Alkyl Mercury-Induced Toxicity: Multiple Mechanisms of Action.

There are a number of mechanisms by which alkylmercury compounds cause toxic action in the body. Collectively, published studies reveal that there are some similarities between the mechanisms of the toxic action of the mono-alkyl mercury compounds methylmercury (MeHg) and ethylmercury (EtHg). This paper represents a summary of some of the studies regarding these mechanisms of action in order to facilitate the understanding of the many varied effects of alkylmercurials in the human body. The similarities in mechanisms of toxicity for MeHg and EtHg are presented and compared. The difference in manifested toxicity of MeHg and EtHg are likely the result of the differences in exposure, metabolism, and elimination from the body, rather than differences in mechanisms of action between the two.

Severe Illness from Methyl Bromide Exposure at a Condominium Resort--U.S. Virgin Islands, March 2015.

On March 22, 2015, the Agency for Toxic Substances and Disease Registry (ATSDR) was notified by the U.S. Environmental Protection Agency (EPA) of four cases of suspected acute methyl bromide toxicity among family members vacationing at a condominium resort in the U.S. Virgin Islands. Methyl bromide is a pesticide that has been banned in the United States for use in homes and other residential settings. An investigation conducted by the U.S. Virgin Islands Department of Health (VIDOH), the U.S. Virgin Islands Department of Planning and Natural Resources (DPNR), and EPA confirmed that methyl bromide had been used as a fumigant on March 18 in the building where the family had been residing, 2 days before they were transported to the hospital; three family members had life-threatening illness. On March 25, 2015, a stop-use order for methyl bromide was issued by DPNR to the pest control company that had performed the fumigation. Subsequent investigation revealed that previous fumigation with methyl bromide had occurred on October 20, 2014, at the same condominium resort. In addition to the four ill family members, 37 persons who might have been exposed to methyl bromide as a result of the October 2014 or March 2015 fumigations were identified by VIDOH and ATSDR. Standardized health questionnaires were administered to 16 of the 20 persons for whom contact information was available; six of 16 had symptoms consistent with methyl bromide exposure, including headache and fatigue. Pest control companies should be aware that use of methyl bromide is banned in homes and other residential settings, and clinicians should be aware of the toxicologic syndrome that exposure to methyl bromide can cause.

The elderly as a sensitive population in environmental exposures: making the case.

The US population is aging. CDC has estimated that 20% of all Americans will be 65 or older by the year 2030. As a part of the aging process, the body gradually deteriorates and physiologic and metabolic limitations arise. Changes that occur in organ anatomy and function present challenges for dealing with environmental stressors of all kinds, ranging from temperature regulation to drug metabolism and excretion. The elderly are not just older adults, but rather are individuals with unique challenges and different medical needs than younger adults. The ability of the body to respond to physiological challenge presented by environmental chemicals is dependent upon the health of the organ systems that eliminate those substances from the body. Any compromise in the function of those organ systems may result in a decrease in the body's ability to protect itself from the adverse effects of xenobiotics. To investigate this issue, we performed an organ system-by-organ system review of the effects of human aging and the implications for such aging on susceptibility to drugs and xenobiotics. Birnbaum (1991) reported almost 20 years ago that it was clear that the pharmacokinetic behavior of environmental chemicals is, in many cases, altered during aging. Yet, to date, there is a paucity of data regarding recorded effects of environmental chemicals on elderly individuals. As a result, we have to rely on what is known about the effects of aging and the existing data regarding the metabolism, excretion, and adverse effects of prescription medications in that population to determine whether the elderly might be at greater risk when exposed to environmental substances. With increasing life expectancy, more and more people will confront the problems associated with advancing years. Moreover, although proper diet and exercise may lessen the immediate severity of some aspects of aging, the process will continue to gradually degrade the ability to cope with a variety of injuries and diseases. Thus, the adverse effects of long-term, low-level exposure to environmental substances will have a longer time to be manifested in a physiologically weakened elderly population. When such exposures are coupled with concurrent exposure to prescription medications, the effects could be devastating. Public health officials must be knowledgeable about the sensitivity of the growing elderly population, and ensure that the use of health guidance values (HGVs) for environmental contaminants and other substances give consideration to this physiologically compromised segment of the population.

Inorganic: the other mercury.

There is a broad array of mercury species to which humans may be exposed. While exposure to methylmercury through fish consumption is widely recognized, the public is less aware of the sources and potential toxicity of inorganic forms of mercury. Some oral and laboratory thermometers, barometers, small batteries, thermostats, gas pressure regulators, light switches, dental amalgam fillings, cosmetic products, medications, cultural/religious practices, and gold mining all represent potential sources of exposure to inorganic forms of mercury. The route of exposure, the extent of absorption, the pharmacokinetics, and the effects all vary with the specific form of mercury and the magnitude and duration of exposure. If exposure is suspected, a number of tissue analyses can be conducted to confirm exposure or to determine whether an exposure might reasonably be expected to be biologically significant. By contrast with determination of exposure to methylmercury, for which hair and blood are credible indicators, urine is the preferred biological medium for the determination of exposure to inorganic mercury, including elemental mercury, with blood normally being of value only if exposure is ongoing. Although treatments are available to help rid the body of mercury in cases of extreme exposure, prevention of exposure will make such treatments unnecessary. Knowing the sources of mercury and avoiding unnecessary exposure are the prudent ways of preventing mercury intoxication. When exposure occurs, it should be kept in mind that not all unwanted exposures will result in adverse health consequences. In all cases, elimination of the source of exposure should be the first priority of public health officials.

Mercury exposure: evaluation and intervention the inappropriate use of chelating agents in the diagnosis and treatment of putative mercury poisoning.

Public awareness of the potential for mercury to cause health problems has increased dramatically in the last 15 years. It is now widely recognized that significant exposure to all forms of mercury (elemental/metallic and both inorganic and organic compounds) can result in a variety of adverse health effects, including neurological, renal, respiratory, immune, dermatologic, reproductive, and developmental sequellae. And while the various media have made the general population cognizant of the need to avoid unnecessary exposure to this naturally occurring element, there has also evolved a growing tendency to attribute unexplainable neurologic, as well as other, signs and symptoms to mercury, whether or not significant exposure to mercury has actually occurred. For the physician, making a diagnosis of mercury intoxication can be difficult, because many of the clinical signs and symptoms of mercury exposure can also be attributed to any number of causes, including undiagnosed neurological diseases, pharmacotherapy, vitamin or mineral deficiencies, and psychological stress. The physician must be able to recognize the clinical manifestations of mercury intoxication, and understand the importance of biological markers in making a definitive diagnosis of mercury poisoning. In a desire to treat the patient complaining of symptoms similar to some that can be caused by mercury, a growing number of physicians, particularly those in alternative medicine fields, result to chelation to "rid" the body of the mercury, believed to be the cause of the ailments. And although the use of chelation is increasing, controlled studies showing that this procedure actually improves outcome are lacking. If chelation therapy is considered to be indicated, the attending physician should communicate the risks of chelation to the patient before beginning treatment with metal-chelating drugs.

Too much of a good thing (fish): methylmercury case study.

Methylmercury is an environmental toxicant that has been shown to cause neurologic damage in both children and adults if ingested in sufficiently high quantities. Poisoning outbreaks in Japan and Iraq have revealed serious effects on developing fetuses at levels far below those that produced clinical signs or symptoms in the mothers. Therefore, health guidance values for methylmercury, such as the chronic oral minimal risk level (MRL) of the Agency for Toxic Substances and Disease Registry, have been set by governmental agencies at levels that would protect fetuses. Since adults are less sensitive than fetuses, chronic intakes within an order of magnitude of the MRL generally have been considered to represent no health risk to otherwise healthy adults. The present report of suspected mercury intoxication in a 53-year-old female suggests that some individuals might be susceptible to adverse health impacts of methylmercury at intakes just 7 to 15 times the MRL.

Elemental mercury poisoning in occupational and residential settings.

In its elemental form, mercury is the only metal that is in a liquid state at room temperature. It readily volatilizes at standard temperature and pressure, and its presence in open containers can result in biologically significant air concentrations in unventilated or poorly ventilated spaces. In recent years, elemental mercury has proven to be a potential source of toxicosis through either unintentional exposure or exposure resulting from inappropriate handling of liquid mercury acquired from school science laboratories or abandoned industrial facilities or warehouses. The shiny, silvery appearance of mercury in its liquid form makes it particularly enticing to children, and its insolubility in water and tendency to form beads when disturbed add to its mystique. This paper presents two case studies in which excessive exposure to elemental mercury vapor has resulted in adverse health effects in the exposed individuals: one in the workplace and one in a residential setting. These case studies serve to emphasize that primary care physicians, public health officials, and science educators need to recognize the potential risk posed by inhalation exposure to mercury vapors, and health practitioners need to be able to recognize the health signs and symptoms of such exposure. Public health professionals and those in charge of public and private education facilities should also be keenly aware of the necessity of prompt mitigation of human exposure should a spill or other mercury exposure scenario occur.

Organic mercury compounds: human exposure and its relevance to public health.

Humans may be exposed to organic forms of mercury by either inhalation, oral, or dermal routes, and the effects of such exposure depend upon both the type of mercury to which exposed and the magnitude of the exposure. In general, the effects of exposure to organic mercury are primarily neurologic, while a host of other organ systems may also be involved, including gastrointestinal, respiratory, hepatic, immune, dermal, and renal. While the primary source of exposure to organic mercury for most populations is the consumption of methylmercury-contaminated fish and shellfish, there are a number of other organomercurials to which humans might be exposed. The antibacterial and antifungal properties of organomercurials have resulted in their long use as topical disinfectants (thimerosal and merbromin) and preservatives in medical preparations (thimerosal) and grain products (both methyl and ethyl mercurials). Phenylmercury has been used in the past in paints, and dialkyl mercurials are still used in some industrial processes and in the calibration of certain analytical laboratory equipment. The effects of exposure to different organic mercurials by different routes of exposure are summarized in this article.