What is Glycol Ether Toxicology?
Glycol ethers are a type of solvent that have been used in many industries since the 1930s. This type of solvent has unique features such as its ability to dissolve many things, slow rate of evaporation, and its ability to mix with both water and other organic substances. They are often used in the making of many common products like paint, cleaners, cosmetics, medicines, electrical circuit boards, and brake fluid for cars.
Glycol ethers are usually categorized based on the molecules they come from. The ones derived from a molecule called ethylene oxide are known as the E-series, while those derived from another molecule called propylene oxide are known as the P-series. The use of E-series glycol ethers, which include types like methyl-, ethyl-, butyl-, and hexyl-GEs, has decreased over time due to concerns about their harmful effects. When broken down in the body, E-series glycol ethers can cause a range of health problems, affecting the nervous system, blood, kidneys, liver, hormone system, causing birth defects and fertility issues. As a result, the safer P-series glycol ethers have largely replaced them.
The P-series includes types like methyl-, ethyl-, n-propyl-, butyl, and phenyl propylene glycol ethers. These are often chosen for their lower risk of causing harm. P-series glycol ethers are commonly found in things like paint, protective coatings, processes used in making semiconductors, resins, cleaning products, sunscreen, and medicines. An important use of propylene glycol is in medical infusions of drugs like lorazepam and diazepam due to its ability to dissolve substances.
People can be exposed to glycol ethers at home or at work through breathing it in, skin contact, or swallowing it. Jobs with the highest risk of glycol ether exposure include cleaning staff, printing machine operators, workers making semiconductors, workers in the chemical industry, car mechanics, cosmeticians, secretaries, and printers.
What Causes Glycol Ether Toxicology?
Glycol ethers can quickly enter the body through the skin, by breathing it in, or swallowing. Though swallowing it is less common, it can result in the most severe harmful effects. There have been instances where people consumed glycol ethers on purpose. Some types of glycol ethers have a component called a primary alcohol, which is converted by the body using an enzyme called alcohol dehydrogenase into harmful substances called toxic alkoxyacetic acids. This build-up of organic acids often leads to side effects affecting the kidneys, nervous system, and reproductive system. However, other types of glycol ethers do not have this primary alcohol part and therefore do not result in harmful substances when processed by the body.
Risk Factors and Frequency for Glycol Ether Toxicology
There’s not a lot of information about the effect of glycol ethers on reproductive health in humans. Most of the studies done have looked at certain types of glycol ethers, including 2-methoxyethanol, 2-ethoxyethanol, and 2-butoxyethanol. These studies have used case reports and animal research, and super small groups of people in what’s called prospective cohorts. It’s important to note that these studies can be muddied by exposure to other chemicals in the workplace.
Interesting to note how we first discovered the negative impacts of these chemicals on reproduction. Animal models first showed these bad outcomes in the 1970s, and this led to studies in the US about a decade later. France started regulating this compound somewhat in 1992, but it wasn’t fully banned in things like drugs and makeup until 1999.
These glycol ethers are really common in industry, which is why most of the exposure cases are work-related. Workers in semiconductor factories are especially at risk for harm to their reproductive health. For example, a study from 1996 found that female workers at these factories had a higher risk of miscarriage. A study a year later in Europe found that women exposed to these chemicals were more likely to have kids with birth defects, like neural tube defects and cleft lips.
Studies also found that shipyard workers exposed to these chemicals had a high rate of conditions that lead to low sperm count or no sperm at all. Worth mentioning is a 2020 study from France that found traces of glycol ether byproducts in 6-year-old kids who were undergoing brain development assessments.
In 2018, the US poison control centers reported more than 6,000 exposures to a type of glycol ether called ethylene glycol. Most of these exposures were accidental (78%), and 469 of the exposures were in kids who were 5 or younger.
Signs and Symptoms of Glycol Ether Toxicology
People exposed to glycol ether, commonly found in products like brake fluid or antifreeze, may visit the ER due to accidental or intentional consumption. The severity of symptoms can range largely; while some people might not show any signs of illness, others may experience severe effects from notable consumption, which, although rare, could be fatal. Chronic exposure to glycol ethers can also result in slowly emerging signs of illness or abnormal lab results.
In cases of acute glycol ether toxicity, patients might experience symptoms related to the stomach and kidneys, such as nausea, vomiting, decreased urine output, breathlessness, and abdominal pain. Other symptoms can include seizures, headaches, confusion, agitation, weakness, chest pain, and upper gastrointestinal bleeding. Large consumption of glycol ether is often linked to these symptoms. Acute hemolysis can also occur, causing symptoms like weakness, paleness, and fainting.
Individuals with kidney damage caused by glycol ether ingestion might first experience decreased urine output (oliguria) due to dehydration, and later, osmotic diuresis, or increased frequency of urination, due to the build-up of osmotically active substances in the kidneys.
Studying detailed past medical and social history can shed light on glycol ether toxicity. One’s occupation is also crucial, as those who work in industries using glycol ether in their products like in electronics, printing, painting, textiles, adhesives, cleaning, and personal care products may be exposed. It’s important to keep in mind that symptoms of glycol ether poisoning can be similar to toxicity from alcohols like methanol and conditions like diabetic ketoacidosis.
The symptoms of a patient who has ingested glycol ethers can vary based on the amount consumed, the timing of ingestion, and their individual characteristics. The symptoms can be grouped into three categories based on their initiation and duration: acute, subacute, and chronic.
- Acute toxicity: Ingesting a large amount can result in visible confusion or even unconsciousness, with symptoms appearing within a few hours. Fast breathing due to kidney-induced metabolic acidosis, various metabolic imbalances, refractory shock, and certain heart-related issues have been reported in some cases. Signs of severe dehydration, such as dry oral cavity, fallen eyeballs, rapid heartbeat, and poor blood flow can be evident.
- Subacute toxicity: After 5 to 10 days, symptoms mainly affect the nervous system including gradual lethargy, bilateral facial paralysis, voice disorders, and non-reactive pupils. Focal nervous system involvement has been reported, along with localized skin redness, dryness, and sometimes allergic reactions, depending on the exposure duration and frequency.
- Chronic toxicity: Occurring at least 2 weeks after initial exposure, chronic toxicity can present with central and peripheral nervous system damage and can progress to coma. Respiratory function can be impaired, and over time, repetitive exposure can cause weakness, drowsiness, irregular pupils, and excessive sleepiness. Patients might also report a long history of infertility, decreased testicular size, spontaneous abortions, and congenital abnormalities in their children.
Testing for Glycol Ether Toxicology
If you’re suspected to have been exposed to a harmful compound known as glycol ether, your doctor may order some basic blood tests to check the levels of certain substances in your blood. These tests can include a complete metabolic panel and blood count, which can help your doctor understand if you’ve developed any imbalances in your body’s chemical levels or signs of anaemia (a condition where your body doesn’t have enough red blood cells). These tests also look at the levels of substances like calcium, creatinine (a waste product of muscle activity), and potassium. Low calcium levels and high creatinine and potassium levels can indicate kidney failure.
If you’re experiencing signs of difficulty breathing, such as rapid breathing, your doctor might order an arterial blood gas test. This test looks at the levels of oxygen and carbon dioxide in your blood and can help your doctor understand how well your lungs and kidneys are functioning. This test can give important information about the severity of glycol ether toxicity and can help guide treatment decisions.
One test that your doctor may use to understand the severity of your condition involves calculating the “anion gap.” This test measures the difference between the measured and calculated amounts of positively and negatively charged substances in your blood. A high anion gap could suggest the buildup of substances not routinely measured in standard laboratory tests, due to glycol ether poisoning.
Lactate levels in your blood might also be measured to see how well oxygen is reaching your tissues and to check for tissue damage. If you’ve been exposed to other harmful substances in addition to glycol ether, some other tests might be run to check for the presence of these substances.
A urinalysis, a test of your urine, is used to see the function of your kidneys and to check for the presence of blood, protein, or crystals in your urine, all of which could be signs of kidney injury due to glycol ether poisoning.
If your heart’s rhythm isn’t normal, an EKG, a test that records the electrical signals in your heart, can be helpful. This test can show if you have problems with the electrical activity of your heart.
If you’re experiencing changes in your mental state, your doctor might order a CT scan, a type of X-ray that takes detailed pictures of your brain, to check for any other possible causes of these changes. However, it might not show every type of brain injury that could occur due to glycol ether exposure.
A chest X-ray might be needed to check for signs of lung inflammation or damage from breathing in glycol ether or potentially from vomiting and breathing in your stomach contents due to confusion or drowsiness. An ultrasound, a type of imaging that uses sound waves to create pictures of your body’s organs, might be used to check your kidneys and liver for signs of damage.
Your doctor might also order tests called nerve conduction studies or an electroencephalogram, which can help understand if your nerves or brain have been injured due to glycol ether exposure.
Treatment Options for Glycol Ether Toxicology
If you’ve been exposed to glycol ether, a type of chemical often used in cleaning and painting products, it’s important to obtain medical care immediately. The first line of treatment will focus on making sure you can breathe properly, your heart is functioning as it should, and your other vital signs are stable. Depending on how severe your reaction is and how much time has passed since the exposure, additional treatments may be necessary.
Glycol ether can become harmful when it’s broken down by your body into a toxic substance. To counter this, doctors may use a medicine called fomepizole to stop your body from breaking down the glycol ether. This medicine works to slow down the breakdown process, buying time for your body to get rid of the harmful substance via a process known as hemodialysis, which is a way to remove wastes and extra fluid from your blood when your kidneys can’t adequately do the job.
If the substance your body has been exposed to doesn’t stay in the body long and you have healthy kidneys, fomepizole alone might be enough for treatment. As such, the sooner doctors can start treatment after glycol ether exposure, the better.
Propylene glycol is a similar substance to glycol ether, but typically less harmful. If you’re exposed to this substance, you’ll likely receive the same treatment.
Depending on how severe your exposure is, additional treatments may be needed. For example, if the chemicals have upset the balance of minerals in your blood or caused severe acid buildup in your body, doctors may need to correct these imbalances. In some cases, you may need a machine to assist your breathing, or a blood transfusion if the substance has damaged your red blood cells to a dangerous level.
It’s not entirely clear if cleaning out your stomach (gastric decontamination) is beneficial in these cases. The procedure might be risky, especially if you’re showing signs of confusion or difficulty maintaining consciousness. Doctors may also hesitate to give you activated charcoal, a commonly used treatment to absorb harmful substances, as it doesn’t work well for this type of exposure. Some laboratory studies suggest that a medication called N-acetylcysteine may be beneficial for glycol ether exposure, although more research is needed to confirm this.
What else can Glycol Ether Toxicology be?
If someone is thought to have consumed glycol ether, a type of toxic alcohol, doctors will need to consider other possible causes that show similar symptoms. These can include the swallowing of other dangerous alcohols like methanol and isopropyl alcohol. But, it’s essential to know that the amount of these substances that can be life-threatening, as well as the way the body handles these chemicals, can vary. Overdoses of drugs can also be considered since they often result in neurological and metabolic problems.
What to expect with Glycol Ether Toxicology
Getting to the hospital early generally can lead to a better outcome. This is also true if your body is able to offset a condition called metabolic acidosis, where the body either produces too much acid or can’t get rid of it effectively, through respiratory compensation – the body’s way of adjusting the respiratory rate to keep the balance of oxygen and carbon dioxide in the blood stable. This suggests you’re more likely to get better.
However, certain factors can lead to a worse outcome. These include severe brain damage (for instance, a coma), difficulty breathing, deep changes in your body’s chemistry that require a treatment called dialysis (where a special machine cleans your blood), acidosis where the blood becomes too acidic (with a pH below 7), and if evaluation at the hospital is delayed.
There have been reported cases where people have died due to ethylene glycol toxicity, which typically results in serious kidney damage requiring hemodialysis, a type of dialysis done to cleanse the blood of toxins when the kidneys fail.
Possible Complications When Diagnosed with Glycol Ether Toxicology
: Complications from glycol ether toxicity mainly impact the neurological and kidney systems. Seizures, evidence of nerve damage, and changes in the brain structure are some of the potential complications. There have been instances in which patients developed different types of nerve-related issues. However, these complications could surface immediately after the poisoning or after several months. Keep in mind that there isn’t much lasting research available on these long-term effects.
Patients might experience severely low calcium levels and acidosis, leading to heart dysrhythmias and acute kidney failure, possibly needing dialysis. Disbalances in electrolytes, pancreatitis, and acidemia are some of the common immediate complications, which are often associated with kidney failure, brain dysfunction, and nerve-related issues. There have been a few reports that talk about potential lung edema after acute glycol ether ingestion, but more research is required to confirm these findings.
For survivors of glycol ether toxicity, the long-term complications can vary a lot. While mild kidney injuries might get better, patients needing hemodialysis may have to continue with it. Neurological issues can also occur due to oxidative stress and damage to the myelin sheath covering nerve fibers. Patients having kidney failure seem to have a higher risk of developing neurological complications. The type of complications can vary depending on the individual’s initial presentation.
There is potential for liver damage due to oxidative stress caused by substances formed after glycol ether is metabolized. While the full range of potential liver complications hasn’t been exactly discovered, as of now, there isn’t enough evidence to say that glycol toxicity could increase the risk of cancer. Research has not shown any significant association between exposure to glycol ether and development of acute myeloid leukemia. No solid evidence has been found to show that glycol ether toxicity could lead to genetic changes. However, there are some studies that suggest that exposure to glycol ether during pregnancy could cause genetic changes, but more research is required in this area.
Possible complications include:
- Seizures
- Brain structural change
- Nerve damage
- Heart rhythm issues
- Kidney failure requiring dialysis
- Electrolyte imbalances
- Pancreatitis
- Acidemia
- Potential lung edema
- Mild kidney injury
- Neurological complications
- Potential liver damage
Preventing Glycol Ether Toxicology
It’s important to store household items like cleaning products, paint, and car fluids in a safe and secure place, especially away from young children. This will help to avoid the risk of them accidentally swallowing these products. To lower the exposure to chemicals called glycol ethers at work, there are actions you should take to protect your lungs and skin.
For example, if you’re in a small, enclosed space, it would be beneficial to use an exhaust fan to reduce chemical exposure. Sometimes, you may need to use personal safety gear like gloves, breathing masks, face shields, and protective clothing. This will help prevent these chemicals from getting on your skin. The type and potential exposure of the specific glycol ether will determine what safety equipment you should use.
