Friday, January 24, 2014

Acute verses chronic toxicity and synergism - long term concerns for West Virginia

Toxicology is the basically the science of poisons. A more precise definition would be "the study of the adverse effects of chemicals or physical agents on living organisms.” Adverse effects include not only death or illness, but also subtle changes that may not be recognized for months, or even years, or until genetic material is passed on to progeny. Many chemicals can be used safely if exposure of people or susceptible organisms is kept below defined tolerable limits and handled with appropriate precautions. However, there are also some substances where no tolerable limit can be defined, in which case one needs to avoid any exposure. 

Toxicity is the relative ability of a substance to cause harm.  If it takes a large quantity of the substance to produce a harmful effect, that substance is said to have a low toxicity.  If only tiny amounts of the substance have a harmful effect, it is considered highly toxic.   But how precisely does one determine a substances toxicity and if there is a safe level of exposure ?

First we need to understand the difference between exposure and dose. Exposure is a function of the amount (or concentration) of the chemical involved and the duration of its interaction with people or organisms at risk. Dose is the actual amount of the substance that enters the body.  Both of these concepts are important when determining the toxicity of a material. 

There are several different ways that a person can be exposed to a toxin. One common method of exposure is skin or dermal absorption. This occurs with chemicals that can penetrate through healthy, intact skin, like organic mercury or phenol. Also common is exposure through inhalation. Gases and vapors are easily inhaled, while the likelihood of the inhalation of particles depends upon their size and shape. The smaller the particle, the further into the respiratory tract it can go.

Ingestion occurs when a substance is swallowed. Airborne particles breathed through the mouth or cleared by the cilia of the lungs will be ingested. In the workplace, accidental ingestion of toxins is generally fairly rare, though in the outdoor environment it can be a serious problem, especially with children. Young children have a tendency to swallow small amounts of soil while playing, and if they display mouthing behaviors (putting their fingers, thumbs or objects into their mouth) even larger amounts of soil can be ingested. When chemicals are spilled into the environment ingestion through drinking water is often the primary exposure route.

Less common is exposure through injection.  This typically occurs with medical workers who work with needles, scalpels and other sharp implements that can be contaminated with biomedical waste. Other possible injection exposures include venomous bites or stings, as with snakes, scorpions and spiders.

For the people in West Virginia the primary exposure routes of concern were/are ingestion via the drinking water supply and inhalation (remember that black licorice smell that people were reporting - that is an exposure).   

Once you have established the routes of exposure, one of the primary goals of toxicology is to define exposure limits. In deciding on what constitutes a tolerable exposure, the chief problem is often in deciding what exactly constitutes an injury or adverse effect.  An adverse effect can basically be defined as an abnormal, undesirable, or harmful effect to an organism, indicated by some result such as mortality, altered food consumption, altered body and organ weights, altered enzyme levels, or visible pathological change.

The amount of exposure to a substance that is required to produce an adverse effect varies over a very wide range depending on the chemical, the form in which exposure occurs and the susceptibility of an exposed organism. 

Another complicating factor is the synergistic effect. A synergistic effect is any effect of two, or more, chemicals acting together which is greater than the simple sum of their effects when acting alone: such chemicals are said to show synergism. We now know for sure that there were at least seven chemicals (not including the water component of the crude MCHC) in the tank that leaked into the Elk River, so one of the unknowns at this point is whether there will be any synergistic effects.

Bioaccumulation of toxins also confounds the establishment of acceptable exposure limits. Some substances may exist in the environment in very small quantities, but will accumulate in living organisms as they are exposed to contaminated water or soil (bioaccumulation). Then as larger predators ingest prey that has absorbed a small amount of the substance, they absorb an ever increasing amount of that toxin, eventually reaching the point where adverse effects are encountered. The dose ingested increases as you move up the food web (biomagnification), so that while prey organisms show no outward signs of exposure, top predators may end up with very significant health effects.  

Finally one also needs to evaluate the types of harm caused by both short-term and long-term exposure. This is where the possible effects of exposures in West Virginia get more worrisome. Substances that have adverse effects at the time of exposure or immediately after are said to be acutely toxic. An acute effect is abrupt and immediately detectable. For example, inhaling bleach fumes will make you start coughing immediately.  Drinking a large does of arsenic will cause intense gastric distress almost immediately and death shortly thereafter. In West Virginia, skin rashes and nausea were some of the signs of an acute exposure the chemicals in the drinking water. It is usually very easy to correlate cause and effect, and the relationship between the exposure and the resulting symptoms is usually obvious. Acute effects can be minor, such as coughing, major, such as lung damage, or fatal. Sometimes acute effects are reversible and once exposure is terminated, the symptoms cease.

Chronic toxicity, on the other hand, refers to the long-term effects of exposure that may not appear for months, years or even decades after the exposure occurred. Chronic effects often involve low levels of exposure resulting in very small doses over longer periods of time. Like drinking or breathing tiny amounts of a chemical every day for 30 years. Many of these substances have long latency periods (time intervals between first exposure and the development of the chronic effect). For example the latency period between exposure to asbestos and the development of mesothelioma according to one study is 14 to 72 years (mean 48.7, median 51). For many chemicals, like the ones that spilled into the Elk River, the chronic effects are unknown. For one reason, it can be very hard to establish the relationship between substances and their effects due to the long periods of time involved. Chronic effects are not reversible.

So now the people of Charleston have unwillingly become a cohort in an epidemiology experiment where we may, some years down the road, finally see if there are going to be long term health impacts to their exposure. Epidemiology is the study of the occurrence of adverse health effects in humans where researchers look for patterns of exposure to chemicals, radiation, or even patterns of diet and attempt to relate these patterns to incidence of disease, damage or impairment. Unlike toxicology, which examines the response of individuals to substances, epidemiology is concerned with groups.

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