Fatal hydrofluoric acid poisoning: histologic findings and review of the literature.

Hydrofluoric acid (HF), the inorganic acid of elemental fluorine, is a highly dangerous substance and death can result from a very small exposure. In addition to local toxicity, HF can trigger fatal systemic reactions by its high affinity for calcium and magnesium. The authors report the autopsy case of a male worker who was exposed to 50% HF while repairing the leakage from an HF tank valve in a semi-conductor washing factory. His colleagues found blisters on his neck after 6 h of work and he was sent to the hospital. However, he expired from cardiac arrest despite an immediate calcium gluconate injection. At autopsy, burns with eschar covering less than 5% of the total body surface were identified on the neck and around both ears, and microscopic examination of the affected skin revealed extensive necrosis of the epidermis and dermis with pustule formation. In chemical analysis, no fluoride ions were detected in blood, vitreous humor, urine, pleural fluid, bile, or skin tissue from the neck. Considering the chemical burns on the neck and the circumstantial information, the cause of death was determined to be HF poisoning. This article presents the clinical manifestations of local and systemic toxicity after the accidental exposure to a high concentration of HF, with histologic demonstrations of chemical burns.

Dermal Hydrofluoric Acid Toxicity Case Review: Looks Can Be Deceiving.

Hydrofluoric acid is a caustic compound found in a wide variety of items for household and industrial uses. Dermal exposures can be visually unimpressive on presentation but still have fatal complications. This case review includes a description of a patient presenting with a dermal hydrofluoric acid burn that was effectively treated with topical calcium gluconate gel. Also highlighted are the challenges faced with recognizing the severity and appropriately treating dermal hydrofluoric acid burns in the emergency department.

Development of mouse models for the study of chloropicrin and hydrogen fluoride ocular injury.

The possibility of chemical terrorism within the United States is a rising concern, with the eye being one of the most sensitive tissues to toxicant exposure. We sought to develop mouse models of toxicant-induced ocular injury for the purpose of evaluating potential therapeutics. Chloropicrin (CP) and hydrogen fluoride (HF) were selected for the study owing to their reportedly high potential to induce ocular injury. Eyes of female BALB/c mice were exposed to CP or HF vapor in order to produce a moderate injury, as defined by acute corneal epithelial loss followed by progressive corneal pathology with the absence of injury to deeper eye structures. Clinical injury progression was evaluated up to 12 weeks postexposure, where a significant dose-dependent induction of corneal neovascularization was measured. Histopathology noted epithelial necrosis and stromal edema as early as 24 h after exposure but was resolved by 12 weeks. A significant increase in inflammatory cytokine concentrations was measured in the cornea 24 h after exposure and returned to baseline by day 14. The ocular injury models we developed here for CP and HF exposure should serve as a valuable tool for the future evaluation of novel therapeutics and the molecular mechanisms of injury.

Morbidity and mortality resulting from acute inhalation exposures to hydrogen fluoride and carbonyl fluoride in rats.

OBJECTIVE: Experiments were undertaken to compare morbidity and mortality from brief inhalation exposures to high levels of hydrogen fluoride (HF) and carbonyl fluoride (COF2). METHODS: Rats from both sexes were exposed for durations of 5 and 10 min to nominal concentrations of 10,000 to 57,000 ppm HF or 500 to 10,000 ppm COF2. Respiration was monitored before, during, and after exposure. Animals were observed up to 6 days post-exposure. Terminal blood samples were collected for routine clinical chemistry and hematology. Post-mortem lung fluoride concentrations and lung weights were measured, and gross pathology noted. RESULTS: Both gases produced respiratory depression independent of concentration or exposure duration with minute ventilation decreasing to approximately 50% of baseline. Estimated mixed-gender HF and COF2 10-min LC50's were 48,661 ppm and 1083 ppm, respectively. HF mortalities were generally delayed 3 to 4 days post-exposure, while COF2 mortalities occurred during or briefly after exposure. Lung fluoride levels increased with COF2 dose, though elevated lung weights occurred only at the mid-level exposures. Lung weights were unaffected in the HF-exposed animals, and their lung fluoride concentrations were variable. Clinical chemistry and hematology had few consistent trends with the exception of hemoconcentration primarily in HF-exposed males. These short-term exposure experiments conclude that COF2 is nearly 45 times more lethal than HF in rats. CONCLUSIONS: These experiments suggest that hydrolysis to HF cannot solely explain COF2 toxicity. Although HF and COF2 may have common injury mechanisms, they are expressed to markedly different degrees and temporal occurrence.

Toxicological response of Sprague Dawley rats from inhalation exposure to perfluorooctane sulfonyl fluoride (POSF).

Perfluorooctane sulfonyl fluoride (POSF) was a volatile starting material in the production of perfluorooctane sulfonate (PFOS), a stable surfactant that has been extensively studied due to its ubiquitous environmental distribution and slow clearance in humans. Because the inhalation toxicity of POSF on repeated exposure has not been previously reported, the current study evaluated the inhalation toxicity of POSF at 30, 100, and 300ppm (v/v) in rats for up to 13 weeks with a four-week recovery period. The extent of PFOS formation was also measured because POSF hydrolyzed to form PFOS. In addition, detailed urinalysis and examination of the urinary bladder were included to determine if factors associated with the development of bladder cancer were present. Exposure to POSF at 300ppm was associated with reduction in body weight-gain, necrosis of laryngeal cartilage, increased lung and bronchi weight with septal thickening, and changes in alveolar macrophages. The microscopic observations in larynx and lung are consistent with likely hydrolysis of POSF to form hydrogen fluoride (HF). Exposure to POSF at 100 and 300ppm was associated with increased relative liver weight, hepatocellular hypertrophy (except for females exposed to 100ppm POSF), and lowering of serum cholesterol (male only). After 13 weeks of exposure to 30, 100, or 300ppm POSF, serum PFOS concentration approximated 7, 35, or 100µg/mL, respectively. Approximately 0.1% of inhaled POSF was converted to PFOS. No changes indicative of bladder effects were observed in these rats exposed to POSF at any dose.

Dermal absorption and skin damage following hydrofluoric acid exposure in an ex vivo human skin model.

The wide industrial use of hydrofluoric acid (HF) poses a high risk for accidental dermal exposure. Despite local and systemic hazards associated with HF, information on percutaneous penetration and tissue damage is rare. In the present ex vivo study, the dermal absorption of HF (detected in terms of fluoride ions) was quantified and the skin damaging potential as a function of concentration and exposure duration was assessed. Percutaneous penetration of HF (c=5, 30, and 50%) at 3 exposure durations (3, 5, and 10 min) was investigated in a static diffusion cell model using freshly excised human skin. Alterations of skin were histologically evaluated. HF rapidly penetrated through skin under formation of a considerable intradermal reservoir (∼ 13-67% of total absorbed fluoride). Histologically, epidermal alterations were detected already after exposure to 5% HF for 3 min. The degree of skin damage increased with rising concentration and exposure duration leading to coagulation necrosis. For HF concentrations of ≥ 30%, skin damage progressed into deeper skin layers. Topically applied HF concentration was the principal parameter determining HF induced skin effects. The intradermal HF retention capacity associated with progression and prolongation of HF induced skin effects must be considered in the review of skin decontamination procedures.

Occupational Hydrofluoric Acid Injury from Car and Truck Washing--Washington State, 2001-2013.

Exposure to hydrofluoric acid (HF) causes corrosive chemical burns and potentially fatal systemic toxicity. Car and truck wash cleaning products, rust removers, and aluminum brighteners often contain HF because it is efficient in breaking down roadway matter. The death of a truck wash worker from ingestion of an HF-based wash product and 48 occupational HF burn cases associated with car and truck washing in Washington State during 2001-2013 are summarized in this report. Among seven hospitalized workers, two required surgery, and all but one worker returned to the job. Among 48 injured workers, job titles were primarily auto detailer, car wash worker, truck wash worker, and truck driver. Because HF exposure can result in potentially severe health outcomes, efforts to identify less hazardous alternatives to HF-based industrial wash products are warranted.

Injuries following a serious hydrofluoric acid leak: First aid and lessons.

Hydrofluoric acid is a dangerous inorganic acid that can cause local corrosion and systemic effects by ongoing absorption via the skin, mucosae, respiratory tract and digestive system. Recently, a serious toxic leak of low-concentration hydrofluoric acid solution occurred in the Pujiang area of Zhejiang Province, China. This accident resulted in 253 cases of chemical injury due to hydrofluoric acid exposure. Despite an immediate response by the local and provincial health-care system, as well as the local government, three people died due to acute poisoning and related complications. This article describes the events that took place leading to casualties as well as presenting the first-aid experience and the lessons learnt from this kind of mass injury.

Methods, setup and safe handling for anhydrous hydrogen fluoride cleavage in Boc solid-phase peptide synthesis.

Solid-phase peptide synthesis (SPPS) using tert-butyloxycarbonyl (Boc)/benzyl (Bzl) chemistry is an indispensable technique in many laboratories around the globe, and it provides peptides to the pharmaceutical industry and to thousands of scientists working in basic research. The Boc/Bzl strategy has several advantages, including reliability in the synthesis of long and difficult polypeptides, alternative orthogonality regarding protecting groups and ease of producing C-terminal thioesters for native chemical ligation applications. In this process, anhydrous hydrogen fluoride (HF) is used to remove the side chain protecting groups of the assembled peptide and to release the peptide from the resin, a process typically described as 'HF cleavage'. This protocol describes the general methodology, apparatus setup and safe handling of HF, with the aim of providing comprehensive information on the safe use of this valuable, well-studied and validated cleavage technique. We explain the cleavage mechanism, the physicochemical properties and risks of HF, first aid measures and the correct use of the apparatus. In addition, we provide advice on scavenger selection, as well as a troubleshooting section and video material illustrating key steps of the procedure. The protocol comprises precleavage sample preparation (30 min-2.5 h), complete HF cleavage procedure (2 h) and reaction workup (30 min).

Clinical arterial infusion of calcium gluconate: the preferred method for treating hydrofluoric acid burns of distal human limbs.

OBJECTIVE: This study was designed to evaluate the efficiency and safety of arterial infusions of calcium gluconate to treat hydrofluoric (HF) acid burns of the distal human limbs. MATERIALS AND METHODS: Eligible patients with HF burn limbs, collected from January 2008 to October 2011, were given the arterial infusion of calcium gluconate into the injured limbs. The measures of pain were conducted before the infusion, immediately after the infusion, 4 h after the infusion, and 2 days after the infusion by the visual analogy score (VAS). If the VAS score was higher than 4.0 at the time point 4 h after the first infusion, the infusion was repeated. The time of wound healing, and the number and ratio of the cases receiving the surgical operation were also evaluated. RESULTS: A total of 118 patients, male (107 cases) and female (11 cases), were collected, including 64 cases of outpatients and 54 cases of inpatients. The age of the subjects ranged from 16 to 60 years, with the mean age of 37.6. The burn sites were located in the lateral limbs (28 cases) and in the unilateral limbs (90 cases). For 107 cases, the pain scores decreased quickly after the first infusion. The other 11 cases, with the VAS score higher than 4.0 at the time point 4 h after the first infusion, received the second infusion. The average time of wound healing and the ratio of the cases receiving the surgical operation were closely related to the interval from the injury to the reception of infusion. CONCLUSIONS: Arterial infusion of calcium gluconate, effectively relieving the pain, blocking wound progressive deepening, and causing no adverse effects, could be the preferential method to treat hydrofluoric acid burns of the distal human limbs.

Acute hydrofluoric acid exposure reported to Taiwan Poison Control Center, 1991-2010.

BACKGROUND: Hydrofluoric acid (HF) is a dangerous chemical that can cause severe cutaneous burns as well as possible systemic toxicity. METHODS: We retrospectively analyzed all human HF exposure cases reported to the National Poison Control Center of Taiwan between 1991 and 2010. RESULTS: In this 20-year survey, 324 calls were identified, with a majority of dermal exposure (84%). Occupational exposure accounted for 80% of all cases, with workers in semiconductor industry (61%), cleaning industry (15%), chemical or metal industry (13%), and other industries (11%). Electrolyte imbalances were uncommon, hypocalcemia, hypomagnesemia, and hypokalemia were recorded in 8.6%, 1.2%, and 1.5% of all cases, respectively. Most cases (64%) of dermal exposure received antidotal treatment. Treatment modalities of dermal exposure included calcium gluconate soaking, 49.8%; intravenous calcium, 20.6%; and topical use of calcium gluconate gel, 13.9%. Twenty patients (7%) received surgery. Following HF exposure, the majority of patients presented with mild (56.5%) or moderate (36.7%) toxic effects. However, four patients were severely intoxicated; two patients died of HF-related dysrhythmia and shock. CONCLUSIONS: Significant symptomology may occur following HF exposure, and most of the HF exposure required hospitals evaluation. Calcium gluconate soaks appear to be effective in reducing local pain and tissue damage. Hyperkalemia should not be overemphasized as a common finding in HF exposure, hypokalemia tends to occur in cases of severe HF poisoning.

Water-based solutions are the best decontaminating fluids for dermal corrosive exposures: a mini review.

AIM: The intention is to assess whether the fundamental principle ("the solution to pollution is dilution") should be the guide for the initial medical management of corrosive dermal exposures. METHODS: The US National Library of Medicine Pubmed database was searched utilizing all combinations of the search terms "decontamination", "corrosive", and "dermal". A separate search was done specifically related to hydrofluoric acid. These searches found 69 relevant papers. RESULTS: Only four controlled clinical studies comparing early and intensive water decontamination with no or less dilution treatment have been published on human corrosive dermal exposures. Although the authors' conclusion in the first study of 273 patients was that those that had more intensive water irrigation tended to have less time to skin grafting and shorter periods of hospitalization, the results were not statistically significant. In the second study of 51 patients, those who had "adequate" decontamination (immediate dilution or neutralization therapy) had shortened length of stay (7.2 vs. 16.2 days), lower mortality (9.5% vs. 21%), and fewer skin grafts (19% vs. 36%) despite having slightly greater burn surface area (19.7% vs. 17.2%). However, no statistical analysis was provided. The third and fourth studies were conducted in the same center. In the third study of 35 patients, those who had "immediate" water lavage (done within 10 min of exposure and continued for at least 15 min) had significantly fewer burns that progressed to full thickness (12.5% vs. 63%; p < 0.01) and significantly shorter mean hospital stays (7.7 days vs. 20.5 days; p < 0.01) than those who did not, despite the mean total burn surface area being twice as large in the adequate water decontamination group (12% vs. 6%; p < 0.05). In the fourth study of 83 patients (35 of whom had been reported in the previous study), those who had copious water lavage within 3 min of injury were less likely to progress to full thickness burns (13.5% vs. 60.8%; p < 0.01), had fewer delayed complications (5.4% vs. 30.4%; p < 0.01) and shorter lengths of stay (6.2 vs. 22 days; p < 0.01), compared with those who did not. In a further study, water was compared to the proprietary agent Diphoterine(®) in a controlled prospective cohort study of 180 dermal alkali exposures. The Diphoterine(®) first group was decontaminated significantly faster than the water first group (median times to irrigation 1 vs. 5 min; p < 0.001). No analysis adjusted for time to decontamination was provided, so the study demonstrated that only those individuals who decontaminated early did better than those who decontaminated later. CONCLUSIONS: The data support water as the best decontaminating solution. It has been shown to be efficacious in clinical trials, is widely available, and inexpensive.

Observation of hydrofluoric acid burns on osseous tissues by means of terahertz spectroscopic imaging.

Terahertz technologies have gained great amount of attention for biomedical imaging and tissue analysis. In this study, we utilize terahertz imaging to study the effects of hydrofluoric acid on both compact bone tissue and cartilage. We compare the differences observed in the exposure for formalin fixed and raw, dried, tissue as well as those resulting from a change in hydrofluoric (HF) concentration. Measurements are performed with THz-TDS, and a variety of spectroscopic-based image reconstruction techniques are utilized to develop contrast in the features of interest.

Hydrogen fluoride damage to vegetation from peri-urban brick kilns in Asia: a growing but unrecognised problem?

The rapid urbanisation of many cities in south and south-east Asia has increased the demand for bricks, which are typically supplied from brick kilns in peri-urban areas. We report visible foliar damage to mango, apricot and plum trees in the vicinity of traditional Bull's Trench brick kilns in Peshawar, Pakistan. Visible injury symptoms, hydrogen fluoride concentrations in air, and foliar fluoride concentrations were all greater in the vicinity of brick kilns than at more distant sites, indicating that fluoride emissions from brick kilns were the main cause of damage. Interviews with local farmers established the significant impact of this damage on their livelihoods. Since poorly regulated brick kilns are often found close to important peri-urban agricultural areas, we suggest that this may be a growing but unrecognised environmental problem in regions of Asia where emission control in brick kilns has not been improved.

Possible hazardous effects of hydrofluoric acid and recommendations for treatment approach: a review.

Hydrofluoric acid (HF) is commonly used for conditioning the glass ceramics either prior to cementation or for intraoral repair in prosthetic and restorative dentistry. The present study offers a review of chemical properties of HF used, highlight the possible hazardous effects of this agent, and to recommend the treatment approach for potential risks. Available published information documented in PubMed, Medline, and Picarta literature databases was reviewed. Additional information was derived from scientific reports, medical and chemical textbooks, handbooks, product information, manufacturers' instructions, Internet web sites of the HF manufacturers. No report was found on the incidence of the hazardous effects of HF in dentistry. Reports from other fields presented incidences of acute and chronic symptoms in exposure to HF. While acute symptoms include skin or nail burns, chronic ones involve systemic toxicity, eye injuries, inhalation and ingestion-related symptoms that can be even fatal. HF can be harmful and particularly aggressive to soft tissues, but symptoms may not be apparent immediately after exposure. The hazardous effects are not based on the pH value, but on the toxicity of HF. Potential hazards of HF known from other applications than dentistry should be considered also in dental applications. Especially the clinicians, who often deal with adhesive cementation or repair of glass ceramics, should take necessary precautions for possible hazards of HF.

Part 2. Comparison of emergency washing solutions in 70% hydrofluoric acid-burned human skin in an established ex vivo explants model.

BACKGROUND: Hydrofluoric acid (HF) is a small and partially dissociated acid (pK(a) 3.2), able to deeply penetrate into human skin in addition to the corrosiveness of the hydrogen ion (H(+)) and the toxicity of the fluoride ion (F(-)). However, there has been a lack of experimental studies to objectively characterize the results of human HF skin exposure decontamination. METHODOLOGY/PRINCIPAL FINDINGS: A previously established experimental method using a human skin explants ex vivo model (Part 1. Experimental 70% hydrofluoric acid (HF) burns: Histological observations in an established human skin explants ex vivo model) described the lesions that appeared following 70% HF penetration. Within 5 min, 70% HF penetrates to the dermis. Using the same experimental conditions, a comparison study of two different washing protocols was performed: water + topical calcium gluconate (CaG) versus Hexafluorine(®). In these conditions, washing for 15 min with running tap water followed by topical CaG ointment only delayed burn onset, while severe tissue damage appeared later. In contrast, after washing with Hexafluorine(®) over 10 min, no histological lesions developed. These results are in accordance with the results of accidental human industrial case reports. CONCLUSION/SIGNIFICANCE: Amphoteric and hypertonic Hexafluorine(®) can deactivate H(+) and chelate F(-) ions. Based on these results, it should be considered as a promising first-aid decontamination solution to prevent or minimize significant local and systemic consequences of concentrated HF skin exposures.

Experimental 70% hydrofluoric acid burns: histological observations in an established human skin explants ex vivo model.

BACKGROUND: Hydrofluoric acid (HF) is particularly dangerous due to the potential for systemic effects and induction of severe skin necrosis through two mechanisms: corrosiveness and local tissue toxicity. In addition, because it is only partially dissociated (pK(a) 3.2), it is capable of penetrating deeply into tissues. There is a lack of experimental studies that objectively characterize the behavior of HF diffusion into human skin, specifically the kinetics of tissue penetration resulting in severe cellular lesions. METHODOLOGY/PRINCIPAL FINDINGS: We describe the cutaneous effects of HF using an established ex vivo human skin model. The diffusion of 70% HF starts within the first minute of contact at the epidermal surface and after 2 min reaches the basal layer. In the subsequent minute, the epidermis is destroyed and lesions appear in the papillary dermis after 4 min. Soon after, damage appears in the upper reticular dermis. Thus, 70% HF needs only 5 min of contact to completely penetrate human skin explants. This experiment is reproducible and corroborates previous studies and clinical effects reported in accidental HF exposures. CONCLUSION/SIGNIFICANCE: This study shows that the management of HF chemical skin exposure is a question of minutes, especially for initial decontamination. These experimental observations could be useful for objectively comparing skin decontamination methods. Further studies should help to confirm these preliminary results.