Fluorides and Fluorocarbons Toxicity

Etiology

Fluoropolymers, also called fluorocarbons or perfluorocarbons, can be found in a variety of household and commercial products.  They are most commonly encountered as components of waterproofing agents. Other uses include lubricants, sealants, and leather conditioners. Fluoropolymers are defined by the International Union of Pure and Applied Chemistry (IUPAC) as molecules consisting solely of carbon and fluorine. However, compounds that contain molecules other than carbon and fluorine (described as fluorocarbon derivatives) are often referred to as fluoropolymers as well.

Epidemiology

Fluoropolymer-related respiratory illness has become a public health concern due to multiple occurrences of large population exposure[4][2]. In some instances, hundreds of victims have suffered respiratory illness due to exposure to fluoropolymers. A seasonal trend is seen with fluoropolymer-related respiratory illness, with an increase in cases during winter months.

The onset of symptoms is rapid, within minutes to hours of exposure[3].  The primary product handler is typically most affected. However, symptoms have been known to develop in patients with only second-hand exposure.

Pathophysiology

Fluoropolymers are ultrafine particles ranging in size from 0.02-0.2 µm[5].  These particles can aggregate and produce particle agglomerates measuring up to 15um[6][7]. This increased particle size is thought to occur with product aging and has been associated with attenuation of toxicity[6].

The compounds used in waterproofing products reportedly underwent a formulation change after the passage of Title IV of the Clean Air Act amendments and transitioned from a fluoroalkane structure to the more toxic fluoroalkene structure[8][9]. Due to their proprietary nature, specific information about the structures is not available to the public.  Gas chromatography/mass spectroscopy (GC/MS) has been performed on some products to gain insight into the structural changes that has accompanied these reformulations[8]. Though these studies did not allow the identification of individual fluorocarbons, a change in composition from a fluoroalkane-containing product to one that contained fluoroalkenes was shown.

Fluoroalkanes contain only single bonds and are more chemically stable and therefore of lower toxicity than fluoroalkenes, which contain double bonds[10][11]. Increasing numbers of carbon-fluorine bonds further increase the strength and stability of other nearby carbon-fluorine bonds; therefore, longer chain, saturated fluorocarbons, such as the fluoroalkanes, are the most chemically stable. Unsaturated structures, such as the fluoroalkenes, are much more reactive because the area of the double bond tends to be deficient in electrons, which makes them susceptible to attack by bases and other nucleophiles, such as fluorine and hydroxyl radicals[10][12].

Because these products have been associated with multiple occurrences of respiratory illness, with hundreds of victims involved in some outbreaks, fluoropolymer-related respiratory illness has become a public health concern. Despite this, a review of the literature on this topic fails to yield a clearly elucidated mechanism to explain why illness develops after exposure to some products and not others.

The most convincing evidence to date regarding a mechanism of disease is the change in fluoropolymer structure (from fluoroalkane to fluoroalkene)[3].  It is theorized that this structural change in conjunction with patient-specific factors (metabolic activation, smoking, preexisting medical conditions, etc.) is most likely to cause the development of illness. Other investigations have reported an association between the occurrence of outbreaks and changes in particle size, particle emission rate, and changes in the propellants or solvents. The presence of multiple different reformulations may explain the varying reports.

History and Physical

Fluoropolymer-related respiratory illness often resembles polymer fume fever, with acute respiratory signs and symptoms often accompanied by flu-like symptoms[4][2][8]. The most common symptoms are a non-productive cough and dyspnea[13]. A physical exam may reveal fever, tachycardia, increased work of breathing, wheezes, or rales.

Evaluation

Abnormal laboratory studies are often limited to those indicating inflammatory reactions, such as leukocytosis and elevated c-reactive protein (CRP)[1][2][13][12][14][15]. Since fluoride is the most electronegative element, it binds tightly to cations such as calcium.  Due to calcium binding, fluorocarbon exposure could theoretically lead to hypocalcemia, similar to that seen following hydrofluoric acid exposures[1]. Despite this, there has been only one reported case of hypocalcemia following fluorocarbon exposure, and this patient did not develop dysrhythmia or other untoward effects[1].  Chest radiography may reveal infiltrates.

Treatment / Management

Basic supportive measures, such as removal of the exposure, fresh air, and supplemental oxygen, are adequate in many cases[1][4][2][13][8][16][15]. Inhaled beta-2 adrenergic agonists and corticosteroids have been used with success in patients with physical exam evidence of bronchospasm and may represent a reasonable intervention in selected cases[15][16][17][2][4]. Non-invasive positive pressure ventilation and endotracheal intubation have been required in some cases[1]. Treatment with antibiotics should be reserved for patients with clinical findings consistent with respiratory infection.(B2)

Differential Diagnosis

• Arsenic toxicity

• Cardiac glycoside plant poisoning

• Chlorine toxicity

• Cough, Cold and Allergy preparation toxicity

• Disulfiram like mushroom toxicity

• Gyromitra mushroom toxicity

• Hallucinogenic mushroom toxicity

• Heavy metal toxicity

• Herb poisoning

• Hydrofluoric acid burns

• Liquorice poisoning

• Orellanine mushroom toxicity

• Scombroid toxicity

• Vitamin toxicity

Prognosis

Most patients recover within 24 hours [18][1][4]. In one study, approximately 50% of reported cases required hospital admission[13].

Pulmonary symptoms may last longer than other symptoms, such as nausea and fever.  In more severe cases, there have been reports of respiratory failure, acute respiratory distress syndrome, and rarely death[3].

Complications

While most patients experience a full recovery, chronic lung abnormalities and the development of pulmonary fibrosis have been reported[8].