Risk and Toxicology

What is Risk?  the possibility of suffering harm from a hazard that can cause injury, disease, death, economic loss, or environmental damage  expressed in terms of probability

Risk Assessment vs. Risk Management  risk assessment : the scientific process of estimating how much harm a particular hazard can cause to human health  risk management : involves deciding whether or how to reduce a particular risk to a certain level and at what cost

Four Major Types of Hazards  cultural   physical   chemical   biological 

Toxicology  toxicity : a measure of how harmful a substance is in causing injury, illness, or death to a living organism  depends on several factors:  dose : the amount of a substance a person has ingested, inhaled, or absorbed through the skin  frequency of exposure  size of person exposed  how well the body’s detox systems work  genetic makeup

Five Major “Harm Factors”  5 major factors that affect how harmful a substance is:  solubility  persistence  bioaccumulation  biomagnification  chemical interactions

Solubility  water-soluble toxins  usually inorganic  can move through the environment and get into water supplies OR the solutions that surround our cells  oil (fat)-soluble toxins  usually organic  can penetrate cell membranes and therefore can accumulate in body tissues and cells (e.g. DDT)

Persistence  resists breakdown  can have long-lasting harmful effects

Bioaccumulation  when molecules are absorbed and stored in specific organs or tissues at higher than normal levels  chemicals can build up to harmful levels in animals  occurs in a single organism

Biomagnification  when levels of some potential toxins in the environment are magnified as they pass through food chains  each animal in low trophic levels ingests a small amount  an animal higher up eats a lot of the lower-level organisms

Biomagnification Illustrated

Chemical Interactions  antagonistic interaction : reduces harmful effects  synergistic interaction : multiplies harmful effects

Types of Response  response : the type and amount of health damage resulting from exposure to a chemical or other agent  acute effect : an immediate or rapid harmful reaction to an exposure  chronic effect : a permanent or long-lasting consequence from exposure to a single dose or to repeated sublethal doses of a harmful substance

Basic Principle of Toxicology  ANY chemical can be harmful if taken in large enough quantity  “the dose makes the poison”  depends on the genetic makeup of the individual

Mechanisms for Reducing Harmful Effects  the body can break down, dilute, or excrete small amounts of most toxins to keep them from reaching harmful levels  cells can sometimes repair damage to DNA and proteins  cells in some parts of the body can reproduce fast enough to replace damaged cells

Toxicity Depends On …  what the chemical is!  top 5 toxic substances are:  arsenic  lead  mercury  vinyl chloride (used to make PVC)  polychlorinated biphenyls (PCBs)

How Do We Estimate Toxicity?  median lethal dose (LD 50 ) : the amount received in one dose that kills 50% of the animals in a test population  dose-response curve : shows the effects of various dosages of a toxic agent on a group of test organisms  typically use fairly high dosages

Dose-Response Curve

EC50

Human Health TOPIC 22

How Do We Estimate Toxicity for Humans?  we use case studies and epidemiological studies  i.e. accidental poisonings, overdoses, homicides, etc.  we can extrapolate from high-dose studies on animals  is this valid??

Chemical Hazards  3 major types of potentially toxic agents:  mutagens  teratogens  carcinogens

Mutagens  chemicals or ionizing radiation that cause or increase the frequency of random mutations, or changes, in the DNA molecules found in cells  most mutations are harmless  harmful mutations in reproductive cells can be passed to offspring

Teratogens  chemicals that cause harm or birth defects to a fetus or embryo  alcohol   thalidomide 

Carcinogens  chemicals or ionizing radiation that cause or promote cancer (i.e. the growth of a malignant tumor, in which certain cells multiply uncontrollably)  there may be YEARS between initial exposure and the appearance of detectable symptoms  metastasis : when malignant cells break off from tumors and travel in body fluids to other parts of the body

Effects of Chemical Hazards on Humans  effects can be seen in the:  immune system  nervous system  endocrine system (network of glands that release hormones)

Immune System  chemicals (such as arsenic and dioxins), as well as ionizing radiation, can weaken the immune system  makes the body vulnerable to allergens, bacteria, viruses, and protozoa

Nervous System  neurotoxins : inhibit, damage, or destroy nerve cells that transmit electrochemical messages throughout the body  cause behavioral changes, paralysis, death  e.g. PCBs, mercury

Endocrine System  hormones : chemicals that turn on/off bodily systems that control reproduction, growth, development, learning ability, and behavior  hormone disrupters (hormonally active agents [HAAs])   hormone mimics  hormone blockers  thyroid disrupters

Biological Hazards  nontransmissable disease : caused by something other than a living organism and does not spread from one person to another  e.g. cardiovascular disorders, diabetes, asthma, malnutrition  transmissable disease : caused by a living organism and can spread from one person to another  caused by infectious agents, or pathogens  spread by vectors 

Types of Pathogens  bacteria  single-celled organisms that can replicate themselves by simple cell division  viruses  microscopic, noncellular infectious agents (must hijack living cells)  parasites  organisms that feed off other organisms  protozoa  a diverse assortment of microscopic or near-microscopic organisms that live as single cells or in simple colonies

Epidemiological Transition  as a country industrializes, deaths from childhood infectious diseases decrease and those from chronic disease of adulthood increase  why?

Considerations  we are starting to see more genetic resistance of bacteria due to the overuse of antibiotics  disease spreads more rapidly due to human travel and the trade of goods  we cannot use antibiotics to deal with viruses!

Most Widespread and Dangerous Viruses  human immunodeficiency virus (HIV)  transmitted by unsafe sex, sharing of drug needles, infected mothers to offspring before or during birth, and exposure to infected blood  influenza (the flu)  transmitted by the body fluids or airborne emissions of an infected person  hepatitis B (HBV)  transmitted in the same manner as HIV

Recent Viruses that Have Received a Lot of Coverage  Ebola  transmitted by the blood or other body fluids of an infected person  West Nile  transmitted by the bite of a mosquito that has become infected by feeding on birds carrying the virus  severe acute respiratory syndrome (SARS)  transmitted by airborne droplets

Problems with Viral Drugs  drugs used to treat viruses also harm host cells  vaccines stimulate the immune system to produce antibodies to ward off viral infections  BUT vaccines are not available for all viruses

Some Diseases are Making a Comeback!  tuberculosis (TB)  bacteria are transmitted through airborne droplets  “silent” global epidemic  factors:  lack of screening  antibiotic resistance  urbanization  malaria  parasites are transmitted through mosquito bite  infects and destroys red blood cells  factors:  mosquitoes are resistant to pesticides  Plasmodium is resistant to drugs  poverty