Risk Toxicology and Human Health April 7 th

Risk, Toxicology, and Human Health April 7 th – April 11 th

Background: Agents: Chemical and Biological Effects: Acute and Chronic, Dose-Response Relationships Relative Risks: Evaluation and Response

Exposure routes to toxic and hazardous environmental factors Water Air Occupational Exposure (oral, dermal, inhalation) Food Medical drugs (oral, intravenous, intramuscular) Incidental and accidental exposure (cosmetics, household accidents)

Comparing Bioaccumulation and Biomagnification: Bioaccumulation refers to how pollutants enter a food chain in concentration of a pollutant from the environment to the first organism in a food chain Biomagnification refers to the tendency of pollutants to concentrate as they move from one trophic level to the next. Increase in concentration of a pollutant from one link in a food chain to another

Importance: even small concentrations of chemicals in the environment can find their way into organisms in high enough dosages to cause problems. In order for bio magnification to occur, the pollutant must be: long-lived mobile soluble in fats biologically active

DDT Story http: //www. pbslearningmedia. org/resource/envh 10. sci. li fe. eco. malariaddt/eradicating-malaria-with-ddt/ By the 1960's, global problems with DDT and other pesticides were becoming so prevalent that they began to attract much attention. Credit for sounding the warning about DDT and bio magnification usually goes to the scientist Rachel Carson, who wrote the influential book Silent Spring (1962). The silent spring alluded to in the title describes a world in which all the songbirds have been poisoned.

Common Human Diseases Anthrax Botulism Cholera Hanta virus Hepatitis Influenza Leprosy

Anthrax Acute infectious disease caused by the sporeforming bacterium Bacillus anthracis, which is commonly found in cattle, sheep, and other herbivores. Symptoms for inhalation anthrax, the most serious and usually fatal, include initial fatigue, fever, difficulty breathing, profuse sweating, cyanosis, and shock. Cutaneious form begins with swelling and boils on the skin.

Botulism Rare illness caused by toxin produced by Clostridium botulinum bacterium. It may enter the body through wounds, or they may live in improperly canned or preserved food. Clostridium botulinum is found in soil and untreated water throughout the world. Foods most commonly contaminated are homecanned vegetables, cured pork and ham, and smoked or raw fish. Respiratory failure caused by weakness in the muscles that control breathing can cause death in up to 10% of food-borne illness and 2% of infant death.

Cholera A disease spread by poor sanitation, resulting in contaminated water supplies. Endemic in India and countries in South America, Southeast Asia, and Africa. Symptoms include abdominal cramps, nausea, vomiting, dehydration, and shock Illness is caused by ingestion of viable bacteria, which attach to the small intestine and produce cholera toxin. This results in watery diarrhea associated with this illness.

Hanta virus Distant cousin of Ebola virus characterized by flulike symptoms followed by respiratory failure. Carried by rodents and is present in their urine and feces. No effective treatment currently. Over 50% of the diagnosed cases have been fatal.

Hepatitis Inflammation of the liver and can be caused by a variety of different viruses such as hepatitis A, B, C, D and E. Development of jaundice is characteristic of liver disease. Some people are carriers for their entire lives while others can pass away in 6 months without knowing they were sick. CDC estimates that each year about 240, 000 Americans get Hepatitis B – spread through unsafe sex or from contact with infected blood or bodily fluids.

Influenza Spread from person to person by inhaling infected droplets from the air. 3 types Type A – responsible for the large outbreaks and is a constantly changing virus. In an avg. year, influenza is associated with more than 20, 000 deaths in the US.

Leprosy Infectious disease characterized by disfiguring skin lesions, neurological damage, and progressive debilitation. Caused by the organism Mycobacterium leprae. Common in many countries – tropical, temperate, and subtropical climates. Approx. 270 cases a year in the US

Chemical Agents Arsenic Asbestos Chlorine Formaldehyde Lead Particulates Benzene

Arsenic Combined with oxygen, chlorine, and sulfur in the environment to form inorganic arsenic compounds. In animals and plants, combines with carbon and hydrogen to form organic arsenic compounds. Exposure to higher than average levels of arsenic can cause death Exposure to lower levels for a long time can cause discoloration of the skin and the appearance of small corns or warts.

Asbestos Causes asbestosis, a respiratory disease. Inhaling asbestos fibers can cause scar tissue (fibrosis) to form inside the lung. Severity depends on duration of exposure and the amount inhaled. Exposure occurs from asbestos mining and milling industries, construction, etc. Cigarette smoking increases the risk of developing the disease. Incidences is 4 out of 10, 000 people

Chlorine Used extensively in manufacturing, especially the plastics, solvents, and paper industries. Can accumulate in body fat, and are toxic.

Formaldehyde Exposure generally occurs by inhalation or skin/eye contact. In cases of acute exposure, formaldehyde will most likely be detected by smell People who are sensitive to formaldehyde may experience headaches and minor eye and air-way irritation at levels below the odor threshold.

Lead Many different uses: batteries, ammunition, devices to shield x-rays, etc. Exposure can happen from breathing workplace air or dust, and eating or drinking contaminated foods/water. Can damage the nervous system, kidneys, and reproductive system.

Particulates Sources include: farming, mining, industries, burning fossil fuels, volcanoes, etc. In the US, particulates contribute to approx. 60, 000 deaths per year. People who live in urban areas have 15 -25% higher mortality rates than those who live in rural areas in terms of particulate risk.

Benzene Clear, colorless liquid with a sweet odor Burns readily Obtained from crude petroleum Small amounts may be found in paints, glue, pesticides, and gasoline. Breathing mild benzene vapor may cause a headache, euphoria (high), dizziness, nausea, etc. More serous exposure causes sleepiness, stumbling, passing out, and even death. Mildly irritating to the skin, eyes, and lungs.

Dose-Response Curves Tells whether the level of response increases or decreases with dose and how rapidly it changes as a function of the dose. X-axis plots concentration of a drug or hormone Y-axis plots response Concentrations of chemicals in the environment are most commonly express as ppm or ppb

3 types of agonist Full agonist – a drug that appears able to produce the full tissue response Partial agonist – a drug that provokes a response, but the maximum response is less than the maximum response to a full agonist Antagonist – a drug that does not provoke a response itself, but blocks agonist-mediated responses

Case Study: Ebola Negative-stranded RNA virus known as Filoviridae. 1 st recognized near the Ebola River in the Democratic Republic of the Congo. Most strains are zoonotic (animal hosts) Humans do not carry the virus; natural reservoir of the virus is still unknown. Current thinking: initial patient becomes infected through contact with an infected animal. Then disease is spread to new hosts by contact with any blood or bodily secretion. Rapid spread occurs through amplification – rapid increase in cases due to cross-contamination of bodily fluids by caregivers and members of a dense community.

Case Study: Lead poisoning Affects approx. 900, 000 children ages 1 -5 in the US (5% of population) Levels greater that 10 ug/dl are dangerous. Low income families are most affected African American children are 5 X more likely to be affected than white children. Greatest among the young because lead is absorbed into tissues at this age Causes damage to the nervous system resulting in mental retardation, reduced attention span, hyperactivity, impaired growth, learning disabilities, and behavioral problems. No effective cure Most lead comes from lead dust from lead-based paints 1978 the Federal government banned the use of lead in household paint

Case Study: Minamata A vinyl-chloride manufacturing plant on a Japanese island allowed mercury to be discharged in the bay. Mercury was converted to methylmercuruy and was an example of bio magnification. Human symptoms varied: nervous system damage, blurred vision, and loss of muscular coordination. It was determined that a threshold amount of methylmercury was required for symptoms to appear

Carcinogen identified by their ability to cause cancer in exposed workers, other human populations, or in test animals. Many occupational cancers have a long latency period cancer may develop 10 -20 years or longer after exposure to the carcinogen. Examples: asbestos, benzene, vinyl chloride and carbon tetrachloride

Tertogen Can cause birth defects, abnormalities, developmental delays, or death in animal offspring in the absence of significant harmful effect on the mother. These materials are usually identified using test animals and may cause similar effects in humans. Examples: carbon monoxide, lead and xylene

Mutagen Can cause changes (mutations) in the genetic material (DNA) of cells from people or test animals, which may result in disease or abnormalities in future generations. Examples - Very Toxic: chloroform, ethylene oxide Examples - Toxic: benzene, lead, and vinyl chloride

Hormone Disruptors (pg 404) Variety of human-made chemicals can act as hormone or endocrine disrupters, known as hormonally active agents (HAAS) Hormone mimics – estrogen-like chemicals that disrupt the endocrine system by attaching to estrogen receptor molecules Hormone blockers – disrupt the endocrine system by preventing natural hormones from attaching to their receptors. Growing concern that pollutants can act as thyroid disrupters causing growth, weight, brain, and behavioral disorders.

Issues: Most natural hormones are broken down or excreted. However, many synthetic hormone impostors are stable, fat-soluble compounds whose concentrations can be bio magnified as they move through the food chains and webs. Pose a special threat to humans and other carnivores dining at the top of food webs.

Possible effects of estrogen mimics and hormone blockers (HAAs) Exposure to PCBs has reduced penis size in some test animals and 118 boys born to women who were exposed to a PCB spill in Taiwan in 1979. Avg. sperm counts among men in the US and Europe have declined by 50% during the past 60 years. Great scientific uncertainty and a reasonable suspicion to harm

Factors that affect spread of transmissible disease (pg 407) Increased international air travel Migration to urban areas Migration to uninhabited rural areas and deforestation in tropical developing countries Hunger and malnutrition Increased rice cultivation Global warming High winds or hurricanes Accidental introduction of insect vectors Flooding

Increased international air travel Rapidly spread diseases such as flu, measles, cholera, yellow fever, and TB. Between 1960 and 2000, international air travel increased from about 50 million to 500 million people per year.

Migration to urban areas Increases the probability of infection from diseases such as TB (case study pg 407), cholera, and sexually transmitted diseases.

Hunger and malnutrition Increase the number of children killed by infectious diseases such as measles and diarrhea.

Increased rice cultivation In flooded fields and paddies, which creates ideal breeding grounds for mosquitoes and other insects that transmit diseases to humans

Global warming Leading to the spread of tropical infectious diseases such as malaria, yellow fever, and dengue fever to temperate areas. 2000 study at John Hopkins School of Public Health found that each 1˚ C rise in temp causes an 8% increase in diarrhea in children under the age of 5 in developing countries.

High winds and hurricanes Transfer infectious organisms and carriers of disease from tropical to temperate areas.

Accidental introduction of insect vectors Asian tiger mosquito is a vector for dengue fever, yellow fever, and other viruses. 1985 it was brought accidentally to the US inside tires shipped from Asia. Today the species has become established in Hawaii and the southeastern US and has begun extending its range north toward Chicago and Washington D. C.

Flooding Often contaminates water supplies with raw sewage Creates areas of standing water and moist soil that are ideal breeding grounds for mosquitoes and other insects that spread infectious diseases

Malaria About 45% of the world’s population lives in tropical and subtropical regions in which malaria is present. Estimated 300 -500 million people are infected with malaria parasites worldwide. Symptoms come and go: fever and chills, anemia, enlarged spleen, sever abdominal pain and headaches, extreme weakness, and greater susceptibility to other diseases. Kills about 1. 5 million people each year

Malaria continued… Caused by 4 species of protozoa of the genus Plasmodium. Most cases are transmitted when an uninfected female of any one of 60 species of Anopheles mosquito: 1. 2. 3. bites an infected person ingests blood that contains the parasite and later bites an uninfected person

Solutions: to prevent or reduce the spread (pg 410) Increase research on tropical diseases and vaccines Reduce poverty Decrease malnutrition Improve drinking water quality Reduce unnecessary use of antibiotics Educate people to take all of an antibiotic prescription Reduce antibiotic use to promote livestock growth Careful hand washing by all medical personnel Slow global warming to reduce spread of tropical diseases to temperate areas Increase preventative health care