Kentucky Windage

Abstract

The effect of dermal exposure to concentrated (48% w/v) hydrofluoric acid (HF) on survival and plasma fluoride concentration was investigated in rats. Results of dermal exposure to abdominal and back skin were compared with intravenous administration of sodium fluoride.

Dermal HF exposure on 6 cm² for 5 min resulted in toxic plasma fluoride concentrations. The location of application on the body influenced both the survival time of the rats and the kinetics of plasma fluoride concentrations.

After abdominal application of 0.25 or 0.5 ml HF, a 50% mortality rate within 300 min (time of death between 75 and 270 min) was observed. After application of 0.25 ml HF on the back all rats survived the 315 min observational period while after application of 0.5 ml HF an LD₅₀ was reached (time of death between 280 and 314 min).

Abdominal exposure caused a gradually increasing plasma fluoride concentration while after exposure on the back a rapid increase of the plasma fluoride concentration was observed, followed by a gradual decrease to a relative constant level.

It is concluded that, after the initial exposure of the back, the back skin tissue layers act as a slow-release storehouse of fluoride.

The course of plasma fluoride concentrations after skin exposure of the back to 0.5 ml HF could be simulated by a two-phase sodium fluoride infusion model. A loading dose of 1.2 mmol/kg/h during 30 min is followed by a maintenance dose of 0.3 mmol/kg/h.     

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.     

A dynamic system for delivering controlled bromine and chlorine vapor exposures to weanling swine skin

Context: Assessing the hazards of accidental exposure to toxic industrial chemical (TIC) vapors and evaluating therapeutic compounds or treatment regimens require the development of appropriate animal models.

Objective: The objective of this project was to develop an exposure system for delivering controlled vapor concentrations of TICs to the skin of anesthetized weanling pigs. Injury levels targeted for study were superficial dermal (SD) and deep dermal (DD) skin lesions as defined histopathologically.

Materials and methods: The exposure system was capable of simultaneously delivering chlorine or bromine vapor to four, 3-cm diameter exposure cups placed over skin between the axillary and inguinal areas of the ventral abdomen. Vapor concentrations were generated by mixing saturated bromine or chlorine vapor with either dried dilution air or nitrogen.

Results: Bromine exposure concentrations ranged from 6.5?×?10^?4 to 1.03?g/L, and exposure durations ranged from 1 to 45?min. A 7-min skin exposure to bromine vapors at 0.59?g/L was sufficient to produce SD injuries, while a 17-min exposure produced a DD injury. Chlorine exposure concentrations ranged from 1.0 to 2.9?g/L (saturated vapor concentration) for exposures ranging from 3 to 90?min. Saturated chlorine vapor challenges for up to 30?min did not induce significant dermal injuries, whereas saturated chlorine vapor with wetted material on the skin surface for 30–60?min induced SD injuries. DD chlorine injuries could not be induced with this system.

Conclusion: The vapor exposure system described in this study provides a means for safely regulating, quantifying and delivering TIC vapors to the skin of weanling swine as a model to evaluate therapeutic treatments.     

Dermal penetration potential of perfluorooctanoic acid (PFOA) in human and mouse skin

Recent data, using a murine model, have indicated that dermal exposure to perfluorooctanoic acid (PFOA) induces immune modulation, suggesting that this may be an important route of PFOA exposure. To investigate the dermal penetration potential of PFOA, serum concentrations were analyzed in mice following topical application. Statistically significant and dose-responsive increases in serum PFOA concentrations were identified. In vitro dermal penetration studies also demonstrated that PFOA permeates both mouse and human skin. Investigation into the mechanisms mediating PFOA penetration demonstrated that dermal absorption was strongly dependent upon the ionization status of PFOA. In addition, PFOA solid, but not 1% PFOA/acetone solution, was identified as corrosive using a cultured epidermis in vitro model. Despite its corrosive potential, expression of inflammatory cytokines in the skin of topically exposed mice was not altered. These data suggest that PFOA is dermally absorbed and that under certain conditions the skin may be a significant route of exposure.     

SHORT-TERM EXPOSURES OF RATS TO AIRBORNE HYDROGEN FLUORIDE

A series of acute inhalation exposures was performed with airborne hydrogen fluoride (HF) to establish the concentration response for nonlethal effects in the rat. Exposures were either 2 or 10 min long; concentrations ranged from 135 to 8621 ppm. Three additional exposures (20 to 48 ppm) were performed for 60 min. A mouth-breathing (MB) model with a tracheal cannula was used in most of the exposures to maximize delivery of the HF to the lower respiratory tract. Endpoints on the day after exposure included hematology, serum chemistry, bronchoalveolar lavage, pulmonary function, organ weights, and histopathology. Nasal resistance was measured in nose-breathing (NB) groups. Effects of exposure were generally limited to the respiratory tract and included alveolitis, bronchial lesions, altered parameters of pulmonary function and bronchoalveolar lavage, and mucosal necrosis, inflammation, and fibrinopurulent exudate in airways. Observed changes were concentration related and appeared more pronounced in major airways near the point of entry (trachea in MB animals and nose in NB animals). One group of MB animals exposed for 10 min to 1454 ppm was evaluated at 3 and 14 wk after exposure; the acute effects had resolved by those times. The effects of 2-min exposures were consistently more severe than those from 10-min exposures to the same product of concentration x time. Exposures of MB animals for 60 min to 20 or 48 ppm HF did not result in observable adverse effects, although quasistatic pressure-volume curves were shifted upward slightly after 48 ppm. These data provide an integrated picture of the concentration-related effects of short nonlethal exposures to HF.     

The concentration of hexachlorophene in the blood of albino rats as a function of time postexposure,number of exposures,route of exposure,previous exposure,and age

The concentration of hexachlorophene (HCP) in the blood of albino rats was studied as a function of time following the last exposure, number of consecutive exposures, route of exposure, previous exposure, and age. All HCP blood concentration determinations were conducted using gas chromatographic techniques. Highest blood concentrations were found approximately 4 hr following oral dosing and 24 hr following dermal treatment, although detectable concentrations were found at earlier evaluations. Repeated oral dosing did not result in increased blood HCP concentrations over the 42-day period of the study. HCP is removed from the blood fairly rapidly, little being detected 4 to 7 days following exposure. Previous exposure to HCP, either in rats exposed for a short term or in the third generation of exposed rats, failed to alter the observed HCP blood concentrations. Rats varying in age from 21 to 200 days had similar blood HCP concentrations.following oral administration. The HCP blood concentration following dermal application to rats of varying ages showed no age-dependent differences.     

Hexafluorine vs. standard decontamination to reduce systemic toxicity after dermal exposure to hydrofluoric acid

INTRODUCTION: Dermal exposure to hydrofluoric acid (HF) may cause severe burns and systemic toxicity. Hexafluorine (Prevor, France) is a product marketed as an emergency decontamination fluid for HF skin and eye exposures. Documentation concerning Hexafluorine is scanty, and a recent study indicates that its ability to reduce HF burns is at most equal to that of water. OBJECTIVE: The present study was conducted to evaluate Hexafluorine's capacity to reduce HF-induced systemic toxicity. METHODS: Sprague Dawley rats were anesthetized, catheterized in the left femoral artery, and shaved on their back. A filter paper (3.5 x 6 cm) was soaked in 50% HF and applied on the back of each rat for 3 min. Thirty seconds after removal of the paper, a 3-min rinsing with either 500 mL Hexafluorine (group H), 500 mL water (group W), or 500 mL water followed by a single application of 2.5% calcium gluconate gel (group Ca) was carried out. Blood samples were analyzed for ionized calcium and potassium (before injury and 1, 2, 3, and 4 h after) and also for ionized fluoride (1, 2, and 4 h after injury). RESULTS: The animals developed hypocalcemia, hyperkalemia, and hyperfluoridemia after the HF exposure. The only significant difference observed among the groups was in serum potassium at 1 h between group Ca and group W. However, there was a constant trend toward milder hypocalcemia and less pronounced hyperkalemia in group Ca compared to the other groups. There were no differences in the electrolyte disturbances between the Hexafluorine-treated animals and those treated with water only. Five of 39 animals died before completion of the experiment as a result of the HF exposure, one from group Ca and two from each of the other two groups. CONCLUSION: In this experimental study, decontamination with Hexafluorine was not more effective than water rinsing in reducing electrolyte disturbances caused by dermal exposure to hydrofluoric acid.     

Reducing Systemic Absorption from Monochloracetic Acid Exposure Through Dermal Decontamination: Use of the Pig Ear Organ Culture System

Abstract

Severe systemic intoxication may occur after skin contamination with monochloracetic acid (MCA). For this reason the effects of decontaminating with either water (most commonly used) or bicarbonate on the rates of percutaneous penetration and dermal accumulation of radiolabeled MCA were measured using the blood-perfused pig ear model. The rate of percutaneous penetration of a 40% solution of MCA was measured after exposure times of 1, 3, and 10 min. Maximal rates of percutaneous penetration (ng/min/cm²; mean ± SEM) were 891 ± 335 for a 1 min exposure; 947 ± 191 for a 3 min exposure; and 3221 ± 515 for a 10 min exposure. Although the initial rate of percutaneous absorption (first 30 min) was directly related to the exposure time, there was no difference in maximal rates of percutaneous penetration for 1 and 3 min exposures. It appears, that for short exposure times, the percutaneous penetration rate is determined by both the rate of penetration into the skin and the rate of diffusion from dermal stores into the blood.

A saturated sodium bicarbonate solution and water proved equally effective in decontaminating the skin after a 10 min exposure to MCA. However, a saturated bicarbonate solution was a slightly more effective decontaminant than water after a 1 min exposure. Our data indicate that decontamination should take place as soon as possible after dermal contamination with MCA. Furthermore, decontamination should continue for as long as possible in order to reduce the systemic burden. In view of the toxicity of MCA and the speed with which dermal deposits can accumulate, it is essential that decontamination facilities (e.g., a shower or bath filled with decontaminant) are available at all points in the workplace where MCA is handled.     

Acute Effects of 10-Minute Exposure to Hydrogen Fluoride in Rats and Derivation of a Short-Term Exposure Limit for Humans

A series of acute inhalation exposures of female rats was conducted with hydrogen fluoride (HF) to establish a concentration–response curve for nonlethal exposures. Durations of 2 and 10 min were used to simulate possible short-term exposures. Concentrations of HF ranged from 593 to 8621 ppm for 2-min exposures and from 135 to 1764 ppm for 10-min exposures. Additional exposures were performed for 60 min at 20 and 48 ppm HF for comparison to existing Emergency Response Planning Guidelines. Animals were evaluated on the day after exposure for changes in parameters of bronchoalveolar lavage, pulmonary function, hematology, serum chemistry, body weight, organ weights, and histopathology. Most exposures were performed with orally cannulated animals to bypass absorption of HF in the nose and achieve maximum delivery of HF to the lower airways. One of the primary uses of the resulting data was to estimate a concentration to which most people could be exposed for 10 min without severe or irreversible health effects. This level was 130 ppm. It was predicted that irritation would occur at this concentration, but the effects on the respiratory tract would not be “serious” and would be expected to be reversible. The results of this experiment and the subsequent analysis of the data provide an important aid in the planning of responses to an accidental release of HF.     

Calcium,magnesium and aluminium ions as decontaminating agents against dermal fluoride absorption following hydrofluoric acid exposure

The fluoride ions of the industrially largely irreplaceable, locally corrosive hydrofluoric acid (HF) can scavenge cations in biological tissues, which explains their high toxic potential, and also leads to local acidification through proton release. The influence of three complexing agents, calcium (Ca²⁺) gluconate (as 2.5% Ca²⁺gel and individually (2.84%) or commercially (10%) formulated Ca²⁺solution), magnesium (Mg²⁺) gluconate (2.84%) solution and aluminium (Al³⁺) solution (Hexafluorine®, pure and diluted) on the absorption of fluoride following HF exposure (1–3 min, 100 μl, 30%/0.64 cm²) through human skin was investigated in an ex-vivo diffusion cell model. Fluoride absorption was assessed over 6–24 h and analysed with a fluoride electrode. Decreasing the contamination time reduced the fluoride absorption distinctly which was further reduced by the application of fluoride-binding decontamination agents (Ca²⁺, Mg²⁺, Al³⁺) or water alone without being significantly different. Ca²⁺ appeared slightly more effective than Mg²⁺ in reducing fluoride absorption. Moreover, the addition of pH adjusting buffer promoted the decontamination efficacy. Fluoride-binding agents can facilitate the decontamination of dermal HF exposure. However, prompt decontamination appeared to be the key to successful limitation of fluoride absorption and pushes the choice of decontamination agent almost into the background.     

Regional deposition and absorption of inhaled hydrogen fluoride in the rat

The regional deposition of inhaled hydrogen fluoride (HF) was investigated by drawing known amounts of this irritant gas through the surgically isolated upper respiratory tract of anesthetized rats, while each animal respired HF-free room air through an endotracheal tube. At HF concentrations ranging from 30 to 176 mg F/m³, greater than 99.7% of the HF drawn into the upper respiratory tract was removed from the airstream during passage through that site. Plasma fluoride concentrations were significantly elevated by this upper respiratory tract exposure to HF and were highly correlated with airborne HF concentrations (r (8) = 0.98, p < 0.01). For comparative purposes, intact anesthetized rats were subjected to nose-only exposure to 63 mg F/m³ HF for 1 hr. Both pulmonary and plasma fluoride concentrations were significantly elevated over control levels by nose-only exposure; however, pulmonary fluoride concentrations in these rats were no higher than plasma fluoride concentrations, providing little evidence that airborne HF penetrates to the lungs of rats respiring normally. These results indicate that in the anesthetized rat virtually all inhaled HF deposits in the upper respiratory tract from which it may be absorbed and/or translocated to other sites, e.g., the gastrointestinal tract, where systemic absorption may occur.     

Chlorpyrifos: pharmacokinetics in human volunteers

The kinetics of chlorpyrifos, an organophosphorothioate insecticide, and its principal metabolite, 3,5,6-trichloro-2-pyridinol (3,5,6-TCP), were investigated in six healthy male volunteers given a single 0.5 mg/kg po and, 2 or more weeks later, a 0.5 or 5.0 mg/kg dermal dose of chlorpyrifos. No signs or symptoms of toxicity or changes in erythrocyte cholinesterase were observed. Plasma cholinesterase was depressed to 15% of predose levels by the 0.5 mg/kg po dose but was essentially unchanged following the 5.0 mg/kg dermal dose. Blood chlorpyrifos concentrations were extremely low (less than 30 ng/ml), and no unchanged chlorpyrifos was found in the urine following either route of administration. Mean blood 3,5,6-TCP concentrations peaked at 0.93 micrograms/ml 6 hr after ingestion of the oral dose and at 0.063 micrograms/ml 24 hr after the 5.0 mg/kg dermal dose. 3,5,6-TCP was cleared from the blood and eliminated in the urine with a half-life of 27 hr following both the po and dermal doses. An average of 70% of the po dose but less than 3% of the dermal dose was excreted in the urine as 3,5,6-TCP; thus only a small fraction of the dermally applied chlorpyrifos was absorbed. Chlorpyrifos and its principal metabolite were rapidly eliminated and therefore have a low potential to accumulate in man on repeated exposures. Based on these data, blood and/or urinary 3,5,6-TCP concentrations could be used to quantify the amount of chlorpyrifos absorbed under actual use conditions.     

In vitro dermal absorption of pesticides: V. In vivo and in vitro comparison of the herbicide 2,4-dichlorophenoxyacetic acid in rat, guinea pig, pig, human and tissue-cultured skin

In vitro dermal absorption tests were conducted with the ¹⁴C-ring-labelled herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), dissolved in acetone and applied to dermatomed skin (0.5 mm) of a number of species at dose rates of 7–8 μg/cm². Skin absorption was determined for 48 hr after exposure using an in vitro flow-through system. Skin absorption was calculated from the sum of the percentage recovery of ¹⁴C activity in the receiver solution and the percentage recovery in the methanol washes of the skin at 48 hr and the skin digest samples. Two receiver solutions, Ringer's saline, and Hanks' HEPES buffered saline with 4% serum albumin were used. Listed in decreasing order, the total percentage in vitro dermal absorptions obtained by 48 hr after exposure for the five skin types were: 47 ± 4.3% [tissue cultured Testskin; Hanks' receiver (HR)], 40 ± 4.5% (rat; HR), 19 ± 1.8% (human; HR), 14 ± 2.3% (hairless guinea pig; HR), 14 ± 8.8% (pig; Ringer's receiver). The percentage recovery of the radiolabel in soapy water skin washes at 24 hr, methanol washes and skin digests at 48 hr, and of ¹⁴C-labelled volatiles collected in air traps at 48 hr after exposure are reported. Comparative in vivo studies were conducted for 14 days after exposure and demonstrated 32 ± 3.9 and 28 ± 7.8% recovery of ¹⁴C in the urine of rats (dose rate, 3 μg/cm²) and guinea pigs (dose rate, 4 μg/cm²), respectively. Total faecal recovery was 2 ± 0.3 and 9 ± 3.5% for rats and guinea pigs, respectively. Analysis of tissue taken at autopsy 14 day after dosing demonstrated a total tissue recovery of ¹⁴C activity of 1 ± 0.1 and 2 ± 0.5% in rats and guinea pigs, respectively. Including the ¹⁴C activity extracted from the skin removed from the dose site at 14 days after exposure, the total recovery of dermally absorbed residues was 49 ± 10.4 and 40 ± 9.9% in rats and guinea pigs, respectively. Recovery of ¹⁴C activity from soapy water skin washes conducted at 24 hr after exposure was 28 ± 8.1 and 43 ± 9.0% for rats and guinea pigs, respectively. Recovery in skin patches was 18% (guinea pigs) and 26% (rats). In summary, the in vitro/in vivo concordance for the rat dermal absorption data was good but the in vitro data for hairless guinea pigs underestimated the in vivo absorption, and therefore for 2,4-D, rat skin may provide a better model of percutaneous absorption.     

Inhalation toxicity of dibutylhexamethylenediamine in rats

Dibutylhexamethylenediamine (DBHMD), a polymer intermediate, is strongly alkaline and is corrosive to eyes and skin. Its inhalation toxicity was defined in rats in both acute and subchronic studies. A 4-hr LC50 of 0.22 mg/litre was obtained for DBHMD of either 80.6 or 98.25% purity. Clinical signs of irritation were apparent during and immediately following exposure and no delayed deaths occurred. The mortality dose-response line was relatively steep. Reduction of exposure times to 5 min produced an LC50 of 51 mg/litre, with similar clinical signs and a steep dose-response line. These data suggest that the product of concentration and time (Ct) is constant for exposure times ranging from 5 min to 4 hr. Repeated (ten) exposures to 0.0125 mg/litre caused no signs of adverse response in rats. A concentration of 0.0234 mg/litre caused some mortality, mucous-membrane irritation, changes in haematological parameters (including erythrocyte counts, haemoglobin, concentration and total and differential leucocyte counts) and an increased acidity and decreased volume of urine. Death at this exposure level was attributed to cardiac failure secondary to pulmonary oedema and congestion, with evidence of hepatic congestion, diffuse cardiac myocytolysis and oedema, and thymic atrophy and congestion. Changes in the heart and thymus were seen in one of two rats killed after the tenth exposure. Clinical and pathological changes observed after the ten exposures were absent after a 14-day recovery period. DBHMD is highly toxic following acute inhalation and produces a steep dose-response following either single or multiple exposures.     

Modulation Of Sulfur Mustard-induced Inflammation And Gene Expression By Olvanil In The Hairless Mouse Vesicant Model

Cutaneous exposure to sulfur mustard [bis(2-chloroethyl) sulfide (SM)] produces a delayed inflammatory skin response that is followed by severe dermal injury. Assessment of anti-inflammatory therapies against SM-induced skin injury has mainly relied on qualitative histopathological evaluation. The goal of this study was to identify proinflammatory biomarkers in the hairless mouse vesicant model that could be used as additional indicators of SM-induced skin injury for evaluating anti-inflammatory treatment. SM-induced inflammation was determined at 2, 6, and 24 hr postexposure by changes in edema. Ribonuclease protection assay (RPA) was used to determine changes in gene expression of inflammatory mediators. At 2, 6, and 24 hr postexposure, a time-dependent increase in edema was observed in SM-exposed skin, which was significant at 6 and 24 hr when compared to unexposed controls. Ribonuclease protection assay analysis revealed a two-fold or greater increase in monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), MIP-1α, tumor necrosis factor-α, and interleukin (IL)-1β following exposure to SM when compared to unexposed controls. A significant time-dependent increase was observed in MCP-1, MIP-1α, and IL-1β over the 24 hr time period. At 24 hr postexposure, skin treated with the anti-inflammatory drug olvanil showed a significant decrease in SM-induced edema. Additionally, mRNA levels of MCP-1, MIP-2, and IL-1β were decreased when compared to skin exposed to SM alone. In this study, we identified molecular biomarkers at the mRNA level, up-regulated in skin exposed to SM, which can be partially suppressed by olvanil. Further characterization of the mRNA and protein expression patterns of proinflammatory biomarkers may enable the use of other classes of anti-inflammatory drugs or therapeutic treatments against SM dermal injury.     

Physiologically based pharmacokinetic modeling of the temperature-dependent dermal absorption of chloroform by humans following bath water exposures.

The kinetics of chloroform in the exhaled breath of human volunteers exposed skin-only via bath water (concentrations < 100 ppb) were analyzed using a physiologically based pharmacokinetic (PBPK) model. Significant increases in exhaled chloroform (and thus bioavailability) were observed as exposure temperatures were increased from 30 to 40 degrees C. The blood flows to the skin and effective skin permeability coefficients (Kp) were both varied to reflect the temperature-dependent changes in physiology and exhalation kinetics. At 40 degrees C, no differences were observed between males and females. Therefore, Kps were determined (approximately 0.06 cm/hr) at a skin blood flow rate of 18% of the cardiac output. At 30 and 35 degrees C, males exhaled more chloroform than females, resulting in lower effective Kps calculated for females. At these lower temperatures, the blood flow to the skin was also reduced. Total amounts of chloroform absorbed averaged 41.9 and 43.6 microg for males and 11.5 and 39.9 microg for females exposed at 35 and 40 degrees C, respectively. At 30 degrees C, only 2/5 males and 1/5 females had detectable concentrations of chloroform in their exhaled breath. For perspective, the total intake of chloroform would have ranged from 79-194 microg if the volunteers had consumed 2 liters of water orally at the concentrations used in this study. Thus, the relative contribution of dermal uptake of chloroform to the total body burdens associated with bathing for 30 min and drinking 2 liters of water (ignoring contributions from inhalation exposures) was predicted to range from 1 to 28%, depending on the temperature of the bath.     

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.     

Percutaneous absorption of m-xylene vapour in volunteers during pre-steady and steady state

Percutaneous absorption of m-xylene (XYL) was determined in volunteers exposed to 29.4 microg cm(-3) XYL vapour on the forearm and hand for 20, 45, 120 and 180 min. The internal exposure was assessed by measuring the concentration of XYL in exhaled air. The systemic kinetics were determined using a reference exposure by inhalation. The dermal permeation rate and the cumulative absorption of XYL as a function of time were calculated using mathematical deconvolution. From these relationships, the average flux into the skin throughout the exposure (J(skin, average)) and the maximal flux into the blood (J(blood, max)) were derived. Both fluxes were dependent on the duration of exposure, approaching each other at longer exposure durations. The values of J(skin, average), adjusted to a concentration of 1 microg cm(-3), were 0.091 microg cm(-2) h(-1) during 20-min exposure falling to 0.072, 0.066 and 0.061 microg cm(-2) h(-1) for 45, 120 and 180 min, respectively. The values of J(blood, max) showed an opposite trend, gradually increasing from 0.034 microg cm(-2) h(-1) at an exposure duration of 20 min to 0.042, 0.059 and 0.063 microg cm(-2) h(-1) for 45, 120 and 180 min of exposure durations, respectively.     

Oral decontamination with calcium or magnesium salts does not improve survival following hydrofluoric acid ingestion

Hydrofluoric acid (HF) ingestion may result in rapid death from systemic fluoride poisoning. Because fluoride binds calcium and magnesium, oral administration of calcium or magnesium salts has been suggested as useful therapy for HF ingestion. This study evaluates oral administration of calcium and magnesium salts for the prevention or attenuation of acute HF toxicity following oral exposure in a mouse model. Mixed breed CF-1 mice were randomized to treatment with a lethal-dose HF premixed with calcium chloride, magnesium sulfate, or deionized water by gavage. Average survival time for the three groups was the same. This study suggests that calcium- or magnesium-containing solutions do not alter the toxic effect of HF following oral exposure.     

Cutaneous uptake of 14C-HD vapor by the hairless guinea pig

The hairless guinea pig (HGP) is used by our laboratory to model the human cutaneous response to sulfur mustard (HD), bis(2-chloroethylsulfide), exposure. We determined the HD content in the skin of HGP after a 7-min exposure to vapors saturated with a mixture of HD and 14C-HD. Concentration/time (CT) values in the range of 2 micrograms/cm2/min were determined by counting skin 14C disintegrations per min (dpm) in animals euthanized immediately after exposure. These values are similar to human penetration rates obtained by other investigators. A rate curve monitoring the reduction in skin 14C dpm was developed for animals euthanized between 0 and 24 hr post- exposure. This curve showed the greatest change after 1 hr. The epidermal (62%) to dermal (38%) ratio of 14C at 24 hr was measured for two animals. We saw no site preference for HD penetration among the 8 sites used. The 14C content of template adhesive tape was determined to follow HD distribution. These results contribute to a better understanding of the cutaneous response to HD in the HGP model.