Management of a Rare Case With Severe Hydrofluoric Acid Burns: Important Roles of Neutralizers and Continuous Renal Replacement Therapy.

Hydrofluoric acid (HF), a dangerous inorganic acid, is widely used in various industries and in daily life. Chemical burns caused by HF exposure occur more frequently in some regions worldwide. It has been reported that some cases with HF burns can be lethal due to the hypertoxicity of HF. In this article, we present a case of a 24-year-old worker who suffered HF burns by 53% HF solution to his face, neck, and nasal cavity. This patient quickly developed electrolyte disturbance, that is, hypocalcemia, and hypopotassemia, and myocardial injury after exposure. Multiple measures had been taken to treat this patient, including fluid resuscitation, electrolyte replacement, timely wound treatment with neutralizers, and respiratory tract care. Moreover, continuous renal replacement therapy was also employed to remove fluoride in the circulatory system and rectify the electrolyte disturbance and acid-base imbalance. The patient smoothly pulled though and survived. High fluoride levels in the dialysate solution were confirmed, indicating that continuous renal replacement therapy is an effective and potentially lifesaving treatment for acute HF poisoning.

Cognitive Impairment and Risk Factors in Elderly People Living in Fluorosis Areas in China.

Residents living in fluorosis areas generally experienced long-term exposure to excessive fluoride in drinking water. The adverse effects of high fluoride levels on the nervous system have been studied; however, the effect of fluoride exposure on cognitive functions of elderly people in fluorosis areas is rarely reported. This study was aimed to find out the potential risk factors of cognitive impairment among elderly people who lived in fluorosis areas of China. A total of 511 subjects, aged 60 years or above, were investigated in fluorosis areas of Heilongjiang Province, Inner Mongolia Autonomous Region, Qinghai Province, and Xinjiang Uygur Autonomous Region. The Mini-Mental State Examination (MMSE) was used to examine cognitive functions of the study subjects. Based on the MMSE scores, the study subjects were divided into normal group and cognitive impairment group that consisted of mild, moderate, and severe groups. Multivariable logistic regression showed that a higher risk of cognitive impairment was associated with increased age and decreased education levels. Multiple linear regression analysis revealed that MMSE scores were negatively associated with serum homocysteine (Hcy) levels. However, both urinary fluoride and serum Hcy levels in the normal group were not the lowest among the four groups. Spearman's correlation analysis showed that urinary fluoride levels were positively correlated with serum Hcy (r s = 0.209, P < 0.01). Our study suggests that people with cognitive impairment in fluorosis areas have elevated serum Hcy levels, which was positively correlated with urinary fluoride concentrations. A certain low dose of fluoride intake may play a potential protective rather than harmful role in cognitive functions; however, high fluoride exposure is a potential risk factor for cognitive impairment.

[CHRONIC FLUORIDE INTOXICATION AS A RISK FACTOR FOR THE DEVELOPMENT OF ATHEROSCLEROSIS].

In workers employed in the aluminum industry, the main harmful production factor is exposure to fluoride salts, which can cause chronic fluoride intoxication. For the assessment of the impact of chronic fluoride intoxication on the development of atherosclerosis, we conducted a comprehensive survey of 87 aluminum-metal makers with chronic fluoride intoxication and 43 aluminum-metal makers without occupational diseases, mean age--52.1 ± 0.4 years. There were considered the presence and severity of atherosclerosis of brachiocephalic arteries, and the arteries of the lower extremities in the studied group, there was evaluated the effect of other risk factors for atherosclerosis (smoking, presence of hypertension, diabetes, dyslipidemia). With the use of Doppler ultrasound of the arteries it was revealed that in metallurgists with chronic fluoride intoxication atherosclerosis was detected in 73.6% versus 55.8% in persons of the comparison group. The performed analysis of the prevalence of main risk factors for atherosclerosis showed that in metal makers with chronic fluoride intoxication in combination with atherosclerosis hypertension is more common (in 54.7%) than in metallurgists with chronic fluoride intoxication without atherosclerosis--only 26.1%. According to the frequency of occurrence of smoking, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia, there were no significant differences between the metallurgists with chronic fluoride intoxication, with and without atherosclerosis, and the control group, the increase in LDL cholesterol occurs significantly more often in metal-makers with chronic fluoride intoxication in combination with atherosclerosis if compared to workers without occupational diseases. Thus, chronic fluoride intoxication acts as a risk factor in the development of atherosclerosis: atherosclerosis in metal-makers with chronic fluoride intoxication occurs more frequently than in workers who do not have professional pathology. Hypertension and elevated levels of LDL cholesterol were established to increase the relative risk of developing atherosclerosis in metallurgists with chronic fluoride intoxication. At that there are no significant differences in the prevalence of common risk factors for atherosclerosis (smoking, diabetes, hypercholesterolemia, hypertriglyceridemia).

Effect of fluoride on insulin level of rats and insulin receptor expression in the MC3T3-E1 cells.

Studies on the role of insulin and insulin receptor (InsR) in the process of skeletal fluorosis, especially in osteogenic function, are rare. We evaluated the effect of increasing F⁻ doses on the marker of bone formation, serum insulin level and pancreatic secretion changes in vivo and mRNA expression of InsR and osteocalcin (OCN) in vitro. Wistar rats (n = 50) were divided into two groups, i.e. a control group and fluoride group. The fluoride groups were treated with fluoride by drinking tap water containing 100 mg F⁻/L. The fluoride ion-selective electrode measured the fluoride concentrations of femurs. The alkaline phosphatase (ALP), OCN, insulin and glucagon of serum were tested to observe the effect of fluoride action on them. Meantime, the pancreas pathological morphometry analysis via ß cells stained by aldehyde fuchsin showed the action of fluoride on pancreas secretion. MC3T3-E1 cells (derived from newborn mouse calvaria) were exposed to varying concentrations and periods of fluoride. The mRNA expression of InsR and OCN was quantified with real-time PCR. Results showed that 1-year fluoride treatment obviously stimulated ALP activity and OCN level along with increase of bone fluoride concentration of rats, which indicated that fluoride obviously stimulated osteogenic action of rats. In vitro study, the dual effect of fluoride on osteoblast function is shown. On the other hand, there was a significant increase of serum insulin level and a general decrease of glucagon level, and the histomorphometry analysis indicated an elevated insulin-positive area and increase in islet size in rats treated with fluoride for 1 year. In addition, fluoride obviously facilitated the mRNA expression of InsR in vitro. To sum up, there existed a close relationship between insulin secretion and fluoride treatment. The insulin signal pathway might be involved in the underlying occurrence or development of skeletal fluorosis.

Efficacy of lycopene against fluoride toxicity in rats.

CONTEXT: Oxidative damage to cellular components such as lipids and cell membranes by free radicals and reactive oxygen species (ROS) is thought to be associated with the development of degenerative diseases. Fluoride intoxication is associated with oxidative stress and altered anti-oxidant defense mechanism. Lycopene is a lipid-soluble powerful anti-oxidant that scavenges free radicals and ROS. OBJECTIVE: This study was extended to investigate lycopene anti-oxidant efficacy in different organs of fluoride-intoxicated rats. METHODS: Twenty-four adult rats were randomly divided into four groups of six animals each. Rats in group I received daily doses of vehicle. Group II rats were given lycopene (10 mg/kg body weight/day), by tubes, dissolved in 0.5 ml of corn oil for 5 weeks. Group III rats were given sodium fluoride (NaF) (10.3 mg/kg body weight/day), by tubes, for 5 weeks. In group IV rats, lycopene was administered 1 h later and NaF was administered for 5 weeks. RESULTS: NaF administration induced oxidative stress as evidenced by elevated levels of lipid peroxidation (51.3, 65.9 and 67.6%) measured as malondialdehyde and total nitrate/nitrite (61.0, 59.7 and 68.9%) in red blood cells, heart and brain tissues. Moreover, significantly decreased reduced glutathione level, total anti-oxidant capacity and superoxide dismutase activity were observed in the examined tissues. The induced oxidative stress and the alterations in anti-oxidant system were normalized by the oral administration of lycopene treatment. CONCLUSION: Lycopene administration could minimize the toxic effects of fluoride indicating its free-radical scavenging and powerful anti-oxidant activities.

Intervention of selenium on chronic fluorosis-induced injury of blood antioxidant capacity in rats.

This study was conducted to further explore the effects of selenium on the blood antioxidant capacity in rats exposed to fluoride to find out the optimal dosage level of selenium. Animals were divided into prevention sequence (Selenium → NaF, water → NaF) and treatment sequence (NaF → Selenium, NaF → water) (sodium fluoride 50 mg/L; sodium selenite 0.375, 0.75, 1.5 mg/L). The exposure time was 12 months. Then, the fluidity of erythrocyte membrane by electron spin resonance was analyzed, and the blood was collected for GSH-Px and SOD activity, total antioxidant capacity (T-AOC) and uric acid assay, sialic acid and MDA content. The results showed that, compared with control group, GSH-Px activity and T-AOC level increased significantly (P < 0.05), and SOD activity was raised in varying degrees in prevention and treatment groups, respectively. Uric acid level was up-regulated, but no significant differences were observed (P > 0.05). The fluidity of erythrocyte membrane showed significant increase (P < 0.05). As evident in this study, when the dose of selenium was 0.75 mg/L, all the activities of antioxidant enzymes increased significantly in prevention sequence; but in treatment sequence, the optimum intervention concentration was 1.5 mg/L. On the basis of results, the preventive effect of selenium was superior to treatment effect on the oxidative stress induced by an overdose of fluoride.

Serum parathyroid hormone levels in chronic endemic fluorosis.

Endemic waterborne fluorosis is a public health problem in Isparta, a city located in southern Turkey. Fluoride is a cumulative element that increases metabolic turnover of the bone and also affects the homeostasis of bone mineral metabolism. There are number of similarities between the effects of excess parathyroid hormone (PTH) and fluorosis on bone. So fluoride might show its effect via PTH. We aimed to determine PTH levels in patients with endemic fluorosis to estimate the possible toxic effects of chronic fluoride intake. Fifty-six patients with endemic fluorosis and 28 age-, sex-, and body-mass-index-matched healthy controls were included in this study. Endemic fluorosis was diagnosed according to the clinical diagnosis criteria of Wang. The urine fluoride levels of fluorosis patients were significantly higher than those of control subjects as expected (1.9 ± 0.1 vs. 0.4 ± 0.1 mg/L, respectively; P < 0.001). PTH levels in fluorosis group were significantly higher than control group (65.09 ± 32.91 versus 47.40 ± 20.37, respectively; P = 0.01). The results of our study demonstrate that serum PTH levels are increased in patients with endemic fluorosis. Fluoride, by interfering calcium balance, may be the cause of secondary hyperparathyroidism.

Bone mineral density of the spine and femur in early postmenopausal Turkish women with endemic skeletal fluorosis.

The aim of this prospective, comparative study was to investigate the bone mineral density (BMD) changes in a group of early postmenopausal Turkish women with endemic skeletal fluorosis and to study effects of endemic fluorosis on BMD. Bone mineral density of L2-L4 vertebra, femur neck, femur trochanter, and Ward's triangle were measured in 45 female patients with endemic skeletal fluorosis and 41 age-matched controls by dual X-ray absorbtiometry (DXA). The BMD of L2-L4 vertebra and Ward's triangle were higher in the endemic fluorosis group than in the control group (P < 0.001). Patients with endemic fluorosis had higher femur neck and femur trochanter BMDs than did controls (P < 0.01 and P < 0.05, respectively). There was a positive correlation between serum fluoride content and BMD at the spine (r = 0.345, P = 0.001), femoral neck (r = 0.274, P = 0.011), Ward's triangle (r = 0.295, P = 0.006), and trochanter (r = 0.217, P = 0.045). In conclusion, higher bone mineral density levels were seen in early postmenopausal women with endemic skeletal fluorosis. BMD measurement is a tool in the diagnosis and management of this preventable crippling disease.

Antioxidant defense system and lipid peroxidation in patients with skeletal fluorosis and in fluoride-intoxicated rabbits.

Fluorosis is a serious public health problem in many parts of the world where drinking water contains more than 1 ppm of fluoride. The main manifestations of skeletal fluorosis are crippling bone deformities, spinal compressions, and restricted movements of joints. Although fluorosis is irreversible, it could be prevented by appropriate and timely intervention through understanding the process at biochemical and molecular levels. As in the case of many chronic degenerative diseases, increased production of reactive oxygen species (ROS) and lipid peroxidation has been considered to play an important role, even in the pathogenesis of chronic fluoride toxicity. However, there is inconclusive proof for an altered oxidative stress and antioxidant balance in fluorosis, and the existing data are not only conflicting but also contradictory. In the present communication we have evaluated the antioxidant defense system (both enzymatic and nonenzymatic) and lipid peroxidation in both humans from an endemic fluorosis area (5 ppm fluoride in the drinking water) and in rabbits receiving water with 150 ppm of fluoride for six months. There was no significant difference in lipid peroxidation, glutathione, and vitamin C in the blood of human fluorotic patients and fluoride-intoxicated rabbits as compared to respective controls. Neither were there any changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, or glutathione S-transferase in the blood due to fluoride intoxication (of rabbits) or fluorosis in humans. The results together do not subscribe to oxidative stress theory in fluorosis. Thus, in the absence of clear proof of oxidative damage and to counter toxic effects of fluoride through supplementation of antioxidants, extensive investigations are needed to conclusively prove the role of oxidative stress in skeletal fluorosis.

[Effects of excess fluoride on bone turnover under conditions of diet with different calcium contents].

OBJECTIVE: To study the effects of excess fluoride on bone turnover under conditions of diet containing different amount of calcium. METHODS: The experiment was performed on rats raised on a balanced diet with adequate calcium or a monotonous diet with low calcium and given amount of fluoride in their drinking water (F, 100 mg/L) for 2 months or 1 year. RESULTS: Osteomalacia, osteoporosis and accelerated bone turnover were observed with elevated serum alkaline phosphatase (ALP), osteocalcin (BGP) and parathyroid hormone (PTH) in rats fed on low calcium diet and fluoridized water for 2 months. In the rats fed on adequate calcium diet and fluoridized water for 2 months, only slightly increased osteoblastic activity was found while the average width of trabecular bone was increased with elevated serum ALP activity in rats raised on the same diet and water for 1 year. CONCLUSIONS: The basic effect of excess fluoride on bone is the causation of a high bone turnover state which can also be induced to a milder extent by low calcium diet itself. Therefore, the formation of a high bone turnover state is the pathogenetic basis for low dietary calcium intake to exacerbate the severity of skeletal fluorosis.

Hydrofluorosis in water buffalo (Bubalus bubalis) in India.

The concentration of fluoride was determined in water, forage and urine and serum samples of buffaloes from the Unnao district of India. The water and forage samples contained 2.01 +/- 0.51 and 22.50 +/- 0.82 ppm of fluoride, respectively. The analysis of biosamples collected from the affected animals revealed higher levels of fluoride in serum (0.58 +/- 0.05 ppm) and urine (10.64 +/- 1.23 ppm). Clinical examination identified a 40.34% prevalence rate of clinical lesions suggestive of fluorosis in buffalo of this locality. Dental lesions were present invariably in all affected animals whereas lameness, painful bony exostosis and emaciation were recorded in 28.17%, 8.45% and 76.00% of the animals. Based on the clinical lesions and fluoride content in water, serum and urine, it was concluded that the problem of fluorosis in buffalo is attributable to drinking water containing toxic levels of fluoride.

Circulating testosterone levels in skeletal fluorosis patients.

OBJECTIVE: The present study focuses on serum testosterone concentrations in patients with skeletal fluorosis, in order to assess the hormonal status in fluoride toxicity. METHODS: Serum testosterones were compared for patients afflicted with skeletal fluorosis (n = 30) and healthy males consuming water containing less than 1 ppm fluoride (Control 1, n = 26) and a second category of controls (Control 2, n = 16): individuals living in the same house as the patients and consuming same water as patients but not exhibiting clinical manifestations of skeletal fluorosis. RESULTS: Circulating serum testosterones in skeletal fluorosis patients were significantly lower than those of Control 1 at p < 0.01. Testosterone concentrations of Control 2 were also lower than those of Control 1 at p < 0.05 but were higher than those of the patient group. CONCLUSIONS: Decreased testosterone concentrations in skeletal fluorosis patients and in males drinking the same water as the patients but with no clinical manifestations of the disease compared with those of normal, healthy males living in areas nonendemic for fluorosis suggest that fluoride toxicity may cause adverse effects in the reproductive system of males living in fluorosis endemic areas.

Serum haptoglobin and C-reactive protein in human skeletal fluorosis.

Circulating levels of haptoglobin and C-reactive protein were studied in patients of skeletal fluorosis and compared with two types of controls. The first type of control included normal healthy individuals consuming water containing permissible levels of fluoride (up to 1 mg/L). The second type of control included individuals consuming water contaminated with fluoride (1.2-14.5 mg/L) but not exhibiting clinical manifestations of skeletal fluorosis. A significant increase in the levels of haptoglobin (p < 0.01) and C-reactive protein (p < 0.01) as well as a raised erythrocyte sedimentation rate were seen in patients of skeletal fluorosis as compared to both types of controls. The present study suggests the possibility of a subclinical inflammatory reaction occurring in patients with skeletal fluorosis.

An outbreak of fatal fluoride intoxication in a long-term hemodialysis unit.

OBJECTIVE: To determine the cause of an outbreak of acute illness and death in a long-term hemodialysis unit. DESIGN: A retrospective cohort and case-control study of patients receiving hemodialysis and a laboratory study of a model deionization system to purify water for hemodialysis. SETTING: An outpatient hemodialysis unit of a university hospital. PATIENTS: 12 patients who became severely ill after hemodialysis treatment and 20 patients who did not become ill after receiving hemodialysis treatment in the same unit. MEASUREMENTS: Medical and dialysis unit records were reviewed to identify and characterize cases. Fluids for dialysis were tested for toxic substances, and fluoride was measured in patients' serum. Resistivity and fluoride were measured in effluent from a model deionization system operated in the same way as the system associated with illness. RESULTS: During five consecutive hemodialysis shifts, 12 of 15 patients receiving dialysis treatment in one room became acutely ill, with severe pruritus, multiple nonspecific symptoms, and/or fatal ventricular fibrillation (3 patients). None of 17 patients treated in the adjacent room became ill (P < 0.0001). Death was associated with longer hemodialysis time and increased age compared with other patients who became ill. Serum concentrations of fluoride in the sick patients were markedly increased to as high as 716 mumol/L, and the source of fluoride was the temporary deionization system used to purify water for hemodialysis only in the affected room. Operation of a model deionization system showed how fluoride was adsorbed and then displaced in a massive efflux. CONCLUSIONS: Because deionization systems are used widely in hemodialysis and can cause fatal fluoride intoxication, careful design and monitoring are essential.

[Death from fluoro-silicate in floor polish].

A fatal case of poisoning due to ingestion of an apparently innocuous household product is described. A healthy 28-year-old man accidentally drank floor polish (Cristalizador, a Spanish import). On arrival at the emergency room a few hours later he passed large amounts of bloody stool and lost consciousness. A call to the Spanish Poison Center revealed that although not indicated on the label, the polish contained a highly poisonous salt, fluoro-silicate. Blood gas analysis revealed severe metabolic acidosis. Serum calcium was 3.8 mg/dL. The post-resuscitation ECG showed subendocardial ischemia and ST-elevation in the anteroseptal wall and prolonged QT-interval. In the intensive care unit he received large amounts of fluids, dopamine, sodium bicarbonate and calcium. Despite the treatment, his condition continued to deteriorate: VPB's appeared, there was a short run of ventricular tachycardia and then atrial fibrillation developed. Further treatment included lidocaine, verapamil, amiodarone, and electrical cardioversion. Blood pressure remained low and 11 hours after admission he died of myocardial infarction, severe arrhythmia and multi-organ failure.

Evolution of fluoride concentrations in cattle and grass following a volcanic eruption.

This study determined fluoride concentrations of forage, water and bovine serum 2-y after the cessation of a volcanic eruption. Three farms within the polluted area were selected, and water and green grass were collected from April 1990 to February 1992. Samples of hay were collected twice from each farm. Five cows exposed during the 13-mo eruption and 6 young bulls not exposed during the volcanic eruption had blood collected monthly or bimonthly. Serum fluoride concentrations and alkaline phosphatase activities were determined and dental conditions observed in all animals. Grass fluoride remained low except during spring of the second year; high fluoride was in the hay. Serum fluoride of the cows remained near acceptable reference values, although some cows had higher values; serum fluoride of the bulls markedly increased during the spring of the second year. Severe incisor attrition occurred in the cows, while the young bulls had less severely eroded teeth.

[Effect of regulatory renal polypeptides on hemocoagulation and lipid peroxidation in fluoride intoxication]. / Vplyv reguliatornykh nyrkovykh polipeptydiv na gemokoaguliatsiiu i perekysne okyslennia lipidiv pry ftorystii intoksykatsii.

Polypeptide cytomedine, isolated from renal tissues has been studied for its regulatory effect on hemocoagulation and lipid peroxidation with fluoric intoxication (FI). FI was caused by inoculation of laboratory animals (guinea pigs) with sodium fluoride (100 mg/kg) for 14 days. Following it polypeptide (0.1 mg/kg) was introduced intramuscularly for 7 days. The development of FI was expressed by hypercoagulation delay of fibrinolysis with para-coagulation products appearing in blood decrease of antiaggregation activity of the renal tissue. These phenomena were estimated as manifestations of the first phase of disseminated intravascular blood coagulability (DIC-syndrome). The above reactions proceeded simultaneously with lipid peroxidation activation decrease of the antioxidant protection. The necrotic-dystrophic processes developed in renal and hepatic parenchyma. The renal peptide-cytomedine induced the normalization of lipid peroxidation in blood and renal tissues and fibrinolysis, the decrease in the concentration of para-coagulation products. The pathological changes decreased both in the renal and hepatic tissues. It is possibly, a result of the normalization of secretion and reabsorption in the kidneys. Thus, cytomedine of the kidney exerts a pronounced regulatory and protective effect in the case of acute renal pathology. These results correspond to the conception of the peptidergic organism regulation.

Serum fluoride as an indicator of occupational hydrofluoric acid exposure.

To define the relationship between ionic fluoride concentration in the serum of workers and the amount of hydrofluoric acid (HF) in the work environment, pre-and postshift serum and urine samples of 142 HF workers and 270 unexposed workers were examined. The maximum and minimum concentrations of HF in the air in each workshop varied from the mean by less than 30%. The preexposure levels of serum and urinary fluoride in HF workers were higher (P < 0.001) than the control values. This suggests that fluoride excretion from the body continues for at least 12h. The postshift serum and urinary fluoride concentrations of these workers were significantly higher (P < 0.001) than the preshift concentrations. A good correlation (r = 0.64) was obtained between postshift serum fluoride and postshift urine fluoride. There was a linear relationship between mean serum fluoride concentration and HF concentration in the workshop. A mean fluoride concentration of 82.3 micrograms/l with a lower fiducial limit (95%, P = 0.05) of 57.9 micrograms/l was estimated to correspond to an atmospheric HF concentration of 3 ppm. This is the maximum allowable environmental concentration recommended by the Japanese Association of Industrial Health, and it is also the threshold limit value suggested by the American Conference of Governmental Industrial Hygienists. The results demonstrate that exposure to HF can be monitored by determining the serum fluoride concentration.