.5 kilometers from a farm) and half lived far from farms (more than 0.5 kilometers from a farm). About two-thirds of both groups had detectable concentrations of glyphosate in their urine.

For participants living near farms, the frequency and concentration of glyphosate detection in urine increased significantly during the pesticide spray season (from May to August) compared to the non-spray season. This change did not occur in participants living far from farms, indicating that increased exposure to glyphosate was likely a result of pesticide spraying. While these findings do not directly track the health effects on pregnant participants or their infants, it is important biological evidence that agricultural use of glyphosate exposes nearby residents. It is the first study to demonstrate that residential proximity to farms using glyphosate is associated with increased glyphosate in the body.

These two studies demonstrate that glyphosate may pose risks to both workers and the public. CHEJ has previously written about the uses and health risks of glyphosate here.

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Cyanide

Cyanide is a chemical usually found in compounds with other chemicals. Cyanide compounds can be

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Thallium

Toxic Tuesdays

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

Thallium

Thallium is a metal found in the Earth’s crust and can be obtained by smelting metal compounds. Today, most thallium is used in the production of electronics, especially semiconductors. It is also used for medical imaging and in the production of glass. Thallium contamination of the surrounding environment most commonly results from the smelting process, but it can also happen during transport or improper disposal. Once in the environment, it remains in the air, water, and soil without breaking down. It can enter the food chain because it is absorbed by plants and builds up in fish.

Eating food contaminated with thallium is the most likely way people in the United States would be exposed to it. Ingesting high levels of thallium over a short period of time can lead to symptoms such as vomiting, diarrhea, and hair loss. It can impair function of the brain, lungs, heart, liver, kidneys, and even lead to death. Little is known about the health effects of ingesting low levels of thallium over a long period of time. People who work in facilities that use thallium or live near waste sites containing thallium can also be exposed by breathing contaminated air or touching contaminated material. Workers exposed to thallium over many years have had nervous system impairments, including numbness in the extremities. Studies on laboratory animals have shown that exposure to high levels of thallium can cause reproductive and developmental defects, but it is not known if this also occurs in people.

Historically, thallium was a common ingredient in rat poisons and insecticides sold in the United States. Recognizing that it is highly toxic, the government banned its use in these consumer products in 1972. In fact, thallium is considered so dangerous that it is no longer produced in the United States. Many other countries also ban or restrict the production of thallium. While these are positive developments to keep people safe, at lease 210 Superfund sites are known to contain thallium, meaning it still poses a danger to people’s health today.

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Cyanide

Cyanide is a chemical usually found in compounds with other chemicals. Cyanide compounds can be

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Endometrial Cancer & Pesticides​

Toxic Tuesdays

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

Endometrial Cancer & Pesticides

Endometrial cancer is an increasingly common form of cancer in developed countries. There are both genetic and environmental risk factors associated with the development of endometrial cancer, and changing the environmental risk factors may be the easiest way of reducing the incidence of endometrial cancer. Pesticides – mixtures of chemicals used in agriculture to protect crop growth – are known to cause certain cancers, but it is unclear if they can cause endometrial cancer. A recent study in Spain found that occupational exposure to pesticides is associated with endometrial cancer.

The study took place from 2017 to 2021, with researchers administering a questionnaire to 180 women with endometrial cancer. To create a control group to compare these women to, researchers also administered the questionnaire to 218 women admitted to hospitals who didn’t have endometrial cancer. The researchers asked about lifetime occupational history, demographic information, tobacco consumption, physical activity, family history of diseases, reproductive factors, and other information.

The researchers systematically coded all respondents’ occupations based on a job exposure matrix (JEM) for Spanish working conditions. A JEM is a list of occupations that provides estimated exposures to a variety of harmful chemicals for each one, respectively. Using a JEM allowed the researchers to estimate respondents’ exposure to pesticides based on their occupations. This was a clever way of creating a history of each person’s occupational exposure to pesticides, whereas collecting their current environmental or biological data would not have been able to capture their accumulated lifetime exposure. The three categories of job titles considered to be exposed to pesticides were: agricultural, poultry, and livestock activities; cleaning staff; and manufacturing and lumber industries. Using the JEM, and estimated occupational exposure to pesticides, the researchers performed statistical tests to determine if occupational exposure was associated with endometrial cancer.

Occupational exposure to pesticides was associated with two times greater odds of developing endometrial cancer than not having occupational exposure. Exposures that happened further in the past were associated with cancer, as were exposures that happened before the age of 32. Surprisingly, increased cumulative exposure was not associated with endometrial cancer. Working in agricultural, poultry, and livestock activities was associated with four times greater odds of developing endometrial cancer. Working as cleaning staff was not associated with endometrial cancer, which could be because the intensity and frequency of exposure in these jobs may be lower.

Cancers like endometrial cancer can be difficult to study because it can take a long time for the disease to develop after someone gets exposed to a cancerous chemical. Once the disease develops, collecting environmental or biological samples from the patient’s time of exposure is not possible. This study got around these limitations by using a job exposure matrix to estimate exposure to pesticides throughout women’s entire working lives. Of course, these exposures are only estimates, their use of personal protective equipment in each job was unknown, and researchers could not know what other potential cancer-causing chemicals respondents may have been exposed to.

Regardless of the limitations, this study is valuable because diseases related to women’s reproductive systems are less studied compared to many other diseases. It is also the first study to show an association between occupational pesticide exposure and endometrial cancer.

New regulations and increased use of personal protective equipment may explain why exposures further in the past were more associated with endometrial cancer. However, the results of this study demonstrate that these improvements may not be enough to keep workers safe when they come into contact with pesticides. Endometrial cancer can now be added to a growing list of diseases associated with pesticides, and more should be done to protect workers and the public from these chemicals.

For more information, CHEJ has previously written about chemicals that have been used in pesticides and herbicides such as atrazinebenzeneethylbenzeneglyphosate, and pentachlorophenol.

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Cyanide

Cyanide is a chemical usually found in compounds with other chemicals. Cyanide compounds can be

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How Individual Sensitivity Affects Toxicity

Toxic Tuesdays

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

How Individual Sensitivity Affects Toxicity

We previously addressed individual variability and how it affects a person’s response to toxic chemicals. Another important factor in toxicology is a person’s individual sensitivity to chemicals. How sensitive a person is to chemical exposure helps determine how susceptible or vulnerable they are to toxic chemicals. Several factors determine how sensitive a person is including age, sex, health, genetics, diet, lifestyle, preexisting conditions and previous environmental exposures. While some people are more sensitive to chemical exposures than others, there is no clear definition of what sensitivity is or what it means. This is partially since so little is understood about the human response to toxic chemicals, especially to low level mixtures of chemicals.

Because of this uncertainty, there is no generally accepted definition of sensitivity. Nicholas Ashford and Claudia Miller describe the various meanings of the term. In traditional toxicology, sensitivity has been defined as individuals who require relatively lower doses to induce a particular response. These individuals are considered more sensitive than people who require relatively higher doses to experience the same response. The distribution of this population is described by the classic bell curve where the sensitive and resilient populations are found in the tails of the curve. Most people fall into this response category. In traditional medicine, sensitivity has been defined as individuals who have a significant and rapid immune-mediated response to an allergen or agent. In this population, some individuals, described as chemically sensitive, have a striking immune response to an allergen or agent, while non-allergic individuals do not, even at high doses. Classic allergens include ragweed or bee venom, but also include chemicals such as nickel or toluene diisocyanate (TDI).

In recent years, a growing population of people have expressed an entirely different sensitivity response. These are people who have developed multiple chemical sensitivities. Ashford and Miller found that people who have developed multiple chemical sensitivities may exhibit a third and entirely different type of sensitivity. These authors stated this about people with multiple chemical sensitivities (MCS): “Their health problems often (but not always) appear to originate with some acute or traumatic exposure, after which the triggering of symptoms and observed sensitivities occur at very low levels of chemical exposure. The inducing chemical or substances may or may not be the same as the substances that thereafter provoke or ‘trigger’ responses.” Unlike classical toxicological or immune mediated responses, people with MCS sensitivity respond in a two-step process of an initial exposure event followed by a second triggering exposure. Much still needs to be understood about this third wave of sensitivity.  

Another factor that influences a person’s sensitivity is the body’s reserve capacity. Researchers have speculated that a chemical exposure may affect the reserve capacity of the body without causing an immediate adverse effect. However, when there are subsequent exposures, the body becomes unable to compensate for the additional stress and toxicity develops.

The science behind what is known about how people respond to chemical exposures, especially to low level mixtures of chemicals, is highly complex and not well understood. We know that people exposed to low level mixtures of toxic chemicals, like the people in East Palestine, OH, the site of that horrific train derailment and subsequent intentional burn of vinyl chloride, continue to suffer adverse health effects despite reassurances from EPA and public health agencies who are relying on traditional toxicology and risk assessments. Perhaps the people in East Palestine have developed a unique chemical sensitivity much like the third wave described by Ashford and Miller. So as their exposures continue during the ongoing cleanup, their chemical sensitivity and the subsequent adverse health responses are not what would be predicted by traditional toxicology or medical models. 

This is an important consideration to consider in East Palestine because it is clear that we do not understand what is happening to the health of the people there. It’s time to recognize that we cannot rely solely on traditional toxicology to address the questions people have about exposures to low level chemical mixtures.

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Cyanide

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Acrylonitrile

Toxic Tuesdays

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

Acrylonitrile

Acrylonitrile is a clear liquid that smells like onions or garlic. It is man-made as it does not naturally occur on Earth. It is used to create other materials, most commonly acrylic fibers in clothing and carpeting. Acrylonitrile can enter the environment from industrial sites that produce it and waste sites where it is disposed of. Because it dissolves easily in water and readily evaporates, it can enter the water, air, and soil. Although acrylonitrile breaks down in water and soil, people can still be exposed to it if they live or work near factories that use it. They can also be exposed to it through acrylonitrile-based plastic products and acrylic fibers. In addition to industrial sources of exposure, acrylonitrile is also found in tobacco smoke and vehicle exhaust.

Inhaling airborne acrylonitrile can cause respiratory, skin, and eye irritation. It can also cause dizziness, headaches, weakness, impaired judgment, and, in extreme cases, convulsions. Exposure of acrylonitrile to the skin can cause burns and blisters, and repeated exposure can cause brain and liver damage. Studies on laboratory animals have also found that inhalation or oral exposure can cause low birth weights and birth defects.

The US Department of Health and Human Services, the US Environmental Protection Agency, and the International Agency for Research on Cancer have all determined that acrylonitrile probably causes cancer in humans. This is likely to occur through DNA damage. Research has found that people who work at facilities that use acrylonitrile have higher rates of lung cancer than the general population. Acrylonitrile is also one of the chemicals in tobacco smoke that is most associated with respiratory cancers. These findings demonstrate that acrylonitrile is dangerous enough that people need to be protected from it, especially if they live or work near facilities that use or dispose of it.

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Cyanide

Cyanide is a chemical usually found in compounds with other chemicals. Cyanide compounds can be

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Metals & Preterm Births

Toxic Tuesdays

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

Metals & Preterm Births

Over 10% of births worldwide are preterm, meaning delivery occurs earlier than 37 weeks of pregnancy. It is a leading cause of neonatal mortality, and evidence suggests that exposure to heavy metals from the environment could be a risk factor. In the US, a major source of exposure to metals is private well water. The Environmental Protection Agency (EPA) sets standards and regulates levels of contaminants in public drinking water, but private well water isn’t regulated. This means private well water – which 13% of the US population receives drinking water from – is vulnerable to contamination. Indeed, studies have found metal contamination in private wells and that people who receive drinking water from private wells have more of these metals in their systems.

A recently published study set out to evaluate if exposure to toxic metals from private well water increased the risk of preterm birth. Because North Carolina (NC) has the largest state population using private well water, the researchers studied live births in NC that occurred from 2003-2015. From birth certificates, they could collect each pregnant person’s address at the time they delivered their babies. The researchers also used the NC-WELL database, which is a database of over 100,000 geocoded well water tests conducted from 1998-2019 from almost all census tracts in North Carolina. These tests include measurements of the concentrations of metals. The NC-WELL database allowed the researchers to assign each pregnant person’s address an estimate of their exposure to private well water and the concentrations of metals measured in that well water. Ultimately, the study included over 1.3 million births. This large sample size allowed the researchers to determine if increased metals in well water was associated with preterm birth.

The study found that people living in census tracts where over 25% of NC-WELL water tests exceeded EPA’s safe standard for cadmium had 11% higher odds of preterm birth than people who did not. People living in census tracts where over 25% of NC-WELL water tests exceeded EPA’s safe standard for lead had 10% higher odds of preterm birth than people who did not. These results indicate that cadmium and lead in private well water were each associated with preterm birth.

The study then modeled how the exposure to mixtures of metals was associated with preterm birth. This is particularly important because few studies assess the risks of multiple chemical exposures, even though it is highly likely people are exposed to more than one chemical at a time. When considering exposure to a mixture of seven metals present in private well water, the researchers found that exposure to the combination of cadmium and lead was associated with preterm birth.

In the US and NC, Black and Native American people have much higher rates of preterm birth than white people. Racial disparities in exposure to toxic chemicals could influence racial disparities in birth outcomes. As the study states plainly, “This is especially pertinent to consider when evaluating private well water-based exposure in NC, as structural environmental racism has led to poor and minority communities being more likely to rely on private well water.” This study found that when considering exposure to a mixture of seven metals present in private well water, the effect on preterm birth was most extreme for Native American people. It was associated with 20% higher odds of preterm birth for Native American people. The researchers say this disproportionate effect of metal exposure on preterm birth reflects the multiple environmental hazards and contaminants disproportionately forced on Native American people over several centuries. They also note that other studies have found that Native American pregnant people have higher levels of toxic metals in their systems than the national average.

This study used publicly available birth information and private well water testing to create a large cohort to study the effects of metals in private well water on preterm birth. The results make clear that private well water needs more regulation in order to ensure the levels of dangerous metals like cadmium and lead do not put people at risk. The results also make clear that not all people bear the same risks of exposure or health effects of exposure. People of color bear a disproportionate burden because they are more likely to receive private well water, which may contribute to disproportionate rates of preterm births.

For more information, CHEJ has previously written about the health effects of leadcadmium, and the importance of considering the health effects of exposure to mixtures of chemicals.

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Cyanide

Cyanide is a chemical usually found in compounds with other chemicals. Cyanide compounds can be

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Asphalt VOCs

Toxic Tuesdays

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

Asphalt VOCs

Asphalt is made of a compacted “aggregate” mixed with a “binder.” The aggregate takes the wear-and-tear of traffic while providing a nonskid surface. It comes from rock quarries, natural gravel, and/or soil. The binder is a type of cement that holds the aggregate together in place and provides waterproofing. It comes from the distillation of crude oil. To mix it with the aggregate, the binder is heated and thinned with other chemicals distilled from crude oil.

Some of these chemicals used to thin asphalt cement are classified as volatile organic compounds (VOCs), which are chemicals that contain carbon and readily evaporate into the air at room temperature. Common examples of VOCs include kerosene, chloroform, benzene, trichloroethylene, and perchloroethylene. Many VOCs are dangerous to human health. Inhaling air contaminated with VOCs can cause nose and throat irritation, headaches, nausea, and loss of coordination. Long-term exposure can cause more serious damage to the brain, liver, and kidneys. Some VOCs are also known to cause cancer in humans. Workers in facilities that make and mix asphalt are at the highest risk for health effects of exposure to VOCs. However, because VOCs diffuse through the air, people who live and work near these facilities could also be at risk.

VOCs aren’t only used in asphalt production; they’re also used in many industrial and commercial products. The US Environmental Protection Agency (EPA) estimates that VOCs are emitted by thousands of products. CHEJ has previously written about specific chemicals classified as VOCs: benzeneethylbenzeneformaldehydetrichloroethylene and perchloroethylenetoluene, and xylene.

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Cyanide

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How Individual Variability Affects the Toxicity of Chemicals

Toxic Tuesdays

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

How Individual Variability Affects the Toxicity of Chemicals

It’s clear that not everyone responds to the same chemical exposures in the same way. There are many examples of this. The most striking is the person who smoked cigarettes for 30 years and never had breathing problems or developed lung cancer.  A major factor in why this happens is “individual variability.”

People process chemicals differently depending on internal factors. There are two major sources of variability in people. The first is variability in the penetration of a chemical to the target organ, referred to as pharmacokinetics. The second factor is the response of the target organ and biological system itself, referred to as pharmacodynamics. Pharmacokinetics is relatively well understood compared to pharmacodynamics.

There are four sources of variability in people: uptake, distribution, metabolism and excretion. Uptake of chemicals through breathing, referred to as respiratory absorption, is mainly influenced by the solubility of the chemical in the blood and its interaction with the respiratory surfaces in the lungs. The solubility of a single chemical in the blood can differ significantly from one person to another. Solubility in the blood can even change in a single person depending on food intake and diet. How much uptake occurs alters the concentration of a chemical in the body which in turn alters its toxicity. Similarly, dermal absorption, or uptake through the skin, depends on the exposed site, the condition of the skin, and the humidity and temperature of the environment. Uptake through the stomach, referred to as gastrointestinal absorption, depends primarily on stomach content.

The distribution of chemicals in the body is also highly variable and depends primarily on body size and composition. Chemicals that are soluble in fat, for example, will be distributed differently in people with different amounts of fat. Distribution is also affected by the degree to which a chemical can bind to molecules, mostly proteins, in the body. The amount of a chemical bound to proteins in a target organ determines how much damage a chemical can cause. Chemicals that are not bound in the body are more easily removed. Chemical binding can be altered if there’s competition for binding sites due to the presence of other chemicals or drugs in the blood system.

Metabolism plays a central role in how the body responds to a chemical and is probably the most important source of pharmacokinetic variability in people. The body has different ways it can interact with or metabolize a chemical. This interaction helps determine the body’s response to chemicals. In some instances, a chemical can become more toxic and in other instances, it can become harmless. Metabolism mainly takes place in the liver but can also occur in the skin and lungs. Metabolism can be altered by several environmental factors. For example, the simultaneous absorption of chemicals in high doses can slow metabolism because of competition for the metabolizing enzyme in the body. Genetic factors also play an important role in metabolizing toxic chemicals. Individual variability in genes results from differences in the DNA sequence of genes (called polymorphisms). These individual differences play an important role in a person’s response to chemicals such as in the development of cancer. Metabolism can also be affected by age and sex, environment, chemical intake, physical activity, protein binding and lifestyle.

Once a chemical has been absorbed, distributed, and metabolized, it will be excreted from the body. The primary way that the body excretes toxic chemicals is through the kidneys. Some excretion may also occur through the lungs, GI track, skin and mammary glands in pregnant women. Renal excretion is influenced by factors such as kidney function, protein binding, urine pH and urine flow, which also varies in individuals. Volatile chemicals, chemicals with a tendency to evaporate, are generally excreted by the lungs. Pulmonary excretion is determined by the same factors that influence pulmonary absorption.

These many sources of variability mean that two people can be exposed to the same concentration of a chemical but absorb, distribute, metabolize and excrete it differently resulting in a different response. This is why scientists and government health officials struggle to explain what will happen to a group of people exposed to the same mixture of chemicals. A person’s response is highly complex and the scientific understanding of how different variables influence toxicity is not well developed. These gaps in our knowledge reflect the many uncertainties in how chemicals produce their toxic effects on the human body.  

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Cyanide

Cyanide is a chemical usually found in compounds with other chemicals. Cyanide compounds can be

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