Lesson 3: Toxicology

Skin

A condition called chloracne may be caused by repeated exposures to PCB's (polychlorinated biphenyls) and other chlorinated hydrocarbons.

Inhalation

A toxic dose of chemicals can be inhaled in a number of ways: as a gas, mist, fumes, dust, or vapor. The result is that a chemical enters the airways. The chemical may only make it as far as the mucous membranes of the nose, or it may reach the smallest cavities of the lungs. Anywhere along the way it can be absorbed and cause an adverse reaction. The reaction can be immediate, for example, as in the reaction to hydrogen sulfide gas. On the other hand, the reaction can be delayed for years as in the reaction to asbestos fibers.

Animal Studies

Animal studies provide most of what we know about the dangerous effects of toxic substances. Humans may react differently than animals exposed to toxic materials.

Route of Exposure

Certain chemicals appear harmless in one form of contact, such as carbon monoxide on the skin. However, carbon monoxide inhaled into the lungs causes much more serious effects.

Liquids, Vapors, Mists

Examples of liquids include acids, organic solvents, and chlorinated organic solvents (examples: benzene, sulfuric acid, 1-trichloroethane). Routes of entry are inhalation and skin absorption. Vapors are gases that result from the evaporation of liquids or the sublimation of solids (examples: gasoline, phosgene and iodine). Routes of entry are inhalation and skin absorption. Mists are liquid droplets suspended in the air (examples: acid mists from electroplating processes or solvent mists from paint spraying operations). Routes of entry are inhalation and skin absorption.

Immediately Dangerous To Life and Health (IDLH)

IDLH exposure concentrations have been established by the NIOSH/OSHA Standards Completion Program (SCP) as a guideline for selecting respirators for some chemicals. The definition of IDLH varies depending on the source. The Mine Safety and Health Administration Standard defines IDLH conditions as those that pose an immediate threat to life or health or that pose an immediate threat of severe exposure to contaminants such as radioactive materials that are likely to have adverse cumulative or delayed effects on health.

Target Organ Poisons

Many chemicals will target a particular tissue or organ and cause disease or damage at that location. They are called target organ poisons. Other types of chemical toxins target body systems and cause a variety of reactions. The following examples are listed according to the tissue or organ affected.

If chemicals are soluble in oil or fat, what happens?

Many chemicals, particularly those that are soluble in oil or fat (lipids), are not removed from the body but are stored instead. Storage usually occurs in the adipose tissue or fat.

IDLH concentrations should be assumed to

Represent concentrations above which only workers wearing respirators that provide the maximum protection (i.e., a positive pressure, full-face piece, self-contained breathing apparatus (SCBA) or a combination positive-pressure, full-face piece, supplied-air respirator with positive-pressure SCBA) are permitted. Specific IDLH values for many substances can be found in the NIOSH Pocket Guide to Chemical Hazards.

Toxic substance forms

Solids, Fumes, Liquids, Vapors, Mists

Response to Chemical Exposure

There are a number of factors that affect the severity of exposure to a chemical. These factors include the toxicity of the substance, route of exposure, chemical dose, interaction with other chemicals, and human response. We will cover each one of these points in detail.

Chemical Dose

This is the amount and length of time that one is exposed to a chemical.

Ceiling

This is the level that can never be exceeded during any part of the working exposure without protective actions. It is not an average unless it cannot be measured any other way. Then, it is measured over a 15-minute time period.

Fumes

Tiny particles are produced from heating, volatilization, and condensation of metals (examples: zinc oxide fumes from welding of galvanized metal). Routes of entry are inhalation, ingestion (saliva), and skin absorption. It is important to note that toxic fumes may result from the burning of non-toxic substances.

Chemical Exposure

Toxic chemicals can react in either an acute or chronic way. Acute (immediate) responses are effects which occur shortly after exposure. Symptoms include headaches, dizziness, nausea and eye, skin, or respiratory damage. An acute response may cause unconsciousness or even death. Chronic (delayed) responses are effects that occur a long time after exposure. Frequently, they are not reversible. Common organs affected are the liver, kidney, and lungs.

Factors effecting Response to Chemical Exposure

Toxicity, Route of exposure, Chemical Dose

Irritants

aggravate various tissues causing redness, rashes, swelling, coughing, or even hemorrhaging. Chlorine and ammonia are two examples of irritants.

Asphixiants

are chemicals that deprive the victim's body tissues of oxygen. Asphyxiants interfere with the body's ability to transport or use the oxygen carried by the blood stream. Any gas heavier than air can easily displace oxygen and cause asphyxiation. Examples of chemical asphyxiants are carbon monoxide and hydrogen cyanide.

Recommended Exposure Limit (REL)

A NIOSH recommended exposure limit, or REL, is the work-place exposure concentration recommended by NIOSH for promulgation by OSHA as a PEL. In some cases, NIOSH has described time-weighted average concentrations in terms of 10-hour, rather than 8-hour, averages.

Highly Toxic

A chemical that is highly toxic has a LD50 (lethal dose 50%) of 50 milligrams of chemical per 1 kilogram of body weight administered orally; LD50 of 200 milligrams or less per kilogram of body weight when administered by continuous skin contact for 24 hours; LC50 (lethal concentration 50%) in air of 200 ppm by volume or less when administered by continuous inhalation for one hour or less; or 2 mg/kg per liter or less of mist, dust, or fume when continuously inhaled for one hour or less.

Lungs

Asbestos fibers and silica dust may cause a fibrosis effect in the lung tissue. Fibrosis is a condition in which the lung becomes scarred and inflexible, making the lung unable to expand and contract.

Protection Against Hazards

When the hazard is known, the hard part is over. One cannot protect from the unknown, but one can protect against the known hazard by doing the following: Use the engineering controls provided, such as ventilation systems. Use administrative controls. Use common sense around chemicals. However, many chemical hazards can't be detected using only common sense, so never rely solely on it. Select and use protective equipment based on MSDS and safety officer recommendations. Wash exposed areas thoroughly before eating, drinking, or smoking.

Chemical Dose

Whenever the term toxicity is used, dosage is generally indicated. Dosage is related to the quantity of a material and length of exposure. The higher the chemical dose, the greater the toxic reaction. A toxic dose is often expressed as a lethal dose (LD), or lethal concentration (LC). A number given as an LD50 or LC100 refers to the specific amount of a particular material that results in a percentage of deaths of a sample group of laboratory animals. For example, an LC50 of 25 mg/m3 means that a concentration of 25 mg/m3 of a certain substance is shown to have been fatal to 50 percent of a test group of animals.

How do we protect ourselves from toxins? The human body can break down, detoxify, or eliminate many harmful chemicals if the dose is not too great. At the same time, exposure to toxins puts stress on the body.

You must know the potential for toxicity of the materials that you work with to adequately protect yourself from toxic exposure. Once the presence and the concentrations of specific chemicals or classes of chemicals have been established, the associated hazards should be determined. Information on the chemical, physical, and toxicological properties of each chemical should be recorded on a Hazardous Substance Information Form. Health and safety personnel should then make the necessary information available in one place. New personnel should be briefed. As many reference sources as possible should be used to fill out the sheets, because the information may vary from one source to another. As data is gathered, a worst-case scenario should be developed so all necessary precautions may be taken. Material safety data sheets (MSDSs) provided by chemical manufacturers are one source for this information.

Toxic

A chemical that is toxic has an LD50 (lethal dose 50%) of more than 50 milligrams/kilogram but less than 500 mg/kg of chemical per 1 kilogram of body weight administered orally; LD50 of more than 200 milligrams per kilogram of body weight but less than 1000 mg/kg when administered by continuous skin contact for 24 hours; LC50 (lethal concentration 50%) in air of more than 200 ppm by volume but less than 2000 when administered by continuous inhalation for one hour or less; or more than 2 mg/kg per liter but less than 20 mg/kg of mist, dust, or fume when continuously inhaled for one hour or less.

Short-Term Exposure Limit

ACGIH defines this as a 15-minute TWA exposure that should not be exceeded at any time during the workday without the proper protective measures. Exposures above the TLV-TWA up to the STEL should not be longer than 15 minutes and should not occur more than four times per day with at least 60 minutes between exposures. This is not a separate independent exposure limit. Instead, it supplements the TWA limit where there are recognized acute effects from a substance that normally has chronic effects.

Health Hazards

Although safety hazards related to the physical characteristics of a chemical can be objectively defined in terms of testing requirements, health hazard definitions are less precise and more subjective. Health hazards may cause measurable changes in the body such as decreased pulmonary function (breathing). These changes are generally indicated by the occurrence of signs and symptoms, such as shortness of breath, in exposed employees. However, shortness of breath is a non-measurable subjective feeling. The determination of occupational health hazards is complicated by the fact that many of the effects or signs and symptoms occur commonly in non-occupationally exposed populations, so that the effects of exposure are difficult to separate from normally occurring illnesses.

Injection

Chemicals can enter through the skin at any wound or injury site. This is commonly called injection. Injection can happen when handling a high-pressure hose with pinhole leaks because a chemical can seep through cracks in a worker's unprotected hands. Once the chemical enters the bloodstream, it has the potential to impact all organs and tissues.

Please note that the smaller the number (toxic dose) the more toxic the material.

Consider this example while referencing the table here. A 175-pound person given three drops (i.e., less than 1.0 mg/kg) of a dangerously toxic material can die. While three drops of a toxic material should not cause the death of a 175-pound person (dependent on personal response).

Epidemiological Studies

Epidemiological studies compare affected people in one group to affected people in another group. Sometimes the information comes from actual exposures to a chemical in the workplace.

Vapors and gases

For vapors or gases the constant of 24.5 liters vapor per mole of contaminant at 25°C and one atmosphere (760 mm Hg) of pressure is important. Some common examples of this constant are: Chlorine 1 ppm = 2.95 mg/m3 Toluene 1 ppm = 3.83 mg/m3 Trichloroethylene 1 ppm = 5.46 mg/m3

Liver

Hepatoxins are substances that are capable of damaging the liver. The liver is the main processing organ for toxins. It can convert toxins into nontoxic forms; however, the liver can generate a more toxic by-product, which can cause cellular and tissue damage. Examples of hepatotoxins are carbon tetrachloride, chloroform, tannic acid, and trichloroethylene. Examples of chemicals that cause cirrhosis (a fibrotic disease that results in liver dysfunction and jaundice) are carbon tetrachloride, alcohol, and aflatoxin. Other effects can range from tumors to enlargement of the liver and fat accumulation.

Protection from Toxins

How do we protect ourselves from toxins? The human body can break down, detoxify, or eliminate many harmful chemicals if the dose is not too great. At the same time, exposure to toxins puts stress on the body.

Human Response

Humans and other living animals vary in their response to chemical exposure. For some, a certain dose may produce symptoms of serious illness; for others only mild symptoms may appear; or there may be no noticeable effect at all. Often a prior exposure to a chemical affects the way an individual responds to being exposed at a later time. Thus, there is not only variation between different individuals; there may be different responses in the same individual at various exposures.

Potentiation (0+2=10)

In some cases a chemical without any known toxic effect can act together with a known toxic substance to make the toxic substance even more potent and thus more dangerous. Ethanol (ethyl alcohol) and chloroform together affect the liver in just such a manner.

Information on skin absorption is provided:

In the ACGIH publication: Threshold Limit Values for Chemical Substances and Physical Agents, OSHA Standard 29 CFR Part 1910.1000, and other Standard references. These documents identify substances that can be readily absorbed through the skin, mucous membranes, and/or eyes by either airborne exposure or direct contact with a liquid. This information, like most available information on skin absorption, is qualitative. It indicates whether, but not to what extent, a substance can pose a dermal hazard. Thus, decisions made concerning skin hazards are necessarily judgmental. Quantitative data on eye irritation is not always available. Where a review of the literature indicates that a substance causes eye irritation, but no threshold is specified, one should have a competent health professional evaluate the data to determine the level of personal protection needed for workers.

Ingestion

Ingestion is not a common route of transmission for industry workers unless personal hygiene is ignored or disregarded. Personnel that handle chemicals need to follow a hygiene program that will prevent the accidental ingestion of hazardous material, for example, properly washing hands before eating.

Routes of Exposure

Knowing how chemicals get into your body and how your body reacts is critical to personal protection. Toxic chemicals can enter the body in any one of, or in a combination of, four ways. The most common toxic dose in the work environment comes through breathing, or inhalation. The next most common route of entry is through eye and/or skin contact. The most common route in the home is swallowing or ingestion. A route that is more accidental is injection.

Individual Response

LD50 numbers represent the average response for a population because there is a great deal of variability caused by genetics. In other words, given the same dosage of a material, one worker's response can be at the opposite extreme of another worker's response. Some individuals experience less of a response while others experience a greater response. To afford the greatest protection to the average worker, "exposure limits" have been developed. An exposure limit is the airborne concentration of a material to which nearly all individuals may be repeatedly exposed without adverse health effects.

Eyes

Lachrymators are chemicals that can cause instant tearing at low concentrations. Examples are tear gas and MACE. Other chemicals can cause cataracts, optic nerve damage, and retinal damage by circulating through the bloodstream and reaching the eye. Examples of these are naphthalene, methanol, and thallium.

Central Nervous System

Neurotoxins are chemicals that affect the brain and spinal cord. Neurotoxins affect the neurons that carry electrical signals by inhibiting their function. This can cause behavior changes, emotional changes, alterations in walking, and loss of hand-eye coordination. A condition called anoxia may occur, due to a lack of oxygen flow to the brain cells. Lack of oxygen results in cell death. Examples of chemicals causing central nervous system effects are tetraethyl lead, chlorinated hydrocarbon pesticides (e.g., DDT), malathion, lead, and mercury.

Exposure Limits

Published exposure level standards have been determined experimentally and in the workplace. Exposure limits are expressed as permissible exposure limits, or PELs. PELs are enforceable standards promulgated by OSHA. In many cases they are derived from threshold limit values, or TLVs, published in 1968. The PEL for a substance is either an average exposure figured over an 8-hour work day (known as TWA or time weighted average) or a ceiling concentration (C), above which workers can not be exposed. Although personal protective equipment may not be required for exposures below the PEL, its use is advisable where there is a potential for overexposure.

Reproductive Organs

Reproductive toxins can cause sterility, infertility, or spontaneous abortions. They can also affect an individual's hormone levels and activity. Examples of male reproductive toxins are mercury, lead, DDT, PCBs, dioxin, benzene, toluene, and xylene. Examples of female reproductive toxins are DDT, PCBs, parathion, and diethylstilbestrol.

Toxicity

Some chemicals produce immediate and dramatic biological effects. Others may produce no observable effects at all or the effects may be delayed.

Additive Effect (2+2=4)

Some toxic chemicals add their effects together in producing a biological effect. In this case the effect is the same as being exposed to double the dose of either chemical alone. Example: acetaminophen and ibuprofen.

Blood

Substances capable of producing blood disorders are called hematoxins. Chemicals that affect the bone marrow, which is the source of most of the components of blood, are arsenic, bromine, methyl chloride, and benzene. Chemicals that affect platelets, which are cell fragments that help in the process of blood clotting, are aspirin, benzene, and tetrachloroethane. Chemicals that affect white blood cells, which help the body defend against infection, are naphthalene and tetrachloroethane. Arsine, naphthalene, and warfarin can affect red blood cells, which carry oxygen throughout the body. Effects in the exposed individual may include reduced red blood count, or anemia; reduced white blood cell count, which leaves the victim susceptible to disease; and reduced platelet count, which increases the possibility of hemorrhaging.

Synergistic Effect (2+2=6)

Synergism is the exposure to two different toxic chemicals that produce a more severe effect than simply doubling the dose of either one alone. An example is isopropyl alcohol and chloroform. The alcohol ties up the enzymes that would normally break down chloroform.

Time-Weighted Average TWA)

TWA is a dose measurement that is more chronic in nature. It is a time-weighted average concentration for a normal 8-hour day/40-hour week, to which nearly all workers can be repeatedly exposed, day after day, without adverse effect.

Threshold Limit Value

The American Conference of Governmental Industrial Hygienists (ACGIH) publishes Threshold Limit Values for Chemical Substances and Physical Agents annually. The ACGIH has derived TLVs for many substances. TLVs are developed as guidelines to assist in the control of health hazards; for example, they may be used to determine the appropriate level of worker protection. TLVs are intended for use in the practice of industrial hygiene, not for use as legal standards. Rather, OSHA's PELs are the enforceable standards. The ACGIH defines three categories of TLVs: Time-weighted average (TWA) Short-term exposure limit (STEL) Ceiling (C) All three categories can be useful in selecting levels of protection at a hazardous waste site. Refer to the Threshold Limit Values for Chemical Substances and Physical Agents publication for additional details.

Antagonism (4+6=8)

The interaction of two toxic chemicals can effectively produce less than the expected result, for example when combining Phenobarbital and benzopyrene. The Phenobarbital increases the enzyme activity that detoxifies the benzopyrene. A prescription drug being taken by a worker may interact with a hazardous chemical encountered in the workplace. Therefore, a doctor needs to know that a worker can be exposed to specific chemicals on the job.

Kidneys

The main function of the kidneys is to filter the blood and eliminate wastes. Because the waste gets concentrated in the process, toxins can be at much higher levels in the kidneys. Toxins that damage this organ are known as nephrotoxins. Most heavy metals fall into this category, including mercury, arsenic, and lithium. Many halogenated (i.e., chlorinated) organic compounds are also nephrotoxins such as tetrachloroethylene, carbon tetrachloride, and chloroform. Other chemicals that damage the kidneys include carbon disulfide, methanol, toluene, and ethylene glycol.

Solids

The principal hazard is usually from dusts or fumes produced when solids change form. For example, polyurethane foam, when burned, gives off cyanide gas. Routes of entry in this case are inhalation, ingestion (saliva), and skin absorption.

Interaction with other chemicals

The study of the interaction of various chemicals with one another is known as chemistry. An example is the reaction between acids and bases. The physical and biochemistry of the living organism is much the same. Chemicals in combination can produce different biological responses than the responses seen when exposure is to one chemical alone.

Measurement

The two common units of measurement used in setting exposure limits are: Parts per million (ppm) or parts per billion (ppb) Milligrams per cubic meter of air (mg/m3) The formula for converting ppm to mg/m3 is: Molecular weight x ppm _______________________ mg/m3 The formula for converting mg/m3 to ppm is: mg/m3 x 24.45 ________________ Molecular weight Ppm and ppb are volume to volume and mg/m3 is weight to volume. Some examples to help imagine parts per million are: An ounce of chocolate in a million gallons of milk A drop of vermouth in a railcar full of vodka An example of parts per billion is: One grain of sugar in a 10 pound bag of sugar.

Toxicolgy

Toxicology is the study of chemical toxicity. Toxicity is the degree to which a chemical or substance has a harmful effect on us or other living things.

Skin and Eye Contact

Unlike inhalation, skin and eye contact with toxic chemicals normally results in damage at the point of contact. Sulfuric acid will do damage only at the point of contact, although there are a few toxic chemicals that can be absorbed through the skin and into the blood stream. Once in the bloodstream, the chemical can move to any spot and do its damage. The most common chemicals that can be absorbed through the skin are in pesticides and herbicides. Just remember, if sweat can come out of your skin, chemicals can get into it.

Sensitizers

are allergens. These chemicals cause an allergic type of reaction due to sensitivity from prior exposure. An acute response may be swelling of the breathing tubes, which causes breathing difficulty. Sensitizers can cause chronic lung disease. Some common examples are epoxies, aromatic amines, formaldehyde, nickel metal, and maleic anhydride.

Mutagen

cause alterations in the genes of a person exposed. The result may be malfunction of a specific organ or tissue, depending upon the type of cell affected. Gene damage can be passed on to children if the mutation occurred in either the sperm or the egg of the parents. Examples of mutagens are ethylene oxide, benzene, and hydrazine.

Carcinogens

cause cancer in humans or in laboratory test animals. This is a chronic effect as there is a time period that elapses before a malignant tumor will appear. Examples of carcinogens are benzene, benzopyrene, asbestos fibers, acrylonitrile, and DBCP (dibromochloropropane).

Teratogen

damage or kill a developing fetus. This damage cannot be passed on to further generations, as it does not affect the genetic code. Examples of teratogens are thalidomide, dioxins, lead, and cadmium.

The NIOSH Pocket Guide to Chemical Hazards defines IDLH concentration as the

maximum level from which one could escape within 30 minutes without any escape-impairing symptoms or any irreversible health effects." The American National Standards Institute, Inc. (ANSI) defines IDLH as "...any atmosphere that poses an immediate hazard to life or produces immediate irreversible debilitating effects on health." Regardless of their exact definition, all IDLH values indicate those concentrations of toxic substances from which escape is possible without irreversible harm should a worker's respiratory protective equipment fail.