Introduction Study Guide (TOX)

Describe the first case of Forensic Toxicology.

1840 Marie Lafarge suspected of using arsenic to kill her husband. Inaccurate "marsh test" on the victim could not produce traces of poison. Orfila retested using accurate procedures and found traces of arsenic.

What are BEIs?

BEIs are recommended maximum concentrations of various types of toxic substances, and are guidelines to evaluate the potential health hazards associated with exposure.

What does analytical toxicology identify?

Identifies the toxicant through analysis of body fluids, stomach content, excrement, or skin.

ACGIH: The American Conference of Governmental Industrial Hygienists

Produces a listing of Threshold Limit Values (TLV) and Biological Exposure Indices (BEI) for several hundred chemicals.

FDA (Food and Drug Administration)

Promotes and protects the public health by helping safe and effective products reach the market in a timely way. Monitors products for continued safety after they are in use. Includes food, pharmaceutical drugs, medical tools, cosmetics and tobacco products. Also regulates the use of feed and pharmaceuticals for pets and animals.

What is dose-response?

Relationship between exposure and health effect. Can be established by measuring the response relative to an increasing dose. Important in determining the toxicity of a particular substance. Relies on the concept that a dose, or a time of exposure will cause an effect on the exposed organism. The larger or more intense the dose, the greater the response, or the effect. This is the meaning behind the statement "the dose makes the poison."

Sub-Chronic Toxicity

Results from repeated exposure for several weeks or months. Usually measured as effects for more than a year but less than a lifetime. This is a common human exposure pattern for some pharmaceuticals and environmental agents.

Classification of Toxicants

Target organ Hepatotoxin, neurotoxin, etc. Intended use Pesticide, solvent, etc. Source Natural, synthetic Special effect Carcinogen, mutagen, endocrine disruptor, etc. Physical state Gas, solid Toxicity Extremely, slightly Chemical composition Heavy metal, organophosphate Mechanism of action Anticholinergic (blocking nerve impulses) inhibitor Uncoupler (ETC chemiosmosis ineffectual)

Specialty Areas in Toxicology Selected Responses

Teratology (study of malformations or serious deviations from the normal type in developing organisms) Carcinogenesis

Toxicity can result from adverse cellular, biochemical, or macromolecular changes such as what?

Cell replacement, such as fibrosis damage to an enzyme system disruption of protein synthesis production of reactive chemicals in cells DNA damage Can be acute, sub-chronic or chronic. Can be selective.

What is an example of how analytical toxicology is involved in research?

Example: determining the pharmacokinetic and toxicokinetic properties of substances or the efficacy of new treatment regimens.

Hippocrates in his treatise Air, Water and Places 400 BC

"...the appearance of disease in human populations is influenced by the quality of air, water, and food; the topography of the land; and general living habits.

Paracelsus (1493-1541)

"What is there that is not poison? All things are poison and nothing without poison. Solely, the dose determines that a thing is not a poison"

Selective Toxicity

A chemical will produce injury to one kind of living matter without harming another form of life, even though the two may exist close together. Selective action of a toxic agent on different species or organisms forms the basis of Economic Toxicology. Used to protect the desired species against the harmful action of undesired ones.

What is a Toxoid?

A chemically modified toxin from a pathogenic microorganism, which is no longer toxic but is still antigenic.

How Does Toxicity Develop?

A substance must come into contact with a body surface such as skin, eye or mucosa of the digestive or respiratory tract. The dose of the chemical, or the amount one comes into contact with, is important when discussing how "toxic" an substance can be.

What is a Toxigen?

Any antigen that stimulates the formation of antitoxin in an animal or human, that is, a toxin or a toxoid.

What is a Toxicant?

Any chemical that can injure or kill humans, animals, or plants. The term is used when talking about toxic substances that are produced by or are a by-product of human-made activities.

Specialty Areas in Toxicology Target Species/ Systems

Aquatic Toxicology, Environmental Toxicology, Wildlife Toxicology, Veterinary Toxicology

In the 19th century the primary type of poison in use was what?

Arsenic No reliable ways of testing for its presence. Orfila created new techniques and refined existing ones.

What does analytical toxicology assist in?

Assists in the diagnosis, management, prognosis, and prevention of poisoning.

What is an example of toxicity?

Drugs that cause dose-dependent toxicity can cause liver disease in most people if enough of the drug is taken. Dose-dependent toxicity of acetaminophen (Tylenol).

Describe Clinical Toxicology

Concerned with diseases and illnesses associated with short term or long term exposure to toxic chemicals. Emergency room physicians must be familiar with the symptoms associated with exposure to a wide variety of toxic substances in order to administer the appropriate treatment.

Describe Descriptive Toxicology

Concerned with gathering toxicological information from animal experimentation. Used to establish how much of a chemical would cause illness or death. The United States Environmental Protection Agency (EPA), the Occupational Safety and Health Administration (OSHA), and the Food and Drug Administration (FDA), use information from these studies to set regulatory exposure limits.

Describe Occupational (Industrial) Toxicology

Concerned with health effects from exposure to chemicals in the workplace. A need to protect workers from toxic substances and to make their work environment safe. Occupational diseases caused by industrial chemicals account for an estimated 50,000 to 70,000 deaths, and 350,000 new cases of illness each year in the United States.

Types of Toxic Responses: Delayed

Days to years after exposure

Describe Analytical toxicology

Detection, identification, and measurement of foreign compounds (xenobiotics) in biological and other specimens.

What are some examples of a toxicant?

Dioxin (2,3-7,8-tetrachlorodibenzop-dioxin {TCDD}), produced as a by-product of certain chlorinated chemicals, is a toxicant. Arsenic, a toxic metal, may occur as a natural contaminant of groundwater as a toxin. May contaminate groundwater as a by-product of industrial activities as a toxicant.

What is a "sensitive sub-population?"

Dose or exposure level below which the harmful or adverse effects of a substance are not seen in a population. Also referred to as the no observed adverse effect level (NOAEL), or the no effect level (NEL). Terms are often used when discussing the relationship between exposure and dose. For substances causing cancer no safe level of exposure exists, since any exposure could result in cancer.

Types of Toxic Responses: Local

Effect at site of contact GIT, lungs

Types of Toxic Responses: Systemic

Effect distant from exposure site

EPA: The United States Environmental Protection Agency

Enforcing federal laws designed to protect human health and the environment. Headquarters in Washington, D.C. Ten regional EPA offices throughout the United States Each is responsible within selected states for implementing the agency's programs, considering regional needs and implementing federal environmental laws

NRC: The Nuclear Regulatory Commission

Established in 1974, regulates the use of nuclear materials for commercial, industrial, academic, and medical purposes. - includes regulating nuclear power plants, nuclear materials used in the diagnosis and treatment of cancer, and nuclear materials used in smoke detectors. Regulates non-power research, test and training reactors; nuclear fuel cycle facilities (the production of nuclear fuel); and the transport, storage, and disposal of nuclear materials and waste. Like OSHA and EPA, NRC obtains and evaluates information about acceptable exposure levels for workers handling nuclear materials.

Describe Regulatory Toxicology

Gathers and evaluates existing toxicological information to establish concentration-based standards of "safe" exposure. The standard is the level of a chemical that a person can be exposed to without any harmful health effects.

ATSDR greatest concerns

Generating the Hazardous Substances and Health Effects Database (HazDat) Maintaining publications: Toxicological Profiles provides information on specific chemicals and possible health effects), Case Studies in Environmental Medicine used to provide information to health care providers about the toxic effects of chemicals) Public Health Statements which contain information on toxic chemical exposures ToxFAQsTM series of summaries about hazardous substances. easy to understand, and answers the most frequently asked questions about exposure to hazardous substances found around hazardous waste sites and the effects of exposure on human health.

Chronic Toxicity

Harmful effects over an extended period of time. Promoted by repeated or continuous exposure. Damage is due to subclinical exposures that may go unnoticed. Repeated exposures or long-term continual exposure results in cumulative damage. Damage becomes so severe that the organ can no longer function normally and a variety of chronic toxic effects may result.

What are TLVs?

TLVs are guidelines for occupational exposure to hazardous chemicals and are published in a booklet called Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents and Biological Exposure Indices

NIOSH's responsibilities

Information gathered from these activities is used to help reduce disease, injury and disability in the workplace. The information is provided to OSHA, which uses it to establish standards to protect health in the workplace. Investigating potentially hazardous working conditions as requested by employers or employees. Evaluating hazards in the workplace, ranging from chemicals to machinery. Creating and disseminating methods for preventing disease, injury, and disability. Conducting research and providing scientifically valid recommendations for protecting workers. Providing education and training to individuals preparing for or actively working in the field of occupational safety and health.

What are some examples of sub-chronic toxicity?

Ingestion of coumadin tablets (blood thinners) for several weeks as a treatment for venous thrombosis can cause internal bleeding. Workplace exposure to lead over a period of several weeks can result in anemia.

Describe Food Toxicology

Involved in delivering a safe and edible supply of food to the consumer. additives are studied to determine if and at what amount, they may produce adverse effects. Food allergies: Almost 30% of the American people have some food allergy. Food Agriculture: pesticides may be applied to a food crop in the field. Lead, arsenic, and cadmium are naturally present in soil and water, and may be absorbed by plants.

Describe acute toxicity?

Involves harmful effects in an organism through a single or short-term exposure. Human tests are not performed because of ethical and legal prohibitions. Informs individuals of the health consequences from a single exposure.

Describe Mechanistic Toxicology

Makes observations on how toxic substances cause their effects. Effects of exposure can depend on a number of factors size of the molecule, the specific tissue type or cellular components affected, whether the substance is easily dissolved in water or fatty tissues.

Types of Toxic Responses: Immediate

Minutes to hours after a single exposure

CDC Centers that deal with environmental health

NCEH: National Center for Environmental Health addresses hazards associated with chemical exposure inside and outside the workplace. NIOSH: National Institute for Occupational Safety and Health established by the Occupational Safety and Health Act of 1970. several functions investigating potentially hazardous work conditions, evaluating chemical hazards in the workplace. The only federal institute responsible for conducting research and making recommendations for the prevention of work-related illnesses and injuries

Specialty Areas in Toxicology Target Organ/System

Neurotoxicology, Genetic Toxicology, Reproductive Toxicology, Immunotoxicology, Endocrine Toxicology

ATSDR: The Agency for Toxic Substances and Disease Registry

Part of the U.S. Department of Health and Human Services (CDC link). Created by Congress in 1980 to provide health-based information for use in the cleanup of chemical waste disposal sites mandated by the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA).

What is the threshold dose?

Persons who are more at risk from illness due to exposure to hazardous substances than the average, healthy person. Usually include the very young, the chronically ill, the very old, pregnant women and women of childbearing age. Depending on the type of contaminant, other factors (e.g., age, weight, lifestyle, sex) could be used to describe the population.

What is Toxic?

Poisonous or deadly effects on the body by inhalation (breathing), ingestion (eating), absorption, direct contact. Naturally occurring plant toxins poinsettia family (but not the poinsettia itself) mushrooms berries. Household products Any xeno-chemical in the right amount

Who established toxicology as a distinct scientific discipline?

Spanish physician Orfila (1787 - 1853)

What is forensic toxicology?

Study of alcohol, drugs (legal and illegal) and poisons, including their chemical composition, preparations and identification; used to help establish cause and effect relationships between exposure to a drug or chemical and the toxic or lethal effects that result from that exposure.

What is a dose?

The actual amount of a chemical that enters the body. The dose received may be due to either acute (short) or chronic (long-term) exposure. The amount of exposure and the type of toxin will determine the toxic effect.

CDC: The Centers for Disease Control and Prevention

The agency is in the Department of Health and Human Services. Mission: promote health and quality of life by preventing and controlling disease, injury, and disability. In the past, it has focused on the study and prevention of infectious diseases such as malaria and smallpox. Now its responsibilities have enlarged to include environmental and occupational hazards.

What is an example of selective toxicity?

The low toxicity of fungicide "Captan" to plants can be explained by the fungicide's lower capacity to penetrate the plant cells but in cells of the fungus it readily enters and kills them.

e-CFR: Code of Federal Regulations

The specific chemicals regulated by EPA and the standards associated with them Different sections of the CFR are called Titles, and the ones that apply to EPA are in Title 40. EPA has developed rules and regulations that activate the requirements of several environmental laws.

What is Toxicity?

The word "toxicity" describes the degree to which a substance is poisonous or can cause injury.

Why does ATSDR assess the presence and nature of health hazards at specific Superfund Sites?

To help prevent or reduce further exposure and the illnesses that result from such exposures. To expand the knowledge-base about health effects from exposure to hazardous substances.

What is a Toxin?

Toxic substances produced naturally. microbial (bacteria or other tiny plants or animals), vegetable, or synthetic chemical origin. Reacts with specific cellular components to kill cells, alter growth or development, or kill the organism.

Factors Influencing Toxicity

form and innate chemical activity dosage, especially dose-time relationship exposure route species age sex ability to be absorbed metabolism distribution within the body excretion presence of other chemicals

Many agencies have public information regarding acute toxicity:

U.S. Environmental Protection Agency (EPA) U.S. EPA Series 870 Health Effects Test Guidelines Aquatic Acute Toxicity Tests Database at the U.S. Geological Survey. Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms, part of the Clean Water Act Analytical Test Methods at the US EPA. Acute Oral Toxicity at the US National Institutes of Health's PubMed. In 1989, 5,000 people died and 30,000 were permanently disabled due to exposure to methyl isocyanate from an industrial accident in Bhopal, India.

Forensic toxicology includes knowledge about what?

absorption, distribution and elimination the manner in which the body responds to their presence the factors which determine drug safety and effectiveness

Medical Management Guidelines for Acute Chemical Exposures

aid emergency department physicians and other emergency healthcare professionals who manage acute exposures resulting from chemical incidents. intended to aid healthcare professionals involved in emergency response effectively decontaminate patients, protect themselves and others from contamination, communicate with other involved personnel, efficiently transport patients to a medical facility, provide competent medical evaluation and treatment to exposed persons.

Analytical toxicology is involved in a range of activities such as what?

assessment of exposure following chemical incidents therapeutic drug monitoring forensic analyses monitoring for drugs of abuse.

Examples of chronic toxic affects are:

cirrhosis in alcoholics who have ingested ethanol for several years chronic kidney disease in workmen with several years exposure to lead chronic bronchitis in long-term cigarette smokers pulmonary fibrosis in coal miners (black lung disease)

Describe Environmental Toxicology

the study of chemicals that contaminate food, water, soil, or the atmosphere. Deals with toxic substances that enter bodies of waters. Addresses how various plants, animals, and humans are affected by exposure to toxic substances.

Toxicology:

the study of how natural or man-made poisons (toxigens) cause adverse effects in living organisms. Harmful or adverse effects are those that are damaging to either the survival or normal function of the individual.