Lethal Range Research Articles

Effects of High Temperatures and Sun Exposure on Sherman Trap Internal Temperatures

Trapping during summer months can expose small mammals to high temperatures inside traps. We measured trap temperatures under different ambient conditions and levels of sun exposure. Internal temperatures of Sherman traps exposed to full sun were 14% higher than those exposed to full sun and fitted with a corrugated cardboard cover and tent. Traps with the surrounding cardboard cover and tent experienced up to a 7.6 °C reduction in internal temperature and could be left out one to two hours longer on average than traps exposed to full sun before internal trap temperatures rose into the minimum lethal range for most small mammal species.

Effects of cadmium exposure on critical temperatures of aerobic metabolism in eastern oysters Crassostrea virginica (Gmelin, 1791)

Cadmium (Cd) and elevated temperatures are common stressors in estuarine and coastal environments. Elevated temperature can sensitize estuarine organisms to the toxicity of metals such as Cd and vice versa, but the physiological mechanisms of temperature–Cd interactions are not well understood. We tested a hypothesis that interactive effects of elevated temperature and Cd stress involve Cd-induced reduction of the aerobic scope of an organism thereby narrowing the thermal tolerance window of oysters. We determined the effects of prolonged Cd exposure (50μgCdl−1for 30 days) on the upper critical temperature of aerobic metabolism (assessed by accumulation of anaerobic end products l-alanine, succinate and acetate), cellular energy status (assessed by the tissue levels of adenylates, phosphagen/aphosphagen and glycogen and lipid reserves) and oxidative damage during acute temperature rise (20–36°C) in the eastern oysters Crassostrea virginica. The upper critical temperature (TcII) was shifted to lower values (from 28 to 24°C) in Cd-exposed oysters in spring and was lower in both control and Cd-exposed groups in winter (24 and <20°C, respectively). This indicates a reduction of thermal tolerance of Cd-exposed oysters associated with a decrease of the aerobic scope of the organism and early transition to partial anaerobiosis. Acute warming had no negative effects on tissue energy reserves or parameters of cellular energy status of oysters (except a decrease in adenylate content at the extreme temperature of 36°C) but led to an increase in oxidative lesions of proteins at extreme temperatures. These data show that transition to partial anaerobiosis (indicated by the accumulation of anaerobic end products) is the most sensitive biomarker of temperature-induced transition to energetically non-sustainable state in oysters, whereas disturbances in the cellular energy status (i.e. decline in adenylate and phosphagen levels) and oxidative stress ensue at considerably higher temperatures, nearing the lethal range. This study indicates that long-term exposure of oysters to environmentally relevant levels of Cd may increase their sensitivity to elevated temperatures during seasonal warming and/or the global climate change in polluted estuaries.

Caffeine: cognitive and physical performance enhancer or psychoactive drug?

Caffeine use is increasing worldwide. The underlying motivations are mainly concentration and memory enhancement and physical performance improvement. Coffee and caffeine-containing products affect the cardiovascular system, with their positive inotropic and chronotropic effects, and the central nervous system, with their locomotor activity stimulation and anxiogenic-like effects. Thus, it is of interest to examine whether these effects could be detrimental for health. Furthermore, caffeine abuse and dependence are becoming more and more common and can lead to caffeine intoxication, which puts individuals at risk for premature and unnatural death. The present review summarizes the main findings concerning caffeine’s mechanisms of action (focusing on adenosine antagonism, intracellular calcium mobilization, and phosphodiesterases inhibition), use, abuse, dependence, intoxication, and lethal effects. It also suggests that the concepts of toxic and lethal doses are relative, since doses below the toxic and/or lethal range may play a causal role in intoxication or death. This could be due to caffeine’s interaction with other substances or to the individuals' preexisting metabolism alterations or diseases.

Presence and Persistence of White Phosphorus On Military Training Ranges

AbstractThe use of obscurants is a common practice by militaries worldwide. One of the most effective of these is white phosphorus (WP). WP is the elemental form of phosphorus that does not occur in nature and is highly toxic. The use of WP rounds on training ranges has led to a number of die‐offs of grazing land animals and dabbling waterfowl, the first recorded in 1930. In the 1980s, thousands of waterfowl were dying annually at an impact range in Alaska, leading to the first large‐scale investigation of WP as a lethal range contaminant. Tests were conducted at an upland impact range in New York to determine the quantity and persistence of WP in a typical environment. At all sites cited in this paper, WP was persistent for months to years following the detonation of WP munitions. At the Eagle River Flats range in AK, WP was identified from rounds fired in the 1950s, persisting over 45 years in a non‐saturated environment. In New York, dispersal of gram quantities of WP occurred at detonation, and high concentrations of WP were found in the detonation craters a year after firing. Caution needs to be exercised when using white phosphorus munitions on ranges.

First detection of ethylphenidate in human fatalities after ethylphenidate intake

Methylphenidate, a psychostimulant drug from the group of amphetamines is, among others, established in the treatment of attention deficit hyperactivity disorder and narcolepsy. It is also known to have a certain potential of abuse. In combination with alcohol, the metabolite ethylphenidate was detected in human plasma in small amounts. However, ethylphenidate is sold as “research chemical” via the Internet. It was put under German narcotics law in July 2013. In a recent case, where a deceased person was found in his apartment, the police seized a plastic bag with the inscription “ethylphenidate”. An autopsy of the 32-year-old man yielded a mitral valve endocarditis, which must have persisted a while before death, in combination with a pneumonia.At the Forensic Toxicological Centre (FTC) in Munich femoral blood, liver, pericardium fluid, urine, stomach content and hair of the deceased were analyzed for ethylphenidate after sample preparation by an LC-Triple TOF 5600. Calibration curves were spiked with a methanolic 1mg/mL solution of ethylphenidate (substance provided by the State Office of Criminal Investigation in Munich) in whole blood in comparison to liver and femoral blood, in serum in comparison to pericardium fluid and in urine in comparison to urine and stomach content, respectively.Ethylphenidate was detected in all analyzed matrices. The spectrums of the human specimen were compared to those obtained from the calibration curves and identified as ethylphenidate. The measured concentrations were for femoral blood 110ng/mL, for liver 180ng/g, for pericardium fluid 131ng/mL, for urine 987ng/mL and for stomach content 20.7ng/mL, respectively. The stomach contained 200mL of a brownish-coloured liquid, resulting in a total amount of 4000ng ethylphenidate. The lowest calibrator for whole blood and serum was 1ng/mL and for urine 10ng/mL.As far as it is known to the authors, these are the first ethylphenidate levels measured in a case of ethylphenidate intake. Therefore these results can only be compared to methylphenidate concentrations with therapeutic levels ranging from 5 to 60ng/mL in serum. As the toxic levels for methylphenidate start from approximately 500ng/mL serum, we estimate that ethylphenidate in the concentrations mentioned above is not in a directly lethal range. But it has to be considered, that amphetamine-like drugs as methylphenidate are known for their cardiovascular side effects (like tachycardia and arrhythmia) and might therefore have contributed to death, which was attributed to endocarditis in combination with pneumonia.

P6: Hair desorption of the sulphur mustard simulants methyl salicylate and 2-chloroethyl ethyl sulfide following vapour exposure

Introduction Chemical warfare agents are compounds whose toxic properties are used to kill or incapacitate people. Their synthesis, use and stockpiling are regulated by the Organisation for the Prohibition of Chemical Weapons. Despite this narrow surveillance, exposure to chemical warfare agents may still happen. Analysis of external contamination of hair could be of high interest, especially for rescue teams. It could be particularly useful to identify chemicals to which victims were exposed, or to distinguish among a large number of potentially exposed individuals those who specifically require thorough decontamination. External contamination of hair by vapours of the sulphur mustard (SM) simulant methyl salicylate has already been demonstrated (Spiandore M., Piram A., Lacoste A., Josse D., Doumenq P., External contamination of hair as a marker of exposure to chemical warfare agents, 18 th Scientific Meeting of the Society of Hair Testing, Geneva, August 20-30, 2013). The main objective of this work is to determine desorption kinetics of SM simulants methyl salicylate (MeS) and blistering agent 2-chloroethyl ethyl sulfide (CEES) from hair following vapour exposure. Methods Locks of human hair were exposed to vaporised CEES or MeS for different times and at different concentrations in order to reach concentration-time products ( Ct ) around 900-1500 mg. min/ m 3 which corresponds to the lethal value range for SM. Desorption of MeS and CEES have been observed when transferring a contaminated lock of hair in an uncontaminated tank. Dichloromethane extracts were then analysed by GC-MS/MS operating in MRM mode. Results As previously shown for MeS, importance of external contamination of hair by CEES vapours increased with exposure duration or concentration. Depending on the vapour concentration or time of exposure, CEES content in hair represented 0.5 to 3 % of the exposure dose. MeS yielded in higher rates as its content retrieved in hair represented up to 15 % of the exposure dose. Conclusion Both SM simulants (MeS and CEES) have been quantified in hair after they have been exposed to vapours, with a simple solvent extraction. It confirms previous results that hair could be used as a marker of vapour exposure to chemical warfare agents.

Bald Eagle Lead Exposure in the Upper Midwest

AbstractIn 2012, we examined lead exposure in 58 bald eagles Haliaeetus leucocephalus found dead in Iowa, Minnesota, and Wisconsin. We determined lead concentrations in livers, examined differences in exposure among ages and between sexes, and recorded clinical signs consistent with lead poisoning. Most (60%) of the bald eagles had detectable lead concentrations, and 38% of the 58 had concentrations within the lethal range for lead poisoning. We found no differences in exposure based on sex or age, but we did find an inverse relationship between body and liver mass and liver lead concentration. The high percentage of lead-exposed bald eagles encouraged us to further examine potential sources of lead in our local environment. We initiated a study on the Fish and Wildlife Service's Upper Mississippi River National Wildlife and Fish Refuge to investigate if discarded offal piles from hunter-killed deer were a potential source of lead exposure to scavenging wildlife such as the bald eagle. Radiographs showed that 36% of offal piles in our sample area contained lead fragments ranging from 1 to 107 particles per pile. Our study indicated that 1) lead exposure rates for bald eagles found dead in our Upper Midwest study area were high, 2) more than one-third of the bald eagles found dead in Iowa, Minnesota, and Wisconsin had liver lead concentrations consistent with lead poisoning, and 3) discarded offal piles from deer shot with lead ammunition can be a potential source of lead exposure for bald eagles.

Pharmacological Approaches That Slow Lymphatic Flow As a Snakebite First Aid

BackgroundThis study examines the use of topical pharmacological agents as a snakebite first aid where slowing venom reaching the circulation prevents systemic toxicity. It is based on the fact that toxin molecules in most snake venoms are large molecules and generally first enter and traverse the lymphatic system before accessing the circulation. It follows on from a previous study where it was shown that topical application of a nitric oxide donor slowed lymph flow to a similar extent in humans and rats as well as increased the time to respiratory arrest for subcutaneous injection of an elapid venom (Pseudonaja textilis, Ptx; Eastern brown snake) into the hind feet of anaesthetized rats.Methodology/Principal FindingsThe effects of topical application of the L-type Ca2+ channel antagonist nifedipine and the local anesthetic lignocaine in inhibiting lymph flow and protecting against envenomation was examined in an anaesthetized rat model. The agents significantly increased dye-measured lymph transit times by 500% and 390% compared to controls and increased the time to respiratory arrest to foot injection of a lethal dose of Ptx venom by 60% and 40% respectively. The study also examined the effect of Ptx venom dose over the lethal range of 0.4 to 1.5 mg/kg finding a negative linear relationship between increase in venom dose and time to respiratory arrest.Conclusions/SignificanceThe findings suggest that a range of agents that inhibit lymphatic flow could potentially be used as an adjunct treatment to pressure bandaging with immobilization (PBI) in snakebite first aid. This is important given that PBI (a snakebite first aid recommended by the Australian National Health and Medical research Council) is often incorrectly applied. The use of a local anesthetic would have the added advantage of reducing pain.

Impact on the Japanese Atomic Bomb Survivors of Radiation Received From the Bombs

The Radiation Effects Research Foundation (RERF) studies various cohorts of Japanese atomic bomb survivors, the largest being the Life Span Study (LSS), which includes 93,741 persons who were in Hiroshima or Nagasaki at the times of the bombings; there are also cohorts of persons who were exposed in utero and survivors' children. This presentation attempts to summarize the total impact of the radiation from the bombs on the survivors from both an individual perspective (both age-specific and integrated lifetime risk, along with a measure of life expectancy that describes how the risk affects the individual given age at exposure) and a group perspective (estimated numbers of excess occurrences in the cohort), including both early and late effects. As survivors' doses ranged well into the acutely lethal range at closer distances, some of them experienced acute signs and symptoms of radiation exposure in addition to being at risk of late effects. Although cancer has always been a primary concern among late effects, estimated numbers of excess cancers and hematopoietic malignancies in the LSS are a small fraction of the total due to the highly skewed dose distribution, with most survivors receiving small doses. For example, in the latest report on cancer incidence, 853 of 17,448 incident solid cancers were estimated to be attributable to radiation from the bombs. RERF research indicates that risk of radiation-associated cancer varies among sites and that some benign tumors such as uterine myoma are also associated with radiation. Noncancer late effects appear to be in excess in proportion to radiation dose but with an excess relative risk about one-third that of solid cancer and a correspondingly small overall fraction of cases attributable to radiation. Specific risks were found for some subcategories, particularly circulatory disease, including stroke and precedent conditions such as hypertension. Radiation-related cataract in the atomic bomb survivors is well known, with evidence in recent years of risk at lower dose levels than previously appreciated. In addition to somatic effects, survivors experienced psychosocial effects such as uncertainty, social stigma, or rejection, and other social pressures. Developmental deficits associated with in utero exposure, notably cognitive impairment, have also been described. Interaction of radiation with other risk factors has been demonstrated in relation to both cancer and noncancer diseases. Current research interests include whether radiation increases risk of diabetes or conditions of the eye apart from cataract, and there continues to be keen interest as to whether there are heritable effects in survivors' children, despite negative findings to date. Introduction of Impact on the Japanese Atomic- Bomb Survivors (Video 1:52, http://links.lww.com/HP/A29).

Thermal tolerance of Crepidula fornicata (Gastropoda) life history stages from intertidal and subtidal subpopulations

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 486:173-187 (2013) - DOI: https://doi.org/10.3354/meps10355 Thermal tolerance of Crepidula fornicata (Gastropoda) life history stages from intertidal and subtidal subpopulations Casey M. Diederich*, Jan A. Pechenik Biology Department, Tufts University, Medford, Massachusetts 02155, USA *Email: casey.diederich@tufts.edu ABSTRACT: The ability to withstand high summer temperatures is an extremely important determinant of species distributions in the intertidal zone; most marine organisms cannot live intertidally because of the harsh conditions experienced during aerial emersion. The members of some species, though, live both intertidally and subtidally, and their physiological tolerance to stressors may differ depending on their genetic connectivity, acclimatization, and differential postsettlement mortality. Furthermore, tolerances of organisms at different life-history stages within both habitats may differ and will play an important role in determining adult distributions. To determine the effect of habitat and life-history stage on physiological tolerance and the likely contribution of upper thermal tolerance limits to the native distribution of an important invasive species, the slippershell snail Crepidula fornicata, we compared the thermal tolerance of intertidal and subtidal embryos and adults in relation to conditions that they experience in the field. We found C. fornicata living both intertidally and subtidally in Bissel Cove, Rhode Island, where they experienced drastically different thermal conditions. Intertidal individuals achieved body temperatures as high as 42°C, more than 15°C higher than those recorded in subtidal conspecifics. However, subtidal individuals had remarkably high thermal tolerances that were nearly identical to those of intertidal conspecifics (lethal range = 33-37°C following a 3 h exposure). Furthermore, embryos were even more tolerant to high thermal stress than adults. These results are surprising: the few previous studies that have compared thermal tolerances among individuals at different life-history stages have found differences among them, and early stages are generally more sensitive than adults. Interestingly, the markedly higher temperatures that intertidal animals experienced in this study had little effect on their thermal tolerance. Intertidal (but not subtidal) slippershell snails are now living dangerously close to their upper thermal limits and will almost certainly be relegated to the subtidal as global temperatures rise. KEY WORDS: Intertidal · Subtidal · Crepidula · Thermal stress · Physiological tolerance Full text in pdf format PreviousNextCite this article as: Diederich CM, Pechenik JA (2013) Thermal tolerance of Crepidula fornicata (Gastropoda) life history stages from intertidal and subtidal subpopulations. Mar Ecol Prog Ser 486:173-187. https://doi.org/10.3354/meps10355 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 486. Online publication date: July 12, 2013 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2013 Inter-Research.

An accurate method for microanalysis of carbon monoxide in putrid postmortem blood by head-space gas chromatography–mass spectrometry (HS/GC/MS)

Carbon monoxide (CO) may be the cause of more than half the fatal poisonings reported in many countries, with some of these cases under-reported or misdiagnosed by medical professionals. Therefore, an accurate and reliable analytical method to measure blood carboxyhemoglobin level (COHb%), in the 1% to lethal range, is essential for correct diagnosis. Herein a method was established, i.e. head-space gas chromatography–mass spectrometry (HS/GC/MS) that has numerous advantages over other techniques, such as UV spectrometry, for determination of COHb%. There was a linear relationship (R2=0. 9995) between the peak area for CO and the COHb% in blood. Using a molecular sieve-packed column, CO levels in the air down to 0.01% and COHb% levels in small blood samples down to 0.2% could be quantitated rapidly and accurately. Furthermore, this method showed good reproducibility with a relative standard deviation for COHb% of <1%. Therefore, this technique provides an accurate and reliable method for determining CO and COHb% levels and may prove useful for investigation of deaths potentially related to CO exposure.

The occurrence of second generation anticoagulant rodenticides in non-target raptor species in Norway

Second generation anticoagulant rodenticides (SGARs) are commonly used for rodent pest control in Norway resulting in the potential exposure of non-target raptor species. In this study the occurrence of flocoumafen, difethialone, difenacoum, bromadiolone and brodifacoum was determined in the livers of five species of raptors found dead in Norway between 2009 and 2011. The SGARs brodifacoum, bromadiolone, difenacoum and flocoumafen were detected in golden eagle (Aquila chrysaetos) and eagle owl (Bubo bubo) livers at a total SGAR concentration of between 11 and 255ng/g in approximately 70% of the golden eagles and 50% of the eagle owls examined in this study. In the absence of specific golden eagle and eagle owl toxicity thresholds for SGARs, a level of >100ng/g was used as a potential lethal range, accepting that poisoning may occur below this level. Thirty percent (7/24) of the golden eagle and eagle owl livers contained total SGAR residue levels above this threshold. Further estimation of the potential mortality impact on the sampled raptor populations was not possible.

Evolution and Mode of Action of Pulsed Radiofrequency

Evolution and Mode of Action of Pulsed Radiofrequency

FEM Simulation of HE Blast-Fragmentation Warhead and the Calculation of Lethal Range

FEM Simulation of HE Blast-Fragmentation Warhead and the Calculation of Lethal Range

One green bottle

<h3>Introduction</h3> Most paediatricians are familiar with the diagnosis and management of neonatal abstinence syndrome in babies of mothers who have taken opiate drugs during pregnancy. We report a case in which parents tried to prevent opiate withdrawal symptoms in their baby by giving her regular doses of methadone from birth without medical advice. <h3>Case report</h3> AB presented to our emergency department at 7 months of age with respiratory symptoms and signs suggestive of a chest infection. This was her third admission within two months, the first two having been with mild RSV (+) ve bronchiolitis and with X-ray changes suggestive of aspiration pneumonia respectively. AB9s family was known to social services owing to previous domestic violence and drug abuse. During this admission nurses had noted erratic maternal behaviour culminating in the discovery of AB being fed green-coloured milk. Analysis of both the milk and AB9s urine revealed significant levels of methadone. AB9s blood methadone level was above the lethal range signifying high tolerance to methadone. With no experience to guide us with this unique case we consulted colleagues from the adult drug service to determine our approach to management. We present our experience. <h3>Conclusion</h3> We found no previous reports of parental ‘diagnosis and treatment’ of neonatal abstinence syndrome or of the medical management of opiate addiction in older babies and children. Although this case appears unique we believe paediatricians should be increasingly alert to the possibility of clandestine methadone administration to babies by parents with a history of drug abuse.

Virulence of Escherichia coli Clinical Isolates in a Murine Sepsis Model in Relation to Sequence Type ST131 Status, Fluoroquinolone Resistance, and Virulence Genotype

Escherichia coli sequence type ST131 (O25b:H4) has emerged over the past decade as a globally disseminated, multidrug-resistant pathogen. Unlike traditional antimicrobial-resistant E. coli, ST131 derives from virulence-associated phylogenetic group B2 and exhibits extraintestinal virulence factors. This, plus preliminary evidence of virulence in experimental animals, has suggested that ST131's epidemic emergence may be due to high virulence potential, compared with other E. coli types. To test this hypothesis, we compared a large number of matched ST131 and non-ST131 E. coli clinical isolates, both fluoroquinolone resistant and susceptible, plus isolates from classic extraintestinal pathogenic E. coli (ExPEC) sequence types (STs) and case report ST131 household transmission isolates, for virulence in a mouse subcutaneous sepsis model. Overall, in mice, the study isolates produced a wide range of lethality and clinical illness. However, neither ST131 status nor fluoroquinolone phenotype correlated with this diversity of illness severity, which occurred within each of the 6 study groups. In contrast, multiple known or suspected ExPEC virulence genes, including pap (P fimbriae), vat (vacuolating toxin), kpsM II (group 2 capsule), ibeA (invasion of brain endothelium), and clbB/N (colibactin synthesis), plus molecularly defined ExPEC status, were significantly associated with virulence. These findings point away from ST131 isolates as having higher virulence potential compared with other E. coli types in causing invasive extraintestinal infections and suggest instead that ST131's epidemiological success may reflect enhanced fitness for upstream steps in pathogenesis or in colonization and transmission. Additionally, the extensive within-ST virulence diversity suggests an opportunity to compare closely related strains to identify the responsible genetic determinants.

The PMMA epidemic in Norway: Comparison of fatal and non-fatal intoxications

During a 6 month period (July 2010-January 2011) we observed 12 fatal intoxications and 22 non-fatal cases related to the drug paramethoxymethamphetamine (PMMA) in Norway (4.8 mill inhabitants). This toxic designer drug, also known as "Death", is occasionally found in street drugs offered as "ecstasy" or "amphetamine". The present study aimed to evaluate the cause of death, and to compare the PMMA blood concentrations in fatal and non-fatal cases. Methods for identification and quantification of PMMA are presented. The median age of fatalities was 30 years (range 15-50) with 67% males; in non-fatal cases 27 years (20-47) with 86% males. In the 12 fatalities, the median PMMA blood concentration was 1.92 mg/L (range 0.17-3.30), which is in the reported lethal range of 0.6-3.1 mg/L in peripheral blood and 1.2-15.8 mg/L in heart blood. In the 22 non-fatal cases, the median PMMA concentration was 0.07 mg/L (range 0.01-0.65). Poly-drug use was frequent both in fatal and non-fatal cases. The PMA concentrations ranging from 0.00 to 0.26 mg/L in both groups likely represented a PMMA metabolite. Three fatalities were attributed to PMMA only, six to PMMA and other psychostimulant drugs, and three to PMMA and CNS depressant drugs, with median PMMA concentrations of 3.05 mg/L (range 1.58-3.30), 2.56 (1.52-3.23) and 0.52 mg/L (0.17-1.24), respectively. Eight victims were found dead, while death was witnessed in four cases, with symptoms of acute respiratory distress, hyperthermia, cardiac arrest, convulsions, sudden collapse and/or multiple organ failure. In summary, all fatalities attributed to PMMA had high PMMA blood concentrations compared to non-fatal cases. Our sample size was too small to evaluate a possible impact of poly-drug use. A public warning is warranted against use and overdose with illegal "ecstasy" or "speed" drugs.

Assessment of Early Acute Lung Injury in Rats Exposed to Aerosols of Consumer Products: Attempt to Disentangle the “Magic Nano” Conundrum

In Germany in 2006 a series of rapidly developing and sometimes severe cases of pulmonary health impairment were observed after normal use of the “Magic Nano Glass & Ceramic” spray and “Magic Nano Bath” spray. In contrast, the previously marketed “Magic Nano” pump spray product (handheld trigger device without propellants) was unobtrusive. Analysis of particles discharged from these products did not reveal stable (solid) nano-sized particles. The precipitous increase of pulmonary health impairment in humans caused by “Magic Nano Sprays” triggered a comparative assessment of the acute inhalation toxicity of “Magic Nano Glass & Ceramic” spray, “Magic Nano Bath” spray, and “Magic Nano” pump spray in rats. The first two test specimens were examined as spray-can aerosols using an intermittent generation principle, whereas the undiluted liquid content of the pump spray was continuously aerosolized. Groups of Wistar rats were nose-only exposed for 4 h. However, due to mortality occurring already during exposure following exposure to Glass & Ceramic spray, the exposure duration was reduced to ∼ 2 h in some groups. In addition to endpoints called for by contemporary testing guidelines, respiratory tract injury was also probed by respiratory function measurements during exposure supplemented by analyses in bronchoalveolar lavage (BAL) fluid on the first postexposure day, including lung histopathology in rats exposed to Glass & Ceramic spray. The Glass & Ceramic spray caused mortality at 2269 mg/m3 and above, the pump spray was in the beginning lethal range at 81222 mg/m3, while the bath spray was tolerated without mortality up to the maximum tested nominal concentrations of 28100 mg/m3. The time-adjusted 4-h LC50 of Glass & Ceramic spray was 5098 mg/m3. The analysis of respiratory patterns revealed changes indicative of both upper and lower respiratory tract sensory irritation. In addition to clinical signs suggestive of marked lung irritation, especially in the rats exposed to the Glass & Ceramic spray, histopathology revealed lung inflammation, hemorrhages, edema, and focal septal thickening. Lung weights and BAL endpoints (lactate dehydrogenase [LDH], protein, γ -glutamyltransaminase, and neutrophilic granulocytes) were markedly increased. In summary, this comparative study demonstrates that the conventional OECD 403 protocol is suitable to comparatively assess the potential and potency of these types of consumer products in their end-use configuration. Measurements in BAL were most suitable for the identification of acute lung injury. By contrast, lung function measurements during exposure did not demonstrate any conclusive association with lung injury. It does not appear that the particle size per se is a key determinant in the toxicity of “Magic Nano Glass & Ceramic” spray (approximately 100% mortality occurred at a MMAD of ∼ 7 μ m; GSD ≈ 3). This might suggest that more volatile substances or substances contained in the test articles that co-evaporate with solvents or water may be causative for the findings observed. Hence, the findings of this study support the notion that the assessment of the acute inhalation toxicity of complex end-use products is methodologically challenging and cannot be readily anticipated based on compositional or physical (particle size) data. Accordingly, in the absence of predictive and validated in vitro assays, in vivo inhalation testing of potentially toxic commercialized spray products appears to be indispensable for consumer safety. In order to prevent indiscriminant testing of such products in bioassays, the development of standardized in vitro alternatives should be considered with high priority.

EXPOSURE TO ARSENIC COMPROMISES ZONA ESCAPE IN HAMSTER EMBRYO

Inorganic arsenic or arsenite has proven extremely detrimental in embryonic development; however, there is little or no information on its toxicity to embryos within the luminal fluid. We evaluated the toxicity of sodium metaarsenite (NaAsO2) to preimplantation stage hamster embryos in vitro to acquire a better knowledge of its direct effects. In particular we looked at the morphological characteristics of 8-cell stage embryos during a 72hr period, their ability to undergo zona lysis, and examined cell death using TUNEL staining. Females were superovulated and mated; embryos were collected at day 3 of gestation and grown in species specific complete culture medium containing vehicle control (distilled deionized water), 25, 50, 250, 500, or 750 nM arsenite. A negative control (lacking bovine serum albumin BSA) was also used. All treatments were incubated for 72 hrs for the morphology evaluation and for 36 hrs for TUNEL assay. Embryo survivability was expressed as a complete failure of zona lysis. The control group had a 78% survivability rate, a normal in vivo figure based on literature, and no evidence of deformities. Embryos in the low concentration of 25 nM exhibited a survival rate of 63%, comparable to control group, and little or no deformities. At 50 nM embryos showed minor levels of deformity and 55% underwent zona lysis. At 250 nM only 27% of the embryos developed normally; the rest exhibited major deformities. Arsenic showed total lethality at 500 and 750 nM; embryos in these groups were characterized by major deformities and a complete failure to undergo zona lysis. The TUNEL assay showed extremely high concentration of apoptotic cells in the lethal range (500nM) and little apoptosis in the control. The study underscores the sensitivity of preimplantation stage embryos to presence of even relatively small amounts of arsenic and other xenobiotics in the luminal fluid. (platform)

Cyanide Adducts with Human Plasma Proteins: Albumin as a Potential Exposure Surrogate

Cyanide (CN) is a ubiquitous environmental toxicant. The measurement of CN in whole blood is a common exposure assay, but values are error prone because of CN's rapid metabolism and clearance (t1/2 < 1 h) from this compartment. This study was undertaken to determine whether CN forms covalent adduct(s) with plasma proteins that could serve as stable biomarker(s) and potential surrogate(s) of exposure. When added to human blood, plasma, or serum, CN formed covalent adducts with immunoglobulin G (IgG) and serum albumin (HSA) in the plasma fraction. Covalent adducts were not detected in the cellular, primarily erythrocyte, fraction. With human, mouse, and rabbit IgGs, the reaction with CN occurred at intra- and/or interchain disulfide linkages in the heavy and light chains. Digestion of CN-treated HSA with trypsin or the endoproteinase Lys-C at basic pH produced tautomeric 2-iminothiazoline-4-carboxylyl/2-aminothiazolidine-4-carboxylyl (itcCys) N-terminal peptides exclusively, consistent with prior model peptide/protein studies showing that under basic conditions internal S-cyanylated-Cys residues cyclize with concomitant release of the upstream peptide. The most readily detectable reaction of CN with purified HSA was at Cys34, the only Cys of the 35 present not connected as internal cystines. Because CN does not react with free sulfhydryl groups, it is probable that S-cyanylation at Cys34 occurs at those residues that carry GSH, Cys, or other small molecules as mixed disulfides. Relatively less detectable, modified Cys residues were also identified at positions 53, 124, 392, 477, and 487. When 14CN was added to human serum or whole blood at concentrations spanning a putative nontoxic to lethal range, stable adduct formation with HSA occurred in a linear, concentration-dependent reaction that was complete within 2 h. These attributes of the reaction, coupled with a plasma compartment location, suggest that quantitation of CN bound to HSA would provide a much more reliable assessment of exposure than does measurement of CN in blood.