Risk, Toxicology and Human Health Chapter 17 Risk, Toxicology and Human Health

Risk Risk: probability of suffering harm from a hazard - values range from: 0 ----> 1.0 can’t will happen happen Risk Assessment: use of data, hypotheses and models to estimate risk caused by certain hazards Risk Management: how serious? how much should it be reduced? how to reduce? how much to spend?

© 2004 Brooks/Cole – Thomson Learning Number of individuals affected Very sensitive Majority of population Very insensitive 20 40 60 80 Dose (hypothetical units)

5 Types of hazards 1) cultural hazards (unsafe working conditions, criminal assault, poverty) 2) chemical hazards (in air, water, soil, food) 3) physical hazards (noise, fire, floods, ionizing radiation) 4) biological hazards (pathogens, allergens, snakes) 5) Lifestyle choices (poor diet, smoking, no exercise)

Nontransmissible diseases not caused by living organism can’t spread from person to person e.g. diabetes

Transmissible diseases Caused by living organisms Bacterium, virus, protozoan, or parasite = pathogen 1) Vectors: nonhuman carriers 2) Bacterium: one celled microorganism 3) Virus: noncellular, infectious agent, a strand of nucleic acid (either DNA or RNA) wrapped in a protein coat a) virus must invade host cell and take over cell’s DNA to make more viruses

Transmissible diseases 80% of all illnesses in developing countries are caused by waterborne infectious diseases e.g. diarrhea, hepatitis, cholera Note: when bacteria are treated with penicillin, survivors have mutant genes that make them immune to medication---> natural selection Epidemiological transition: industrialized, less infectuous, more chronic

Tuberculosis Infects 9.2 m million per year. Kills 1.7 million per year. Bacterium spreads by airborne droplets (coughing, talking) Half of infected people don‘t know they are Most strains are genetically resistant to almost all previously effective antibiotics

Lyme Disease A bacterial disease spread from deer and mice to humans, tick is vector.

(massive epidemic = pandemic) Viral Diseases e.g. flu, HIV, hepatitis B, ebola, rabies From 1918-1919, flu epidemic killed 20-50 million people worlwide, 250,00 to 500,000 in US (massive epidemic = pandemic)

Viral Diseases Once a viral infection starts, it is harder to fight than bacteria or protozoan infections 1) antibiotics are useless and increases resistance of bacteria 2) preventative vaccines are the only effective weapon

Viral Diseases West Nile virus is transmitted by mosquito bite West Nile, SARS, and Avian flu have moved from animals to humans

AIDS Due to AIDS, life expectancy among 700 million in sub-Saharan Africa: 62-->42 years 2nd biggest viral killer (kills 2.1 mil/year) Expensive drug cocktail ($25k/yr) extends life tens of years Priorities to slow spread: focus on high risk group (IV drug users), research, education program for children, free testing, provide low cost drugs to slow progress

Malaria 40% of world population lives in regions where malaria is present Symptoms: chills, weakness, anemia Kills about 1 million people per year Spread by: anopheles mosquito bites person infected with plasmodium parasite (type of protozoa), mosquito later bites uninfected person, spreading disease Parasite invades red blood cells ---> decreases body’s ability to transport O2 (anemia) ---> lower resistance

Malaria Spread of malaria was cut by draining swamps, spraying with insecticide, treating parasite with drugs Since 1970, disease has come back, mosquito became resistant to insecticides and parasite became resistant to drugs Spread is increasing because irrigation and hydropower has led to more breeding places, global warming has led to increased range In 2006, the WHO supported use of DDT for malaria control

Chemical Hazards Toxic Chemicals can cause temporary or permanent harm or death to humans and animals EPA’s top five most toxic: arsenic, lead, mercury, vinyl chloride (PVC), and PCBs Hazardous Chemicals flammable or explosive irritating or damaging to skin or lungs (e.g. oven cleaner) interfere with oxygen uptake (e.g. CO) induce allergic reactions of immune system (allergens)

Chemical Hazards Carcinogens chemicals, radiation or viruses that cause growth of malignant tumors examples include: PCBs, radon, UV radiation, chemicals in tobacco smoke, X-rays, vinyl chloride cancer can be spread by metastasis: malignant cells break off from tumors and travel in body fluids to other parts

Chemical Hazards Mutagens chemicals or radiation that causes mutations in DNA if mutation occurs in reproductive cell, affects future generations may cause tumors in exposed person Teratogens chemicals, radiation or viruses that cause birth defects while embryo is growing (especially first 3 months) e.g. alcohol, PCB’s, thalidomide (sleeping pill, never approved in US), mercury, etc

PCBs b/w 1929 and 1977 used in transformers and capacitors (common in railroad yards) Causes cancer, learning disability Fat soluble so can be biomagnified Stable so persists in environment, mat travel great distances

Immune System 2 levels of defense Specialized cells and tissues that protect body against disease and harmful substances 2 levels of defense 1) antibodies detect and mark invaders for other immune cells to attack 2) cellular defenses (e.g. T-cells) kill invaders Pesticides can suppress human immune system Neurotoxins can attack nerve cells (neurons) e.g. methyl mercury, DDT, PCB’s, dioxins

Mercury Teratogen and neurotoxin 1/3 naturally occurring 2/3 human caused: burning coal, waste incineration, fluorescent bulbs Bacteria can convert to methyl mercury which is fat soluble so can be biomagnified High levels found high on food chain (tuna)

Endocrine system Set of glands that release hormones into the bloodstream 1) Hormones control sexual reproduction, growth, behavior, mix of estrogens and androgens determines sex 2) Hormones (key and lock) connect with receptor molecule and move onto nucleus to execute message

Hormone Disrupters 1) Human-made chemicals, DDT, PCBs 2) hormone mimics ---> attack estrogen receptor molecules 3) hormone blockers ---> prevent androgen from attaching to receptor molecules 4) thyroid disrupters cause growth, brain, weight, behavior disorders

Hormone Disrupters 4) More than 60 chemicals (HAAs) are identified e.g. dioxins (chlorinated hydrocarbons) are produced when chlorine compounds are incinerated (found in Agent Orange, defoliant used in Vietnam) e.g. PCB’s, pesticides, lead, mercury, bisphenol A (found in plastic water bottles and baby bottles: brain damage on test animals)

Toxicology Study of health affects caused by chemicals 1) Toxicity: how harmful a chemical is 2) Detoxification system: liver, kidney, etc 2) Dose: amount of substance or radiation taken into body [acute (one dose), chronic (lifetime of doses)] 3) Response: type and amount of damage to health a) acute effect: immediate, rapid reaction to dose b) chronic: permanent or long lasting result

Bioaccumulation (typically occurs in organisms low on food chain) a) toxins accumulate in fat cells over time b) biological half-life: time required for 1/2 of chemical to be removed c) water soluble toxins pass through in urine

Biomagnification (high on food chain) a) each consumer ingests toxins accumulated by each organism lower on the food chain e.g. 10 minnows eat toxin. small fish eats 10 minnows. big fish eats 10 small fish. human eats big fish and the equivalent of 1000 minnows worth of toxin. DDT ---> zooplankton ---> insects ---> spiders ---> mice ---> falcon

DDT in fish-eating birds (ospreys) 25 ppm DDT in large fish (needle fish) 2 ppm DDT in small fish (minnows) 0.5 ppm DDT in zooplankton 0.04 ppm DDT in water 0.000003 ppm, Or 3 ppt

Dose e.g. NO2, O3 react synergistically with allergens Synergistic effects (antagonistic effects) e.g. NO2, O3 react synergistically with allergens LD 50 (or LC 50) dose required to kill 50% of test population a) Poison: chemical with an LD 50 of 50 mg or less per kg of body weight EPA lists top 5 toxic substances: arsenic, lead, mercury, vinyl chloride (PVC), PCBs

Methods to determine toxicity (public health threat) 1) Case reports (anecdotal info on rxn to chemical) 2) Lab study (done on test animals) a) metabolites: products of body’s rxn to chemical 3) Epidemiology a) study of human populations exposed to chemicals or diseases b)why do some get sick, others don’t

Epidemiology Study of patterns of disease or toxicity to find out why some people get sick and others do not. Not useful for predicting affects of new technologies, substances or diseases.

Dose-response curve Shows effects of various doses of a toxic agent on a group of test organisms Requires a controlled experiment (test group vs control group) To save time and money, high doses are used and results are extrapolated to lower doses (and to human response, which is controversial)

Terms to know: Independent variable Dependent variable Control Standard conditions Replicates Control group Experimental group

Recommended Dose Because of uncertainty, standards for exposure to toxic chemicals or radiation are set at levels 100 to 1,000 times lower than estimated harmful levels

© 2004 Brooks/Cole – Thomson Learning Nonlinear dose-response Linear dose-response Effect Effect Threshold level Dose Dose No threshold Threshold Usually used

Percentage of population killed by a given dose 100 75 Percentage of population killed by a given dose 50 25 LD50 2 4 6 8 10 12 14 16 Dose (hypothetical units)

Some substances that can kill us at high doses Hormesis Some substances that can kill us at high doses can be beneficial at low doses (digitalis)

Ionizing radiation can cause 1) Genetic damage from mutations in DNA 2) Somatic damage: causes harm during victims life e.g. burns, eye cataracts, certain cancers 3) Super linear hypothesis: low doses produce more cancer per unit than high doses 4) Main source of radiation is radon

Epidemiological transition In 1994, 23 million people died of all causes 39% ---> heart attacks and strokes 24% cancer 5% infectious diseases (pneumonia, flu, aids) 4% accidents (2% auto)