Human health and toxicology

Major health issues May seem more important today than in the past In part because of so many people But are not new to the planet

Toxicity What is toxic? Chronic Acute Can rank toxicity Some things are much more toxic than other, but . . . Varies depending on individual age health genes

Dose-response Some things are bad for you - How much before harm is done? Some things are good - How much is too much? Too much of a good thing

Lab tests Expose animals to potential toxics See how many die or get cancer or … Depending on dosage LD50 = lethal dose for half the population Of course Tough to translate to humans And we can’t do human experiments But, experiments confirm that very small amounts can be very bad

Top 10 most toxic substances (arguably) and estimated LD50 for 200 lb person based on lab experiments on various mammals tetanus (bacteria) 0.1 μg botulinal neurotoxin (bacteria) 0.1 μg shigella (bacteria) 0.1 μg palytoxin (coral) 6 μg diphtheria (bacteria) 10 μg ricin (from castor beans) 0.1 μg aflatoxins (mold which grows on nuts, legumes, seeds) 0.1 μg saxitoxin (shellfish) 0.3 μg tetrodotoxin (fugu pufferfish) 1 μg diphtheria (bacteria) 0.2 μg 1 grain of salt is about 60 micrograms (μg)

Cancer and related problems Carcinogens Cause cancer Malignant melanoma

Cancer and related problems Mutagens Cause mutation

Cancer and related problems Teratogens Cause birth defects Two-headed kitten Cancer, mutation, birth defects caused by exposure to toxics But often hard to tell which Some, such as cigarettes, are obvious

Endocrine disrupters Act like hormones in the endocrine system Cause cancer, reduced sperm counts, immune problems . . . Definitely affect animals – what about people? Very difficult to determine dose-response for humans Examples DDT - pesticides PCBs - transformers Bisphenol A – epoxy, plastics PDEs - solvents Phthalates - plastics Many others Male sperm counts have decreased all around the world during the past 15-20 years. Cause is unknown. But, at this rate there will be widespread infertility within decades. Many suspect endocrine disruptors are the cause.

What are the risks/costs/odds? Risk-benefit Hard to evaluate risk And, how safe do we want to be? Cost-benefit What is a human life worth? And, what is the cost of not doing something? Precautionary principle One major problem is that we know there are synergies, and antagonistic interactions -- but it is almost impossible to evaluate them.

Started really being Concerned about Hazardous waste Because . . . 1977 Love Canal Niagara Falls New York Chemical company and school board Really brought concerns to forefront Dioxins Next major issue Form during chemical manufacturing involving chlorine-bearing compounds Also comes from burning waste that contains chlorine in dumps or backyards Also produced by paper mills, production of PVC plastic, and other industries Times Beach MO 1970s PCBs PCBs are also chlorine-containing compounds Once used as coolants, flame retardants, lubricants . . . Now banned in US Manufacturers knew PCBs causes health problems since the 1930s and 1940s Many reports of serious health problems Did not become real concern until 1970s Chlorine is a key component in many toxics – plastics, pesticides, etc.

Hazardous waste So, we have RCRA 1976 CERCLA and Superfund 1980 Requires cradle to grave tracking of toxics CERCLA and Superfund 1980 Passed in response to Love Canal And dioxin at Times Beach And other such laws Superfund sites in US As of January 2013, there were 1,312 NPL sites in the U.S. None in North Dakota any longer Since 1980, <300 taken off the list

But, many things we encounter in our daily lives are toxic Pesticides Industrial chemicals PVC, etc. And more And . . . Even cautious use releases some stuff to the environment

Toxics are all around us: plastics polystyrene HDPE PVC PET polypropylene LDPE When we use them, we absorb some . . . although generally in small amounts.

Plastics in food FDA says all plastics put toxics in our food Question is: how much, and how much is bad? Manufacturers are required to “prove” safety Which cannot be done

PVC In toys, clear food and non-food packaging (e.g., cling wrap), some squeeze bottles, shampoo bottles, cooking oil and peanut butter jars, detergent and window cleaner bottles, shower curtains, medical tubing, and numerous construction products PVC has been described as one of the most hazardous consumer products ever created. PVC leaches di(2-ethylhexyl) phthalate (DEHP) or butyl benzyl phthalate (BBzP), depending on which is used as the plasticizer or softener (usually DEHP). DEHP and BBzP are endocrine disruptors mimicking the female hormone estrogen. This type of plastic has been strongly linked to asthma and allergic symptoms in children; may cause certain types of cancer; is linked to negative effects on the liver, kidney, spleen, bone formation and body weight. In Europe, DEHP and BBzP and other dangerous pthalates have been banned from use in plastic toys for children under three since 1999.

PET Soft drink, juice, water, beer, mouthwash, peanut butter, salad dressing, detergent and cleaner containers Leaches antimony trioxide: workers exposed to antimony trioxide for long periods of time have exhibited respiratory and skin irritation; among female workers, increased incidence of menstrual problems and miscarriage. The longer a liquid is left in such a container, the greater the concentration of antimony is released into the liquid.

PS = polystyrene In styrofoam containers, egg cartons, disposable cups and bowls, take-out food containers, plastic cutlery, and compact disc cases. Polystyrene leaches styrene, which is an endocrine disruptor mimicking the female hormone estrogen, and thus has the potential to cause reproductive and developmental problems. Long-term exposure by workers has shown brain and nervous system effects. Polystyrene is also present in secondhand cigarette smoke, off-gassing of building materials, and car exhaust. Styrene migrates significantly from polystyrene containers into the container’s contents when oily foods are heated in such containers.

HDPE In opaque milk, water, and juice containers, bleach, detergent and shampoo bottles, garbage bags, yogurt and margarine tubs, cereal box liners Research on risks associated with this type of plastic is ongoing

LDPE In grocery store, dry cleaning, bread and frozen food bags, most plastic wraps, squeezable bottles (honey, mustard) Research on risks associated with this type of plastic is ongoing Nalgene

PP = polypropylene In ketchup bottles, yogurt and margarine tubs, medicine and syrup bottles, straws, opaque plastic storage containers, baby bottles, clothing Research on risks associated with this type of plastic is ongoing.

PC = polycarbonate In most plastic baby bottles, clear plastic “sippy” cups, hard “sports” water bottles, three and five gallon large water storage containers, metal food can liners, some juice and ketchup containers, compact discs, cell phones, computers Polycarbonate leaches Bisphenol A (some effects described above), and numerous studies have indicated a wide array of possible adverse effects from low-level exposure to Bisphenol A including chromosome damage in female ovaries, decreased sperm production in males, early onset of puberty, various behavioral changes, altered immune function, and sex reversal in frogs.

Cancer rates Seem to be higher today Men Women Diet Life style Environment Men Prostate Lung – accounts for 75% of deaths Colorectal Women Breast Lung – accounts for 40% of deaths Cancer clusters?

Cancer Worldwide – about 12% of deaths are due to cancer US has highest cancer rates in the world 4 in 10 people in US get cancer today Expected to increase in next decade Due to continued smoking Aging population We have many products, including food, that contain toxics And especially poor diet and unhealthy lifestyles Brain cancer cells

Why Cancer clusters? Prostate cancer

How should we handle toxics? Ideally – use them safely But, we don’t know what that is, and . . . Routine use poses risk Even if only a little escapes into the environment . . . Small doses can be very bad For many toxics we don’t know risk Synergies and bioaccumulation not understood Skeptics say we must prove risk Before doing anything Precautionary Principle says the opposite

Sadly, we mostly only act after catastrophe e.g., Superfund after Love Canal and Times Beach

Pollution and human health Are things getting better or worse? Cancer has reached epidemic proportions Billions of pounds of chemicals escape each year Other new things causing alarm Endometriosis Emerging new problem affecting women’s uterus ADD/ADHD 3% more victims each year Asthma Doubled between 1980 and 1996 Sperm counts Falling rapidly

Pollution and human health What is cause of increase in problems? No certain answers but most experts say 1. exposure to toxics 2. lifestyles For example food is routinely sprayed with pesticides whose safety is in question Pesticide residues show up on all foods unless organic Delaney clause says no carcinogens can be in food But is not well enforced

Could problems be genetic, not environmental? Study identical twins Find that breast cancer rates do not match Instead correlate with environmental factors Study adopted children Find that cancer rates do not correlate with biological parents Instead with adopted parents and exposure to toxics

Why not do something? We do, sometimes: e.g., Delaney Clause But delays caused by: Scientific uncertainty Economic cost And, sadly: Things may be worse than we think If we delay, it could be too late Even worse: Politics: Government often will not do it even when it is clear that action is needed

And, what about (“natural”) diseases Lyme disease

And, what about (“natural”) diseases Novel infections seem more common these days Not necessarily due to toxics but there could be a connection In part probably due to Better detection People no longer die of unknown causes People travel a lot more Food and other things are shipped all over Overuse of antibiotics means Organisms are more virulent and resistant

New (“emerging”) and old diseases Legionnaire’s disease 1976 Caused by bacteria living in air conditioners Many people very ill Half died

New (“emerging”) and old diseases Legionnaire’s 1976 Aids First recognized in 1981 30 million people infected worldwide Most in Africa Due to HIV virus Many new drugs Prolong life but most victims still die

New (“emerging”) and old diseases Legionnaire’s Aids Exotic diseases from Africa Lhasa fever Ebola virus Marburg infection

New (“emerging”) and old diseases Legionnaire’s Aids Lhasa fever Ebola virus Marburg infection Lyme disease

New (“emerging”) and old diseases Legionnaire’s Aids Lhasa fever Ebola virus Marburg infection Lyme disease Hanta virus From Korea Killed people in southwest US in 1993

New (“emerging”) and old diseases Legionnaire’s Aids Lhasa fever Ebola virus Marburg infection Lyme disease Hanta virus Some old diseases seem to be coming back: Malaria Tuberculosis In part because they are becoming resistant to antibiotics

Food poisoning

Food poisoning E coli Botulism Campylobacter Salmonella Bovine spongiform encephalitis (BSE) bacteria bacteria bacteria bacteria protein

Food poisoning E coli Botulism Campylobacter Salmonella Widespread organism Many different types Some very bad Most associated with sewage E coli Botulism Campylobacter Salmonella Mostly due to improper food handling Found in raw poultry and meat, Unpasteurized milk, untreated water Most common identified form of food poisoning Found in raw poultry, dairy and meat, and unwashed vegetables, In the gut and feces of animals and humans

Food poisoning E coli Botulism Campylobacter Salmonella All of these got much worse because of: Large centralized food production facilities Intensive feed lots and agriculture Overuse of antibiotics, etc “Big box” food stores

mortality today In HDC countries Sanitation and drugs help Disease and pathogens (mostly) under control In U.S., leading causes of death: heart disease, cancer Non-infectious, chronic, associated with lifestyle and aging Not so In LDC countries Malnutrition Sanitation Water supplies Air pollution  many infectious disease problems Cholera occurrences

Should we be scared? Some people worry about pandemics There are some warning signs

Should we be scared? Aids Out of Africa Most cases in Africa Many in US Many others in India, Asia, etc. Not curable, but can be slowed

Should we be scared? BSE Bovine spongiform encephalopathy a.k.a. mad cow disease Disease in cattle Especially in UK May be transmitted to people Leads to Creutzfeldt-Jakob disease Causes brain degeneration in people Contributing cause is that cattle are fed meat and bone meal, causing disease to spread Not necessary because cattle are herbivores But cattle operators make more profits if fattened with animal based feed

Should we be scared? BSE Led to slaughter of entire British dairy industry in late 1980s But spread to Canada So, temporary bans put on importing Canadian beef So, how bad is it?

Should we be scared? Swine flu a.k.a. pig flu or pig influenza Common in pigs Especially pigs in feed lots So, operators give lots of antibiotics to pigs Which are the same antibiotics humans use So, super strains of flu and other pathogens develop that are antibiotic resistant Pigs die And . . . humans catch disease that originated in pigs CDC has warned for years that we need to stop giving antibiotics to livestock But intensive livestock operations need it So pig/cattle operators make more profits So, how bad is it?

But, so far, these disease risks are small compare with risks from . . . Cancer Second leading cause of death in US (following heart disease) Many different kinds (>200) Can start in any type of body tissue Not a pandemic Many factors contribute Most important Tobacco Diet/weight/physical activity Ultraviolet radiation Carcinogens

So . . . Don’t smoke (There are lots of reasons not to smoke besides cancer . . .) Eat healthy foods and get exercise

Cosmetics and other beauty products

Avoid carcinogens? Carcinogens include Antiperspirants Talcum powder Hair dyes, cosmetics, and almost everything else in a beauty salon Dry cleaning fluid Insect spray Food ingredients: aspartame, bovine growth hormone, artificial colors and flavors And many more common product ingredients

Everything causes cancer . . . ? They say: A cop out Excuse not to think about a very complex problem Some things are known to be carcinogens (or possibly to be carcinogens) Others are not Which do you want in your life?

So, should you be worried? Only if you haven’t thought about these issues . . . And don’t plan to think about them now.