Full recovery from a potentially lethal dose of mercuric chloride.

INTRODUCTION: Mercuric chloride poisoning is rare yet potentially life-threatening. We report a case of poisoning with a potentially significant amount of mercuric chloride which responded to aggressive management. CASE REPORT: A 19-year-old female presented to the Emergency Department with nausea, abdominal discomfort, vomiting of blood-stained fluid, and diarrhea following suicidal ingestion of 2-4 g of mercuric chloride powder. An abdominal radiograph showed radio-opaque material within the gastric antrum and the patient's initial blood mercury concentration was 17.9 µmol/L (or 3.58 mg/L) at 3 h post-ingestion. Given the potential toxicity of inorganic mercury, the patient was admitted to the intensive care unit and chelation with dimercaprol was undertaken. Further clinical effects included mild hemodynamic instability, acidosis, hypokalemia, leukocytosis, and fever. The patient's symptoms began to improve 48 h after admission and resolved fully within a week. DISCUSSION: Mercuric chloride has an estimated human fatal dose of between 1 and 4 g. Despite a reported ingestion of a potentially lethal dose and a high blood concentration, this patient experienced mild to moderate poisoning only and she responded to early and appropriate intervention. Mercuric chloride can produce a range of toxic effects including corrosive injury, severe gastrointestinal disturbances, acute renal failure, circulatory collapse, and eventual death. Treatment includes close observation and aggressive supportive care along with chelation, preferably with 2,3-dimercapto-1-propane sulfonate or 2,3-meso-dimercaptosuccinic acid.

Ricin as a weapon of mass terror--separating fact from fiction.

In recent years there has been an increased concern regarding the potential use of chemical and biological weapons for mass urban terror. In particular, there are concerns that ricin could be employed as such an agent. This has been reinforced by recent high profile cases involving ricin, and its use during the cold war to assassinate a high profile communist dissident. Nevertheless, despite these events, does it deserve such a reputation? Ricin is clearly toxic, though its level of risk depends on the route of entry. By ingestion, the pathology of ricin is largely restricted to the gastrointestinal tract where it may cause mucosal injuries; with appropriate treatment, most patients will make a full recovery. As an agent of terror, it could be used to contaminate an urban water supply, with the intent of causing lethality in a large urban population. However, a substantial mass of pure ricin powder would be required. Such an exercise would be impossible to achieve covertly and would not guarantee success due to variables such as reticulation management, chlorination, mixing, bacterial degradation and ultra-violet light. By injection, ricin is lethal; however, while parenteral delivery is an ideal route for assassination, it is not realistic for an urban population. Dermal absorption of ricin has not been demonstrated. Ricin is also lethal by inhalation. Low doses can lead to progressive and diffuse pulmonary oedema with associated inflammation and necrosis of the alveolar pneumocytes. However, the risk of toxicity is dependent on the aerodynamic equivalent diameter (AED) of the ricin particles. The AED, which is an indicator of the aerodynamic behaviour of a particle, must be of sufficiently low micron size as to target the human alveoli and thereby cause major toxic effects. To target a large population would also necessitate a quantity of powder in excess of several metric tons. The technical and logistical skills required to formulate such a mass of powder to the required size is beyond the ability of terrorists who typically operate out of a kitchen in a small urban dwelling or in a small ill-equipped laboratory. Ricin as a toxin is deadly but as an agent of bioterror it is unsuitable and therefore does not deserve the press attention and subsequent public alarm that has been created.

Diethylene glycol poisoning.

INTRODUCTION: Diethylene glycol (DEG) is a clear, colorless, practically odorless, viscous, hygroscopic liquid with a sweetish taste. In addition to its use in a wide range of industrial products, it has also been involved in a number of prominent mass poisonings spanning back to 1937. Despite DEG's toxicity and associated epidemics of fatal poisonings, a comprehensive review has not been published. METHODS: A summary of the literature on DEG was compiled by systematically searching OVID MEDLINE and ISI Web of Science. Further information was obtained from book chapters, relevant news reports, and web material. AIM: The aim of this review is to summarize all main aspects of DEG poisoning including epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, toxicity of DEG, diagnosis, and management. EPIDEMIOLOGY: Most of the documented cases of DEG poisoning have been epidemics (numbering over a dozen) where DEG was substituted in pharmaceutical preparations. More often, these epidemics have occurred in developing and impoverished nations where there is limited access to intensive medical care and quality control procedures are substandard. TOXICOKINETICS: Following ingestion, DEG is rapidly absorbed and distributed within the body, predominantly to regions that are well perfused. Metabolism occurs principally in the liver and both the parent and the metabolite, 2-hydroxyethoxyacetic acid (HEAA), are renally eliminated rapidly. MECHANISMS OF TOXICITY: Although the mechanism of toxicity is not clearly elucidated, research suggests that the DEG metabolite, HEAA, is the major contributor to renal and neurological toxicities. CLINICAL FEATURES: The clinical effects of DEG poisoning can be divided into three stages: The first phase consists of gastrointestinal symptoms with evidence of inebriation and developing metabolic acidosis. If poisoning is pronounced, patients can progress to a second phase with more severe metabolic acidosis and evidence of emerging renal injury, which, in the absence of appropriate supportive care, can lead to death. If patients are stabilized, they may then enter the final phase with various delayed neuropathies and other neurological effects, sometimes fatal. TOXICITY OF DEG: Doses of DEG necessary to cause human morbidity and mortality are not well established. They are based predominantly on reports following some epidemics of mass poisonings, which may underestimate toxicity. The mean estimated fatal dose in an adult has been defined as approximately 1 mL/kg of pure DEG. MANAGEMENT: Initial treatment consists of appropriate airway management and attention to acid-base abnormalities. Prompt use of fomepizole or ethanol is important in preventing the formation of the toxic metabolite HEAA; hemodialysis can also be critical, and assisted ventilation may be required. CONCLUSIONS: DEG ingestion can lead to serious complications that may prove fatal. Prognosis may be improved, however, with prompt supportive care and timely use of fomepizole or ethanol.

The adverse effects of hydrogen cyanamide on human health: an evaluation of inquiries to the New Zealand National Poisons Centre.

INTRODUCTION: Hydrogen cyanamide is used in New Zealand to induce bud break in kiwifruit vines. The aim of this investigation was to evaluate the calls received by the New Zealand National Poisons Centre (NZNPC) attributed to acute hydrogen cyanamide exposure, and to ascertain the clinical effects of such exposures. METHODS: Call data from the NZNPC telephone collection databases regarding human hydrogen cyanamide exposures were analyzed retrospectively for the years 1990-2006. RESULTS: There were 68 human exposures, 69% were male and 22% female; 88% were adults and there were no suicide attempts. Common exposure routes were inhalation (56%) and skin contact (28%). The workplace accounted for 45% of calls. The predominant toxic effects were nausea and vomiting (29%), headache (22%), contact dermatitis (19%), and erythema (18%). DISCUSSION: Reported symptoms and signs were consistent with the expected effects of hydrogen cyanamide exposure. Other reports of similar exposures describe higher degrees of illnesses among workers using hydrogen cyanamide, which might have been because of lack of training, inadequate access to personal protective equipment, and the absence of engineering controls. CONCLUSIONS: Based on the calls received by the NZNPC, acute exposure to hydrogen cyanamide in the workplace or acute exposure to those living within the vicinity of its use may not pose a significant immediate threat to human health.

The use of myocardial and testicular end points as a basis for estimating a proposed tolerable daily intake for sodium monofluoroacetate (1080).

This paper presents the development of a tolerable daily intake (TDI) for sodium monofluoroacetate (1080) using the quantal myocardial and testicular toxicity end points derived from the traditional NOAEL and newer benchmark dose (BMD) methods. 1080 is a highly toxic vertebrate pesticide that has been proven to be effective in controlling possums and other pests. By convention, the TDIs are derived using the traditional no-observed-adverse-effect-level (NOAEL) and applying appropriate default uncertainty factors (UF). In addition to the default UF, a statistically derived UF was also employed in deriving the TDI. The TDIs derived from the NOAEL and BMD approach, 0.075 and 0.10 mg/kg bw/day, respectively, were compared. The resulting TDI estimates using the BMDL, a statistical lower confidence bound on the BMD, were generally consistently slightly higher than those derived using the NOAEL approach. Based on the best fit of modelled dose-response data, a TDI of 0.03 micro g/kg bw/day is proposed for human health risk assessment of 1080.

A benchmark dose analysis for sodium monofluoroacetate (1080) using dichotomous toxicity data.

The use of a benchmark dose (BMD) as an alternative to a no-observed-adverse-effect-level (NOAEL) approach was investigated as a means to improve current risk assessment values of sodium monofluoroacetate (1080). The feasibility of implementing the two approaches was investigated for three critical toxicological end points, namely cardiomyopathy, testicular toxicity and teratogenic effects identified from the few available critical studies. The BMD provides better representation of the dose-response relationship, offering an advantage over the current NOAEL approach. The calculated BMDs and lower-bound confidence limits (BMDLs) for the three end points were estimated using the Weibull, probit and quantal linear models for each end point. All models passed the chi2 test statistics (p > or = 0.1) for all three toxicity endpoints tested. A benchmark response (BMR) of 10% (extra risk) was chosen and the Akaike's information criterion (AIC) was used in selecting the appropriate model. The BMDL estimates derived were found to be generally slightly higher but comparable to the NOAEL for those same endpoints. The BMD(10) and BMDL(10) for cardiomyopathy and testicular effects were 0.21 mgkg(-1) bw and 0.10 mgkg(-1) bw, respectively. These values are proposed for use in the eventual determination of the tolerable daily intake (TDI) for 1080.