General Toxicology

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Environmental Science

Module 3

General Toxicology

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Contents

1. What is Toxicology?2. Types of toxic effect

3. Effect of Dose4. Types of Exposure5. Routes of Exposure6. Bioaccumulation

Environmental ScienceDr. Nazmul A. Khan, PhDNorth South University

General Toxicology

i. Toxicology

Toxicology is the study of harmful effects to living organisms from substances which are foreign to them. The toxins may be naturally occurring in the environment or synthetic chemicals. The following definitions will describe some basic concepts in toxicology.

Toxicity can be generally broken down into two categories:

Acute toxicity refers to the rapid development of symptoms/effects after the intake of relatively high doses of the toxicant. Acute toxicity refers to immediate harmful effects generated by sufficiently large doses.

Chronic toxicity refers to the harmful effects of long-term exposure to relatively low doses of toxicant. This would include traces of pesticides in foods, air pollution, etc.

A single compound may generate both acute and chronic toxic effects depending on the dose and duration of exposure.

There are two general types of toxic effect:

Lethal Effects: resulting in the death of individuals

Sub-lethal Effects: other effects not directly resulting in death

There are four basic types of damage caused by toxic materials:

1. Physiological damage: reversible/irreversible damage to the health of the organism

2. Carcinogenesis: induction of cancer

3. Mutagenesis: induction of genetic damage / mutation(s)

4. Teratogenesis: induction of birth defects


ii. Epidemiology

In contrast to the rapid effects observed in toxicology, epidemiology examines the relationship between exposure to a specific toxic agent and the development of health problems in a group of humans. In essence epidemiology examines the health patterns in humans with respect to an agent/toxicant. An example might include the health effects of chronic, low-level exposure to pesticides found on un-washed fruit. Simply put, epidemiology looks for trends and effects in human health following exposure to a specific compound or other toxic agents.

iii. Effect of Dose

Relative toxicity of a substance is often expressed in the dose-response relationship. This simply relates the dose (quantity administered) of a substance to the response generated in a test organism. In order to relate this information to humans, dose is often expressed as dose per organism weight, or mg / kg (where mg represents toxicant dose and kg expresses animal weight.). It is also important to consider the method of application, whether oral, dermal, intravenous, etc., as these may greatly affect relative toxicity of a given compound.

Very commonly the quantity of a toxicant required to cause death is used as an indication of relative toxicity. This is most often expressed as: LD50. This expresses the mg/kg dose required to kill 50% of a test population. For example the LD50 for sugar is >10,000 mg/kg, while for the botulism toxin is ~ 0.0001 mg/kg. Obviously the botulinum toxin is highly toxic even in relatively low doses. An alternative measurement of dose response is the ED50 where there an effect on 50% of the test population. This represents a measurement of sub-lethal effects.

Some Example LD50Values

Substance LD50 (mg/kg)

Sugar >10,000

Caffeine 100


Strychnine sulfate 2

Nicotine 1

Rattlesnake venom 0.1

Botulism toxin 0.0001

Dose-response curves are generated for various agents by plotting "percent of population affected vs. Dose (mg/kg). When examining such graphs, often there is a minimum concentration (or "threshold") of dose below which there is no observable effect in the test population. This is referred to as the NOEL (no observable effects limit).

With respect to human safety, NOEL dose information is often obtained from animal experimentation and then divided by a "safety factor" (i.e. 100) in order to establish safe levels for humans. This generates two kinds of values: ADI (acceptable daily intake) and MDD (maximum daily dose). While these values suggest a large margin of safety, in reality it is quite possible that the more sensitive individuals in a population may still suffer ill effects within the dose limits set by these guidelines.

Pharmaceutical safety / effectiveness can be indicated by the pharmaceutical TI (therapeutic index). The therapeutic index is the ratio of LD50 / ED50. A high TI value indicates an effective treatment at low doses and a lethal effect at higher doses. A low TI value indicates an ineffective treatment at low doses with lethality at the same low levels. The objective of using the therapeutic index is to have a pharmaceutical that is highly effective at low doses with minimal toxic effects.

iv. Exposure Types: Typically exposures can be classified according to the duration of the exposure. There are four main categories of exposure:


Acute Exposure: describes exposures over a short period of the life of an individual (which may be relatively intense). An acute exposure is often referred to as being less than 24 hours duration.

Subacute Exposure: describes exposures over a relatively short period of time, often less than one month.

Chronic Exposure: describes repeated exposures for a "significant" portion of an individual’s life-span. (More than three months for mammals).

Subchronic Exposure: describes exposures shorter than chronic exposures but longer than subacute (1-3 months is typical for mammals).


v. Exposure Routes:

In order for a toxic agent to have an effect an individual (or population) must be exposed. There are several exposure routes: oral (mouth), dermal (through the skin), inhalation (breathing) and /or injection (subcutaneous, intravenous, intramuscular, intraperitoneal). The specific route of exposure may have a significant impact on relative toxicity: specific substances may even have substantially reduced or enhanced toxicity dependant upon the type of exposure.

It is rare for chemical interactions with living systems to occur in complete isolation. Often there are specific interactions between multiple agents / chemicals which can be quite different than the action of an individual toxicant. Generally, these interactions can be described as being:

1. additive: compounds X + Y combine toxicity proportionally (i.e. 2+3 = 5)

2. antagonistic: compounds X + Y combine to be less toxic than either individually (i.e. 2+3 = 1)

3. synergistic: compounds X + Y combine to be more toxic than either individually (i.e. 2+3 = 9)

With these distinctly different interactive effects being possible, it is often very difficult to anticipate combined effects purely on the basis of chemical structure or other isolated data. It is obviously much easier to acquire toxicity-effect data for individual compounds as opposed to complicated mixtures with many unknown interactions.

Data on individual toxicity's and safety can be obtained from a number of sources. MSDS (Material Safety Data Sheets) are listings that describe (in detail) the known potential hazards for many individual compounds. This type of information usually accompanies commercial chemicals and is also offered on numerous websites. MSDS information includes handling, equipment, safety measures and potential risks / hazards associated with a given substance and can be an excellent starting point for assembling information on a specific compound.

vi. Bioaccumulation

In general, the accumulation of a toxic agent into a living system is referred to as the process of bioaccumluation, while the


concentration of such an agent in living tissues is referred to as bioconcentration. An indicator of relative solubility in organic/water phases is the partition coefficient (Kow = [octanol] / [water] ) which demonstrates the affinity of a specific compound for polar/non-polar environments. Generally a partition coefficient of 4-7 indicates a compound will bioconcentrate to a high degree, while values >8 suggest the compound will bind so strongly to sediments that it is relatively unable to migrate into living tissues. Partition coefficients can therefore be used as indicators of potential assimilation of compounds into living tissues.

Another consideration for potential toxic compounds is biomagnification, which occurs as small organisms ingest and bioconcentrate specific toxins, which in turn are eaten and further bioconcentrated by larger organisms (i.e. insects eat pesticides, birds eat many insects, etc.).

The relative persistence of a specific toxic agent is often expressed as "half-life" (T0.5) or the length of time required for one half of a toxic material to be degraded / eliminated. There is a simple relationship: the longer the half-life of a given toxic agent, the greater the potential period of bioaccumulation / concentration.

vii. Risk Assessment

Risk assessment attempts to estimate the expected toxicity's or potential effects from a substance on an exposed human population. This is conducted by examining both toxicological and epidemiological data. Risk assessment is often used to help establish permissible levels of exposure to a specific material. As stated above, the NOEL limits are adjusted with a 100-fold safety factor to establish limits that are deemed "safe" for the majority of the population. While this may work for direct toxic effects, it may not be so simple for carcinogens.

In the United States the EPA limits exposures to potential carcinogens by simply assuming there is no threshold for the dose-response relationship. The EPA then determines the quantity of MDD an individual could be exposed to in a lifetime and sets a limit that this dose should not increase the probability of cancer in more than one in a million individuals.

Risk assessment is not an exact science: there are often powerful arguments put forward by various groups for both health and/or economic reasons to alter exposure limits. Careful scrutiny is required


when examining reports/data concerning toxicological information to establish relevance and non-bias in the results. No matter what safety levels are finally established for a specific compound, it is important to consider that a few individuals within a population will almost certainly suffer effects (lethal or sublethal) from exposure to doses that have no apparent effect on the majority of the population.


TOXICOLOGY of SOLID MATERIALS

Pesticides / Herbicides / PCBs / PAHs / Heavy Metals

i. Pesticides

Pesticides are simply chemicals / materials designed to selectively kill unwanted organisms. Pesticides are typically categorized on the basis of the target organism(s). The table below indicates various pesticide groups and the targeted organisms.

Selected Pesticide Types

Pesticide Group Organism Targeted

Bacteriocide Bacteria

Fungicide Fungus

Insecticide Insects

Herbicide Plants/weeds

Rodentocide Mice/rats

Since the earliest agrarian activities, people have attempted to improve yields and quality of the crops they harvested. Initial pest removal consisted of hand-picking weeds and other competitive growth from desired crops, but later civilizations employed chemicals such as arsenic-compounds (early Chinese, Romans) to reduce pests. Today, pesticides are used to help improve crop yields and enhance production by reducing a wide range of pests. Because of their extensive use in modern times, pesticides are a significant concern because humans are continually exposed to persistent traces/residues of these compounds through the foods they eat. The exposure may be direct (i.e. pesticides applied directly to food crops) or indirect (i.e.


http://xnet.rrc.mb.ca/davidb/solid1.htm

ingested by animals later consumed as food). One specific concern is the fact that pesticides (such as inorganic and organometallic compounds) are often quite toxic to humans at the levels needed to be effective against the target organisms. Because of this, both toxicology and persistence of pesticides (and other toxicants) must be closely examined.

One group of insecticides includes organochlorine compounds which have several characteristics. These compounds do not degrade easily (they are highly stable), they are soluble in fatty tissues, and have relatively low water solubility. These compounds also are relatively toxic to insects but less so to humans. An example of this type of typical organochlorine pesticide would be HCB (hexachlorobenzene). The combination of environmental persistence and affinity for fatty tissues make organochlorine compounds a continuing concern.

Another insecticide with both a high degree of notoriety and substantial health risks is DDT (para-dichlorodiphenyltrichloroethane). This compound was used extensively when it was first developed (during WW II) since it very effectively kills many disease-carrying insects and has a tremendous persistence in the area of application. DDT was used extensively to combat malaria (through the elimination of disease-carrying mosquitos) and to fight insect-borne diseases around the world. It was the overuse of DDT, however, that led to dangerous environmental levels to the extent that bird mortality was greatly affected and avian fetal effects (soft shell formation, mutagenesis) were occurring. In the 1960s when Canadian women showed elevated levels of DDT in breast milk there was great concern over the potential health effects. Currently, the use of DDT is now banned from almost all Western industrialized nations. This is slowly having a positive effect: the measured levels of DDT in breast milk of Canadian women had fallen to <10ng/g by 1992. In many developing nations however, heavy use of DDT continues, raising concerns over both health and safety. Two other examples of persistent organochlorine insecticides include toxaphene and chlorinated cyclopentadienes.

Modern Insecticides include both organophosphate and carbamate compounds. While the organophosphates are far less persistent than their DDT predecessors, these compound are far more acutely toxic to humans. In particular, the people who apply and use these compounds are at far greater risk than the general population. On the positive side, these compounds decompose in a matter of days or weeks. There are three main classes of organophosphates: Type


A, (phosphates) such as "dichlorvos", Type B, (phosphorothioates) such as "parathion" and Type C (phosphorodithioates) such as "malathion". Despite a lack of persistence, non-target organisms (such as honey bees) can be killed by these compounds. The carbamates also have a low environmental persistence, as well as a low dermal toxicity. Examples include "Carbofuran" and "Carbaryl". "Aldicarb" is highly toxic to humans.

http://www.planetecologie.org/ENCYCLOPEDIE/RubriqueMois/ChloreEnvt/images/pesticides.gif

Certain natural compounds are also used as insecticides, such as pyrethrins, extracted from chrysanthemum. Another example of a "natural pesticide" would include nicotine. These natural agents often have a toxic approaching that of natural A drawback to the use of natural compounds is that they are often unstable in sunlight. In general, a mixture of pest control strategies is the probably the most responsible and effective over the long term. Some of the methods could include biological control (using parasites for problem


organisms), chemical treatments (appropriate natural/synthetic chemicals) crop rotation to minimize pest development, and regulation to avoid introduction of new pests.

ii. Herbicides

Agents which kill plant materials are termed "herbicides". They may affect a broad spectrum of plants or be quite specific for an individual problem weed. Today’s market is largely dominated by organic herbicides which are pest-specific and less likely to persist for extended periods.

Triazines are a modern herbicide that is based on an aromatic ring structure. An example of this type of herbicide is Atrazine, which has been employed since the 1950s to reduce grassy weeds in corn and other crops. This herbicide is degraded by microbes yielding non-toxic metabolites. There is a draw-back, however: Atrazine is moderately soluble in water, and as a result can often be found in well-water (and other ground-water systems) in areas where its used. The removal of atrazine from potable water requires the use of PAC (powdered activated carbon) during filtration. While low concentrations of this agent do not appear to have harmful effects, high concentrations have been associated with both birth defects and cancer in humans. Atrazine is now listed as a possible carcinogen and its’ use has been banned from certain areas of the United States.

Other types of organic herbicides include chloroacetamides such as alachlor, (banned in Canada as a risk to health) and its' replacement, metolachlor, a similar compound. The EPA has recommended that the use of chloroacetamides be carefully regulated to avoid the risk of groundwater contamination.

Another group of herbicides includes the phenoxy compounds. Phenoxy herbicides have break-down products more toxic than the original molecule, degrading to produce phenol compounds. This group includes 2,4-D compounds used to kill broad-leaf weeds. Used widely on lawns and golf-courses, there are concerns over the development of cancer as a result of chronic over-exposure. The most toxic chemically-related compound is dioxin (a chlorophenol derivative), a suspect in increased incidences of cancer. These chloro-phenol types of compounds are also used as fungicides (wood preservatives).

iii. PCBs


Polychlorinated biphenyls (PCBs) are a serious environmental concern. They are stable, chemically inert liquids which are not readily flammable and are excellent electrical insulators. Because of this, these compounds were used extensively as coolants in transformers and other electrical equipment. Use of PCBs as a transformer coolant was halted in North America in the late 1970s, but there are still numerous transformers in operation that contain these compounds. When inadvertently released in to the atmosphere, PCBs persist for many years. Low-level contamination of PCBs is world-wide, from the Great Lakes to the North and South Poles, and this contamination is expected to persist for many years due to the extremely slow decomposition of these compounds. PCBs are also highly susceptible to bioaccumulation and bioconcentration in the organisms involved in many food chains. Concentrations in wildlife around affected watersheds are often thousands of times higher than that of the contaminated water itself. Although this remains a concern, the general trend has been an overall decrease in most organisms. For example, decreases have been measured at approx. 0.078% / year for PCBs measured in Lake Michigan. While PCBs do not have a high acute toxicity in humans, they are certainly a potential carcinogen in high doses and have suspected effects on fetal development.

PCBs (as well as dioxins and chlorinated furans) are not easily metabolized and tend to be stored in fatty tissues. Relative toxicity of these compounds can be expressed as TEQ (toxicity equivalency factor) which rates relative toxicity proportionally to the compound 2,3,7,8-TCDD (which is rated as being 1.0).

iv. PAHs

PAHs (polynuclear aromatic hydrocarbons) are multiple benzene structures which share carbon atoms between fused rings. These molecules are typically the product of combustion (i.e. soot, smoke) especially from industrial production of coal, etc. These compounds are strongly suspected of having a serious impact on human health; not only as air-borne pollutants, but also as compounds leached into watersheds.

The most noted PAH is benzo-a -pyrene which is derived from burning / combustion of fossil fuels and is a concern due to both its carcinogenic nature and its high degree of bioaccumulation. The carcinogenic nature of BaP is not immediate: rather it is the biological breakdown of the compound in humans (via the cytochrome p450 system) which leads to the formation of carcinogenic compounds.


v. Heavy Metals

Heavy metals are extremely dense metals found naturally as trace elements. Some examples include mercury (Hg), Lead (Pb), Cadmium (Cd), etc. While some heavy metals are not highly toxic as elements, their cationic states are far more reactive. The degree of relative toxicity of a given heavy metal can therefore vary with the exact chemical form of the element. One particularly toxic form involves attachment of alkyl groups which permit passage through the blood-brain barrier. Heavy metals in these states are responsible for immediate, long-term and fetal toxic effects and can cause irreversible damage.

Bioaccumulation of heavy metals is similar to that observed in other toxic agents: the toxic agents become progressively more concentrated as they are consumed further and further up the food chain. Bioconcentration/accumulation is often a far more serious source of heavy metal exposure than through the direct route of drinking water. Since many heavy metals have a relatively long T0.5

(half-life) (i.e. methyl mercury is 70 days) there is a long period for potential exposure and bioconcentration for humans consuming fish or other foods with elevated mercury levels. A summary of drinking water limits for heavy metals is listed below.

WHO Heavy Metal limits for Drinking Water

Heavy Metal Limit (ppb)

Hg 1

Cd 3

Pb 10

As 10

Mercury, (perhaps more than any other heavy metal) has achieved a high level of notoriety. Industrial production of certain chemicals


(NaOH, Cl) often results in inadvertent / fugitive release of both gaseous and solid amalgams of mercury. Accumulation and bio-concentration of mercury in fish is a well-publicized concern in many water systems world-wide. Mercury often forms methyl-mercury in aqueous systems, by reacting with light and various organic compounds. Methyl-mercury is of particular concern because of its affinity and persistence in fatty tissues and lipids in humans.

Mercury can also enter the ecosystem through leaching from soils/rocks and can be exasperated by activities such as dams (altering water levels) and flooding. Mercury poisoning is, and will continue to be a major issue in environmental chemistry for years to come.

Lead, a soft heavy metal, is now used far less in most western industrialized nations than previously. Previously used in leaded gasoline's, many paints and as "shot" for shotgun ammunition, these sources of lead contamination have been banned in Canada. Lead is still a component of certain solders used in electrical wiring and exists as a component of the plumbing in many older Canadian residences. The current major source of lead exposure for most Canadians continues to be drinking water. Long term accumulation of lead results in accumulation in the brain, often as a result of numerous years exposure and accumulation. Most vulnerable are fetuses and young children undergoing rapid brain growth/development.

Cadmium, is a by-product of industrial activities (such as zinc production) and is often found in high-power batteries in phones, portable tools and video cameras. When such batteries are incorrectly disposed of, each battery can release as much as several grams of cadmium, particularly a concern during incineration. Higher levels of cadmium can be found near smelters and mines, but the greatest general human exposure is through diet. Cadmium is absorbed by plants and is consumed by humans and animals. Acute toxicity is high (lethal dose < 1g) but cadmium itself is not biomagnified like mercury.

Arsenic, is commonly known as an acute poison but is introduced into the environment through the smelting / mining of metals (nickel/gold, etc.), through the burning of coal and as a component of pesticides. Considerable amounts of arsenic continue to be leached from abandoned gold mines resulting in considerable water contamination. Human intake is largely through drinking water, leading to carcinogenic toxicity, particularly in combination with smoking, although elevated skin cancer has also been associated with chronic exposure to arsenic.


What is Risk Assessment?

First, risk is defined as the probability that an event will occur. It can also be defined as the probability that a health effect will occur after an individual has been exposed to a specified amount of a hazard. Risk assessment is the process of gathering all available information on the toxic effects of a chemical and evaluating it to determine the possible risks associated with exposure. The process of gathering and evaluating the information can be divided into the following:

o Hazard Identification o Hazard Evaluation or Dose-Response Assessment o Exposure Assessment o Risk Characterization

Hazard Identification - this first step in risk assessment consists in collecting data from different sources to determine whether a substance is toxic. It involves gathering and examining data from toxicological and epidemiological studies.

Epidemiology' is the study of the causative factors that are associated with the occurrence and number of cases of disease and illness in a specific population. Information from these studies should answer these questions:

Does exposure to the substance produce any adverse effects?

If yes, what are the circumstances associated with the exposure?

Information collected and considered when performing a risk assessment are listed below.

Substance Identification (name) Physical/chemical properties of the toxic substance

(Does it dissolve? Is it reactive [explosive, flammable, etc.], What is its size?)

Source of the toxicity information

Epidemiological studies - The two major types of epidemiological studies are retrospective and prospective. Retrospective studies attempt to gather information from the past. Sometimes the information is incomplete because of the way the data was gathered. Because of that, it is sometimes difficult to determine if there is a


relationship between the effect and a specific factor, such as exposure to a particular toxic substance. Prospective studies gather information from current, ongoing investigations. For that reason, the results are more complete and accurate than retrospective studies. Both methods are useful in identifying adverse health effects associated with a given toxic substance (1).

Toxicological studies - Different types of studies fall under the category of toxicological studies, including acute toxicity studies, which look at short-term exposures, and chronic toxicity studies, which look at exposures over a long period of time.

Other factors to consider include the species of test animal (was the study done in rats, mice, man, etc.), and other variables affecting toxicity (including age, sex, and health of the study population).

Exposure to Toxic Substances

Exposure to toxic substances depends on the

Route of exposure (skin contact, inhalation, ingestion, injection),

Duration of exposure (acute or chronic), Frequency of exposure, and Exposure to other toxic substances. Other factors to consider when

determining potential exposures to toxic substances include diet, lifestyle choices, and occupation.

Hazard Evaluation and Dose-Response Assessment

If the hazard identification process produces evidence of a hazard, then a hazard evaluation is performed. The purpose of this step is to calculate, if possible, the dose at which a harmful effect will occur. Since an effect in animals may not be the same in humans, at the same dose, "safety factors" are used. Safety factors account for the differences in response of test animals and differences in toxicity. The dose-response assessment tells the toxicologist what dose causes a response, usually illness or death, in the test animal.

Exposure Assessment

An exposure assessment is performed to identify the affected population and, if possible, calculate the amount, frequency, length of


time, and route of exposure. Exposure is "an event that occurs when there is contact at a boundary between a human and the environment at a specific (contaminant) for a specified period of time". Units to express exposure are "concentration times time"(1). Factors to consider when performing an exposure assessment include

General information for each chemical

- Identification of molecular formula and structure (how the chemical looks and is made) and other identifying characteristics

- Chemical and physical properties

Sources- Characterization of production and distribution- Uses- Disposal- Summary of environmental releases

Exposure Pathways and Environmental Fate

- Transport and transformation- Identification of principal pathways of exposure- Predicting environmental distribution

Measured or Estimated Concentrations

- Uses of measurements- Estimation of environmental concentrations

Exposed Human Populations

- Size and characteristics- Location- Habits

Integrated Exposure Analysis

- Calculation of exposure includes identification of the exposed population and identification of pathways of exposure.

Definition of Each Component in an Exposure Assessment

General Information for Each Chemical - The physical/chemical properties of the toxic substance affects how it is transported, how it is accumulated in the environment and in tissues, and how it is transformed when it


is released into the environment. Some examples of characteristics include:

- Vapor pressure (how easily can a chemical change from a solid or liquid to a gas?)

- Its ability to dissolve in water- Its ability to stick to soil or sediments- Knowing these facts will help determine the dose and route

of exposure. Sources of Exposure - Exposure to chemicals can

occur anywhere, including the home (cleaning products, paints, pesticides, etc.). Outside the home, exposure to chemical pollutants in the air occurs through inhalation.

Exposure Pathways and Environmental Fate - Once the source has been identified, the route and nature of the exposure must be determined. For exposure could occur through drinking water (the route could be ingestion of contaminated water).

Measured or Estimated Concentrations - If possible, it is best to obtain actual samples from the source of exposure to calculate the amount of toxic substance present. However, samples are not always available and estimations of exposure can be calculated using a mathematical model. These models attempt to estimate the concentration of a substance at the point of exposure. Modeling is mostly used when determining concentrations of substances in air, but can be used to determine the amount in lakes or other bodies of water.

Exposed Population - It is important to identify and characterize the exposed population in terms of sex; age; number of small children, pregnant women, and chronically ill individuals. Other information such as eating, work, exercise, and play habits is also necessary. Some populations are more at risk for illness than others, such as young children and older adults.

Measuring Exposures - The effects from exposure to simple and complex mixtures are very important, as well as the health impact of these substances on susceptible populations (e.g., children, elderly, people of color). Exposure can also vary greatly within geographic areas. Measurement of exposure is often determined through questionnaires or surveys, employment records, and evaluation of environmental contamination data for areas in which a study population lives (10). A problem seen in most communities is the absence of actual data, because no personal monitoring was conducted. This could lead to exposure calculations that could be too high or too


low (10). How much exposure occurred and how much of a dose a person received is significant in documenting exposure.

Two major approaches for assessing total exposure include indirect methods and direct methods. Indirect methods include environmental monitoring; use of fate and transport (migration); computer models; (use of questionnaires, and/or surveys for residents). Direct methods, include the use of personal workplace monitoring equipment and biologic markers (2). The extent of exposure may depend on the size of the population, its proximity to the contamination source, a person's degree of personal contact with the site, and the extent of the release of hazardous substances. Children are one population particularly susceptible to the toxic effects of contaminants at hazardous waste sites. While playing outside, young children come into contact with environmental toxicants via dermal contact and subsequent hand-to-mouth activity. Therefore, children who play in areas where there is little to no vegetative cover, as in many urban areas, and pica children (those who ingest greater than an average amount of non-food items [dirt] per day) are particularly sensitive to contaminants in soil.

Calculation of Exposure (1) - Once the information is available, exposure can be estimated. Exposure can occur through more than one route, and when that is the case, the total exposure may be measured by adding the contributions of all routes. When data is not available, certain guesses are made, using standard reference values.

Risk Characterization

The last and final step in the risk assessment process is putting all of the information gathered from the other steps together to determine the actual risk of exposure to a specific toxic substance. This step relies on the expertise of the assessor in analyzing the information.

Risk Management

Based on information obtained from the risk assessment, decisions are made about the best way to address environmental contamination and exposure. The risk manager also includes an evaluation of social, legal, economic, and policy issues to determine the best approach to address an exposure issue.


ATSDR's public health assessment is an evaluation of environmental data, health outcome data, and community concerns associated with a site where hazardous substances have been released. The health assessment identifies populations living or working on or near hazardous waste sites for which more actions or studies are needed.


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