Chemistry Safety

Appendix I: Industrial Toxicology - An Overview

Chemical Toxicology

  • Toxicology is the study of the nature and action of chemical poisons.
  • Toxicity is the ability of a chemical molecule or compound to produce injury once it reaches a susceptible site in or on the body.
  • Toxicity hazard is the probability that injury will occur considering the manner in which the substance is used.

    Dose-Response Relationship

    The potential toxicity (harmful action) inherent in a substance is exhibited only when that substance comes in contact with a biological system. A chemical normally thought of as "harmless" may evoke a toxic response if added to a biological system in sufficient amount. The toxic potency of a chemical is thus defined by the response that is produced in a biological system.

    Routes of Entry into the Body

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

    Exposure Limits as Related to Routes of Entry

    Most exposure standards are based on the inhalation route of exposure. They are normally expressed in terms of parts per million (ppm) or milligrams per cubic meter (mg/m ) concentration in air.

    The Occupational Safety and Health Administration (OSHA) has established Permissible Exposure Limits (PELs) and the American Conference of Governmental Industrial Hygienists (ACGIH) has established Threshold Limit Values (TLV's) for employee exposure limits. In many instances, the PEL and TLV are represented as the same number. In the instances where one is lower than the other, it is a prudent safety practice to maintain exposures at the lowest level achievable.

    If a significant route of exposure for a substance is through skin contact, the TLV or PEL will have a "skin" notation. Examples are pesticides, carbon tetrachloride, cyanides, ethylenediamine and thallium.

    For a complete list of PELs and TLVs, see the ACGIH publication "Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices."

    Types of Effects

  • Acute poisoning is characterized by rapid absorption of the substance when the exposure is sudden and severe. Normally, a single large exposure is involved. Examples are carbon monoxide or cyanide poisoning.
  • Chronic poisoning is characterized by prolonged or repeated exposures of a duration measured in days, months or years. Symptoms may not be immediately apparent. Examples are lead or mercury poisoning, or pesticide exposure.
  • Local refers to the site of action of an agent where the action takes place at the point or area of contact. The site may be skin, mucous membranes, the respiratory tract, gastrointestinal system, eyes, etc. Absorption does not necessarily occur. Examples are strong acids or alkalis.
  • Systemic refers to a site of action other than the point of contact and presupposes absorption has taken place. For example, an inhaled material may act on the liver. For example, inhaled benzene affects the bone marrow.
  • Cumulative poisons are characterized by materials that tend to build up in the body as a result of numerous chronic exposures. The effects are not seen until a critical body burden is reached. Examples are heavy metals.
  • Synergistic or potentiating effects occur when two or more hazardous materials present at the same time have a resulting action greater than the effect predicted based on the individual substances. For example, workers exposed to benzene may show a direct toxicity in hematopoietic tissue and therefore be more susceptible to oxygen-displacing agents such as carbon monoxide.

    Other Factors Affecting Toxicity

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

    Physical Class Affects on Toxicity

    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 have longer residence times in the body.

    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 concentration in milligrams per cubic meter (mg/m3). For a proper assessment of the toxic hazard, the size of the aerosol's particles is important. Particles above 1 micrometer tend to deposit in the upper respiratory tract. Particles less than 1 micrometer in diameter enter the lung. Very small particles ( < 0.2 µm) are generally not deposited.

    Physiological Classifications of Toxic Materials

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

    Irritants can also cause changes in the mechanics of respiration and lung function. Examples include: Long term exposure to irritants can result in increased mucous secretions and chronic bronchitis.

    A primary irritant exerts no systemic toxic action because the products formed on the tissue of the respiratory tract are non-toxic or because the irritant action is far in excess of any systemic toxic action. An example is hydrogen chloride.

    A secondary irritant's effect on mucous membranes is over-shadowed by a systemic effect resulting from absorption. Examples include:

    Exposure to a secondary irritant can result in pulmonary edema, hemorrhage, and tissue necrosis.

    Corrosives are chemicals which may cause visible destruction of or irreversible alterations in living tissue by chemical action at the site of contact. Examples include:

    Asphyxiants have the ability to deprive tissue of oxygen. Simple asphyxiants are inert gases that displace oxygen. Examples include: Chemical asphyxiants render the body incapable of utilizing an adequate oxygen supply. They are toxic at very low concentrations (few ppm). Examples include: Primary anesthetics have a depressant effect upon the central nervous system. Particularly the brain. Examples include: Hepatotoxic agents cause damage to the liver. Examples include: Nephrotoxic agents cause damage to the kidneys. Examples include: Neurotoxic agents damage the nervous system. The nervous system is especially sensitive to organometallic compounds and certain sulfide compounds. Examples include: Neurotoxic agents damage the nervous system. The nervous system is especially sensitive to organometallic compounds and certain sulfide compounds. Examples include: Pulmonary tissue (lungs) agents can be toxic, through other mean than by immediate irritant action. Fibrotic changes can be caused by free crystalline silica and asbestos. Other dusts can cause a restrictive disease called pneumoconiosis. Examples include: A teratogen (embryo toxic or fetotoxic) agent is an agent which interferes with normal embryonic development without damage to the mother or lethal effect on the fetus. Effects are not hereditary. Examples include: A mutagen is a chemical agent which may able to react with nucleophilic structures such as DNA. Mutations can occur on the gene level (gene mutations) when, for example, one nucleotide base-pair is change to another. Mutations can also occur on the chromosomal level (chromosomal mutations) when the number of chromosomal units or their morphological structure isaltered. Examples of mutagens include most radioisotopes, barium permanganate and methyl isocyanate.

    A sensitizer causes a substantial proportion of exposed people to develop an allergic reaction in normal tissue after repeated exposure to the chemical. The reaction may be as mild as a rash (contact dermatitis) or as serious as anaphylactic shock. Examples include:

    Target Organ Effects

    The following is a target organ categorization of effects which may occur from exposure to hazardous chemicals, including examples of signs and symptoms and chemicals which have been found to cause such effects.