Per- and polyfluoroalkyl substances (PFAS) are a vast group of synthetic chemicals manufactured and used globally since the 1940s. These compounds are valued for their unique ability to repel water, grease, and heat, making them ubiquitous in modern consumer products. The defining characteristic of PFAS is the exceptionally strong carbon-fluorine bond, which makes them highly resistant to natural degradation. This resistance has earned them the informal designation of “forever chemicals.” Because they do not break down in the environment, PFAS accumulate over time, leading to wide-ranging health effects in the human body.
Sources of Exposure and Persistence in the Body
Human exposure to per- and polyfluoroalkyl substances is nearly universal across developed nations, primarily through environmental contamination. The most common route of entry is contaminated drinking water, especially near industrial sites, military bases, or where PFAS-containing firefighting foams were used. Food also serves as a significant source of exposure, either from eating fish caught in contaminated waters or from contact with grease-resistant food packaging.
Once these chemicals enter the body, they resist metabolic breakdown and are not easily excreted, leading to bioaccumulation. The concentration of PFAS within human tissues, particularly the blood, liver, and kidneys, builds up over a lifetime of exposure. The persistence of these chemicals is evident in their extremely long half-lives, which is the time required for half of the substance to be eliminated.
The half-life of perfluorooctanoic acid (PFOA) in humans is estimated to range from 2.1 to 10.1 years, while perfluorooctane sulfonate (PFOS) can persist even longer, with estimates spanning 3.3 to 27 years. This slow clearance rate ensures that low-level, continuous exposure results in clinically significant concentrations over time. The long-term retention of these compounds drives the potential for chronic health outcomes, as tissues are exposed for years or decades.
Impacts on Vulnerable Systems: Development and Reproduction
The effects of PFAS are particularly concerning during periods of rapid development and reproduction due to the heightened sensitivity of these biological processes. PFAS compounds are classified as endocrine disruptors, interfering with the body’s hormonal systems that govern fertility and growth. Research indicates that women with elevated levels of these chemicals face a reduced likelihood of conceiving.
Women with higher PFAS levels were approximately 40% less likely to achieve pregnancy within a 12-month period. For men, exposure has been linked to detrimental effects on reproductive health, including altered hormone levels and reduced sperm quality, motility, and viability. These chemicals can cross the placental barrier, leading to direct prenatal exposure of the fetus, as they have been detected in cord blood.
Exposure during pregnancy is associated with several adverse outcomes, including an increased risk of preeclampsia, a condition characterized by high blood pressure. Elevated PFAS levels in the mother have also been associated with a higher risk of miscarriage and a reduction in infant birth weight. After birth, infants continue to be exposed, as PFAS are readily transferred through breast milk.
Systemic Health Outcomes: Immune, Liver, and Metabolic Function
Beyond reproductive and developmental concerns, PFAS induce widespread functional changes across several major organ systems. The immune system is a well-documented target of PFAS toxicity, with exposure linked to overall immune suppression. This suppression can manifest as a reduced response to vaccines in children, indicating that the body’s ability to mount a protective defense is diminished.
The liver, which functions as the body’s primary detoxification center, is particularly vulnerable to the effects of these persistent chemicals. PFAS accumulate in liver tissues, and studies show that exposure can lead to elevated liver enzymes, a clinical sign of cellular damage. The mechanism of liver impairment involves the disruption of lipid metabolism. For instance, PFOA has been observed to stimulate the synthesis of new fat within liver cells, while PFHxS can inhibit the release of existing fat.
This interference with metabolic pathways extends to the regulation of cholesterol and other lipids. Epidemiological studies consistently find an association between higher PFAS exposure and elevated total cholesterol levels, a condition known as dyslipidemia. These metabolic disruptions also include links to markers for obesity and insulin dysregulation, suggesting a broad impact on the body’s ability to manage energy.
Long-Term Concerns: Thyroid Disruption and Cancer Risk
The most severe long-term concerns regarding PFAS involve their capacity to disrupt the endocrine system and increase the risk for certain cancers. PFAS compounds interfere directly with the thyroid gland, which produces hormones that regulate metabolism, growth, and development. This interference can lead to altered levels of thyroid hormones, resulting in conditions such as hypothyroidism.
The mechanism for this disruption includes the ability of PFAS to mimic natural hormones and bind to thyroid receptors, and their capacity to interfere with iodine uptake. This prolonged hormonal imbalance and resulting cellular stress contribute to more serious outcomes. Recent human data suggests a specific link between exposure to perfluorooctane sulfonate (PFOS) and an increased rate of thyroid cancer diagnosis.
Epidemiological studies have also established associations between the most well-known legacy PFAS compounds and other forms of cancer. Exposure to PFOA has been linked to an increased risk of developing kidney and testicular cancer in human populations. Based on a review of the evidence, the International Agency for Research on Cancer (IARC) has classified PFOA as “carcinogenic to humans,” highlighting the seriousness of this long-term health hazard.