Impact of sublethal exposure to synthetic and natural acaricides on honey bee (Apis mellifera) memory and expression of genes related to memory.

Acaricides are used by beekeepers in honey bee (Apis mellifera L.) colonies to control parasitic mites, but may also have adverse effects to honey bees. In this study, five commonly used acaricides were tested for their sublethal effects on memory and expression of neural-related genes in honey bees. Memory measured with the proboscis extension reflex (PER) assay was significantly reduced by topical treatment of bees with a single LD05 dose of formic acid at 2 and 24 h post treatment (hpt). However, tau-fluvalinate, amitraz, coumaphos, and formic acid, but not thymol, resulted in memory loss at 48 hpt. The LD05 doses of the acraricides did not affect expression of neuroligin-1, related to memory, or expression of major royal jelly protein-1, related to both memory and development, although expression of both genes was affected at LD50 doses. The LD05 doses of thymol, formic acid, amitraz and coumaphos increased defensin-1 expression, which is related to both memory and immunity. The effect of thymol, however, may have been due to its impact on the immune response rather than memory. This study demonstrates that acaricides vary in their effects on bee's memory, and that the widely used acaricide, formic acid, is particularly damaging.

Sensory irritation of vapours of formic, acetic, propionic and butyric acid.

In mice, inhalation of formic, acetic, propionic and butyric acid caused a rapid decrease in the respiratory rate, which decreased to a stable level during the remaining part of the 30 min exposure period; this was due to sensory irritation. The concentration decreasing the respiratory rate (RD) by 50% (RD50) was 438, 308, 386 and 285 ppm, respectively, which allowed an adequate prediction of the Threshold Limit Values. In mice inhaling through a tracheal cannula, bypassing the trigeminal nerves, caused a slower decrease in respiratory rate due to pulmonary irritation. In the low concentration range, the pulmonary irritation response was less pronounced than the sensory irritation response. As the response in the normal (non-cannulated) mice was not influenced by pulmonary irritation, sensory irritation is the key effect, presumably due to the scrubbing effect of the upper airways, preventing access to the lungs. The activated receptors were in a non-lipophilic (hydrophilic) environment, from where the receptors may be activated by means of liberated protons. At the RD0, formic acid may, at least partly, activates ASIC, TRPV1 and TRPA1 receptors, whereas acetic, propionic and butyric acid may activate ASIC and TRPA1 receptors, based on the estimated pH in the mucus layer.

Effects Induced by Organic Acids in a Human Lung Alveolar Carcinoma Cell Line A549.

The present study examined the effects of formic acid and acetic acid on human adenocarcinoma-derived alveolar basal epithelial A549 cells. The organic acids were administered either individually or in combination, into either the culture medium (aqueous phase) or the gaseous phase of an air-liquid interface. When either of the acids was administered into the aqueous phase, cell proliferation was inhibited at doses of 1-10 mg/mL. In contrast, when the acids were administered either individually or in combination, into the gaseous phase of the air-liquid interface, cell proliferation was not altered. Under the gaseous phase administration, acetic acid and mixed acids caused a slight increase, decrease and increase on the interleukin-8 production, the mRNA expression of the heme oxygenase-1 (HO-1) gene and the HO-1 production, respectively, at one or more time points. The results therefore indicated that organic acids might be less reactive in the gaseous phase than in the aqueous phase. However, acetic acid in the gaseous phase either individually or in combination with formic acid exerts some effects on A549 cells.

Deep Full Thickness Burn to a Finger from a Topical Wart Treatment.

We present a case of a deep full thickness burn from topical formic acid. Our patient developed a burn over her proximal interphalangeal joint (PIPJ) of her finger, secondary to inappropriate application of an anti-wart treatment. The burn required extensive deridement, and the resultant defect was reconstructed using a subcutaneous flap from the adjacent finger (a reverse cross finger flap). She was reviewed six months post-surgery, and overall she has a sub-optimal result. This incident was referred to the Irish Medicine's Board who have since reviewed the case and ordered the manufacturer to alter their usage instructions.

Adverse placental effect of formic acid on hCG secretion is mitigated by folic acid.

AIMS: Formic acid has recently been detected in maternal blood and umbilical cord blood of infants born to alcohol abusing mothers. This toxic metabolite of methanol requires folate for detoxification. We hypothesized that formic acid produced in the maternal circulation will transfer across the placenta and will be toxic to the placenta. Our objectives were, first, to determine whether formic acid transfers across the human placenta and whether it is toxic to the placenta and second, to determine whether folate can decrease transplacental transfer of formic acid and mitigate toxicity. METHODS: Dual perfusion of a single placental lobule ex vivo was used to characterize the transfer of formic acid across the placenta. After a 1-h control period, formic acid (2 mM) was introduced into the maternal circulation with (n = 4) or without folate (1 µM) (n = 4) and was allowed to equilibrate for 3 h. RESULTS: Formic acid transferred rapidly from the maternal to the fetal circulation, and transfer was not altered with the addition of folate. Compared with the control period, there was a significant decrease in hCG secretion (P = 0.03) after addition of formic acid. The addition of folic acid to the perfusate mitigated the decrease in hCG. CONCLUSIONS: Formic acid rapidly transfers across the placenta and thus has the potential to be toxic to the developing fetus. Formic acid decreases hCG secretion in the placenta, which may alter steroidogenesis and differentiation of the cytotrophoblasts, and this adverse effect can be mitigated by folate.

Formic acid poisoning in a tertiary care center in South India: A 2-year retrospective analysis of clinical profile and predictors of mortality.

BACKGROUND: Formic acid (FA), a common industrial compound, is used in the coagulation of rubber latex in Kerala, a state in southwestern India. Easy accessibility to FA in this region makes it available to be used for deliberate self-harm. However, the literature on intentional poisoning with FA is limited. STUDY OBJECTIVES: To determine the patterns of presentation of patients with intentional ingestion of FA and to find the predictors of mortality. A secondary objective was to find the prevalence and predictors of long-term sequelae related to the event. METHODS: We performed a 2-year chart review of patients with acute intentional ingestion of FA. Symptoms, signs, outcomes and complications were recorded, and patients who survived the attempt were followed-up by telephone or personal interview to identify any complications after their discharge from the hospital. RESULTS: A total of 302 patients with acute formic acid ingestion were identified during the study period. The mortality rate was 35.4% (n = 107). Bowel perforation (n = 39), shock (n = 73), and tracheoesophageal fistula (n = 4) were associated with 100% mortality. Quantity of FA consumed (p < 0.001), consuming undiluted FA (p < 0.001), presenting symptoms of hypotension (p < 0.001), respiratory distress (p < 0.001), severe degree of burns (p = 0.020), hematemesis (p = 0.024), complications like metabolic acidosis (p < 0.001) and acute respiratory distress syndrome (p < 0.001) were found to have significant association with mortality. The prevalence of esophageal stricture (n = 98) was 50.2% among survivors and was the most common long-term sequela among the survivors. Stricture was significantly associated with hematemesis (p < 0.001) and melena (p < 0.001). CONCLUSION: This study highlights the magnitude and ill-effects of self-harm caused by a strong corrosive, readily available due to very few restrictions in its distribution. Easy availability of FA needs to be curtailed by enforcing statutory limitations in this part of the world. Patients with hematemesis or melena after FA ingestion may be referred for early dilatation therapy in a setting where emergency endoscopic evaluation of all injured patients is not practical.

The influence of chlorhexidine on the remineralization of demineralized dentine.

OBJECTIVES: To examine the differences in the amounts of bound chlorhexidine (CHX) on demineralized dentine blocks and to investigate the different aspects of remineralization of demineralized dentine according to different concentrations of CHX. METHODS: Dentine blocks (2 mm × 7 mm × 0.9 m) were demineralized in 0.2 M formic acid solution. Amount of bound CHX on the dentine blocks was measured on a spectrophotometer after the dentine block was soaked in 0.02%, 0.2%, or 2% CHX solutions for 1 min. The change in elastic modulus of dentine block stored in simulated body fluids was measured at 0 (baseline), 2, 4, and 6 weeks after storage. The micromorphological aspects of the samples were observed using a field emission scanning electron microscope after 6 weeks of storage. RESULTS: Higher concentrations of CHX caused a greater amount of CHX to bind to the dentine blocks (p<0.05). The group treated with the higher concentration of CHX had a smaller decrease in the elastic modulus at 2 weeks and a greater increase at 4 and 6 weeks. Dentine specimens with the 0.2% and 2% CHX had a greater deposition of granular minerals along the collagen fibrils compared to the 0.02% CHX-treated group. CONCLUSION: The application of the 0.2% and 2% CHX seemed to be effective in promoting the remineralization of demineralized dentine. CLINICAL SIGNIFICANCE: The application of the 0.2% and 2% CHX positively influences on the dentine remineralization.

Ocular and systemic morbidity profile in mass formic acid injuries.

BACKGROUND AND OBJECTIVE: A report on formic acid-induced ocular and systemic injuries. PATIENTS AND METHODS: Forty-two passengers (84 eyes) with formic acid burns following a tanker and bus collision were evaluated and treated. The severity of ocular chemical injury was assessed using the Roper-Hall classification. Standard protocol for management of ocular chemical burns was adopted in all patients. Immediate irrigation of the eyes was done with tap water and all patients received frequent topical steroids, cycloplegics, and lubricating eye drops. Systemic injuries were evaluated and managed collectively by plastic and orthopedic surgeons and internists. RESULTS: On presentation, 48 (57.14%) eyes had grade 0, 13 (15.48%) eyes had grade I, 16 (19.1%) eyes had grade II, 3 (3.57%) eyes had grade III, and 4 (4.76%) eyes had grade IV chemical injuries. Thirty patients (71.43%) had superficial and 12 (28.57%) had deep skin burns. One (2.38%) patient died due to severe pulmonary edema and 6 (14.29%) patients had severe pulmonary complications requiring oxygen treatment. Seventy-two (87.8%) eyes healed without residual sequelae, 10 (12.2%) eyes had nebulo-macular corneal opacities, and 2 (2.44 %) eyes developed secondary glaucoma and dry eye. CONCLUSION: Formic acid injuries can lead to a significant ocular and systemic morbidity. Immediate ocular and systemic management is necessary to reduce morbidity and mortality. Strict regulations are needed for the transportation of dangerous chemicals to prevent accidental chemical injuries.

Ocular and systemic safety evaluation of calcium formate as a dietary supplement.

PURPOSE: The objective of this study was to perform a preliminary evaluation of the ocular and systemic safety of calcium formate, a dietary calcium supplement for prevention and management of osteoporosis. Although formate is an endogenous product of metabolism, high concentrations are associated with toxicity during methanol overdose. METHODS: In this prospective clinical trial, 12 healthy women ingested calcium formate (1,300 mg) three times a day for 14 days. Study evaluations included physical and ocular examination, extensive laboratory testing, serum calcium and formate levels, Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, color vision, visual fields, visual evoked potential (VEP), and full-field, pattern, and multifocal electroretinograms (MERG). RESULTS: The mean baseline serum level of formate was 0.572 +/- 0.06 mM. Peak serum levels and final serum formate did not differ significantly from baseline. The final concentration was 0.582 +/- 0.091 mM. Accumulation of serum formate did not occur. There was also no evidence of toxicity with calcium formate ingestion. All examinations and tests remained normal, including optic nerve and retinal function. Three subjects had mild transient symptoms attributable to any calcium formulation. CONCLUSIONS: Calcium formate is highly bioavailable and well-tolerated. Serum formate remained at basal levels and did not accumulate with repeated dosing. Systemic and ocular safety was demonstrated by objective testing. Given its high oral bioavailability, calcium formate may be a good choice for calcium supplementation in the prevention and management of osteoporosis. Further study will be needed to evaluate its long-term safety in a larger group of subjects representing more varied age, health, dietary, and nutritional status.

Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation.

OBJECTIVES: To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study. METHODS: Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N=20), 3 days (N=20), and 28 days (5 days/week) (N=20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days. RESULTS: There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p=0.022) or 6 ppm (p=0.010), compared with the control. The parenchymal density of the rats exposed to 12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48+/-32.82 HU, 3 ppm: -720.65+/-34.21 HU, 6 ppm: -756.41+/-41.68 HU, 12 ppm: -812.56+/-53.48 HU) (p=0.000). There were significant density differences between each dose in the groups exposed for 28 days (p=0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow-up study, the groups exposed for 3 days showed diffusely increased parenchymal density on the 7 days study, but the lung densities were lower at 14 and 28 days than at 3 days. In the rats exposed to lowest concentration, the pulmonary parenchymal density and pathologic findings rapidly returned to normal within 1 week. CONCLUSIONS: Decreased parenchymal density of the lung was a common CT finding in acute and repeated inhalation injury. The air accumulation is believed to be the results of tracheolaryngeal inflammatory edema, bronchial dilatation, and alveolar rupture from the early period.

[Hygienic assessment of components of smoking fume]. / Gigienicheskaia otsenka komponentov koptil'nogo dyma.

Analyzing the chemical composition of smoking fume has indicated that maximum allowable concentrations (MACs) have been established for 50 of 400 well-known compounds, working area MACs were standardized for 42 of the 50 compounds, the maximum single and daily average concentrations were standardized for 34 and 30 compounds, respectively. All standards were established for 25 compounds. Despite the fact that there a large list of MACs, it is difficult to calculate the objective hygienic risk of smoking smoke since 32 compounds are contained in traces. Hygienic assessment of fume discharges from the smoking chamber by taking into account their mass and MACs demonstrated that phenols, carbonyl compounds, acids, and benz(a)pyrene which should be used to work out the unified hygienic standard are of the greatest importance.

The phytotoxicity to tobacco plants of short-chain carboxylic acids at atmospheric concentration levels in urban areas.

In this paper, we describe the influence of monocarboxylic acids (formic acid and acetic acid) and dicarboxylic acids (succinic acid and adipic acid), which are usually contained in aerosol particles and fog water, on the growth of tobacco plant. Their influence was examined by spraying the acid solutions on intact plants and by administering them in a culture medium for suspension-cultured cells. Their growth rates suggest that the influence of short-chain monocarboxylic acids was not significant in both the intact plant experiment and the cell culture experiment. In contrast, dicarboxylic acids exhibited significant influence on the growth of intact plants and no influence on culture cells, indicating that their toxicity is exerted mainly on the tissue of leaf surface. Phytotoxicity of dicarboxylic acids is higher than that of monocarboxylic acids.

Gingival inflammation induced by food and short-chain carboxylic acids.

Earlier studies in our laboratories demonstrated that particles of a number of snack foods that are retained on the dentition accumulate fermentable sugars and short-chain carboxylic acids (SCCA; acetic, formic, lactic, and propionic) to different degrees. The present study was undertaken to test the hypothesis that the accumulated SCCA can induce a gingival inflammatory response. Five periodontally and medically healthy subjects were given portions of plain doughnuts (high SCCA levels) or oatmeal cookie (low SCCA), or had the SCCA applied directly to the gingival margins of designated teeth. Subjects were given wax to chew, or nothing, as controls. Inflammation was assessed by measurements of subgingival temperature, flow rates of gingival crevicular fluid (GCF), and neutrophil emigration into GCF. Subgingival temperatures of the maxillary gingiva rose by 1.32 +/- 0.30 degrees C (mean +/- SE) 5 min after the subjects consumed the doughnuts and remained elevated for at least 1 hr. These values were significantly higher than those obtained from subjects after ingestion of oatmeal cookies (0.63 +/- 0.17 degree C; p < 0.01), consistent with the low levels of SCCA in the retained cookie particles. Wax chewing elicited a similar response, indicating a masticatory effect on the gingiva. Gingival temperatures in the unchallenged controls remained unchanged. Neutrophil emigration into the GCF was significantly elevated in subjects after doughnut consumption. Rinses with a solution of SCCA, or application of the SCCA to the gingiva, also brought about significant elevations in subgingival temperature and neutrophil emigration. The findings describe the inflammatory effects of food ingestion on the gingiva of healthy human subjects, and support the hypothesis that SCCA in the particles of retained food are at least partly responsible for the observed responses.

Formic acid inhalation injury: a case report.

We report a case in which a patient sustained an inhalation injury as a result of aerosolized formic acid. The patient sustained a partial-thickness burn to the face from a chemical spray; however, as a result of aerosolization, he also inhaled formic acid. This resulted in a reversible pulmonary chemical injury. Inhalation of formic acid results in a reactive airway dysfunction syndrome--a common response to inhalation of an occupational irritant.

Kinetics and renal effects of formic acid in occupationally exposed farmers.

Twelve male farmers (38 +/- 14 years of age, mean +/- SD) were exposed to 7.3 +/- 2.2 mg formic acid/m3 for 8 h in the silage making (mean +/- SD, N = 12). Each gave urine samples immediately, 15 h and 30 h after the end of the exposure. The excretion of formate was linearly related to the exposure 15 and 30 h after the exposure. Exposure increased renal ammoniagenesis and urinary calcium at 30 h post-exposure. Both biochemical effects may be explained by the interaction of formic acid with the oxidative metabolism of renal tubular cells, as formic acid is a known inhibitor of the cytochrome oxidase. In view of these renal effects, the current hygienic limits may not entirely protect exposed individuals.

Acute toxicology of components of vegetation smoke.

Only in recent times, systematic attention has been paid to the occupational health of forest firefighters and workers who manage prescribed fire. Two parts of the effort to learn the impact on worker health are medical observation of those workers, and study of occupational hygiene. It is also necessary to learn what components of smoke are most likely to affect firefighters, and to learn something of the manner in which those substances might compromise health; this review is a step toward that end. The number of possible products of vegetation combustion is almost limitless, and every fuel and condition of burning produces a unique pattern. Nonetheless, it is possible and practical to select a limited number of products that are most likely to be involved in the acute toxicity of smoke. Two products that are almost certainly important are formaldehyde and acrolein. Both appear to occur in all smoke. The toxicology of both is well studied; in particular both are powerful mucosal irritants. Estimates of exposure suggest strongly that concentrations are high enough in smoke to contribute some or all of the irritant activity. There seems to be a reasonable prospect that free radical precursors with half-lives in the tens of minutes are produced when cellulosic materials burn. If so, they will reach the respiratory tract, and liberate free radicals that react immediately on or in pulmonary cells. Ozone is not produced in the fire, but the various hydrocarbons of smoke are substrates for reactions that eventually produce ozone, and that production may continue for miles down-plume. Some measured plume concentrations approach the threshold for human health effects. The effects of the best known component, the particulate material, are unknown in isolation from all of the other substances in smoke. In spite of that ignorance, particulate loading is the principal index of smoke pollution for regulatory purposes, and sometimes is incorrectly used to represent smoke emissions regardless of source. The need to understand health impacts of these components of smoke seems obvious. Perhaps less obvious is the need to use such knowledge in management of both prescribed burning and wildfire. To some extent, it is possible to either manage fire itself to alter emission patterns, or control exposures in certain situations. Whether that should be done to protect worker health can only be judged if enough is known about health effects to direct the management decisions.

Chemical burns.

In chemical skin injuries, reduction of the time of exposure to the causative agent and recognition of systemic toxicity are necessary to lessen the severity of the insult, reduce morbidity, and maximize survival. During a 17-year period (1969 through 1985), 87 (2.1%) of the 4,212 burned patients admitted to the U.S. Army Institute of Surgical Research sustained chemical burns. Twelve of 87 patients died (13.8%). White phosphorous, the most common causative agent, produced cutaneous injury in 49 patients. Acids (13 patients), alkalies (ten patients), and organic solvents (five patients) were the other common causes of injury. Initial treatment consisted of water lavage. Later wound management was carried out with topical antibiotic therapy and excision and grafting as necessary. Systemic toxicity due to phenol, nitrate, and formate absorption occurred, as did acute tubular necrosis following copper sulfate treatment of white phosphorus burns. Inhalation injury occurred in five patients. A decrease in hospital stay for chemically injured patients was observed. To minimize chemical injury, clothing should be removed promptly and water lavage begun. Systemic toxicity and inhalation injury are rare but often severe and increase mortality.

Urinary formic acid as an indicator of occupational exposure to formic acid and methanol.

A sampling strategy was developed to detect personal exposure to methanol and formic acid vapors. Formic acid is the metabolic end product of methanol, and part of inhaled formic acid is excreted directly in urine, so that urinary formic acid would reveal exposure to both agents. A linear relationship to inhaled vapors, however, could be shown only if urinary sampling were delayed until 16 hr (next morning) after exposure. Exposure to methanol vapor at the current Finnish hygienic limit level (200 ppm) produced 80 mg formic acid/g creatinine; exposure to formic acid at the hygienic limit (5 ppm) caused 90 mg/g creatinine. The similarity of these figures may indicate a common toxicological foundation of these empirically set values.