Toxicology: Chemical Risks Ch 17 APES

CHEMICAL HAZARDS A toxic chemical can cause temporary or permanent harm or death. Mutagens chemicals or forms of radiation that cause or increase the frequency of mutations in DNA. Type of carcinogen Carcinogens chemicals or types of radiation that can cause or promote cancer. Teratogens chemicals that cause harm or birth defects to a fetus or embryo. Allergens Chemicals that cause allergic reactions. Can cause abnormally high response of the immune system

Mutagens Ionizing Radiation PAH – polycyclic aromatic hydrocarbons Gamma, X and UV Radioactive decay PAH – polycyclic aromatic hydrocarbons PAH – mutagen and carcinogen - largest group of known carcinogens – major components in fossil fuel and released during fossil fuel combustion If affect sperm/egg can be passed down to children Cystic Fibrosis, Down Syndrome, Sickle Cell Benzo[a]pyrene

Carcinogen Asbestos (synergistic with smoking tobacco) Acrylamide (used as a polymer; plastics) Dioxins (herbicides & paper bleaching) BPA (bisphenol-A), PCB BPA found in plastics PCB used to manufacture electronics (banned in 1979) Many chemicals in cigarette smoke Viruses- HPV Key factors in cancer risk: #1 Smoking (30%) #2 Diet (30%) #3 Industrial Chemicals (30%) Occupational (15), Environmental (10) #4 Genetic (10%)

Teratogen PCB’s (polychlorinated biphenyl ) Herbicides Thalidimide Acutane (acne medicine) Heavy Metals Arsenic, lead, cadmium, mercury Alcohol

Endocrine Disrupters Chemicals that interfere with the normal functions of hormones. Found in drinking water from sewage, farming, & pesticides that mimic animal hormones Growth hormones in cattle etc., human birth control pills Many male fish, amphibians, and reptiles becoming feminized: Low sperm count Testes that produce both egg and sperm Examples: DDT, Atrazine (herbicide)

Effects of Chemicals on the Immune, Nervous, and Endocrine Systems Endocrine Disruptors p235 Reduced penis size, female shellfish with male organs, decreased fertility rates, decreased sperm counts and endometirosis, early puberty Figure 18-9

CHEMICAL HAZARDS A hazardous chemical can harm humans or other animals because it: Is flammable Is explosive An irritant Interferes with oxygen uptake Induce allergic reactions.

Effects of Chemicals Immune, Nervous, and Endocrine Systems Chronic vs. Acute Long-term exposure to some chemicals at low doses may disrupt the body’s: Immune system: affect cells and tissues that protect the body against disease and harmful substances. Synthetic Pesticides, PCB Nervous system: brain, spinal cord, and peripheral nerves. DDT, Heavy Metals – Pb, Hg, Cd Endocrine system: complex network of glands that release minute amounts of hormones into the bloodstream. DDT, BPA, PCB, Dioxin, Pthalates, diethylstilbestrol (DES) Epidemiological studies from Canada and the former Soviet Union find that children and adults exposed to pesticides suffer similar immune system alterations and higher rates of infectious disease. The risks of pesticide-induced immunosuppression are known to be greatest to infants and children, the aged, people malnourished or chronically ill.

Industrial Disasters Bhopal, India – The world’s worst industrial accident occurred in 1984 at a pesticide plant in Bhopal, India. An explosion at Union Carbide pesticide plant in an underground storage tank released a large quantity of highly toxic methyl isocyanate (MIC) gas. 15,000-22,000 people died Indian officials claim that simple upgrades could have prevented the tragedy. Minamata, Japan – methylmercury, caused Minimata Disease Love Canal – Industrial Waste near town and site turned school. NIAGARA FALLS, N.Y .--Twenty five years after the Hooker Chemical Company stopped using the Love Canal here as an industrial dump, 82 different compounds, 11 of them suspected carcinogens, have been percolating upward through the soil, their drum containers rotting and leaching their contents into the backyards and basements of 100 homes and a public school built on the banks of the canal.

Toxicity Measurement of how harmful a substance is Depends on Chemical or ionizing radiation Depends on Dose Exposure Age Genetic Make-up of Individual Detoxification System Solubility Persistence Bioaccumulation Biomagnification Chemical Interactions

Dose-Response Studies Expose organism to different amounts of a chemical and observe a variety of responses to: Mortality (most common; i.e. LD-50) Changes in behavior Changes in reproduction Measured as a concentration of a chemical in air, water or food. Also measured as a dose – the amount of chemical absorbed/consumed by an organism Because of their short duration (1-4 days) called acute studies.

Dose-Response Studies Count how many die after exposure to each concentration Data usually exhibits an S-shaped curve Lowest dose no mortality Threshold – dose at which effect can be detected LD50 – measurement useful in comparing harmful effects of different chemicals Important in assessing the toxicity of new chemicals to determine if the new chemical is more or less lethal LD50 can be different among species and rats and mice are usually used to test LD50 in humans. Extrapolate to account for mass differences.

Testing Standards Chemicals are regulated by EPA as of 1976 Manufacturer of chemical must demonstrate that chemical will not cause adverse effects. Devised a system of testing a bird, mammal, fish & invert. Using LD50 values: Safe concentrations for animals are determined by taking the LD50 value/10 For humans LD50 values determined for rats/mice are divided by 1000 to ensure an extra level of caution (very conservative).

Toxicity - Dose LD50 Median lethal dose The amount of chemical in 1 dose that kills 50% of animals within a 14 day period Poison - LD50 of 50mg/kg of body weight

Toxicity - Dose “The dose makes the poison” Paracelsus, 1540 Supertoxic (dioxin, nerve gas and botulism toxin) Extremely toxic (nicotine) Very toxic (mercury salts, codeine) Toxic (lead salts, caffeine, DDT) Moderately Toxic (methyl alcohol, aspirin) Slightly Toxic (ethyl alcohol, soap) Essentially nontoxic (water)

Toxicity - Exposure Methods of Exposure How often and for how long? Ingestion Inhalation Through Skin How often and for how long? Acute vs. Chronic For example DDT was shown to be safe by spraying on children because it does not easily penetrate the skin, however it is eaten in food and inhaled as well.

TOXICOLOGY: Exposure Estimating human exposure to chemicals and their effects is very difficult because of the many and often poorly understood variables involved. Figure 18-11

Persistence Bioacculumlation and Biomagnification Lipid soluble POP – persistent organic pollutants PCB, Dioxin, DDT Heavy Metals – methyl mercury, tetraethyl lead Algal Blooms – “red tide” makes mussels toxic.

DDT and Bioaccumulation(absorbed or stored in organs) and Biomagnification (through a food chain) Fig. 11-4 p. 231

TOXICOLOGY: genetic make-up Typical variations in sensitivity to a toxic chemical within a population, mostly because of genetic variation. Figure 18-10

Other Studies Chronic Studies: Retrospective vs. Prospective Studies: Toxicology studies conducted over a long period of time. Goal is to examine the long-term effects of chemicals on survival and impacts on reproduction Retrospective vs. Prospective Studies: Epidemiology – understanding the causes of disease in humans & wildlife Retrospective Studies – monitor people who have been exposed to a chemical in the past. Ex: Bhopal, India – still monitoring people who were exposed. Prospective Studies – monitor people who might be exposed to chemicals.