unit 6: human health and toxicology. how do we define health? a state of complete physical, mental,...

Unit 6: Human Health and Toxicology

How do we define HEALTH?

• A state of complete physical, mental, and social wellbeing

• NOT JUST being free from disease or injury

Health can be affected by

• Child development• Lifestyle***• Career• Trauma• Income/ Social

status• Education

• Where you live• Availability of

health care• Culture• Gender• Sleep• Genetics

Health CareWho can we go to in order to maintain our health?• Medical doctors• Dentists• Optometrists• Psychologists/ Psychiatrists• Counselors• Nutritionists• Personal Trainers• Chiropractors• Massage Therapists

Center for Disease Control & Prevention (CDC)

• Part of the Department of Health and Human Services

• HQ in ATL• Study viruses/ bacteria to find vaccines/

treatments• Tell us how unhealthy we are and why• Try to find ways to make Americans more

healthy

World Health Organization (WHO)• Part of the UN• Coordinate efforts to

stop the spread of global diseases

• Sponsors programs to help prevent and treat diseases

• Help develop and distribute vaccines

Importance of Public Health

• Attempting to stop/ lessen outbreaks of diseases, especially ones we can prevent

• Education programs• Vaccines• Increase access to health care• Limit disparity

Leading causes of death in the US1. Heart disease: 597,6892. Cancer: 574,7433. Chronic lower respiratory diseases: 138,0804. Stroke (cerebrovascular diseases): 129,4765. Accidents (unintentional injuries): 120,8596. Alzheimer's disease: 83,4947. Diabetes: 69,0718. Nephritis, nephrotic syndrome, & nephrosis: 50,4769. Influenza and Pneumonia: 50,09710. Intentional self-harm (suicide): 38,364

The Information Blanket

• Educates mothers about child health

http://informationblanket.com/

Epidemiology

• Study of health characteristics, events, or patterns within a population

• Studies the cause of diseases– Abnormal condition affecting

the body

• Important because it can help inform public health policy

Causes of disease• Pollution:

– Radiation sickness– Respiratory disease caused by air pollution

• Has caused an increase in cancer – Abnormal cell growth

Causes of disease

• Zoonotics– Diseases that pass

from animals to humans (such as Ebola and HIV)

– Bush meat and poaching

Causes of disease

• Humans are invading previously undisturbed habitats and coming into contact with crazy new organisms and the diseases they carry

• We don’t have immunity to those diseases! (think Native Americans and smallpox!)

Altering Ecosystems• In the US we have caused the decline of deer

and mice predators more ticks more Lyme disease

Other causes of disease• Dirty water (cholera, typhoid fever)• Insects that act as a secondary host (malaria,

West Nile)• Undercooked food (salmonella)

Disease Classification

• Noninfectious: Non-communicable, major killer in industrialized society; often have multiple causes– Cardiovascular disease,

Cancer, Sickle-Cell, Diabetes, Emphysema, Asthma, Cerebral Palsy

Disease Classification

• Infectious: Can pass from person to person; caused by a pathogen such as– Bacteria– Viruses– Protozoan– Parasitic Worms– Fungus– Prions

Transmission

• Vector: any organism that carries & transmits an infectious pathogen into another organism

• Fomite: any inanimate object capable of carrying an infectious pathogen and transferring it– Smooth non-porous surfaces transfer pathogens

more readily than rough porous ones.

Disease Classification

• Endemic- normal rate of occurrence• Epidemic- above normal rate of occurrence,

an “outbreak”• Pandemic- worldwide epidemic

– 1918 Flu that killed 21 million people worldwide– The Black Plague

Disease Classificiation

• Acute- short duration illness or high dose exposure. If victim survives initial “attack”, they usually survive (ex: influenza)

• Chronic- Long duration illness or low dose exposure. Kills you slowly. (ex: tuberculosis, heart disease, cancer…)

Big 3 Killers

1. HIV- Human Immunodeficiency Virus 1. Infects 5 million/ year & kills 3 million/ year

2. Influenza1. Kills about 1 million/ year

3. Hepatitis B Virus1. Kills about 1 million/year2. Damages liver

What about antibiotics?

• Antibiotics are compounds that kill bacteria• Overusing them! They are in our food and people are

demanding them when not needed

• People don’t take entire prescription• Travel around and may already have a

resistance• Bacteria reproduce and evolve rapidly (16+

BILLION OFFSPRING in 24 HOURS!)

What about antibacterial soap?

• Makes things worse!• You need small doses of bacteria to develop

an immunity when you get larger doses• Kids are developing super weak immune

systems

What about vaccines?• Small doses of living or dead virus injected/

inhaled to stimulate the body’s immune system

• Give your body info to develop antibodies against if you do get the virus later

• Virtually wiped out some diseases!

But I heard vaccines cause autism…

• WRONG! • The guy that wrote this paper was proven to

be a fraud- he made up data!• There is NO LINK between vaccines and

autism (studies now think autism might be caused by illnesses when mothers are pregnant)

• Vaccinate your kids! You can’t rely on “herd immunity” (everyone else is vaccinated so I’ll be okay)

How can we reduce disease?• Vaccinate your kids/ yourself• Reduce poverty (specifically in Africa)• Increase research on tropical diseases • Educate people on antibiotics• WASH YOUR HANDS! • Reduce antibiotics use in food• Improve drinking water quality

Mutagens

• Mutagens are substances capable of inducing mutations (changing the nucleotide sequence).

• Mutagens may be chemical, physical or biological agents.

• In 1927, X-rays were the first mutagens to be recognized.

Mutagens

• Chemical mutagens include formaldehyde, mustard gas, vinyl chloride and many other chemicals.

• Thousands of workers are exposed to mutagenic substances in the workplace.

• A mutation can be passed on only if it occurs in the sex cells.

Birth Defects

• Mutations are believed to account for ~25% of all birth defects.

• Birth defects are the leading cause of infant mortality in the US.

• Teratogens are substances that cause birth defects.

Birth Defects• Men working as painters, farmers, or mechanics -

jobs involving exposure to solvents and pesticides - tend to be at higher risk of fathering children with birth defects.

• The most sensitive period for a human embryo is during the formation of the organs (from the 18th day to the ~60th day -> peak at ~ day 30).

Types of teratogens: Ionizing Radiation

• X-rays -> central nervous system disorders• Nuclear fallout ->microcephaly, eye problems,

mental retardation

Types of teratogens: Pathogenic Infections

• German measles -> heart defects, deafness, cataracts

• Syphilis & Herpes simplex 2 -> microcephaly, mental retardation

• Toxoplasmosis -> fatal legions in the CNS

Types of teratogens: Drugs and Chemicals

• Thalidomide – a nonprescription sleeping pill

used extensively in Germany and the UK during the early 1960’s

– causes phocomelia (‘seal limbs’) in the babies of 40% of the women who took thalidomide during their 1st trimester

Types of teratogens: Drugs and Chemicals

• Dioxin – structural deformities, miscarriages

• Methyl mercury– mental retardation, sensory and motor problems

Types of teratogens: Drugs and Chemicals

• DES (Diethylstilbestrol) – resembles natural estrogen– prescribed to prevent miscarriage (it actually

increased risk)– in the late 1950’s one company urged all pregnant

woman to take the drug in order to have ‘bigger and stronger babies’

– ~5 million pregnant women used it– disrupted the endocrine system– causes vaginal cancer in girls, genital abnormalities in

boys

Types of teratogens: Drugs and Chemicals

• Cigarette smoke– low birth weight,

miscarriage, still birth

• Alcohol – mental retardation,

growth deficiencies, microcephaly, facial irregularities

Cancer

• Cells that have uncontrollable growth • 20-25% of all deaths in industrialized countries• Highest incidence among the elderly; 2nd

leading cause of death among US children age 1-14.

Environmental Carcinogens

• In 1775, an English doctor, Sir Percival Pott, recognized an association between cancer of the scrotum and exposure to soot - benzopyrene was the carcinogenic agent (the 1st known environmental carcinogen)!!!

Cancer

• Tobacco use is by far the leading cause of cancer mortality. Tobacco smoke contains 4,700 chemicals; 43 are known carcinogens (arsenic, benzene, radioactive polonium, etc.).

Cancer• Aflatoxins are potent carcinogens produced by the

fungus Aspergillus flavus. • The fungus grows on peanuts, pistachios, corn, rice and

certain grains and nuts when temperatures and humidity are high.

• Aflatoxins are among the strongest carcinogens known!

Cancer• Many foods contain anticarcinogenic compounds

(broccoli, cauliflower, cabbage, kale and brussels sprouts contain sulforaphane - one of the most potent anticarcinogens known.

• Cooked tomato products, yellow and green vegetables, citrus fruits, apricots, cantaloupe, brown rice, wheat germ soy products, onions, and garlic

Linking environmental agents to human cancers is difficult because:

• Ethics in human testing• Long latency periods• Animal testing is sometimes difficult to apply to

humans• Similar chemicals may act very differently• Chemicals may be transformed by the body (ex.

nitrite, a food preservative, is transformed by the body into nitrosamine, a carcinogen)

Preventing cancer can be accomplished by

• Decreasing tobacco use• Decreasing alcohol consumption• Improving nutritional choices, exercising regularly,

and maintaining proper body weight• Avoiding sun exposure and using sunscreen• Fixing structures with excess radon

Bioterrorism

• Terrorist act that releases some infectious disease into air, water supply, food supply, at a large event

• Increasing threat (H5N1 dispute)• Cheaper and more effective than bombs• Could spread quickly before anyone knew

what happened

What is Risk?

• Risk is the possibility of suffering from harm that can result in injury, disease, death, economic or environmental damage

• Risk assessment is the scientific process of estimating how much harm a particular hazard can do to humans

• Risk management involves deciding how to reduce a risk to a certain level and the cost

Risk Analysis

• Identification of hazards and their risks (negative or unwanted outcomes)

• Informing people about risk is important• GREATEST RISK= POVERTY

Probable v Possible

• Risk is defined as a probability• When we say it is possible a smoker will get

lung cancer we mean that it might happen.• Probability gives us a numerical estimate of

the likelihood of the event happening.

Risk Perception

Risk Perception• We participate in high-risk

situations everyday that we do not think of as high-risk– Motorcycling: 1 in 50– Smoking: 1 in 300 by age 65– Hang gliding: 1 in 1250– DRIVING A CAR:

– 1 in 3300 WITHOUT a seatbelt – 1 in 6070 WITH a seatbelt

Risk Perception• We are ridiculously afraid of low-risk

activities because they are perceived as “scary”– Getting shot: 1 in 28,000– Nuclear Plant Accident: 1 in 200,000– West Nile Virus: 1 in 1 million– Struck by Lightning: 1 in 3 million– Commercial airplane crash: 1 in 9 million– Snakebite: 1 in 36 million– Shark attack: 1 in 281 million

Risk Perception

• We are more afraid of the unknown or things we have no direct control over

• We are afraid of things that are not considered voluntary

• We are afraid of catastrophic risks instead of chronic risks

• We are worried about unfair distribution of risks

Toxicology

• Toxicology is the study of toxic substances.• Toxicants have the ability to harm organs or

biochemical processes away from the site on the body where exposure took place.

• Irritants damage only the tissue they contact.

Poison Ivy Rash

Toxicology Principles

• Anything is dangerous if ingested in a large enough quantity.

• How do we know how much exposure causes a harmful response?

4 Major Hazards1. Cultural hazards• Unsafe working conditions• Smoking• Poor diet• Drugs/ drinking• Driving• Criminal assault• Poverty• UNSAFE SEX

4 Major Hazards

2. Physical hazards• Ionizing radiation• Fire• Tornado• Earthquake• Volcanic eruption• Floods• Hurricanes

4 Major Hazards

3. Chemical Hazards• Chemicals in the air• Chemicals in the water• Chemicals in the ground

4 Major Hazards4. Biological hazards• Pathogens

– Bacteria– Viruses– Parasites

• Pollen and allergens• Animals like bees & poisonous snakes (on

planes…)

Toxicity

• Measure of how harmful a substance is in causing injury, illness, or death

• Depends on DOSE (amount that has been inhaled, ingested, or absorbed through the skin), age, and health of the person/ animal

• Also depends on genetic makeup

5 factors that affect toxicity

1. Solubility2. Persistence3. Bioaccumulation4. Biomagnification5. Chemical interactions

Chemical Interactions

• Can decrease or multiply the harmful effects• Antagonistic interaction reduces harmful

effects• Synergistic interaction multiplies harmful

effects

Response

• Type and amount of damage resulting from exposure to a chemical or other agent

• Acute effect- immediate or rapid harmful reaction to exposure (dizziness to death)

• Chronic effect- permanent or long-lasting consequence from single dose or repeated sublethal doses (organ damage)

Dose is important

• Dose makes the poison but it is different for different people!

• 3 mechanisms to combat harmful effects:– Break down, dilute, or excrete small amounts of

most toxins– Enzymes can sometimes repair damage done to

DNA– Cells can reproduce quickly to replace damaged/

lost cells

VerySensitive

Majorityof population

VerySensitive

0 20 40 60 80

Dose (hypothetical units)

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LD50

• Acute toxicity is described by the LD50:– the amount of chemical, administered in one dose,

that is required to kill 50% of a population of test animals within a 14-day period.

– Expressed as: (mg of chemical / kg of body weight).

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Dose (hypothetical units)

LD50

• Animal testing combined with data from accidental poisonings, suicides, murders, industrial accidents to estimate lethal doses for humans.

• Testing for subchronic and chronic toxicity is more difficult, time consuming, and expensive than acute toxicity testing. (involves feeding experiments over several months or more, and subsequent animal autopsies)

LD50

Eff

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Dose

Nonlineardose-response

Lineardose-response

No threshold

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Nonlineardose-response

Lineardose-response

Threshold

Thresholdlevel

Dose

The data collected is plotted on a dose-response curve. The threshold is the point on the curve where increasing dosage is beginning to provoke symptoms

• Regulators establish margins of safety - A 100-fold margin of safety is used for regulatory control of toxicants based on two assumptions:1. humans are 10 times more susceptible to toxic

effects than laboratory animals2. children, elderly, and the immunocompromised are

10 times more susceptible to toxic effects than the average healthy adult

LD50

Polychlorinated Biphenyls (PCBs)

• PCBs were first synthesized in 1929.

• Production was halted in the US in 1977.

Polychlorinated Biphenyls (PCBs)

• Oily liquids to waxy solids. • Extremely stable substances; non-flammable• Primarily used as insulating liquids in electrical

transformers and capacitors• In addition, PCBs were used as plasticizers in paints,

plastics and rubber products, in pigments, dyes, carbonless copy paper and many other applications.

• Highly soluble in fat and insoluble in water

Polychlorinated Biphenyls (PCBs)

• PCBs escape into the environment through:– discharge waste from industries

into waterways– vaporization from paints or landfill

burnings– leaks in industrial equipment,

especially transformers– accidental spills or illegal dumping

Polychlorinated Biphenyls (PCBs)

• PCBs accumulate in fatty tissues (liver, kidneys, heart, lungs, brain, and breast milk).

• In 1976, 99% of all breast milk sampled in the US contained PCBs.

• Bioaccumulation -> PCB concentrations in the body increase over time.

DDT in fish-eatingbirds (ospreys)

25 ppm

DDT in largefish (needle fish)2 ppm

DDT in smallfish (minnows)0.5 ppm

DDT inzooplankton0.04 ppm

DDT in water0.000003 ppm,Or 3 ppm

PCB health effects:• Miscarriage• Causes cancer in rats ->

probable human carcinogen• Chloracne -> acne-like skin

disorder caused by acute exposure

• Known endocrine disruptor• Impairs the immune system• Negative effects on the

intellectual development of children and adults

Dioxin (TCDD)

• Dioxins form a large group of chemicals of widely varying levels of toxicity - the most dangerous being TCDD

Dioxins• Dioxins have no industrial uses; formed as an

unwanted by-product of industrial processes.• In the absence of light TCDD breaks down very

slowly.

Major contributors of dioxin to the environment include:

• Incineration of Municipal Solid Waste• Incineration of Medical Waste• Secondary Copper Smelting• Forest Fires• Land Application of Sewage Sludge• Cement Kilns• Coal Fired Power Plants• Residential Wood Burning• Chlorine Bleaching of Wood Pulp• Backyard burning of household waste may also be an

important source

Human exposure

• Most of us receive almost all of our dioxin exposure from the food we eat: specifically from the animal fats associated with eating beef, pork, poultry, fish, milk, dairy products.

• Since most of the meats and dairy products we consume are not produced locally but have been transported hundreds or thousands of miles, the majority of our dioxin exposure does not come from dioxin sources within our own community.

Ukrainian President Viktor Yushchenko(acute dioxin poisoning resulting in chloracne)

Lead• “Lead poisoning is entirely preventable, yet it

is the most common and societally devastating environmental disease of young children.” -Dr. L Sullivan, former Secretary of Health and Human Services

Lead• In the US, the largest use of lead is for

lead storage batteries (virtually every car has at least 20 pounds of lead in its battery).

• Other lead containing products – Ammunition– Brass– glass TV tubes– Solder– Lead-glazed ceramic ware– Lead-crystal decanters– Pigments & artists’ paint– Moonshine (distilled in lead-soldered auto

parts)– Some types of vinyl miniblinds, etc.

• Lead is found in soil, water, air, and food.

• The amount of lead entering the atmosphere has declined sharply since the phaseout of leaded gasoline in the mid-1970s (completed in 1995).

• Leaded gasoline is still widely used in other countries

• Many people are exposed to lead in drinking water through lead pipes or solder. Now plastic (PVC) pipes are used.

• Lead used in soldering the seams of canned foods and beverages was once the main source of lead intake in the US (banned in 1991).

Original Roman lead pipe Copper pipe with

lead solder

PVC pipe

Lead

• Lead house paint was used in the US from 1884-1978 - it is still used to paint bridges, ships, and other steel structures.

• House paint is the most important source of lead poisoning exposure.

• Infants and toddlers are at highest risk because the blood-brain barrier is not fully developed.

Health effects of lead exposure:

• Increased blood pressure• Anemia• Miscarriages• Altered immune function• Kidney damage• Injury to the CNS -> hyperirritablity, poor memory, mental

retardation, convulsions, coma, death

• In children, chronic low-level exposure can inhibit intellectual development -> amount of lead in teeth correlates to IQ , learning disabilities and drop-out rate.

Mercury• Mercury (‘quicksilver’) has been used for more than

2500 years.• Mercury’s first medicinal use was for the treatment

of syphilis in 16th century Europe.

Mercury• Mercury is used:

– in thermometers, thermostats & barometers

– in fluorescent light bulbs– as a fungicide in paints– as an alloy in dental fillings– ritualistic uses

• Coal burning and municipal waste incineration are the largest sources of mercury in the atmosphere.

• Gold mining tailings are another important source mercury.

CFL

Mercury

• Mercury caused the ‘Mad Hatter’s Disease’ made famous in Alice in Wonderland.

• Hat-makers soaked animal hides in mercuric nitrate to soften hairs.

Mercury

• Inorganic mercury (mercury nitrate) can be inhaled or absorbed through the skin.

• Inorganic mercury attacks the liver and kidneys.• Organic mercury (methyl mercury) is much more

toxic than inorganic mercury.

Methylmercury, an organic mercury compound released in factory wastewater and the cause of Minamata disease

Mercury• In Minamata Bay, Japan, a plastics factory released

inorganic mercury into the water from 1932-68.

• The inorganic mercury was converted to methyl mercury by bacteria in the anaerobic sediments.

• The methyl mercury was biomagnified and caused a variety of health effects in cats and then humans.

• 1700 people died and 9000 were left with varying degrees of paralysis and brain damage.