Movement, Distribution and Fate of Toxins

STOP - You must read Chapter 9 and 17 before doing this lesson

Introduction

The route used by chemicals to enter our bodies play important roles in determining toxicity. The major routes of absorption of toxins are inhalation, ingestion, and skin contact. Inhalation is the fastest route and dermal (skin) absorption the slowest. For toxins to enter the body they have to cross barriers and membranes in our bodies. How water soluble or lipid soluble is a substance will play a major role in absorption and excretion from the human body.

Water soluble chemicals tend to have access to most cells in the body because aqueous solutions bathe all cells. However, since the cell membrane is a lipid bilayer, aqueous substance may have to use different transport mechanism, such as passive transport, facilitated transport or active transport to get inside the cells. Lipid soluble chemicals in the other hand can cross the cells lipid bilayer easier than water soluble compounds. Once inside the body oil soluble toxins penetrates into tissues and cells. Lipid soluble chemicals can also be stored in the body fat.

Movement of Toxins

Toxic chemicals can move through the food chain from one trophic level to the next. This movement of toxins can lead to bioaccumulation and biomagnification of toxic chemicals in different organisms at each trophic level of the food chain.

Bioaccumulation- it is the selective absorption and storage of a great variety of molecules. Toxins that are rather dilute in the environment can reach dangerous levels inside cells and tissues through bioaccumulation.
Persistent Organic Chemicals such as PCBs bioaccumulate. The diagram on the right shows the degree of concentration in each level of the Great Lakes aquatic food chain for PCBs (in parts per million, ppm). The highest levels are reached in the eggs of fish-eating birds such as herring gulls.

Biomagnification - effects of toxins are magnified (increase) in the environment through food chains. It occurs when the toxic burden of a large number of organism at a lower trophic level is accumulated and concentrated by a predator in a higher trophic level. The small fish and zooplankton eat a vast quantities of phytoplankton. In doing so, any toxic chemicals accumulated by the phytoplankton are further concentrated in the bodies of the animals that eat them. This is repeated at each step in the food chain. This process of increasing concentration through the food chain is known as biomagnification. The top predators at the end of a long food chain, such as lake trout, large salmon and fish-eating gulls, may accumulate concentrations of a toxic chemical high enough to cause serious deformities or death even though the concentration of the chemical in the open water is extremely low. The concentration of some chemicals in the fatty tissue of top predators can be millions of times higher than the concentration in the open water.

Chemical Interactions

Toxic chemicals in the environment exists as a mixture of chemicals which can lead to interactions among then. Modern society is dependent on thousands of chemicals, and most of us are exposed to many different substances in many different ways. Predicting the effect of these chemicals is therefore very difficult. This can be even more difficult with the fact that chemical substances interact in a variety of ways. There are different types of chemical interaction that can take place in the body or the environment. These are:

Additive effect - is the situation in which the combined effect of two chemicals is equal to the sum of the effect of each agent given alone. It is an effect that is the sum of the individual responses. For example, 2 + 3 = 5.

Synergistic effect - it is a super-additive effect. The combined effect of two chemicals is much greater than the sum of the effect of each agent given alone. For example, 2 + 3 = 10. One of the most familiar examples is the combination of barbiturate tranquilizers and alcohol. Although neither taken alone in small concentrations is dangerous, the combination can be deadly. Air pollutants can also act synergistically. For example, sulfur dioxide gas and particle matter (airborne particles) inhaled together can reduce the airflow through the lung. The combine response is much greater that the sum of the individual responses.

Potentiation effect - it occurs when a chemical with no toxic effect combines with a toxic chemical and makes the toxicant even more harmful. For example, 0 + 2 = 8. Isopropyl alcohol (rubbing alcohol) has no effect in the liver, but when combined with carbon tetrachloride, it greatly increase the toxicity of the latter.

Antagonism effect - it is when chemicals negate each other's effects. When two chemicals are given together interfere with each other actions or one interfere with the action of the other. It is the principle of antidotes in medicine. For example, 4 + 6 = 2.

Tolerance effect - Is the decrease of response to a toxic effect of a chemical resulting from a prior exposure to that chemical or to a structurally related chemical. When the tolerance is due to exposure to a structurally related chemical it is also known as cross-tolerance. For example, animals exposed to non lethal doses of ozone may survive a lethal dose of ozone weeks later. Also, animals exposed to a non lethal dose of nitrogen dioxide may survive a lethal dose of ozone weeks later (cross-tolerance).

Measuring Toxicity

The effect a chemical has on the body is determined by its reactivity, as well as the amount one is exposed (known as dose), and the duration of exposure (how long one is exposed to a particular substance). Highly reactive chemicals generally have a greater effect on the body than those that are less reactive. Also, the effect is determined by the dose. In general, the greater the dose the greater the effect.

Dose-response curve - To study the effect of dosage, toxicologist often expose laboratory animals to varying amounts of a substance, determining the response at each level. The resulting graph is called dose-response curve. To compare one chemical to another, toxicologist often determine the dose that kills half of the test animals. This is call LD50 or lethal dose for 50% of the animals. By comparing LD50 values, scientists can judge the relative toxicity of two chemicals. For example, a chemical with an LD50 of 200 milligrams per kilogram of body weight is half as toxic as one with an LD50 of 100 milligrams. The lower the LD50, the more toxic a chemical. (See table below).

Approximate Acute LD50
of a variety of Chemical Agents
Material LD50 (mg/kg)
Sucrose
(sugar cane) 29700
Sodium bicarbonate
(baking soda) 4220
Sodium chloride
(table salt) 3000
Ethanol
(grain alcohol) 2080
Caffeine 192
Sodium cyanide 6.4
Nicotine 1
VX
(nerve agent) 0.14
Botulinus toxin 0.00001

Approximate Acute LD50 of a variety of Chemical Agents
Material	LD50 (mg/kg)
Sucrose (sugar cane)	29700
Sodium bicarbonate (baking soda)	4220
Sodium chloride (table salt)	3000
Ethanol (grain alcohol)	2080
Caffeine	192
Sodium cyanide	6.4
Nicotine	1
VX (nerve agent)	0.14
Botulinus toxin	0.00001

The duration of exposure is the amount of time an individual or laboratory animal is exposed to a toxic substance. Exposure generally fall into two categories: acute, or short-term exposures, generally last less than 24 hours; chronic, or long term exposures, last more than three months. Obviously, these are very broad categories, and many intermediate exposure possibilities exist. Studies show that for many toxicants, acute exposure results in very different effects than those resulting from repeated (chronic) exposure. For example, an acute exposure to benzene may result in a transient bout of depression. Repeated, chronic exposure may result in leukemia, a cancer of the white blood cells.

Routes of Exposure - The toxicity of a chemical is also dependent on the route of exposure, that is, how it gets into a body. As mentioned before, three route of exposure are most common: inhalation, ingestion, and dermal exposure.

Inhalation exposure results from breathing a chemical. Smokers inhale many potentially toxic substances, as do workers in chemical factories or commuters in heavy traffic. Toxic substances that are inhaled enter the blood-stream via the lungs and quickly become dispersed throughout the body. Inhalation is the most rapid route for chemicals to enter the body.

Ingestion occurs when toxic substances enter our bodies or the bodies of other animals in the food we eat and the water or liquids we drink. Ingestion is the next most rapid form of exposure. Toxicants, however can be neutralized by acids in the stomach and enzymes in the small intestine.

The slowest and least effective route of exposure is the skin. Toxic substances spilled on the skin may penetrate this layer and enter the blood vessels. As general rule, the more readily a toxic substance is absorbed, the more effect it has.

EPA: Pesticides and Toxics web site.

Persistent Organic Pollutants web site.

Toxic Chemicals and Health