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CHEMICAL TOXICOLOGY OVERVIEW

Definitions

Toxicology is the study of the nature and action of poisons.

Toxicity is the ability of a chemical substance or compound to produce injury once it reaches a susceptible site in, or on, the body.

A material’s hazard potential is the probability that injury will occur after consideration of the conditions under which the substance is used.

Dose-Response Relationships

The potential toxicity (harmful action) inherent in a substance is exhibited only when that substance comes in contact with a living biological system. The potential toxic effect increases as the exposure increases. All chemicals will exhibit a toxic effect given a large enough dose. The toxic potency of a chemical is thus ultimately defined by the dose (the amount) of the chemical that will produce a specific response in a specific biological system.

Routes of Entry into the Body

There are four main routes by which hazardous chemicals enter the body:

  • Absorption through the respiratory tract via inhalation.
  • Absorption through the skin via dermal contact. There are 170 known “skin-absorbing” chemicals.  Please consult the following Web site to identify chemicals that have this property:  www.osha.gov/web/dep/chemicaldata/#target
  • Absorption through the digestive tract via ingestion.       (Ingestion can occur through eating or smoking with contaminated hands or in contaminated work areas.)
  • Absorption through percutaneous challenge (syringe needle or broken glass).This is possible but not a common route of exposure in chemical laboratories. However, needle sticks are significant routes of exposure in biomedical, health care and radiological work.

Most exposure standards, such as the Threshold Limit Values (TLVs) and Permissible Exposure Limits (PELs), are based on the inhalation route of exposure. These limits are normally expressed in terms of either parts per million (ppm) or milligrams per cubic meter (mg/m3) concentration in air. If a significant route of exposure for a substance is through skin contact, the MSDS, PEL and/or TLV will have a “skin” notation. Examples of substances where skin-absorption may be a significant factor include: pesticides, carbon disulfide, carbon tetrachloride, dioxane, methanol, acetonitrile, mercury, thallium compounds, xylene, and hydrogen cyanide.

Types of Effects

  • An acute effect is characterized by sudden and severe exposure and rapid absorption of the substance. Normally, a single large exposure is involved. Adverse health effects are often reversible.

Examples: carbon monoxide or cyanide poisoning.

  • A chronic effect is characterized by prolonged or repeated exposures of a duration measured in days, months or years. Symptoms may not be immediately apparent. Health effects are often irreversible. Examples: lead or mercury poisoning.
  • A local effect refers to an adverse health effect that takes place at the point or area of contact (skin, the respiratory tract, eyes, etc.). Absorption does not necessarily occur.

Examples: strong acids or alkalis.

  • A systemic effect refers to an adverse health effect that takes place at a location distant from the body’s initial point of contact and presupposes absorption has taken place.

Examples: arsenic affects the blood, nervous system, liver, kidneys and skin; benzene affects bone marrow.

  • Cumulative poisons build up in the body as a result of numerous chronic exposures. The effects are not apparent until a critical point is reached.

 Example: heavy metals.

  • Synergistic effect: When two or more hazardous materials are present at the same time, the resulting effect can be greater than the effect anticipated based on the cumulative effect of the individual substances.  This is also called “potentiating effect.” 

Example:  exposure to alcohol and chlorinated solvents; or smoking and asbestos.

Other Factors Affecting Toxicity

  • Rate of entry and route of exposure; that is, how fast the toxic dose is delivered and by what means.
  • Age can affect the capacity to repair tissue damage.
  • Previous exposure can lead to tolerance, increased sensitivity or make no difference.
  • State of health, physical condition and life style can affect the toxic response.
  • Pre-existing disease can result in increased sensitivity.
  • Environmental factors such as temperature and pressure.
  • Host factors including genetic predisposition and the sex of the exposed individual.

Physical Classifications

A gas is a substance that is in the gaseous state at room temperature and pressure.

A vapor is the gaseous phase of a material that is ordinarily a solid or a liquid at room temperature and pressure.

When considering the toxicity of gases and vapors, the solubility of the substance is a key factor. Highly soluble materials, like ammonia, irritate the upper respiratory tract. On the other hand, relatively insoluble materials, like nitrogen dioxide, penetrate deep into the lung. Fat-soluble materials, like pesticides, tend to be retained longer in the body and have a cumulative effect.

An aerosol is composed of solid or liquid particles of microscopic size dispersed in a gaseous medium.

The toxic potential of an aerosol is only partially described by its airborne concentration. For a proper assessment of the toxic hazard, the size of the aerosol’s particles must be determined. A particle's size will determine whether a particle is deposited within the respiratory system and the location of deposition. Particles above 10 micrometers tend to be deposited in the nose and other areas of the upper respiratory tract. Below 10 micrometers, particles enter and are deposited in the lung.  Very small particles (<0.2 micrometers) are generally not deposited but exhaled.

Physiological Classifications of Chemicals

Chemicals and hazardous materials can be classified according to the effect they have on individuals.

Irritants

Irritants are materials that cause inflammation of mucous membranes with which they come in contact. Inflammation of tissue results from exposure to concentrations far below those needed to cause corrosion. 

Examples include:

      • Ammonia
      • Alkaline dusts and mists
      • Arsenic trichloride
      • Diethyl/dimethyl sulfate
      • Halogens
      • Hydrogen chloride
      • Hydrogen fluoride
      • Nitrogen dioxide
      • Ozone
      • Phosgene
      • Phosphorus chlorides

Irritants can also cause changes in the mechanics of respiration and lung function.

Examples include:

      • Acetic acid
      • Acrolein
      • Formaldehyde
      • Formic acid
      • Iodine
      • Sulfur dioxide
      • Sulfuric acid

Long-term exposure to irritants can result in increased mucous secretions and chronic bronchitis.

A primary irritant exerts no systemic toxic action, either because the products formed on the tissue of the respiratory tract are nontoxic or because the irritant action is far in excess of any systemic toxic action.

Example: hydrogen chloride.

A secondary irritant’s effect on mucous membranes is overshadowed by a systemic effect resulting from absorption.

Examples include:

      • Alcohols
      • Aromatic hydrocarbons
      • Asphyxiants have the ability to deprive tissue of oxygen.
      • Halogenated hydrocarbons
      • Hydrogen sulfide

Simple Asphyxiants

Simple asphyxiants are gases that displace oxygen.

Examples include:

  • Carbon dioxide
  • Helium
  • Nitrogen
  • Argon

Chemical Asphyxiants

Chemical asphyxiants reduce the body’s ability to absorb, transport, or utilize inhaled oxygen. They are often active at very low concentrations (a few ppm).

Examples include:

      • Carbon monoxide
      • Cyanides
      • Hydrogen sulfide

Primary Anesthetics 

Primary anesthetics have a depressant effect upon the central nervous system, particularly the brain.

Examples include:

  • Diethyl ether
  • Chloroform

Hepatotoxic Agents

Hepatotoxic agents cause damage to the liver.

Examples include:

      • Carbon tetrachloride
      • Nitrosamines
      • Tetrachloroethane

Nephrotoxic Agents

Nephrotoxic agents damage the kidneys.

Examples include:

      • Halogenated hydrocarbons
      • Uranium compounds

Neurotoxic Agents

Neurotoxic agents damage the nervous system. 

The nervous system is especially sensitive to organometallic compounds and certain sulfide compounds.

Examples include:

      • Carbon disulfide
      • Methyl mercury
      • Manganese
      • Organic phosphorus insecticides
      • Tetraethyl lead
      • Thallium
      • Tri-alkyl tin compounds

Hematopoietic System Toxins

Some toxic agents act on the blood or hematopoietic system. The blood cells can be affected directly or the bone marrow (which produces the blood cells) can be damaged.

Examples include:

  • Aniline
  • Benzene
  • Nitrites
  • Nitrobenzene
  • Toluidine

Pulmonary Toxins

There are toxic agents that produce damage of the pulmonary tissue (lungs) but not by immediate irritant action. Fibrotic changes can be caused by free silica and asbestos. Other dusts can cause a restrictive disease called pneumoconiosis.

Examples include:

      • Coal dust
      • Cotton dust
      • Wood dust

Carcinogens

A carcinogen is an agent that can initiate or increase the proliferation of malignant neoplastic cells or the development of malignant or potentially malignant tumors. 

Known human carcinogens include:

      • Asbestos
      • Alpha-naphthylamine
      • Bis-chloromethyl ether
      • 3,3'-Dichlorobenzidine
      • Ethylene oxide
      • N-nitrosodimethylamine
      • 4-nitrobiphenyl
      • Methyl chloromethyl ether
      • Inorganic arsenic
      • 1,2-Dibromo-3-chloropropane (DBCP)
      • Coal tar pitch volatiles
      • Vinyl chloride

Reproductive Toxins (Mutagens and Teratogens)

A mutagen interferes with the proper replication of genetic material (chromosome strands) in exposed cells. If germ cells are involved, the effect may be inherited and become part of the genetic pool passed onto succeeding generations.

A teratogen (embryotoxic or fetotoxic agent) is an agent that interferes with normal embryonic development without causing a lethal effect to the fetus or damage to the mother. Effects are not inherited.

Examples include:

      • Lead
      • Thalidomide

Sensitizers

A sensitizer is a chemical that can cause an allergic reaction in normal tissue after repeated exposure to the chemical. The reaction may be as mild as a rash (allergic dermatitis) or as serious as anaphylactic shock.

Examples include:

Last updated: 06/20/2008
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