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Toxic Tuesdays

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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Toxic Tuesdays

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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Toxic Tuesdays

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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Toxic Tuesdays

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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Toxic Tuesdays

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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Backyard Talk

Small Victory for North Carolina Residents Fighting CAFOs: Governor Vetoes House Bill 467

The Bill:
“Elise Herring has been fighting for decades against the industrial hog farm that moved in beside her family’s Eastern North Carolina property in 1986 and began spraying the fecal material of +2,000 hogs onto the field that ends eight feet outside her kitchen window.
But last Friday, when the state’s newly elected Democratic Governor Roy Cooper vetoed a bill that would protect the hog industry from lawsuits like the one Herring and about 500 others have filed against a subsidiary of Smithfield Foods, she breathed a sigh of relief- at least for the moment…
The North Carolina legislature, in which the Republicans hold a supermajority in both houses (35-15 in the Senate; 74-46 in the House), could override the veto with a 3/5ths majority vote if they take up the issue again. The House would need 72 votes to override the veto, and the Senate would need 30; during each chamber’s last vote on the bill, 74 representatives and 30 senators supported it.”
The Problem:
“In North Carolina, 6,500 industrial hog farms, known as concentrated animal feeding operations (CAFOs), house more than 9.5 million animals in the flat, hot eastern stretches of the state.
Together, the pigs produce 10 billion gallons of feces and urine each year, which the operations store in large, open-air pits, euphemistically referred to as “lagoons.” To make sure the pits do not overflow, the operations periodically lower their levels by shooting the fecal mixture over “sprayfields” of feed crops with high-pressure sprinklers.
Scientific studies confirm that discharging animal waste into the air damages human health in the surrounding areas. The foul-smelling chemicals the CAFOs release – namely ammonia and hydrogen sulfide – are associated with breathing problems, blood pressure spikes, increased stress and anxiety, and decreased quality of life, studies have found.”
Read the entire story about the North Carolina House Bill 467 and CAFOs here