Toxicology

1. Toxicology

2. I. Studying Chemical Hazards • To assess the risk a chemical poses to any organism, we need to determine the concentrations that cause harm. To learn this, scientists use • Dose-response studies • Prospective studies • Retrospective studies

3. B. Dose-response analysis = measuring how much effect a toxicant produces at different doses 1. Dose = the amount of toxicant the test animal receives 2. Response = the type or magnitude of negative effects of the animal 3. Dose-response curve = the plot of dose given against response

4. Dose response curves C. Threshold = dosage that must be reached before any harmful effects occur 1. Organs can metabolize or excrete low doses of a toxicant

5. D. Dose-response studies test subjects are usually rats or mice, but also invertebrates and fish (FIFRA – no environmental harm). No amphibian studies.

6. I. Studying Chemical Hazards E. Most dose-response tests look for an LD50 value, which is the dose at which 50% of the test subjects die (over a set time period, usually 18 days). F. Dose-response tests can also be used to determine different sub lethal effects - teratogen, neurotoxin, carcinogen. The experiments are then termed TD50 tests, for toxic dose – the dose required to show the sub lethal effect in 50% of the population. G. Effective dose 50, or ED50 can be used to see dose required to see results in 50% of the population (ie how many milligrams for pill dosing, 50% of the population has headache relief with the dose etc).

8. LD50 192 mg/kg each cup of coffee Not fat soluble, so exits, half life is 2.5 to 4.5 hrs. 100 lb person, 45.5 kg 45.5 kg x 192 mg/kg = 8,727 mg caffeine Each cup of coffee is ~ 100 mg so 87 cups of coffee in ~2 hrs 19year old James Stone died after consuming 25 to 30 No-Doz caffeine pills to stay awake and alert. 200 mg caffeine per No Doz ~6,000 mg of caffeine

9. I. Studying Chemical Hazards H. When looking at LD50 data, regulatory agencies often divide it by 10 to determine safe concentrations for animals in the environment to ingest. I. Scientists extrapolate downward from animal studies to estimate the effect on humans – the mammal model used is always rats or mice. J. For humans, the LD50 value is divided by 1,000 to determine safe concentrations of the chemical to be exposed to.

10. H. Pharmaceutical dose-response testing A = concentration at which benefits first noticed B = maximum + benefit C= Harmful effects first exceed benefits D, E = increasing dosage concentrations increase harm

11. Human studies K. Human studies are also used to study chemical hazards. L. Epidemiology = large-scale comparisons between groups of people M. Retrospective studies – monitor people who have been exposed to chemical some time in the past • Identify exposed group • Control group (no exposure, similar demographics) • Usually done after issue (Bhopal, Times Beach)

12. I. Studying Chemical Hazards • N. Prospective studies – monitor large groups of people that may become exposed to harmful chemicals in the future. Tricky because of synergistic interactions of multiple toxins.

13. O. The type of exposure affects the response 1. Acute exposure = high exposure for short periods of time to a hazard • Easy to recognize • Stem from discrete events: ingestion, oil spills, nuclear accident 2. Chronic exposure = low exposure for long periods of time to a hazard • Hard to detect and diagnose • Affects organs gradually: lung cancer, liver damage • Cause and effect may not be easily apparent

14. I. Studying Chemical Hazards P. Different people respond differently to hazards 1. Affected by genetics, surroundings, etc. 2. People in poor health are more sensitive 3. Sensitivity also varies with sex, age, and weight 4. Fetuses, infants, and young children are more sensitive

15. I. Studying Chemical Hazards Q. We can’t determine the impact of mixed hazards • They may act in ways that cannot be predicted from the effects of each in isolation R. Synergistic effects = interactive impacts that are more than or different from the simple sum of their constituent effects 1. Mixed toxicants can sum, cancel out, or multiply each other’s effects 2. New impacts may arise from mixing toxicants

16. II. Children A. Infants and young children are more susceptible to the effects of toxic substances than are adults for four major reasons: • Children generally breathe more air, drink more water, and eat more food per unit of body weight than adults • They are exposed to toxins in dirt and dust when they eat things off the ground, or put their toys in their mouth.

17. 3. Children have less well-developed immune systems and body detoxification processes than adults. 4. Children’s bodies are organs are still developing and growing, which make them even more sensitive to endocrine disrupters.

18. B. The National Institute of Environmental Health and Safety has 13 research centers devoted exclusively to children’s environmental health and disease prevention. C. Studying the role of environmental toxicants in asthma autism, and neural and behavioral development.

19. D. Asthma Findings – research on indoor/outdoor air quality and childhood asthma has found: 1. Asthma most common chronic disease in childhood (9.4% of childhood population), the incidence of asthma has more than doubled in the U.S. since 1980. 2. Increased nitrogen dioxide and ozone exposure levels correlate to higher probability of asthma development 3. Children who live in polluted communities are five times more likely to have clinically low lung function (only 20% or less of expected lung function for their age). 4. Indoor biological allergens are among the most important and potent triggers of asthma attacks.

20. E. Autism Findings – 1. In the last 30 years, the rates of autism have doubled 2. Vaccine scare – original research paper that started issue has been retracted for scientific inaccuracy 3. Looking at PCBs, methyl mercury, other toxic chemicals, including medicines 4. Major prospective and retrospective studies taking place, no definitive conclusions yet.

21. F. Development and toxicology findings: • 17% of all U.S. children have one or more developmental, learning, or behavioral disability and the National Academy of Sciences Estimates about 3% of these disabilities are caused by known exposures to toxic substances • Exposures to both PCBs and methyl mercury showed no major impact individually, but synergistically showed significant deficits in learning and neurological function.

22. G. Louisiana and Texas lead the nation in air and water emissions of developmental and neurological toxins. Of the top 100 counties for releases nation wide, Texas has 7 (5 in the top 25).

23. Texas “Dirty Seven” – Top counties nationally for release of developmental and Neurological Toxins 3. 7. 14. 20. 25. 56. 78.

24. III. Heavy metals • Heavy metals that are toxic to humans and prevalent in the environment from mining, electronics, and refining include lead, mercury, cadmium, nickel, arsenic, and chromium, and thallium. Mercury, thallium, and lead are considered very toxic. • Heavy metals tend to be stored in fatty tissue, and bioaccumulate. • The term body burden refers to the content of heavy metals in our body

25. D. Mercury 1. Pathway: Mercury is released as an atmospheric pollutant from coal-fired power plants, incinerating waste, and processing metals, specifically gold.

26. E. Mercury is removed from the atmosphere via precipitation. It is deposited into water directly via or on land and runs off into water. F. The mercury deposited in the water is elemental mercury (Hg), which actually can’t be absorbed by aquatic organisms. G. In aquatic environments, bacteria facilitate a complex process of methylation, transforming elemental mercury into methyl-mercury (CH3Hg). Methyl mercury is more toxic and can easily be taken up by aquatic organisms.

27. H. Methyl mercury biomagnifies up aquatic food chains. Top predator fish often have high levels of mercury in their tissues. I. Pregnant women are advised not to eat: Shark, Swordfish, King Mackerel, blue fin tuna, or Tilefish J. Additionally, Wahoo, marlin and grouper should be limited to one or two times a month for young women and children

28. K. Methyl mercury only enters the body through ingestion, and people are exposed almost entirely by eating aquatic top predators. L. Effects of mercury ingestion include immune system dysfunction, altering of genetic and enzyme systems, damaging the nervous system, including coordination and the senses of touch, taste, and sight. M. Methyl mercury is particularly damaging to developing embryos, which are five to ten times more sensitive than adults.

30. “Mad as a Hatter” referred to people working in the hat industry in England in the 1800s. Solution used to turn fur into hats contained mercury, and working with this all day gave hatters mercury poisoning.

31. N. Lead is another heavy metal of concern. Greatest risk is for children under 5. Lead poisoning has been linked to lower IQs, seizures, apathy, bizarre behavior, learning disorders, and severe mental issues. In adults or in higher concentrations, lead causes nerve disorders M. Lead is found in old paints, drinking water from older pluming and soldering, in some lead-glazed pottery, in some inexpensive jewelry, and in soil around older homes that may have picked up paint chips. The most common exposure is deteriorated lead paint in older homes.

32. O. Lead can enter the body through inhalation or ingestion. Taking lead additives out of gas has decreased children’s blood lead levels by 86% since the late 1970s. P. Best ways to remediate lead include professional cleaning and painting over old lead paint, and removing hazardous building components like old pipes. Q. Lead is one of the most common toxic metals in inner-city environments. In some populations, over 20% of children have blood concentrations of lead that are higher than those believed safe.

33. The Roman Empire used and smelted tremendous amounts of lead. Lead was used for cooking pots, dishes, and pipes that carried water. It has been hypothesized that widespread lead poisoning among the upper-classes in Rome lead to the Empire’s downfall.

34. IV. Endocrine Disrupters • Endocrine disruptors = compounds that mimic hormones and interfere with the functioning of animals’ endocrine (hormone) systems. Four main points about endocrine disruption: • Low dose matters • Wide range of health effects • Persistence of biological effects • Ubiquitous exposure

35. B. Endocrine disrupting chemicals work at very low concentrations. Evidence now suggests that LD50 studies, or studies where organisms are given huge doses of toxins and evidence of major toxicity (tumors, malformations) are not showing the more subtle but equally problematic effects of endocrine disruption.

36. C. Endocrine disrupters work by turning on, shutting off, or modifying signals that hormones carry, which may affect the normal functions of tissues and organs. D. Many of these substances have been linked with developmental, reproductive, neural, and immune issues. E. Endocrine disrupters have also been linked to decreased fertility and increased progressions of some diseases including obesity, diabetes, and some cancers.

37. F. Exposure to endocrine disrupters may be through diet, air, skin, and water. G. Greatest risk may be for pre-natal and early childhood development.

38. H. Chemicals are ubiquitous and we are exposed to them constantly – found in plastic bottles and containers, liners of metal food cans, detergents, flame retardants, food, toys, cosmetics, and pesticides.

39. Examples of Endocrine disrupters: • Dioxin – over 75 different compounds, manufacturing byproduct exposed via diet (meat, milk highest concentration) Probable carcinogen as well. • PCBs – over 205 chemicals, used in electrical components, carcinogen and endocrine effects. • BPA – found in plastic water bottles and lining of metal food cans

40. 4. DDT/other pesticides 5. Polybrominated diphenyl ethers (PBDEs) = has fire-retardant properties; used in computers, televisions, plastics, mattresses, furniture, clothes

41. J. Evidence for hormone disruption 1. Frogs also have gonadal abnormalities • Male frogs became feminized from atropine concentrations well below EPA guidelines 2. PCB-contaminated human babies were born weighing less, with smaller heads

42. K. Male sperm counts are dropping 1. Scientists attribute the shocking drop in men’s sperm counts to endocrine disruptors • The number and motility of sperm has dropped 50% since 1938 2. Testicular cancer, undescended testicles, and genital birth defects are also increasing

43. V. Noise and legislation • Noise is also a pollutant – Any sound above 80 decibel (db) is potentially dangerous – chain saw 15 m away. • Db scale is exponential by 10. Between 70 and 80 is ten times louder, between 70 and 90 is 100 times louder. • Toxics Release Inventory (TRI) is public list of toxins released by industry. This is mandated by the Emergency Planning and Community Right to Know Act (EPCRA), enacted in 1986.