Fluorocarbons are fluorinated carbon chain polymers that are used in an assortment of household and commercial products as waterproofing agents, lubricants, sealants, and leather conditioners[1].
These products have been implicated in sporadic outbreaks of respiratory illness characterized by dyspnea, cough, and chest pain[2]. Though typically self-limited, more severe exposure may lead to respiratory failure, acute respiratory distress syndrome (ARDS), and even death. Studies investigating the mechanism of fluoropolymer-related respiratory illness in humans have been difficult to perform for the following reasons: chemical formulation of these products is proprietary, chemical formulations are intermittently reformulated, product labels and safety data sheets (SDS) may not report fluorocarbon presence if present only in small amounts[3].
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.
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.
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.
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.
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.
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.
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].
While most patients experience a full recovery, chronic lung abnormalities and the development of pulmonary fibrosis have been reported[8].
Poison centers have played a crucial role in the recognition of these disease outbreaks, with voluntary recalls beginning the first few days after the first reported illness in many cases and therefore, consultation with poison control is strongly recommended.
General hygiene, such as the use of personal protective equipment, use in well-ventilated areas (outdoors if possible), frequent hand washing, and avoidance of smoking to avoid exposure to pyrolysis products, should be encouraged[8][5][19]. These products should be applied with a paintbrush when possible, as opposed to being volatilized by a spray apparatus[8][5].
Patients should be educated about the association of these products with respiratory illness and reminded to use these products only as directed to help avoid future breakouts. Additionally, patients should be made aware of the fact that many products do not list the presence of a fluorocarbon on the SDS since it comprises less than 1% of the total ingredients. [13]
[1] | Bracco D,Favre JB, Pulmonary injury after ski wax inhalation exposure. Annals of emergency medicine. 1998 Nov [PubMed PMID: 9795328] |
[2] | From the Centers for Disease Control and Prevention. Severe acute respiratory illness linked to use of shoe sprays--Colorado, November 1993. JAMA. 1993 Dec 22-29 [PubMed PMID: 8254842] |
[3] | Hays HL,Spiller H, Fluoropolymer-associated illness. Clinical toxicology (Philadelphia, Pa.). 2014 Sep-Oct [PubMed PMID: 25200453] |
[4] | Brief report: respiratory illness associated with boot sealant products--five states, 2005-2006. MMWR. Morbidity and mortality weekly report. 2006 May 5 [PubMed PMID: 16675946] |
[5] | Vernez DS,Droz PO,Lazor-Blanchet C,Jaques S, Characterizing emission and breathing-zone concentrations following exposure cases to fluororesin-based waterproofing spray mists. Journal of occupational and environmental hygiene. 2004 Sep [PubMed PMID: 15559330] |
[6] | Warheit DB,Seidel WC,Carakostas MC,Hartsky MA, Attenuation of perfluoropolymer fume pulmonary toxicity: effect of filters, combustion method, and aerosol age. Experimental and molecular pathology. 1990 Jun [PubMed PMID: 2115007] |
[7] | Lee KP,Seidel WC, Pulmonary response to perfluoropolymer fume and particles generated under various exposure conditions. Fundamental and applied toxicology : official journal of the Society of Toxicology. 1991 Aug [PubMed PMID: 1765219] |
[8] | Lazor-Blanchet C,Rusca S,Vernez D,Berry R,Albrecht E,Droz PO,Boillat MA, Acute pulmonary toxicity following occupational exposure to a floor stain protector in the building industry in Switzerland. International archives of occupational and environmental health. 2004 May [PubMed PMID: 15007653] |
[9] | Hubbs AF,Castranova V,Ma JY,Frazer DG,Siegel PD,Ducatman BS,Grote A,Schwegler-Berry D,Robinson VA,Van Dyke C,Barger M,Xiang J,Parker J, Acute lung injury induced by a commercial leather conditioner. Toxicology and applied pharmacology. 1997 Mar [PubMed PMID: 9073590] |
[10] | Clayton JW, Toxicology of the fluoroalkenes: review and research needs. Environmental health perspectives. 1977 Dec [PubMed PMID: 612451] |
[11] | Brown RF,Rice P, Electron microscopy of rat lung following a single acute exposure to perfluoroisobutylene (PFIB). A sequential study of the first 24 hours following exposure. International journal of experimental pathology. 1991 Aug [PubMed PMID: 1883743] |
[12] | Heinzer R,Ribordy V,Kuzoe B,Lazor R,Fitting JW, Recurrence of acute respiratory failure following use of waterproofing sprays. Thorax. 2004 Jun [PubMed PMID: 15170049] |
[13] | Daubert GP,Spiller H,Crouch BI,Seifert S,Simone K,Smolinske S, Pulmonary toxicity following exposure to waterproofing grout sealer. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2009 Sep [PubMed PMID: 19655284] |
[14] | Woo OF,Healey KM,Sheppard D,Tong TG, Chest pain and hypoxemia from inhalation of a trichloroethane aerosol product. Journal of toxicology. Clinical toxicology. 1983 Jun [PubMed PMID: 6689182] |
[15] | Wright GM,Lee A, Alveolitis after use of a leather impregnation spray. British medical journal (Clinical research ed.). 1986 Mar 15 [PubMed PMID: 3082413] |
[16] | Khalid I,Godfrey AM,Ouellette DR, Chemical pneumonitis and subsequent reactive airways dysfunction syndrome after a single exposure to a household product: a case report. Journal of medical case reports. 2009 Nov 9 [PubMed PMID: 19946590] |
[17] | Laliberté M,Sanfaçon G,Blais R, Acute pulmonary toxicity linked to use of a leather protector. Annals of emergency medicine. 1995 Jun [PubMed PMID: 7755212] |
[18] | Severe acute respiratory illness linked to use of shoe sprays--Colorado, November 1993. MMWR. Morbidity and mortality weekly report. 1993 Nov 26 [PubMed PMID: 8232172] |
[19] | Vernez D,Bruzzi R,Kupferschmidt H,De-Batz A,Droz P,Lazor R, Acute respiratory syndrome after inhalation of waterproofing sprays: a posteriori exposure-response assessment in 102 cases. Journal of occupational and environmental hygiene. 2006 May [PubMed PMID: 16574608] |